CHEMICAL ENGINEERING METHODS AND TECHNOLOGYTRANSITION METALS CHARACTERISTICS, PROPERTIES AND USES No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services. CHEMICAL ENGINEERING METHODS AND TECHNOLOGY Additional books in this series can be found on Nova’s website under the Series tab. Additional E-books in this series can be found on Nova’s website under the E-book tab. MATERIALS SCIENCE AND TECHNOLOGIES Additional books in this series can be found on Nova’s website under the Series tab. Additional E-books in this series can be found on Nova’s website under the E-book tab. CHEMICAL ENGINEERING METHODS AND TECHNOLOGY TRANSITION METALS CHARACTERISTICS, PROPERTIES AND USES AJAY KUMAR MISHRA EDITOR Nova Science Publishers, Inc. New York Copyright © 2012 by Nova Science Publishers, Inc. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: Telephone 631-231-7269; Fax 631-231-8175 Web Site: http://www.novapublishers.com NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works. Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book. Library of Congress Cataloging-in-Publication Data Transition metals : characteristics, properties and uses / editor, Ajay Kumar Mishra. p. cm. Includes index. 1. Transition metal alloys. I. Mishra, Ajay Kumar, 1965- TN693.T7T73 2011 661'.06--dc23 Published by Nova Science Publishers, Inc. † New York ISBN: 978-1-62417-380-6 (eBook) CONTENTS Preface vii Chapter 1 Role of Reactivity of Transition Elements in Life 1 Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam and Afaf Ezzat Chapter 2 Nonlinear Optical Properties of Transition Metal Nanoparticles Synthesized by Ion Implantation 63 Andrey L. Stepanov Chapter 3 Self-Organization of the Nanocrystalline Structure and Radiation Resistance of Structural Materials 119 V. P. Kolotushkin and A. A. Parfenov Chapter 4 Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid: Synthetic Pathways and Useful Properties 165 Saikat Sarkar and Kamalendu Dey Chapter 5 Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate Molecular Systems 221 Bogumiła Żurowska Chapter 6 Review: Transition Metals in Medicine 263 Hanan F. Abdel-Halim Chapter 7 Application of Transition Metals as Active Compounds in Separation Techniques 299 Iwona Rykowska and Wiesław Wasiak Chapter 8 Chromium Pigment 327 Mohammad Fikry Ragai Fouda , Hanan. F.Abdel-Halim and Samia Abdul Raouf Mostafa Chapter 9 Transition Metals: Bioinorganic and Redox Reactions in Biological Systems 349 Marisa G. Repetto and Alberto Boveris Contents vi Chapter 10 Hydrodesulfurization of Dibenzothiophene over Various CoMoP/Al 2 O 3 Sulfide Catalysts Prepared from Co and Mo Phosphoric Acids 371 Masatoshi Nagai, Yuki Nakamura and Shoji Kurata Chapter 11 Mixed Transition Metal Acetylides with Different Metals Connected by Carbon-Rich Bridging Units: On the Way to Hetero-Multimetallic Organometallics 383 Heinrich Lang and Alexander Jakob Chapter 12 Reactivity of Unstable Chemicals in the Presence of Transition Metals 453 Mieko Kumasaki Index 483 PREFACE In this book, the authors present topical research in the study of the characteristics, properties and uses of transition metals. Topics discussed include the nonlinear optical properties of transition metal nanoparticles synthesized by ion implantation; the structural and magnetic characterization of Cu-Picolinate and Cu-Quinaldinate molecular systems; application of transition metals as active compounds in separation techniques; the reactivity of unstable chemicals in the presence of transition metals and the bioinorganic and redox reactions in biological systems of transition metals. (Imprint: Nova) Transition metals are commonly known as d-block elements that forms the bridge between the main group elements of the periodic table. These elements are lustrous / shiny solids or liquids and possess metallic properties which include hardness, toughness and strong metallic atom-atom bonding. Some of the characteristic properties of these metals include its ability to form colour compounds, exhibiting many oxidations states and their magnetic behaviour. Besides these properties, these metals are good conductors of heat and electricity and have many free electrons per atom to carry thermal and electrical energy. These metals can be easily hammered and bent into different shapes. Due to the strong metallic bonding, the transition elements show high melting point, boiling point and high density. Transition metals are used as alloy and useful as structural materials due to their strength and hardness properties. They are also used as pigments for artwork and give bright colours to stained glass and ceramic glazes. Due to metallic properties, the transition metals have been exploited for many industrial, commercial, strategic, environmental, ornamental, medial, biomedical applications. Among these, the common use at technological scale is their use as catalysts in industrial chemical processes and also in the anti-pollution catalytic converters in car exhausts. Due to the catalysis behaviour of the transition metals, a variety of new synthetic methodologies has been developed and applied to industrial processes. It is very difficult to find a multi-step synthesis of complex organic molecules where transition metal catalyzed processes are not employed. Significant progress in homogeneous catalysis and the depth understanding of the mechanisms and also from developments based on the new information derived in studying the behaviour of organotransition metal complexes. The organotransition metal chemistry and homogeneous catalysis area has been extensively studied with the ferrocene, Ziegler catalyst, and the Hoechst-Wacker process. This prompted the organotransition metal chemistry in a significant increase in the number and novel chemical features that are applicable to catalysis. The advantage of homogeneous catalysis over conventional heterogeneous catalysis allows Ajay Kumar Mishra viii the clarification of the reaction mechanisms at the molecular level by catalytic cycles consisting of elementary processes. Transition metals have a key role in the development of medicine, coordination chemistry, plant biology, materials science, polymer science and also by biochemists and biologists as well. The transition metals ions and complexes play a central role in controlling the reactivity and mechanism of the chemical reaction of interest. This can be due to the actual reaction occurring at the metal centre and/or the catalytic activity of the metal complex in an overall chemical process. The unique ability of transition metal ions and complexes to control the chemistry of environmental, industrial, and biological processes has increased the importance of clarifying their mechanistic behaviour in simple and complex chemical processes. The role of the central metal atom or ion has received considerable attention not only in fundamental inorganic and organometallic chemistry but also in more applied areas such as in environmental, bioinorganic, and bioorganic chemistry. Transition metal catalyzed polymerization, synthesis of compounds of interest for material research, the use of non-conventional solvents such as water, supercritical fluids, and ionic liquids, and reactions employing polymer supported reactants have gained enormous attentions. The polymer synthesis has also been widely studied by the olefin polymerization and copolymerization by late transition metal catalysts. Polymer synthesis has been influenced by the development of single-site polymerization of olefins by complexes of the transition metals where the coordination and insertion modes of monomers are controlled by the ligand. Ring opening metathesis polymerization developed the studies of metal carbene type transition metal complexes. This methodology can be involved through studies on the elementary processes which can be applied to prepare new materials of unique properties for various applications. This book covers the a wider domain of research and development where the use of transition metals have been investigated for various applications such as drug delivery, organometallics, bio-organometallic chemistry, chemotherapy, clinical and pharmaceutical aspects. This will enlighten the beginners by providing an excellent source of high quality information for experts in the field. This book will also allow the bioinorganic chemists, the pharmaceutical industry, chemists and biochemists to innovate their ideas using multidisciplinary approach and applications of transition metals. The book covers broad literatures in the area of transition metals in organic synthesis including novel reactions, new catalysts, ligands, and reaction conditions and applications in synthesis of complex organic molecules. The book is especially beneficial to the scholars who are planning or are working towards their graduate and postgraduate degrees in this field of bioinorganic chemistry. The advance aspects of the bioinorganic chemistry is a platform for all levels of academics and research as it provides background for the recent research literature, abbreviation summaries of the inorganic chemistry, biochemistry and spectroscopy. The book is thus an interesting read for those who wish to obtain a general overview of the most important transition metals, fundamentals concept and also will provide a useful steppingstone for further exploration of the literature. The book also covers a wide research area that integrates biology, chemistry, materials science, engineering and nanotechnology to present an interdisciplinary approach for solving multitude problems. The unique approach to cover the fundamental knowledge along with the recent advancements for the research and development in the field of transition metals is sure to make a niche for extensive knowledge dissipation to all ages. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 1 ROLE OF REACTIVITY OF TRANSITION ELEMENTS IN LIFE Mohamed Fikry Ragai Fouda 1 , Omar Mohamed Abdel-Salam 2 and Afaf Ezzat 3 1 Professor of Inorganic Chemistry, Department of Inorganic Chemistry, National Research Centre, Cairo, Egypt 2 Professor of Pharmacology, Department of Toxicology and Narcotics, National Research Centre, Cairo, Egypt 3 Professor of Biochemistry, Department of Nutrition and Food Sciences, National Research Centre, Cairo, Egypt INTRODUCTION In the last two decades, the field of biological inorganic chemistry has shown a rapid explosion with a tremendous increase in our understanding of the roles of transition metals in both higher plants and human life. The 25 elements that have been shown to be essential to life in microorganisms are belonging to "s", 'b' and 'd' block elements. The "s" block elements are namely H, Na, B, K, Mg and Ca, whereas the "b" block elements are; C, N, O, F, Si, P, S, Cl, Se, I and As. The "d" block elements namely are V, Cr, Mn, Fe, Co, Ni, Cu and Mo, whereas the "d" closed shell elements are Zn and Cd. Amongst all the following four 'b" block elements, H, C, N and O are the most abundant elements in living organisms, where they make up 99.3% of all the atoms in the body, but the remaining 21 elements only account for 0.7 %. Apart form the last four elements, which constitute the outermost percentage of elements essential for life, the remaining twenty one elements can be divided into two groups: (i) the macronutrients: these consist of seven elements; calcium, phosphorous, potassium, sulphur, chlorine, sodium and magnesium, which are found in greater concentrations in the body than are the remainder of the 21 elements; (ii) the trace elements: these consist of fourteen elements; iron, manganese, copper, zinc, molybdenum, cobalt, vanadium, chromium, nickel, fluorine, silicon, selenium, arsenic and iodine. All the 21 elements of the macronutrients and Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 2 the trace elements are found in living systems, either as ions, or covalently bonded to organic residues. This monograph is confined to throw the light on the importance of V, Cr, Mn, Fe, Co, Ni, Cu, which are belonging to first transition series, as well as closed shell zinc element, in addition to molybdenum which is a member in the second transition series. This monograph is also oriented to clarify the importance of the elements mentioned before as micronutrients for higher plants and their participation in various enzyme systems in the plant. In that context the sources of these inorganic micronutrients in the soil is taken into consideration. In addition, it is aimed to explain the important role of these elements in body life, where they are able to create oxidative stress inside the body on one hand and the ability of them to act as antioxidants in case of attachment to some proteins, on the other hand. Some of these metals are contained in several enzymes such as iron (transferrin), molybdenum (xanthine oxidase), vanadium (hemovanadin), zinc (carbonic anhydrase), and copper (hepatocuprein). There is also an evidence linking some diseases and the deficiency of a number of transition elements. At the same time, an increase in some of transition elements has been suggested to lead to neurodegenerative disorders e.g., iron in case of Parkinson's disease and copper in Alzheimer's disease. In addition, the so called metallo- therapeutics have been used in the last few decades in the treatment of some human aliments. The application of metallo-therapy includes the use of some organometallics or metal-organic complexes, such as using some gold and platinum complexes as antiarthritis and antitumour drugs, respectively. The metal-based photodynamically active compounds are in use nowadays in treatment of some types of human malignancies. Deficiency in the first raw transition elements as well as Zn and Mo leads to deficiency in enzymes containing them in the body. The excess amounts of these soft and borderline metals prefer to react with the soft bases e.g., glutathione and sulfur proteins which are considered antioxidants. The different phenomena showed by the aforementioned elements will be discussed in the light of affinity of their cations towards several anions. TRANSITION METALS AND PLANTS The higher plants which are usually contain chlorophyll as a photosensitizer synthesize their nutrients and tissues from simple substances from air and different constituents in the soil (e.g.CO 2 ,O 2 , H 2 O, NO - 3 , SO -2 4 , Cl - , Ca 2+ , Mg 2+ , Fe +2 , Mn 2+ , CO 2- 3 , etc.). These elements can be classified to three categories based on demands of them by plant. These categories are macro-micro- and benefitial nutrients [1, 2]. The macronutrients are those elements which are required for plant with a quantities ranged between few- and many hundreds of kilograms / hectare. These elements namely are, hydrogen, oxygen, nitrogen, carbon, phosphorous, calcium, magnesium and sulphur. Based on the electronic configuration of these elements one can be classified as "s" and "b" block elements [3]. On the other hand both micro- and beneficial elements (Mn, Fe, Co, Ni, Cu, Zn, Mo, B) are belonging to "d" block elements except B which belongs to "s" block elements. The last two categories of elements are required for healthy plants, with a quantity ranged between few and several hundreds of grams/hectare. These elements have important roles in Role of Reactivity of Transition Elements in Life 3 plants and microbial vital processes [4]. The most common ones of these roles especially their participation in the enzyme systems [see table (1)][2]. Table 1. Functions of several micronutrients in higher plants Micronutrients Functions in higher plants Manganese Activates decarboxylase, dehydrogenase, and oxidase enzymes; important in photosynthesis, nitrogen metabolism, and nitrogen assimilation. Iron Present in several peroxidase, catalase, and cytochrome oxidase enzymes; found in ferredoxine which participates in oxidation reduction reactions (e.g. NO - 3 and SO 4 2- reduction, nitrogen fixation; important in chlorophyll. Cobalt Essential for nitrogen fixation; found in vitamin B 12 . Nickel Required as a component of the urease enzyme. Zinc Present in several dehydrogenase, proteinase and peptidase enzymes; promostes growth hormones and starch formation; promotes seed maturation and production. Molybdenum Present in nitrogenase (nitrogen fixation) and nitrate reductase enzymes; essential for nitrogen fixation and high oxidizing. Boron Activates certain dehydrogenase enymes; facilitates sugar translocation and synthesis of nucleic acids and plant hormones; essential for cell division and development. Copper Present in laccase and several other oxidase enzymes; important in photosynthesis, protein and carbohydrate metabolism, and probably nitrogen fixation. Based on these foregoing findings one can notices that macronutrient elements all among the highly abundant elements in nature, where as micro- and beneficial elements are considered as ones from less common elements [3], except iron. The requirements of higher plants for hard acidic ions such as Ca 2+ , K + , [PO 2 ] 1 can be gained from constituents of soil as well as from artificial fertilizers such as Ca(NO 3 ) 2 , (NH 4 ) 2 SO 4 , Ca (H 2 PO 4 ) 2 , K 2 SO 4 , KNO 3 etc. These fertilizers do not suffer from inconsistency in case if they applied in an alkaline soil. The microand beneficial nutrients are considered as soft and borderline elements except Fe 3+ and B 3+ . The positive ions of these elements are being soft or borderline ones except Fe 3+ and B 3+ which are hard acidic species. Based on the foregoing discussions one can say that their bearing compounds are found as of insoluble compounds. The last ones are found in nature [3] according to the following: Mn (Mn-oxides, silicates and carbonates); Fe (Fe-oxides, sulphides and silicates); Co(Co- sulphides and silicates); Ni (Ni-sulphides and silicates); Cu (Cu- sulphides, hydroxy carbonates and oxides); Zn (Zn-sulphides, carbonates, and silicates). The molybdenum may be found as sulphides, oxides and molybdates [3]. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 4 The previous forms are mostly insoluble so that they are converted to soluble salts (e.g. sulphates, nitrates) before application as fertilizers). In case of application of these salts as fertilizers in an alkaline soil, their ions suffer from inconsistancy and transformed to insoluble hydroxides. In such case these nutrients given to the plant in the form of metal- organic complexes stable at alkaline medium [4]. Here in the following one can find the nomenclature as well as chemical formulae and abbreviations of the most chelating agents used in preparation of the corresponding micro and beneficial metal – organic complexes which derived from ethylencdiaminetelra acetic acid and its derivates as well as citric and oxalic acids: Ethylendiaminetetroacetic acid, (C 10 H 16 O 8 N 2 , EDTA); Diethylemetriamepenta acetic acid (C 14 H 22 O 12 N 3 ); cyclohexanediaminetetroacetic (C 14 H 22 O 8 N 2 , CDTA); Nitriloacetic acid (C 6 H 9 O 6 N, HEDTA); Hydroxyethylemediaminetetroacetic acid (C 10 H 18 O 7 N 2 ); Ethylenediaminedichydroxyphenyl-acetic acid (C 18 H 20 O 6 , EDDHA); Citric acid (C 6 H 8 O 7 , CIT); Oxalic acid (C 2 H 2 O 4 ,OX) [5]. CHEMICAL ELEMENTS IN LIFE Chemical elements essential to life forms can be divided into: (1) bulk elements (H, C, N, O, P, S) which are present in large quantities; (2) macrominerals and ions; are those needed by the body in relatively large amounts; being composed of the "s" block elements Na, K, Ca, Mg and "p" block elements Cl and PO3- 4); (3) micro/trace minerals; are those needed in small amounts and consist of the d-block elements vanadium, chromium, molybdenum, manganese, iron, cobalt, nickel, copper and zinc, and are also known as the trace metals as well as fluorine, silicon, selenium, arsenic and iodine. The bulk metals form 1–2% of the human body-weight whereas the trace elements represent less than 0.01% [6]. Within cells, distribution of metal ions is more complex in that the cells must themselves control any competition between the metal ions in the same internal compartment; moreover, the metal ions must also have a functional value. Those elements that are found prominently in most cells, together with their free concentrations in the central cell compartment [6-8]. The concentration of these elements varied from an element to another. Table 2. The concentration of selected elements in the human body [6,7] Element Concentration in body (Wt) Concentration in cytoplasm (mol/L) Na + 0.1 10 -3 K + 0.1 10 -1 Mg 2+ 0.04 10 -3 Ca 2+ 10 -7 Mn 2+ 2 x 10 -5 10 -7 Fe 2+ 0.005 10 -7 Co 2+ 9 x 10 -6 < 10 -9 Ni 2+ 2 x 10 -5 < 10 -9 Cu 2+ (Cu + ) 2 x 10 -4 < 10 -14 Zn 2+ 0.003 10 -11 MoO 4 -2 10 -8 Role of Reactivity of Transition Elements in Life 5 NUTRITIONALLY ESSENTIAL AND NON-ESSENTIAL METALS Metals can also be classified as being nutritionally essential for humans such as cobalt, chromium (III), copper, iron (II) and iron (III), manganese and molybdenum, in addition to non-metal namely selenium and "d" closed zinc element. On the other hand metals one such as arsenic, cadmium, lead, and mercury, and their inorganic compounds can even be toxic to human health [9]. One can satte that these elements are considered as soft ones and can perform stable compounds with soft sulfur compounds such as glutathione reductase and thioproteins, preventing the last ones from preventing oxidative stress. Still there are some metals which are not essential to human health but may have some beneficial effects at low levels of exposure e.g., silicon, nickel, boron, and vanadium. These elements have the capability of forming oxygen compounds. Meanwhile, boron, nickel, silicon, and vanadium have been shown to have biological functions in plants and some animals but essentiality for humans has not been demonstrated [9]. Soft elements are characterized by high polarizability, low electronegativity, small negative charge, large size, covanent π type of bond usually associated with the base (electron donor), available empty orbitals on donor atom are low lying and associative. Hard elements are characterized by low polarizability, high electronegativity, large negative charge, small size, ionic electrostatic type of bond usually associated with the base, high energy and associative available empty orbitals on donor atom. Table 3. Nutritionally essential and non-essential elements Nutritionally essential elements (soft and borderline elements) Elements with possible beneficial effects (hard and borderline elements) Elements with no known beneficial effects (soft and hard elements) Cobalt : d block element Chromium III : d block element Copper : d block element Iron: d block element Manganese : d block element Molybdenum : d block element Zinc : d block element Selenium : b block element Boron : s block element Vanadium : d block element Nickel : d block element Silicon : p block element Aluminum s: block element Barium s : block element Beryllium s : block element Strontium s: block element Thallium s: block element Silver : d block element Antimony : p block element Arsenic : p block element Cadmium : p block element Lead : p block element Mercury (p) THE BIOLOGICAL VALUES OF IRON, COPPER, MANGANESE, NIKEL, CHROMIUM, ZINC, MOLYBDENUM, COBALT AND VANADIUM IN HUMAN Trace elements are those elements occurring in the human body but constituting 0.01% of body weight [10]. The trace elements include iron, manganese, copper, zinc, molybdenum, Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 6 cobalt, vanadium, chromium, nickel, fluorine, silicon, selenium, arsenic and iodine. Their concentrations, however, vary in different tissues. In particular iron, copper, selenium, manganese, chromium, molybdenum and iodine are essential to human health that metalloproteins represent about one third of all structurally characterized proteins with a biological activity and over 40% of all enzymes contain metals [6, 11]. These metals are also required to maintain the brain's biochemistry. Their interchangeable prevalent ionic forms and affinity for functional groups occurring in proteins are unique properties of transition metals that make them useful in biochemical redox reactions [12, 13]. Metals determine the geometry of enzymatic active sites, act as centers for enzyme reactivity, and act as biological oxidation–reduction facilitators [8]. Transition metals that exist in multiple oxidation states serve as electron carriers e.g., iron ions in cytochromes; as facilitators of oxygen transport e.g., iron ions in hemoglobin and as sites at which enzyme catalysis occurs e.g., copper ions in superoxide dismutase. Transition metal ions that exist in single oxidation states, such as zinc(II), function as structural elements in superoxide dismutase and zinc-finger motifs [8]. Proteins with which transition metals and zinc are most commonly associated catalyze the intramolecular or intermolecular rearrangement of electrons. Although the redox properties of the metals are important in many of the reactions, in others the metal appears to contribute to the structure of the active state, e.g., zinc in the Cu-Zn dismutases and some of the iron in the photosynthetic reaction center. Sometimes equivalent reactions are catalyzed by proteins with different metal centers; the metal binding sites and proteins have evolved separately for each type of metal center [7].Copper- and zinc-containing superoxide dismutase, manganese- containing superoxide dismutase, catalase, and glutathione peroxidase form the primary enzymic defense against toxic oxygen reduction metabolites. But, metal-induced uncontrolled redox reactions or displacement of endogenous metal cofactors from their cellular binding sites can also lead to cellular perturbations [12, 13]. Moreover, any of the trace elements has the potential to be toxic if given in sufficiently large quantities, but that for most trace elements normal physiological or dietary conditions are extremely unlikely to achieve such levels [14]. Whilst Fe, Cu, Cr, V and Co undergo redox-cycling reactions, for a second group of metals, Hg, Cd and Ni, the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical thiols, however, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed [15]. [As 5+ + H 2 O 2 → • OH + As 3+ ]. Iron and copper are redox-active metals (i.e. can switch between oxidized and reduced forms: Cu 2+ /Cu 1+ and Fe 3+ / Fe 2+ ) and often participate in electron transfer [16] (see below). Iron and copper are also involved in dioxygen (O 2 ) storage and carriage via metalloproteins [e.g. hemoglobin, myoglobin and hemocyanin] [6]. Copper is found in essential proteins such as cytochrome c oxidase, catechol oxidase, and ascorbate oxidase, a Cu/Zn superoxide dismutase, and many other oxidoreductases, and monooxygenases. It is responsible for oxidation-reduction processes that involve electron transfer, dioxygen chemistry, and reduction of nitrogen oxides. Its position in the middle of the elements of the first transition series (so designated because their ions have incompletely filled d orbitals) implies that iron has the possibility of various oxidation states (from −II to +VI), the principal ones being II (d6) and III (d5), although a number of iron-dependent monooxygenases generate high valent Fe(IV) or Fe(V) reactive intermediates during their catalytic cycle [17](Crichton, 2001). Copper exists mainly in two oxidation states, Cu(I) and Cu(II), and often changes between these two states while catalyzing reactions. Transition metals such as iron and copper are Role of Reactivity of Transition Elements in Life 7 involved in both metal-catalyzed (“auto”) oxidations and reactions leading to hydroxy1 radical production from superoxide, a species frequently proposed to initiate lipid peroxidation. Similar mechanisms involving the Fenton-like production of superoxide anion and hydroxyl radical appear to be involved for iron, copper, chromium, and vanadium. However, with some metal ions, such as mercury, nickel, lead, and cadmium, depletion of glutathione and protein-bound sulfhydryls may play a primary role in the overall toxic manifestations [12]. 2O 2 - +2H + →H 2 O 2 +O 2 Fe 2+ +H 2 O 2 → Fe 3+ + • OH+OH - Traces of Fe 3+ can react further with H 2 O 2 : Fe 3+ +H 2 O 2 →Fe 2+ +O 2 - +H + Possible more reactions: OH+H 2 O 2 →H 2 O+H + +O 2 - O 2 - +Fe 3+ →Fe 2+ +O 2 OH+Fe 2+ →Fe 3+ +OH - 2H 2 O 2 + Fe salt catalyst→2H 2 O+O 2 Cu + + H 2 O 2 → Cu 2+ + • OH +OH - CH 3 OH+ • OH →H 2 O+ • CH 2 OH Cl+ • OH→Cl • +OH - H 2 O 2 +O 2 - →O 2 +OH - + • OH Fe 3+ +O 2 - →Fe 2+ + O 2 (O2- reducing the iron salt) Fe 2+ + H 2 O 2 →Fe 3+ + • OH +OH - (Fenton reaction) Net : O 2 -+H 2 O 2 + Fe salt catalyst →O 2 + • OH+OH - The levels of essential metals are strictly regulated by specific metal transporters at gastrointestinal tract and blood-brain barrier. When dietary levels of essential metals are low, levels of the corresponding transporters increase in the intestine, after which there is a greater potential for increased transport of toxic metals. The divalent metal transporter 1 (DMT1), actively transport Fe, Zn, Mn, Co, Cd, Cu, Ni, and Pb, via a proton-coupled mechanism [18]. Involvement of intracellular transporters for copper and zinc has been shown in animal models of Alzheimer's disease, raising the possibility that higher levels of iron, zinc and copper might be due to a disruption in the activity of transporters. Accordingly, exposure to toxicants that affect the activity of transporters potentially could contribute to the aetiology/progression of neurodegenerative diseases [19] as we will see later. Two non- enzymatic proteins, ferritin and ceruloplasmin, also appear to play important roles in transition-metal storage and antioxidant defense in vivo. Ferritin, which binds iron in the cytoplasm of mammalian cells, and ceruloplasmin, which binds copper in plasma, are thought by many to contribute a significant antioxidant capacity to bodily fluids. Other proteins that Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 8 bind metals include transferrin, haptoglobin, albumin and metallothioneins are in the same sense protective. The latter belong to a family of low molecular weight, cysteine rich intracellular proteins that bind transition metals, including zinc and cadmium [20]. Iron Iron is the most abundant transition metal and the second most prevalent metal of the earth’s crust [17]. Iron is essential for microbial, plant, animal, and human life [21]. The amount of total body iron is around 3 to 4 grams which is contained mainly in the haemoglobin of the erythrocytes. The major site of iron storage in the body is the liver. Red cell turnover constitutes the major pool of iron turnover in the body [22, 23]. Most iron is in the form of heme iron that is found in hemoglobin, myoglobin, and iron-containing enzymes (such as catalase and the cytochromes). More than two thirds of the body’s iron content is incorporated into hemoglobin in developing erythroid precursors and mature red cells. The rest of the total body iron exists as a nonheme iron, which consists of plasma iron, iron bound to transferrin, and stored iron in ferritin and hemosiderin [22, 24]. Iron is a key player in some of the most central processes of biological systems, including oxygen transport and utilization, electron transfer, metabolism of nucleic acids and many other key biological molecules, degradation of biological pollutants, and many other reactions [25]. The duodenum and proximal jejunum are the main sites of absorption of dietary iron. Haem iron is absorbed more efficiently than non-haem iron, apparently by endocytosis of the intact iron– protoporphyrin complex at the enterocyte brush border. Iron is then liberated from the haem moiety by the action of haem oxygenase and enters the intracellular iron pool from which it can be transferred across the basolateral membrane, bind to transferrin and enter the circulation. Meanwhile, absorption of non-haem iron requires reduction of ferric iron at the brush border membrane, followed by internalization by a proton coupled transporter [2]. In normal human plasma, serum iron (~ 20 µM) exists primarily in the Fe 3+ form and is complexed with the high affinity iron binding protein transferrin, an 80-kd glycoprotein that is synthesized in the liver (Tf; ~ 40 µM) in a 2:1 ratio. At blood pH (7.4), each molecule of transferrin can bind two atoms of ferric iron [27]. Only one third of the transferrin is saturated with iron which implies that all the iron in the circulation is bound to transferring. In circumstances in which the binding capacity of transferring becomes saturated, as for example in iron loading disorders, iron forms low-molecular-weight complexes, the most abundant of which is iron citrate [26]. Most cellular uptake of ferric iron (Fe 3+ ) occurs via receptor-mediated endocytosis of transferrin (vesicular import pathway IN2) which binds to specific membrane-bound transferrin receptor (TfR). Inside the cell, members of the Steap family of ferric reductases localize to the endosome and reduce Fe 3+ (ferric) to its Fe 2+ (ferrous) form before Fe 2+ is released into the cytosol by the divalent metal transporter-1 (DMT1) in an H + -dependent manner [28]. DMT1 is not specific to iron; it can transport a wide variety of divalent metal ions, including manganese, cobalt, copper, zinc, cadmium, and lead [22]. Free Fe 2+ in the cytosol constitutes a “labile iron” pool (~ 2-3 µM) for cellular utilization, supplying Fe 2+ molecules as co-factors for many Fe 2+ -dependent enzymes in the cytosol, mitochondria, and nucleus. If cytosolic iron is not immediately used, it can also be rapidly sequestered by cytosolic Ft into a non-reactive Fe 3+ - Ft complexes. Iron can be Role of Reactivity of Transition Elements in Life 9 released from cells by the iron exporter ferroportin [29]. Fe 3+ can be bound in the extracellular space by Tf, citrate, ascorbate, or ATP. Cytosolic or intralysosomal iron overload may catalyze the production of free radical oxides via the Fenton reaction. Radical oxides may cause cellular damage by oxidizing macromoleucles such as lipids, DNA, and proteins. Iron transport across the blood brain barrier is the result of receptor-mediated endocytosis of iron-containing transferrin by capillary endothelial cells, followed by recycling of transferrin to the blood and transport of non-transferrin-bound iron into the brain. The principle sources of extracellular transferrin in the brain are hepatocytes, oligodendrocytes, and the choroid plexus [30]. Copper Copper is the third most abundant metallic element in the human body, following iron and zinc, and it is important in all other life forms. The daily intake of Cu ranges from 0.6 to 1.6 mg / day with the main sources of Cu being seeds, grains, nuts, beans, shellfish, and liver. It is estimated that the adult human body contains between 50-150 mg [31, 32]. Free Cu2+ content of human plasma is approximately 2x10-16 M [33-36] and total copper concentrations in most tissues are approximately 5x10-5 M total copper [37]. Clinically apparent copper deficiency is extremely rare and difficult to achieve by dietary means, but loss-of-function mutations in the ATP7A gene encoding a copper-transporting P1B-type Atpase, involved in the delivery of copper to the secreted copper enzymes and required for copper absorption and homeostasis is associated with Menkes disease, resulting severe tissue copper deficiency, seizures, neurodegeneration, psychomotor deterioration, failure to thrive, and death in early infancy [38, 39]. On the other hand, the toxicity associated with excess copper manifest in Wilson disease, a rare, autosomal recessive disorder of copper metabolism where tissue copper accumulation results in hepatic, neurologic, or psychiatric disturbances. Mutations in the ATP7B gene which is located on the long arm (q) of chromosome 13 (13q14.3) cause failure of copper excretion into the bile and a defective incorporation of copper into ceruloplasmin [40]. Copper homeostasis is maintained by adjusting intestinal copper absorption and copper excretion in bile. Copper is absorbed in the proximal intestinal tract, facilitated by the simultaneous absorption of amino acids and decreased by zinc and vitamin C. Excretion which occurs primarily through the bile is increased by molybdenum, as well as by diets high in calcium and phosphorus. The excretion of copper into the gastrointestinal tract increases when dietary copper is high and more is absorbed, thereby, protecting against excess accumulation of copper in the body. Vice versa, low copper intake is associated with little endogenous copper is excreted, protecting against copper depletion [41]. This is controlled by specific transporters that take up metals at the apical surface and export them at the basolateral surface of intestinal cells, and are involved in their intracellular distribution. The level of these transporters increases or decreases in the intestine according to the dietary levels of essential metals [19]. The uptake of Cu into the cells is mediated by two transporter proteins; Cu transporter 1 (Ctr1) and divalent metal transporter 1 (DMT1) that transports Cu across the plasma membrane (located on the plasma membrane). ATP7A and ATP7B are membrane-bound copper-transporting P-type ATPases that catalyze an ATP-dependent transfer of Cu to intracellular compartments or participate in Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 10 Cu efflux from the cell [42]. Cellular copper excretion also involves COMMD1 [copper metabolism (Murr1) domain containing 1] [43]. Most of Cu ions absorbed from the small intestine are distributed to liver and kidneys; they are transported in blood mostly (65-90%) by tightly binding to protein "ceruloplasmin", synthesized in the liver where it binds Cu and the rest of Cu loosely binds with albumin, transcuprein and amino acids (e.g., histidine) [33]. Only reduced Cu can be transported [43]. Cu is transported into the brain through the blood brain barrier as a free Cu ion [44]. Redox cycling between Cu 2+ and Cu 1+ can catalyse the production of highly toxic hydroxyl radicals, with subsequent damage to lipids, proteins, DNA and other biomolecules. Free intracellular copper is detoxified primarily by metallothionein (MT) proteins. Metallothioneins are ubiquitous low molecular weight proteins rich in cysteine residues that have high metal-binding capacities. They bind heavy metal ions (mainly Cd, Zn and Cu) via metal-thiolate clusters, thus they are essential in metal homeostasis and protect against metal toxicity [45, 46]. The incorporation of intracellular copper into the structure of different cuproenzymes is carried out by copper chaperones; Atox1 (delivers copper to copper transporting ATPases in the late Golgi), CCS (copper chaperone for SOD, required for copper incorporation into Cu/Zn superoxide dismutase), and Cox17, Sco1 and Sco2 (delivers copper to subunits of mitochondrial cytochrome c oxidase) [43, 47]. Copper chaperones through transporting copper in the cytoplasm to the site of utilization by copper-dependent proteins, ensure that copper can reach its specific target protein and also prevent inappropriate copper interactions with other cellular, protecting the cell from the deleterious effects of free copper e.g., protection against oxidative stress [48]. An increase in the endogenous level of Atox1 expression have been demonstrated protect neurons against oxidative stress. Furthermore, overexpression of an Atox1 metal binding mutant is detrimental to cell viability. Furthermore, mutations in the copper binding motif of Atox1 result in a dominant negative phenotype where the cell viability is diminished [49]. The copper chaperone for the superoxide dismutase gene is necessary for expression of an active, copper-bound form of superoxide dismutase in vivo in spite of the high affinity of superoxide dismutase for copper. This metallochaperone protein activates the target enzyme through direct insertion of the copper cofactor and apparently functions to protect the metal ion from binding to intracellular copper scavengers. Thus intracellular [Cu] free is limited to less than one free copper ion per cell and a pool of free copper ions is not used in physiological activation of metalloenzymes [50]. The highest concentration of CCS is found in the kidney and liver. There is also a significant amount of this copper chaperone protein in the CNS being found throughout the neuropil, with expression largely confined to neurons and some astrocytes [51]. Cu is required as a catalytic cofactor in various cuproenzymes, including the mitochondrial cytochrome c oxidase, a component of the electron transport chain, caeruloplasmin, monoamine oxidase, dopamine B-hydroxylase, tyrosinase, involved in the production of melanin histaminase, lysyl oxidase, involved in the cross-linking of elastin and collagen, and Cu/Zn-superoxide dismutase. The enzyme superoxide dismutase (SOD) occurs in three forms in mammalian systems: (1) CuZnSOD (SOD1) found in the cytosol, (2) MnSOD (SOD2) found in mitochondria, and (3) CuZnSOD found in extracellular space (SOD3). The active site in Cn/Zn superoxide dismutase consists of one Cu atom and one Zn atom, coordinated to a common histidine ligand; His63 in human SOD1 and His61 in human SOD2. The copper atom is coordinated by three other histidine residues and zinc is coordinated by two other histidine residues and one asparagines [52]. Additionally, many Role of Reactivity of Transition Elements in Life 11 bacterial SOD enzymes contain iron. Copper is also an essential component of chromatin and is involved in chromatin scaffold proteins. Food copper (organic copper) is processed by the liver and is transported and sequestered in a safe manner. Inorganic copper, such as that in drinking water and copper supplements, largely bypasses the liver and enters the free copper pool of the blood directly. This copper is potentially toxic because it may penetrate the blood/brain barrier [53]. Cu toxicity comes about from its ability to produce reactive oxygen species, displace other metal ions, peroxidize lipids, and directly cleave DNA and RNA. Copper exists physiologically in two redox states, as cuprous Cu1+ (reduced) or cupric Cu 2+ (oxidized) and can interchange between these forms by accepting or donating an electron. This allows the cation to participate in biochemical reactions as a reducing or oxidizing agent [54]. This same properties which make copper being essential for various enzymatic reactions, is also responsible for copper toxicity via its ability to generate free radicals, in particular, the highly reactive hydroxyl radical through Fenton chemistry, which subsequently can damage lipids, proteins, DNA and other biomolecules [55]. Most extracellular copper is Cu(II) and most, if not all, intracellular copper is Cu(I). Typical intracellular copper-binding proteins, such as the Cu-transporting P-type ATPases ATP7B and ATP7A bind copper as Cu(I)[54]. It has been suggested that, the toxic and carcinogenic potential of mineral dusts inhaled into the lungs is related, in part, to biochemical reaction mechanisms involving iron and reactive oxygen species that occur at the mineral surface [56, 57]. Many cancer tissues contain highly elevated levels of Cu [58, 59]. The reasons for this elevation are unclear but one possible result is increased angiogenesis [60, 61]. The copper-chelating agent, trientine, suppressed tumor development and angiogenesis in the murine hepatocellular carcinoma cells [62]. A copper transporter, Ctr1p, was discovered to mediate cisplatin uptake in yeast and mammals. Increased cisplatin resistance caused by deletion of the Ctr1 gene suggests its important role in cellular resistance. This finding presents a potential target for modulating cisplatin antitumor efficacy [63].The combined treatment with a copper chelator and cisplatin increased cisplatin-DNA adduct levels in cancerous but not in normal tissues, impaired angiogenesis, and improved therapeutic efficacy. Others reported increased accumulation of iron, nickel, chromium, zinc, cadmium, mercury, and lead in breast cancer samples [64]. Cancerous cells have more transferrin receptors than normal cells [65] because of their need for oxygen. In our opinion, the high levels of singlet oxygen attacks the species of sulphur (glutathione) which acts as an antioxidant. The complexation of metals with SH bearing compounds leads to a decrease in antioxidant capacity. Manganese Manganese (Mn) is the 12th most abundant element in the earth’s crust comprising about 0.1% of the earth’s crust [66, 67]. Manganese is an essential mineral for humans, animals, and plants. It is present in virtually all diets at low concentrations. Mn is present in most tissues of all living organisms and is present naturally in rocks, soil, water, and food. Humans maintain stable tissue levels of Mn via tight homeostatic control of both absorption and excretion of ingested Mn and limit tissue uptake at low to moderate levels of inhalation exposure [68-70]. The most significant source of manganese exposure for the general population is food. The highest manganese concentrations are found in nuts (up to 47 µg/g) and grains (up to 41 µg/g). Lower levels are found in milk products (0.02–0.49 µg/g), meat, poultry, fish, and eggs Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 12 (0.10–3.99 µg/g), and fruits (0.20–10.38µg/g). Tea and leafy green vegetables have also been found to be dietary sources of manganese [71]. Mn is absorbed from the gastrointestinal tract, within the plasma, Mn is largely bound to gamma-globulin and albumin, and a small fraction of trivalent (3+)Mn is bound to the iron-carrying protein, transferring [70]. The Mn adequate intake for adult men and women is 2.3 and 1.8 mg/day, respectively [71]. Serum concentration of Mn in healthy subjects is about 0.05–0.12 µg/dl [72]. The total amount of manganese in the adult human (70 kg) has been determined to be about 10-20 mg, most of which is found in skeleton, liver, kidney, pancreas and the heart. The rest is distributed widely throughout all the tissues and fluids. A daily requirement for manganese has not been established; however, it appears that a minimum intake of 2.5 to 7 milligrams per day meets human needs. In humans, manganese is an essential nutrient that plays a role in bone mineralization, protein and energy metabolism, metabolic regulation, cellular protection from damaging free radical species, and the formation of glycosaminoglycans. An adequate amount of this trace mineral would be absolutely vital during gestation for normal foetal growth and development [73,74]. Mn dependent enzyme families include oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Manganese metalloenzymes include arginase (liver urea), glutamine synthetase (brain ammonia metabolism), phosphoenolpyruvate decarboxylase (gluconeogenesis). Mn is also the key component of superoxide dismutase (Mn-SOD) found in mitochondria of the cells. The manganese-containing superoxide dismutase (MnSOD) is a major component of the cellular defence mechanisms against the toxic effects of the superoxide radical [75]. While Mn deficiency is extremely rare in humans, toxicity due to overexposure of Mn is more prevalent. Mn toxicity has been reported in individuals exposed to high environmental levels of Mn e.g. miners, welders and those living near ferroalloy processing plants. Toxicity can also result from dietary overexposure and is evidenced primarily in the central nervous system, although lung, cardiac, liver, reproductive and fetal toxicity have been noted [72]. The brain appears to be especially vulnerable to Mn accumulation resulting in is an established clinical entity, referred to as manganism which is a progressive disorder of the extrapyramidal system similar to Parkinson's disease in its clinical features, both in laboratory animals and humans [69, 70]. Neurotoxicity due to excessive brain manganese (Mn) accumulation can occur via occupational exposure to aerosols or dusts that contain extremely high levels (>1-5 mg Mn/m(3)) of Mn, consumption of contaminated well water, or parenteral nutrition therapy in patients with liver disease or immature hepatic functioning such as the neonate(decreased biliary excretion). Although Mn exposure via parenteral nutrition is uncommon in adults, in premature infants, it is more prevalent [76]. Transport of manganese across the blood-brain barrier occurs by means of a series of transporters. Movement can take place by facilitated diffusion, active transport [77] via divalent metal transport and transferring (Tf)-dependent transport. Biliary excretion represents the main mechanism by which manganese is eliminated from the body [78]. Mn disposition in vivo is influenced by dietary iron intake and stores within the body since the two metals compete for the same binding protein in serum (transferrin) and subsequent transport systems (divalent metal transporter, DMT1). There appear to be two distinct carrier- mediated transport systems for Mn and ferrous ion: a transferrin-dependent and a transferrin- independent pathway, both of which utilize DMT1 as the transport protein [79]. In primary astrocyte cultures derived from neonatal rats.. Both iron deprivation (ID) and iron overload (+Fe) caused significant increases (p<0.05) in (54)Mn uptake in astrocytes. The decreased Role of Reactivity of Transition Elements in Life 13 TfR associated with +Fe treatment and the increased DMT-1 levels suggest that DMT-1 is a likely putative transporter of Mn in astrocytes [80]. Fe deficiency can enhance brain Mn accumulation even in the absence of excess Mn in the environment or the diet, suggesting that there is homeostatic relationship among several essential metals in the brain and not simply between Fe and Mn [81]. Mn transport appears to be temperature, energy, and pH dependent, but not Fe or Na(+) dependent. These data suggest that Mn transport across the BBB is an active process [82]. After intravenous contrast injection, normal (enteral) regulation mechanisms for manganese homeostasis are bypassed, and there is a danger of individual overdosing. Excess manganese, for example in patients with chronic liver disease or with chronic parenteral nutrition, has already been detected by magnetic resonance imaging in the basal ganglia and was found to coincide with neurologic symptoms [83]. Zinc Zn is the trace element which is essential for cell growth and maintenance of cellular integrity. It is an integral structural component of nearly 300 enzymes and other proteins involved in the expression of genetic information and cellular signal transduction. Zinc is present in all body tissues and fluids. The total body zinc content has been estimated to be 30mmol (2g). Skeletal muscle accounts for approximately 60% of the total body content and bone mass, with a zinc concentration of 1.5–3µmol/g (100–200µg/g), for approximately 30%. Lean red meat, whole-grain cereals, pulses, and legumes provide the highest concentrations of zinc: concentrations in such foods are generally in the range of 25–50mg/kg (380– 760µmol/kg) raw weight. Fish, roots and tubers, green leafy vegetables, and fruits are only modest sources of zinc, having concentrations <10mg/kg (<150µmol/kg) [84]. Zinc deficiency can result from low-zinc-containing diets (e.g., vegetarians), prolonged intravenous alimentation, gastrointestinal disease associated with diarrhea [85]. In humans, inherited zinc deficiency is rare and associated with defects in membrane-bound putative zinc transporters leading to impairment of zinc absorption in the gut and the syndrome of acrodermatitis enteropathica, characertized by skin lesions, alopecia, diarrhoea, neuropsychological disturbances and reduce immune function and led to death of the patient in the absence of treatment. A zinc deficiency disorder also occurs in premature breast fed infants [86]. Zinc is relatively abundant in biological materials being an essential component of hundreds of proteins and metalloenzymes including alkaline phosphatase, lactate dehyrogenase, carbonic anhydrase, angiotensin-converting enzyme, collagenase, δ- aminolevulinic acid anhydrase, protein kinase C, phospholipase C, aspartate transcarbamylase, nucleotide phosphorylase (5’-nucleotidase) carboxypeptides, and DNA and RNA polymerases found in most body tissues [85, 87]. The major location of zinc in the body is metallothionein, which also binds copper, chromium, mercury, and other metals. Among the well-characterized zinc proteins are the Cu-Zn superoxide dismutases (other forms have Fe or Mn), carbonic anhydrase (an abundant protein in red blood cells responsible for maintaining the pH of the blood), alcohol dehydrogenase, and a variety of hydrolases involved in the metabolism of sugars, proteins, and nucleic acids. Zinc is a common element in nucleic-acid polymerases and transcription factors, where its role is considered to be structural rather than catalytic [88]. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 14 Zinc plays specific and important catalytic, co-catalytic and structural roles in enzyme molecules and in many other proteins and biomembranes. A well-known example of the structural role of zinc in cellular and subcellular metabolism is the zinc finger motif, ubiquitous in transcription proteins. The configuration of zinc fingers, critical to DNA binding, is determined by the single zinc atom at their base. The linking of zinc fingers to corresponding sites on the DNA initiates the transcription process and gene expression. Motifs similar to zinc fingers have been identified in nuclear hormonal receptors including those for vitamin D, estrogen and testosterone. Zinc plays an important role as ionic signaling in large number of cells and tissues. Zinc-binding proteins account for nearly half of the transcription regulatory proteins in the human genome, and during the past two decades, well over 2000 zinc-dependent transcription factors involved in gene expressions of various proteins have been reported [87, 88]. Among the transition metals playing key roles in biological systems, zinc is second only to iron in biological prevalence. Unlike iron and copper, zinc has only one oxidation state accessible under physiological conditions, and therefore does not participate in catalysis of redox chemistry or electron transfer reactions. Unlike other first-row transition metals (e.g., Sc 2+ , Ti 2+ , V 2+ , Cr 2+ , Mn 2+ , Fe2+, Co 2+ , Ni 2+ and Cu 2+ ), the zinc ion (Zn 2+ ) contains a filled d orbital (d10) and therefore does not participate in redox reactions but rather functions as a Lewis acid to accept a pair of electrons [89]. The types of enzymatic reactions in which zinc is found to play a role include peptidases and amidases, phosphatases, phospholipase, phosphotriesterase, deaminases and alcohol dehydrogenase, among others. One mechanism by which zinc is believed to facilitate some of these reactions is through binding and thereby lowering the pKa of water, generating a localized high concentration of metal-bound hydroxide in the active site, which can act as a nucleophile in the hydrolytic reactions [25]. Zinc is very different from magnesium, manganese and calcium. It binds nitrogen and sulfur much more readily and also shows lower coordination numbers in spite of its size (which is intermediate between that of magnesium and divalent manganese. It was found that the predominant ligand to zinc depends on the coordination number of the metal ion, whereas the other metal ions just listed each prefer oxygen at all coordination numbers. Zinc tends to form 4-, 5-, and 6- coordinate complexes with about equal ease. When the coordination number is four, sulfur is as likely a ligand as oxygen, when it is 5 nitrogen is the most common ligand, and for coordination numbers 6 and 7 oxygen predominates as a ligand. Thus, zinc can possibly replace magnesium or divalent manganese (since they both bind oxygen when their coordination number is 6), but it has other options for coordination, in keeping with its reactivity in the active sites of enzymes (often involving a change in coordination number). [90]. Molybdenum Molybdenum is a very rare element with a crustal abundance of about 1.2 mg/kg [91]. Molybdenum is the only second-row transition metal that is required by most living organisms [92]. The tolerable upper intake level for the United States and Canada was set at 2 mg/d in 2002 [93], and the European Commission suggested an upper limit of 0.6 mg/d [94].The availability of molybdenum to biological systems is due to the high water solubility of oxidized forms of the metal. In man, absorption of molybdenum after oral intake is in the Role of Reactivity of Transition Elements in Life 15 range of 28-77% and urinary excretion is 17-80% of the total dose [95]. Stable-isotope studies of molybdenum metabolism have been conducted in which molybdenum was added to the diet and was assumed to be absorbed and utilized similarly to the molybdenum in foods. These studies showed that molybdenum is well absorbed over a range of intakes, that it is rapidly excreted via the urine, and that total body molybdenum retention is regulated primarily via urinary excretion. With high molybdenum intake, molybdenum absorption increases and excretion is more rapid [96]. In healthy young men, absorption of molybdenum from the intestine increased at higher molybdenum intakes.Urinary output appears to be the key pathway for regulating the body's exposure to molybdenum. Higher molybdenum intake resulted in higher rates of urinary excretion [97]. Because molybdenum toxicity is associated with copper intake or depleted copper stores in the body, humans who have an inadequate intake of dietary copper or some dysfunction in their copper metabolism that makes them copper-deficient could be at greater risk of molybdenum toxicity [95]. Deficiency is rare in humans and is limited primarily to genetic defects leading to serious abnormalities. Molybdenum cofactor deficiency in humans results in the loss of the activity of molybdoenzymes sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. The resultant severe phenotype, which includes progressive neurological damage leading in most cases to early childhood death, results primarily from the deficiency of sulfite oxidase. Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency are autosomal recessive inborn errors of metabolism with severe neurological symptoms resulting from a lack of sulfite oxidase activity [98, 99]. The metal itself is biologically inactive unless it is complexed by a special cofactor. With the exception of bacterial nitrogenase, where Mo is a constituent of the FeMo-cofactor, Mo is bound to a pterin, thus forming the molybdenum cofactor (Moco) which is the active compound at the catalytic site of all other Mo-enzymes. Several enzymes in humans contain molybdenum catalysing diverse redox reactions. In man, these enzymes, sulfite oxidase, xanthine oxidase, and aldehyde oxidase, contain the same molybdenum complex, molybdopterine. The molybdenum enzymes xanthine oxidase, sulfite oxidase and aldehyde oxidase are involved in the human diseases of gout, combined oxidase deficiency and radical damage following cardiac failure. Sulfite oxidase catalyzes the final step in the degradation of sulfur-containing amino acids and is involved in detoxifying excess sulfite. Xanthine oxidase is the final enzyme in the conversion of hypoxanthine to xanthine, and subsequently, to uric acid. Aldehyde oxidase catalyzes the oxidation of aldehydes, pynmidines, purines, pteridines, and related compounds [100, 101]. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 16 The metal is found in three different oxidation states (IV, V and VI) and has the desirable ability to couple biological compounds that are obligatory two-electron carriers (e.g. NADH) with obligatory one-electron carriers (e.g. iron-sulphur centres and cytochromes) [102]. Cobalt Cobalt is the least abundant 3dr transition metal (in sea water and earth crust). Cobalt is found in vitamin B12 , its only apparent biological site. Vitamin B12 occurs in the body mainly as methylcobalamin, adenosylcobalamin and hydroxycobalamine(a precursor to methyl and adenosylcobalamine). Hydroxycobalamine is most stable form of all cobalamine and is water soluble. B 12 is found in animal protein and not in vegetables. Cobalt is an essential metal for humans and has to be ingested in the form of cobalamines (vitamin B12). Only microorganisms can biosynthesize cobalamine. Cobalt in cobalamines can be reduced and oxidized (2-one electron steps), thus cobalamine containing enzymes participate in redox reactions. Vitamin-B 12 deficiency causes the severe disease of pernicious anemia in humans, which indicates the critical role of cobalt [103, 104]. The vitamin B 12 cofactors coenzyme B 12 or 5’-deoxy-5’-adenosylcobalamin (AdoCbl), and methylcobalamin (MeCbl) consist of cobalt(III) bound to a substituted corrin ring and an alkyl group (either adenosyl or methyl). Adenosylcobalamin (AdoCbl) or coenzyme B12 is an organometallic cofactor that functions as a radical reservoir and is used by enzymes to catalyze rearrangement reactions in which a hydrogen atom and a variable group on adjacent carbons are interchanged (mutases and eliminases). Methylcobalamin (MeCbl) is the cofactor of several methyltransferases, such as methionine synthase (MetH), which catalyzes methionine biosynthesis both in mammals and bacteria [104, 105]. Chromium Chromium is an essential nutrient required for sugar and fat metabolism. The estimated safe and adequate daily dietary intake for Cr is 50 to 200 microg. However, most diets contain less than 60% of the minimum suggested intake of 50 microg, suggesting that the normal Role of Reactivity of Transition Elements in Life 17 dietary intake of Cr for humans is suboptimal. Trivalent Cr has a very large safety range and there have been no documented signs of Cr toxicity in any of the nutritional studies at levels up to 1 mg per day [106]. Trivalent chromium is an essential nutrient required for sugar and fat metabolism. Most recent evidence strongly supports the conclusion that there is little fear of toxic reactions from chromium consumption. In addition to type 2 diabetes mellitus, chromium supplementation may be useful to direct overall weight decrements specifically towards fat loss with the retention of lean body mass and to ameliorate many manifestations of aging [107]. There is growing evidence that chromium may facilitate insulin signaling and chromium supplementation therefore may improve systemic insulin sensitivity. However, supplementation with chromium picolinate, a stable and highly bioavailable form of chromium, has been shown to reduce insulin resistance and to help reduce the risk of cardiovascular disease and type 2 diabetes [108]. However, controversy exists as to whether dietary supplementation with chromium should be routinely recommended in subjects without documented deficiencies [109]. Whether chromium is an essential element has been examined for the first time in carefully controlled metal-free conditions using a series of purified diets containing various chromium contents. Animal studies reveal that a diet with as little chromium as reasonably possible had no effect on body composition, glucose metabolism, or insulin sensitivity compared with a chromium-"sufficient" diet [110]. Vanadium Vanadium, a dietary micronutrient, is yet to be established as an essential part of the human diet. Vanadium is abundant in rocks and soil [110]. Constituting 0.015% of earth's crust, vanadium is about as abundant as zinc [111]. In water the presence of vanadium derives almost exclusively from the solubilization of the metal present in soil and in rocks [110]. Exposure to the vanadium in water is enough to affects its presence in the daily diet and determines greater values of the element in the principal biological liquids in people [112]. The metal is present in comparatively high concentration of vanadium in sea water, being second most abundant transition metal (30 nM Na + 2VO - 4 ), only surpassed by molybdenum (100 nM molybdate), and clearly more abundant than iron (0.02–1 nM). Vent-derived iron oxides have been shown to scavenge vanadium from sea water and thus to contribute in controlling the concentration and cycling of vanadium in the oceans [111]. Concentrations in soil vary in the range 3-310 μg/g and may reach high values (up to 400 μg/g) in areas polluted by fly ash. The concentration of vanadium in water is largely dependent on geographical location and ranges from 0.2 to more than 100 μg/litre in freshwater, and from 0.2 to 29 μg/litre in seawater [113]. Vanadium is introduced into man through the intake of food, especially whole meal cereals, but also beef, chicken, milk, spinach, mushrooms, parsley [114]. The mean vanadium concentration in the diet was reported to be 32 μg/kg (range 19-50 μg) and the mean daily intake was estimated to be 20 μg/day [113]. Absorbed vanadium is transported mainly in the plasma, bound to transferrin. Pentavalent vanadium is reduced in erythrocytes to the tetravalent form. This reduction is a glutathione-dependent process [113]. It appears that values, around 1 nmol/l for blood and serum and around 10 nmol/l or slightly lower for urine may be considered tentative normal values [115]. This transition element is known to influence a battery of enzymatic systems, namely phosphatases, ATPases, peroxidases, ribonucleases, protein kinases and oxidoreductases. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 18 In biological conditions, vanadium fulfils two conditions for a potential biometal: (i) redox activity in an electrochemical potential (and free energy) frame relevant for biochemical processes, and (ii) susceptibility for nucleophilic substrates.Vanadium easily switches between the oxidation states V and IV (which, along with III, are the oxidation states of naturally occurring vanadium compounds). The redox potential at pH 7 for the couple H 2 VO 4 - +4H + +e - VO 2+ + 3H 2 O amounts to -0.341 V and thus is in the range where vanadyl (VO 2+ ) is oxidised to vanadate under aerobic conditions, and vanadate reduced to vanadyl by cellular components such as cysteine containing peptides (glutathione) and proteins, ascorbate, NADH, and phenolic compounds. The main species present under physiological aerobic conditions is the acid-base pair H 2 VO 4 - → HVO 4 2- + H + (pk a = 8.1) [111]. Nickel Nickel is widely distributed in the environment. Natural sources of atmospheric nickel include dusts from volcanic emissions and the weathering of rocks and soils. Thus, humans are constantly exposed to this ubiquitous element although in variable amounts. The daily dietary intake of nickel is 25–35 g, and it is more than triple the daily requirement [116]. Generally, greater than 250 µg nickel of Ni/g of diet are required to produce signs of Ni toxicity such as depressed growth and anaemia in animals [117]. Ni-dependent enzymes are urease, [NiFe] hydrogenase, [Ni] superoxide dismutase, CO dehydrogenase, and S-methyl- CoM reductase, which catalyzes the terminal step in methane production by methanogenic bacteria. All the Ni-proteins known to date are from plants or bacteria [116]. TRANSITION METALS AND HUMAN DISEASE Role of Transition Elements in Cancer Cancer is undoubtly one of the most grave human disease known so far. Several transition metals, including chromium(vi), nickel, and cadmium have been suggested as human carcinogens [118]. All these elements are soft and borderline elements i.e., they are able to associate with thiols or compounds containing SH group. Metals are widely distributed elements, usually occurring at low levels in the earth’s crust, although some geographic areas have naturally high levels in soil. Metals are released into the environment during mining operations, industrial and manufacturing processes, and as by-products of combustion. Metals are generally present at low concentrations in ambient air, although much higher concentrations have been measured near metal processing facilities. Metals typically do not require bioactivation, at least not in the sense that an organic molecule undergoes enzymatic modification that produces a reactive chemical species [119]. Cadmium, lead, and nickel compounds have been shown to be mutagenic and carcinogenic in rodent studies [120] because of their ability to inhibit the repair of damaged DNA. In addition, they can enhance the mutagenicity and carcinogenecity of directly-acting genotoxic agents [121]. Role of Reactivity of Transition Elements in Life 19 A case-control study of breast cancer and metal exposure found an increased risk for women exposed to a group of metals (chromium, arsenic, beryllium, and nickel), as well as exposure to lead and cadmium individually [122]. A highly significant accumulation of iron, nickel, chromium, zinc, cadmium, mercury, and lead was found in the cancer samples when compared to the control group [63]. Increased Cu concentrations were also found in human lung cancer biopsies [123] and in other tumors [124]. Excessive lipid peroxidation induced malondialdehyde-DNA adducts was detected in the breast tissue of women with breast cancer leading to endogenous DNA modifications [125]. The most common airborne exposures to nickel compounds are to insoluble nickel compounds such as elemental nickel, nickel sulfide, and the nickel oxides from dusts and fumes. Contributions to nickel in the ambient air are made by combustion of fossil fuels, nickel plating, and other metallurgical processes. The most common oxidation state of nickel is the divalent (Ni 2+ ) form [126]. Nickel is also used in electroplating baths, batteries, textile dyes, and catalysts. Ni (II) in the presence of H2O2 produced greater base damage to the DNA in chromatin than to isolated DNA, unlike Co (II) [127]. Nickel compounds are carcinogenic to humans and metallic nickel is possibly carcinogenic to humans. A 2-year inhalation study of nickel oxide in rats and mice conducted by the National Toxicology Program [128] indicated a carcinogenic effect of nickel oxide in the lungs. Occupational exposure to nickel producing anelevated risk of nasal cancer and a 30% excess of lung cancer in the workforce nasal cancer and a 30% excess of lung cancer [129]. It has been shown that histone demethylase JMJD1A and DNA repair enzyme ABH2 family of dioxygenases is highly sensitive to inhibition by nickel ions through by replacing the ferrous iron in the catalytic centers. Inhibition of these dioxygenases by nickel is likely to have widespread impacts on cells (e.g. impaired epigenetic programs and DNA repair) and may eventually lead to cancer development [130]. The U.S. National Toxicology Program (NTP, 2002)[131] carcinogenicity study of inhaled V(2)O(5) in rats and mice, concluded that clear evidence of lung tumors was seen in mice of both genders and that there was some evidence of carcinogenicity in male rats. In response to this study, vanadium pentoxide (V(2)O(5)) and other inorganic vanadium compounds have recently been evaluated by several occupational exposure limit setting committees and expert groups. It has been argued that, because of inherent weaknesses in design and procedure, the U.S. National Toxicology Program study of the carcinogenicity of inhaled vanadium pentoxide does not provide adequate evidence to support the classification by regulatory authorities of vanadium pentoxide as a Group 2B (possible) human carcinogen [132, 133]. The lungs are a significant site of entry of vanadium in the case of community exposure [113]. Vanadate enters cells where it is reduced by glutathione and other agents to vanadyl species (VO 2+ ) and stabilized as such by various ligands. Vanadyl binds readily to proteins, amino acids, nucleic acids, phosphates, phospholipids, glutathione, citrate, oxalate, lactate, ascorbate, edetate, etc. [134]. Welding fumes contain many different metals including vanadium typically present as particulates containing vanadium pentoxide (V2O5). Recently, inhalative exposure to vanadium pentoxide in workers from a V(2)O(5) factory has been reported to cause oxidation of DNA bases, affect DNA repair, and induce formation of nucleoplasmic bridges and nuclear buds in leukocytes, suggesting that the workers are at increased risk for cancer and other diseases that are related to DNA instability [135]. In vitro, human peripheral lymphocyte cultures were exposed to 1, 2, 4, or 8 microg/mL of Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 20 vanadium(III) trioxide, vanadium(IV) tetraoxide, or vanadium(V) pentoxide (V(2)O(3), V(2)O(4), or V(2)O(5), respectively. These cultures were then screened for structural chromosomal aberrations, and mitotic index (MI) measurements were made. Cytogenetic evaluations showed that only V(2)O(4) increased the percentage of aberrant cells (without gaps) and chromosome damage (including and excluding gaps), while all compounds led to a decrease in the MI. These results demonstrate that vanadium(III), vanadium(IV), and vanadium(V) are all capable of inducing cytotoxicity, but only oxidation state IV induces clastogenic effects [136]. Furthermore, vanadium pentoxide induced pulmonary inflammation and tumor promotion in some strains of mice [137]. Vanadate generates the hydroxyl radical via a Fenton-like reaction rather than a Haber-Weiss reaction [138]. V(V)+O 2 •- → V(ΙV)+ O 2 V(ΙV)+ H 2 O 2 → V(V) + • OH+OH - Some essential metals e.g., chromium VI and iron can also be carcinogenic. Chromium is naturally occurring in rocks, animals, plants, soil and in volcanic dust and gases. Trivalent chromium (III) is an essential nutrient for the body. Hexavalent chromium (VI), is generally produced by industrial processes. Non-occupational exposure to Cr(VI)compounds occurs from cigarette smoke, automobile emissions, areas of landfills and hazardous waste disposal sites [139, 140]. Cr(VI) compounds have been classified as group I human carcinogens by the International Agency of Research in Cancer in 1990 [141]. When inhaled, chromate particles dissolve to form soluble Cr(VI) oxyanions that enter cells through non-specific anionic transporters and are metabolically reduced within the cell by ascorbic acid and low molecular weight thiols glutathione and cysteine to their lower oxidation states such as Cr(V), Cr(IV) and Cr(III) ), the most stable form of Cr in cells. During the one-electron reduction of Cr(VI), superoxide anion (O 2 ·– ) and hydroxyl radicals are produced causing DNA damage [142,-146]. Reactive oxygen species were produced by the decomposition of Cr(V)(O2)4 -3 ion, resulting in DNA damage. The generation of hydroxyl radical was detected by ESR [147]. Cr(III) forms coordinate covalent and ionic interactions with DNA bases and the phosphodiester backbone, respectively [148, 149]. Cr(ΙΙΙ)+O 2 •- → Cr(ΙΙ)+ O 2 Cr(ΙΙ)+ H 2 O 2 → Cr(ΙΙΙ) + • OH+OH - Cr(VΙ)+O 2 •- → Cr(V)+ O 2 Cr(V)+ H 2 O 2 → Cr(VΙ) + • OH+OH - Hypervalent Cr species (Cr(V), Cr(IV)), and carbon based and oxygen radicals may also react with DNA following Cr(VI) reduction [147, 150]. During Cr(VI) reduction, a diverse range of genetic lesions are generated including Cr-DNA binary (mono) adducts, Cr-DNA ternary adducts, DNA-strand breaks, DNA-protein crosslinks, oxidized bases, abasic sites, and DNA inter- and intrastrand crosslinks. The damage induced by Cr(VI) can lead to Role of Reactivity of Transition Elements in Life 21 dysfunctional DNA replication and transcription, aberrant cell cycle checkpoints, dysregulated DNA repair mechanisms, microsatelite instability, inflammatory responses, and the disruption of key regulatory gene networks responsible for the balance of cell survival and cell death, which may all play an important role in Cr(VI) carcinogenesis [151, 152]. Electron spin resonance (ESR) and fluorescence analysis revealed that Cr(VI) increased intracellular levels of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide anion radical in dose-dependent manner [153]. Mitochondrial ROS, specifically superoxide anion (O 2 ·– ), mediates Cr(VI)-induced apoptosis of human lung epithelial H460 cells [154]. Cr(VI) induced a mitochondrial-mediated and caspase-dependent apoptosis in skin epidermal cells through reactive oxygen species-mediated activation of p53 [153]. Evidence indicates that trivalent chromium compounds do not cause cancer, although high concentrations in some in vitro systems have shown genetic toxicity. Hexavalent chromium compounds cause cancer in humans, in experimental animals and exert genetic toxicity in bacteria and in mammalian cells in vitro. Epidemiological evidence and animal studies indicate that the slightly soluble hexavalent salts are the most potent carcinogens [155]. In their study, Gibb et al.[156] demonstrated a strong dose-response relationship of cumulative hexavalent chromium exposure and the risk for lung cancer in exposed human workers; cumulative trivalent chromium exposure was not. The excess risk of lung cancer associated with cumulative hexavalent chromium exposure was not confounded by smoking status. Several epidemiological studies have reported a possible correlation between measures of iron status and cancer among people in the general population and it is possible that iron accumulation in the liver is a risk factor for hepatocellular carcinoma in patients with haemochromatosis who also had increased incidence of extrahepatic cancer as well [157- 159]. In this disease status in which Fe ++ accumulates in tissues as a result of an autosomal recessive genetic disease leading to enhanced gastrointestinal absorption of iron that leads to a progressive increase of iron stores, the concentration of this redoxactive transition metal capable of catalyzing and/or generating free radicals like superoxide, hydrogen peroxide, and hydroxyl radical is markedly increased inducing cellular lipid peroxidation and DNA-attack [160, 161]. Studies have shown a greater ability than normal cells for tumor cells to grow and survive in the presence of high concentrations of iron [162]. In contrast, tumor growth in iron- deficient mice [163]. Iron may also act as a promoter of already initiated hepatocytes in the development of liver cancer in the rat [164]. A study of a national cohort of United States adults suggested an increased risk of dying from cancer with higher levels of serum iron, transferrin, and serum copper at baseline in males and females. The association of cancer with serum iron and transferrin tended to be stronger among women, whereas the association with serum copper tended to be stronger among men [165]. One study found higher serum iron concentrations in individuals with colorectal cancer than control subjects [9]. However, the evidence for a relationship between dietary iron intake and cancer, particularly colorectal cancer in the general population, is inconclusive, with reports linking high dietary Fe and Cu to colorectal cancer [166, 167] and a more recent study founding a non-significant inverse association for dietary iron and colorectal cancer risk, and a significant inverse association for serum ferritin and colorectal cancer risk. In this study, serum ferritin, serum iron and transferrin saturation were all inversely associated with colon cancer risk specifically, but not rectal cancer risk, whereas serum serum unsaturated iron binding capacity was associated with a greater risk for colon cancer [168]. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 22 There is a clear evidence linking over production of free radical species and the risk of cancer development. Oxidative damage to DNA can cause single point mutations which, when undetected and unrepaired by enzyme repair systems, can lead to transversion mutations, and errors in the DNA sequence. Indeed the chemical properties of some transition metals suggests a role for them in carcinogenesis. Fe or Cu can generate the reactive oxygen species including hydroxyl radicals via Fenton- and Haber-Weiss-reactions, ascorbate autoxidation, lipid peroxidation processes, and formation of DNA strand breaks [169, 170]. Several mechanisms have been proposed to explain the carcinogenic potential of iron. First, ferric ions are reduced by superoxide and the ferric product is reoxydized by peroxide to yield hydroxyl radicals which can attack DNA causing point mutations, DNA cross linking and DNA strand breaks. Second, iron can bolster the growth of cancer cells by suppressing host defenses. Finally, being an essential micronutrient, iron is important tumour cell multiplication [161]. It has been suggested that three predominant mechanisms generally account for carcinogenicity: (1) interference with cellular redox regulation and induction of oxidative stress, which may cause oxidative DNA damage or trigger signaling cascades leading to stimulation of cell growth; (2) inhibition of major DNA repair systems resulting in genomic instability and accumulation of critical mutations; (3) deregulation of cell proliferation by induction of signaling pathways or inactivation of growth controls such as tumor suppressor genes. In addition, specific metal compounds exhibit unique mechanisms such as interruption of cell-cell adhesion by cadmium, direct DNA binding of trivalent chromium, and interaction of vanadate with phosphate binding sites of protein phosphatase [171]. In our opinion it is thus possible to categorize transition metals that has been suspected in the process of carcinogenesis into two categories depending on their reactivity. The first of them are the oxidizing ones i.e., metals that have high oxidation number which can liberate free radicals via the Fenton reaction eg., [VO 3 ] 1- , [CrO 4 ] 2- ,[FeO 2 ] 1- ,[CuO 2 ] 2- or V 5+ , Cr 6+ , Fe 3+ and Cu 2+ . The second group of them includes the soft and borderline (between soft and hard) metals that can react with the antioxidant compounds containing SH or OH reactive groups such as glutathione and picolines. These metals are namely Cu 2+ , Fe 2+ , Co 2+ , Ni 2+ and Zn 2+ . Thus Fe 3+ complexes can react with H 2 O 2 to produce free radicals while Fe 2+ an react with the antioxidant glutathione thus impairing antioxidant defense mechanisms increasing the vunerability of the cell to carcinogenic stimuli. It should also be noted that As 5+ reacts with H 2 O 2 leading to the formation of As 3+ + H 2 O + O -• 2 . (the latter species is a highly reactive one which can lead to DNA alterations). Role of Transition Elements in Some Neurodegenerative Diseases The brain contains a relatively high concentration of a number of metals such as Fe, Zn, and Cu (in the order of 0.1–0.5 µM) [172]. Metal ions, particularly redox-active metal ions like copper and iron are the transition metals of marked significance in human disease and have been reported to accumulate in particular brain regions with aging [173]. An increase in their tissue concentration has been associated with the development of two important human diseases; haemochromatosis and Wilson's disease. The former is characterized by a genetic predisposition to an increased absorption of enteral iron with a consequent increased iron Role of Reactivity of Transition Elements in Life 23 level in the blood and tissues [174]. Wilson's disease, is a disorder of copper metabolism in which copper accumulation in tissues causes liver inflammation, fibrosis and neurologic complications including movement and psychiatric disorders [175]. Under these pathological conditions, transition metals and their transport proteins may accumulate in different target organs inducing cellular lipid peroxidation and DNA-attack. Redox active metals such as Cu, Fe and Mn can result in metal-catalyzed protein oxidation, while metal-protein associations can result in protein aggregation [176]. Recently, there has been much interest in the contribution to transition metals and in particular iron and copper to neurodegenerative diseases which will be highlighted in the following sections. We will focus on two well known and indeed the most common brain diseases namely Alzheimer's disease and Parkinson's disease. Fe(ΙΙΙ)+O 2 •- → Fe(ΙΙ)+ O 2 Fe(ΙΙ)+ H 2 O 2 → Fe(ΙΙΙ) + • OH +OH - Cu(ΙΙ)+O 2 •- → Cu(Ι)+ O 2 Cu(Ι)+ H 2 O 2 → Cu(ΙΙ) + • OH+OH - 2O 2 •- +2H + → H 2 O 2 +O 2 Cu 2+ + H 2 O 2 → • OH + Cu 1+ TRANSITION METALS AND ALZHEIMER'S DISEASE This progressive neurodegenerative disorder is characterized by a profound memory impairment and cognitive decline [177, 178] which is associated with loss of central cholinergic neurons in the neocortex. The disease is estimated to affect 15 million people worldwide. The most common risk factor is age with an incidence of 0.5% per year at the age of 65 years to nearly 8% per year after the age of 85 years [179]. Most cases (95%) are sporadic, with only 5% of genetic origin. Neuropathologically, there is gliosis and tissue atrophy, most pronounced in the frontal and temporal cortices [180]. The disease is also characterized by the presence of amyloid beta (Aβ) senile plaques and neurofibrillary tangles as well as dystrophic neuritis and degenerating neurons [181]. Senile or neuritic plaques consist principally of extracellular deposites of an ~ 4.3 kDa polypeptide, amyloid β (Aβ) peptide, derived from the proteolytic cleavage of the amyloid precursor protein (APP), a membrane bound normal protein molecule with 771 amino acids produced by neuronal and non-neuronal cells [182-184]. (forms when an alternative (beta-secretase and then gamma- secretase) enzymatic pathway is utilized for processing.). The Aβ peptide can be between 39 and 43 residues in length. Neuritic plaques are composed of an extracellular core of filaments that measure 5-10 nm in diameter and are surrounded by dystrophic neurites and other debris, as well as microglial cytoplasmic processes and astrocytic processes containing glial filaments. Dense bodies, autophagic vacuoles and other membranous debris are common [185]. Neurofibrillary tangles are intracellular aggregates of a hyperphosphorylated form of the microtubule associated protein "tau", whose function is to regulate microtubule assembly and helps stabilize stabilize the neuronal microtubule skeleton [186]. Strong evidence implicates transition metals such copper, iron, and zinc in the pathophysiology of Alzheimer’s disease. In this respect, copper appears to have an important Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 24 role, though zinc as well as iron have also been implicated. Increased iron was found within the glial cells surrounding the neuritic plaques [187](Cu 2+ is soft acid whereas Zn 2+ and Fe 2+ are borderline ones). High concentrations of copper (0.4 mM), zinc (1 mM) and iron (1mM) have been found within amyloid plaques [188]. In red blood cells patients affected by Alzheimer's disease, levels of Cu, Zn SOD activity increased early in the disease [189]. Studies suggested increased Zn in hippocampus, amygdala, and multiple neocortical areas of patients with Alzheimer’s disease [190-192]. More recent studies suggest a significant decrease of serum Zn in men with mild cognitive impairment (which accompany normal aging) (MCI) compared to women with MCI and with normal men [193]. There were significant elevations of the Zn transporter proteins ZnT-1 and ZnT-6, responsible for export of Zn to the extracellular space in brain of Alzheimer's disease patients [194,195]. Copper serum was increased in patients with Alzheimer’s disease patients when compared with healthy controls [196] while a high concentration of copper was found within senile plaques and neurofibrillary tangles of Alzheimer’s disease brains [188, 197, 198]. Free serum copper (not bound to ceruloplasmin) was significantly elevated in patients with Alzheimer’s compared to controls [53]. Free copper in serum predicted the annual change in Mini-Mental State Examination. Hyperlipidemic patients with higher levels of free copper seemed more prone to worse cognitive impairment [199]. In those with normal mental state, there was a significant inverse correlation of the serum levels of free copper (though not ceruloplasmin- bound copper) with both Mini-Mental State Examination and attention-related neuropsychological tests scores [200]. Studies suggested that an increase of 1 micro mol/L in serum copper account for 80% of the risk of having Alzheimer’s disease and correlate with poor neuropsychological performance and medial temporal lobe atrophy. The latter correlated also with decreased antioxidant capacity [196]. Oral Cu supplementation itself [Cu-(II)- orotate-dihydrate; 8 mg Cu daily] in patients with mild Alzheimer’s disease for 12 months, however, had neither a detrimental nor a promoting effect on the progression of the disease [201]. Ceruloplasmin fragmentation occurs in the serum of Alzheimer’s disease patients, possibly related to ‘free’ copper deregulation in this disease [202]. The loss of the copper chaperone for superoxide dismutase (CCS) which binds to the β-site AβPP cleaving enzyme, increases Aβ production [203, 204]. Strozyk et al. [204] suggested that excessive interaction with copper and zinc may induce neocortical Aβ precipitation in Alzheimer’s disease, but soluble Aβ degradation is normally promoted by physiological copper and zinc concentrations. The authors observed a significant inverse correlation of cerebrospinal fluid Aβ42 with copper, zinc, iron, manganese and chromium, but there was no association with selenium or aluminum. In vitro data suggested that low concentrations (2 μM) of exogenous Zn and Cu promoted the degradation of synthetic Aβ added to CSF samples. Our opinion is that soft acid ion such as Cu 2+ and borderline (laid between soft and hard ions) ions such as Fe 2+ , Mn 2+ , Cr 3+ could have a role in Alzheimer’s disease. On the contrary, Alzheimer’s disease is not associated with hard acid ions e.g., Al 3+ . Based on the results of numerous investigations, we can conclude that the first step in the pathogenesis of Alzheimer’s disease (and possibly other neurodegenerative diseases)is the interaction between reactive oxygen species e.g., O 2 ·– , 1 O 2 with the cell membrane which in turn suffers from alteration of its chemical structure; the highly polymerized membrane being changed to a less polymerized one with the above mentioned species forming tetrahydral coordination Role of Reactivity of Transition Elements in Life 25 compounds. Change in membrane structure may lead to changes in its electricity, which enhances the transportation of different metals such as Zn, Cu and Fe. Amyloid Beta Protein (Aβ) Deposition in the Brain is a Hallmark of Alzheimer's Disease The analysis of the assembly pathway of Aβ in vitro and biochemical characterization of Aβ deposits isolated from Alzheimer’s disease brains indicate that Aβ oligomerization occurs via distinct intermediates, including oligomers of 3–50 Aβ monomers, annular oligomers, protofibrils, fibrils and plaques. Of these, the most toxic species appear to be small Aβ oligomers. Aggregation is believed to be transition metal-dependent [205]. Monomeric Aβ + metal ions → Dimers → Oligomers→Protofibrills→Amyloid Peptides containing the 40- or 42-residue forms of Aβ, and shorter derivatives, form amyloid-like fibrils in vitro, which are morphologically, tinctorially, immunologically, spectroscopically and ultrastructurally similar to fibrillar aggregates extracted from Alzheimer’s disease amyloid plaques. Structural model of amyloid-like fibrils have been proposed that is composed of several protofilaments, which consist of hydrogen-bonding β- sheet structures with the β-strands running perpendicular to the long fibre axis, a structure known as a cross-βconformation [206]. There exist two conformational states for Aβ aggregates: (i) the nonβ-sheet, an amorphous, non-fibrillar, state and (ii) the β-sheet, a highly ordered, fibrillar, state which is neurotoxic [26]. It is largely thought that Aβ peptide aggregation into insoluble fibrils is an important early event in a cascade of events leading to neuronal cell death in the brains of Alzheimer’s disease patients [184, 207]. There is however more convincing evidence that soluble oligomers may in fact be the most toxic species [208]. Oligomeric Abeta can disturb the structure and function of cell membranes and alter membrane mechanical properties, such as membrane fluidity and molecular order. Much of these effects are attributed to their capability to trigger oxidative stress and inflammation [209].These oligomeric assemblies of Aβ, which surround plaques, induce calcium mediated secondary cascades that lead to dystrophic neurites, dendritic simplification, and dendritic spine loss in both neurons in culture and in the adult mouse brain [210]. The observation of the co-deposition of metals and amyloid-β 42 (Aβ 42 ) in brain tissue in Alzheimer’s disease indicated the need to understand the role of metals in Aβ aggregation. The aggregation of Abeta can be induced by Zn(2+) or Cu(2+) [211]. Huang et al. (1999) [212] suggested an obligatory role for metal ions in initiating Abeta amyloidosis and oligomerization. In vitro precipitation and amyloidosis of Abeta1-40 initiated by Abeta1-42 were abolished by chelation of trace metal contaminants. Iron(III) ion produced both the oligomerization of the peptide and iron-rich high molecular mass complexes [213]. In our opinion, the oxidation of thiol compounds to sulphoxides decreases the ability of soft and borderline ions such as Cu 2+ , Hg 2+ , Co 2+ , Ni 2+ and Zn 2+ so that these ions preferentially form coordination complexes with monomer and oligomer Aβ peptide species. Human Aβ can bind metal ions [214, 215] due to the presence of a low and high affinity binding site for both Cu and Zn via three N-terminal histidine imidazole rings with the Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 26 stoichiometry for Cu:Aβ being 1:1 and for Zn:Aβ ranging from 1:1 to 3:1[216, 217]. It has been suggested that interaction of both Zn2+ and Cu2+ ions with Abeta peptides may occur in brain areas affected by Alzheimer's disease and Zn2+-induced transition in the peptide structure might contribute to amyloid plaque formation [218]. Elucidation of the chemistry through which transition-metal ions participate in the assembly and toxicity of Abeta oligomers is important to drug design efforts if inhibition of Abeta containing bound metal ions becomes a treatment for Alzheimer's disease. Figure 1. Illustration of CU 2+ coordination by Aβ, where the metal is believed to be coordinated by His- 6, His-13 and His-14 and Tyr-10. The imidazole side chain of a His residue bridges between two CU 2+ atoms to form dimeric Aβ. The N-terminal region of Aβ can access different metal-ion-coordination environments and different complexes can lead to profound changes in Aβ self-assembly kinetics, morphology, and toxicity [219]. Metals can bind Aβ-peptides in an intra- as well as in an inter-peptide coordination mode [220, 221]. Raman microscopy showed that Zn 2+ ions are bound to Aβ via the histidine imidazole rings within senile plaque cores [222]. One form of metal coordination that can drive peptide aggregation is the formation of histidine bridges, where the imidazole side chain of a His residue in a Cu-bound Aβ can also coordinate to the copper of a second Aβ peptide [223]. The novel distorted six-coordinated (3N3O) geometry around copper in the Aβ-Cu 2+ complexes include three histidines: glutamic, or/and aspartic acid, and axial water [217]. Aβ1-40 bound easily one copper ion to form the [M+Cu+ 4H]6+ complex [213]. Stellato et al [221]suggested differences in the structural conformation of the complex that depend on the nature of the coordinated metal. In (Cu-Aβ)1 complex, the metal is tightly bound to three histidines in a fairly closed structure, which “protects” the metal against any further interaction. This contrasts with the open structure of the (Zn-Aβ)1 complex, making available the metal for further interaction [221]. Zn 2+ coordination is dominated by inter-molecular coordination and the formation of polymeric species. His6, His13 and His14 residues are implicated in Zn-Ah binding [224]. Miller et al. [225] observed that Zn 2+ coordination promotes Aβ 42 aggregation leading to less uniform structures. In oligomeric Zn 2+ -Aβ 42 , Zn 2+ can simultaneously coordinate intra- and intermolecularly, bridging two peptides. Zinc coordination significantly decreases the solvation energy for large Zn 2+ -Aβ 42 oligomers and thus enhances their aggregation tendency. Increasing Zn 2+ concentration could slow down the aggregation rate, even though the aggregation rates are still much higher than in Zn 2+ -free solution. Investigation of the temperature dependence of the EPR signal for Cu 2+ bound to soluble Aβ or Cu 2+ in fibrillar Abeta showed that the Cu 2+ center displays normal Curie Role of Reactivity of Transition Elements in Life 27 behavior, indicating that the site is a mononuclear Cu 2+ site. Fibrils assembled in the presence of Cu 2+ contained one Cu 2+ ion per peptide. Thus the ligand donor atom set to Cu 2+ does not change during organization of Abeta monomers into fibrils and neither soluble nor fibrillar forms of Abeta(1-40) with Cu 2+ contain antiferromagnetically exchange-coupled binuclear Cu 2+ sites in which two Cu 2+ ions are bridged by an intervening ligand [214]. Jun et al. [226] proposed that Aβ (1-40) has a second copper-binding site in a proton-rich environment and that the second binding Cu(II) ion interferes with a conformational transition into amyloid fibrils, inducing the formation of granular amorphous aggregates. Sarell et al. [227] suggested that Aβ fibers are able to bind a full stoichiometric complement of Cu 2+ ions with little change in their secondary structure and have coordination geometry identical to that of monomeric Aβ. A Cu 2+ affinity for Aβ of 10 11 M −1 supports a modified amyloid cascade hypothesis in which Cu 2+ is central to Aβ neurotoxicity. Zn 2+ causes rapid aggregation of Aβ [228]. It has also been reported that Zn 2+ may play a neuroprotective role since Aβ may capture redox inactive Zn 2+ ion thereby preventing Aβ from participating in redox cycling with other metals, in particular, Cu2+ ions [229]. Zn(II) induces the Abeta aggregation at acidic-to-neutral pH, while Cu(II) is an effective inducer only at mildly acidic pH. Zn(II) binds to the N(tau) atom of the histidine imidazole ring and the peptide aggregates through intermolecular His(N(tau))-Zn(II)-His(N(tau)) bridges. The N(tau)-metal ligation also occurs in Cu(II)-induced Abeta aggregation at mildly acidic pH. At neutral pH, however, Cu(II) binds to N(pi), the other nitrogen of the histidine imidazole ring, and to deprotonated amide nitrogens of the peptide main chain. The chelation of Cu(II) by histidine and main-chain amide groups results in soluble Cu(II)-Abeta complexes. Under normal physiological conditions, Cu(II) is thus expected to protect Abeta against Zn(II)- induced aggregation by competing with Zn(II) for histidine residues of Abeta [220]. pH- dependent metal binding to Aβ1-40 may induce conformational changes, which affect the affinity toward other metals. A significant copper and zinc binding to Aβ1-40 peptide at pH 5.5 (and a 1:1 Cu:Aβ molar ratio ) was found, whereas nickel ions commonly bind to each molecule of β-amyloid peptide. On increasing pH, up to 12 ions of zinc may bind to a single Aβ molecule. Aβ1-40 peptide displayed a high affinity toward nickel ions even at low pH and nickel ions proved to enhance Aβ oligomerization [213]. In that respect we can say that Zn 2+ ions are not involved in the creation of oxidation stress like Cu 2+ , Cr 3+ , Cr IV-V , Fe 3+ and [MoO 2 ] 2+ , but only involved in formation of tetrahedral complexes with monomeric and oligomeric Aβ species. Suzuki et al. [230]found that Cu(II) effectively inhibits the Abeta aggregation by competing with Zn(II) for histidine residues. The cross-linking of Abeta through binding of Zn(II) to the N(tau) atom of histidine is prevented by chelation of Cu(II) by the N(pi) atom of histidine and nearby amide nitrogens. The inhibitory effect is strongest at a Cu/Abeta molar ratio of around 4. Above this ratio, Cu(II) itself promotes the Abeta aggregation by binding to the phenolate oxygen of Tyr10. The authors emphasized the importance of regulation of Cu(II) levels to inhibit Abeta aggregation. Other researchers provided data suggesting that both Zn(II) and Cu(II) may in fact prevent Aβ from participating in fibrillogenesis by forming metal-induced aggregates, whose structural characteristics are distinct from fibrous self β- aggregates. Moreover, this inhibitory effect of metals on Aβ-aggregation via conformational enforcement was directly correlated with their protective effects against cell toxicity. Soluble Aβ also promoted cytotoxicity in the presence of Cu(II), indicating that Cu(II) is capable of promoting potentially toxic, pro-oxidative reactions [231]. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 28 Karr et al. [232]suggested that peptides that contain the proposed binding site for Cu(2+)-three histidines (H6, H13, and H14) and a tyrosine (Y10)-but lack one to three N- terminal amino acids, do not bind Cu(2+) in the same coordination environment as the native peptide. Cu(2+) binds to Abeta fibrils in a manner that permits exchange of Cu(2+) into and out of the fibrillar architecture. More recently, Smith et al. (2006) [223] have reported the formation of a toxic Aβ-Cu 2+ complex formed via a histidine-bridged dimer, as observed at Cu 2+ /peptide ratios of >0.6:1 by EPR spectroscopy. The toxicity of the Aβ-Cu 2+ complex to cultured primary cortical neurons was attenuated when either the π -or τ-nitrogen of the imidazole side chains of His were methylated, thereby inhibiting formation of the His bridge. Aβ and Aβ-Cu 2+ complexes interacted at the surface of a lipid membrane. The binding of metals to Aβ was found to be dependent on the Abeta conformation. The latter was found to depend on pH and trifluoroethanol (TFE). The aggregation induced by Abeta itself or its associated metals is completely diminished for Abeta in 40% TFE. Only in 5% and 25% TFE can Aβ undergo an alpha-helix to beta-sheet aggregation, which involve a three-state mechanism for the metal-free state, and a two-state transition for the metal-bound state, respectively. The aggregation-inducing activity of metals is in the order, Cu 2+ > Fe 3+ > or = Al 3+ > Zn 2+ .[233]. Copper facilitated the Aβ aggregation and precipitation of both wild-type and a mutant Aβ in which a histidine residue was replaced by arginine [234]. Ha et al. [235]found that Cu 2+ and Zn 2+ ions accelerated both Abeta40 and Abeta42 deposition but resulted only in the formation of "amorphous" aggregates. In contrast, Fe3+ induced the deposition of "fibrillar" amyloid plaques at neutral pH. Under mildly acidic environments, the formation of fibrillar amyloid plaques was not induced by the metal ions. Studies with mixed metal ions suggested that Zn 2+ was required at much lower concentrations than Cu 2+ to yield nonfibrillar amorphous Abeta deposits. Sequential addition of Zn 2+ or Cu 2+ on fibrillar aggregates formed by Fe3+ demonstrated that Zn 2+ and Cu 2+ could possibly change the conformation of the aggregates induced by Fe 3+ [236]. Yang et al. [237]found that Cu(II) could disrupt the already formed beta-sheet structure, convert beta-sheeted aggregates into non-beta-sheeted aggregates and promote oligomeric Aβ to precipitate in a non-beta-sheeted aggregation way. Other researchers have shown that copper abolished the β-sheet secondary structure of pre-formed, aged amyloid fibrils of Aβ 42 . Copper may thus protect against the presence of β-sheets of Aβ 42 in vivo, and its binding by fibrillar Aβ 42 could have implications for Alzheimer’s disease therapy [238]. In our opinion, one can say that reactive oxygen species (ROS) have two drawbacks. The first arises from the formation of oxidized cellular molecules resulting from the interaction with different chemical compounds (e.g., DNA , RNA ). The second arises from the oxidation of thiols and mercaptans and the corresponding sulphoxides which leads to variation in their function. The increase in ROS may lead to abstraction of borderline elements such as Zinc which is found for example in the insulin molecule. The soft acidic ions such as Cu2+ and Fe2+ play a role in the formation of reactive oxygen species in case of their interaction with sulphur Aβ species as we can see later. Role of Reactivity of Transition Elements in Life 29 TRANSITION METALS, Aβ AND OXIDATIVE STRESS Oxidative stress is increased in Alzheimer’s disease. Medial temporal lobe atrophy appears to correlate with decreased antioxidant capacity [196] (Squitti et al., 2002b). Abeta (1-42) causes oxidative stress and neurotoxicity to neurons in mechanisms that are inhibited by Vitamin E and involve the single methionine residue of this peptide [239-241]. The ability of Aβ to bind metals and the presence of redox-active iron in plaque cores could explain the development of oxidative stress in the brain of Alzheimer’s disease patients. Oxidative stress, probably mediated by the hydroxyl radical and generated by the Fenton reaction, is essential for Aβ 1–42 toxicity in vivo. Rival et al. [242] have shown that the expression of the 42-amino- acid isoform of Aβ (Aβ 1–42 ) changes the expression of genes involved in oxidative stress in a Drosophila model of Alzheimer’s disease. the iron-binding protein ferritin and the H 2 O 2 scavenger catalase were the most potent suppressors of the toxicity of wild-type and Arctic (E22G) Aβ 1–42 . Copper may participate in oxidative stress through redox-cycling between its +2 and +1 oxidation states to generate reactive oxygen species (ROS).Aβ peptide can reduce Cu(II) and Fe(III) ions leading to Fenton and Haber-Weiss chemistry, the formation of hydroxyl radicals, and oxidative damage in brain tissue. Solutions of A(beta) 1-40, A(beta) 1- 42, A(beta) 25-35 all liberate hydroxyl radicals upon incubation in vitro followed by the addition of small amounts of Fe(II). These hydroxyl radicals were readily detected by means of electron spin resonance spectroscopy, employing 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent. Hydroxyl radical formation was inhibited by the inclusion of catalase or metal-chelators during A(beta) incubation. The direct production of hydrogen peroxide during formation of the abnormal protein aggregates might thus be one fundamental molecular mechanism underlying the pathogenesis of cell death in Alzheimer’s disease [243]. Ascorbate radical and hydroxyl radical (either via fluorescent detection or spin-trapped adducts) have been detected upon redox-cycling of the AβCu system [244]. Metal-binding to Aβ is thought to induce its aggregation and redox chemistry that is toxic to neurons through the generation of reactive oxygen species which induces membrane lipid peroxidation and oxidative modification of various membrane and associated proteins (e.g., receptors, ion transporters and channels, and signal transduction and cytoskeletal proteins) [245]. Neuronal cell death induced by GSH depletion was dependent on trace levels of extracellular copper in the culture medium (1.6 microM). Neurons were protected against GSH depletion-mediated toxicity when cultured in Chelex 100-treated medium containing tenfold less copper (0.16 microM) than normal medium. The addition of copper, but not iron or zinc, to Chelex 100-treated medium restored the neurotoxicity induced by GSH depletion. The neurotoxic effects of copper in GSH-depleted neurons involved generation of copper(I) and subsequent free radical-mediated oxidative stress [246]. The abnormal combination of Aβ with Cu or Fe induces the production of hydrogen peroxide, which may mediate the oxidative damage to the brain in Alzheimer’s disease [247]. An inevitable, age-dependent rise in brain Cu and Fe might hypermetallate the Aβ peptide, causing the catalysis of H(2)O(2) production that mediates the toxicity and auto-oxidation of Abeta [172] (Bush, 2003). In cellular environments, the reduction potential of the Abeta-Cu(II) complex is sufficiently high to react with antioxidants (e.g., ascorbic acid) and cellular redox buffers (e.g., glutathione), and the Abeta-Cu(I) complex produced could subsequently reduce oxygen to form hydrogen peroxide via a catalytic cycle. Hydrogen peroxide produced, in addition to its role in damaging DNA, Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 30 protein, and lipid molecules, can also be involved in the further consumption of antioxidants, causing their depletion in neurons and eventually damaging the neuronal defense system. Another possibility is that Abeta-Cu(II) could react with species involved in the cascade of electron transfer events of mitochondria and might potentially sidetrack the electron transfer processes in the respiratory chain, leading to mitochondrial dysfunction [248]. In human cerebrospinal fluid, copper but not iron supplementation provoked a significant increase in hydroxyl free radical generation in cerebrospinal fluid (CSF) treated with H 2 O 2 . However, in a binary copper/iron containing Fenton system, iron catalytically activated copper. EDTA completely prevented copper's redox activity in CSF, while iron chelation led to a significant increase in hydroxyl radical generation, indicating that copper and iron do not only have diverse catalytic properties in the CSF but also that their redox activities are differently modulated by ligands [249]. Jiang et al. [250]found that in the presence of ascorbic acid, Abeta-Cu(II) complexes facilitate the reduction of oxygen by producing H 2 O 2 as a major product. Cu(II) bound to oligomeric and fibrous Abeta aggregates was less effective than free Cu(II) and the monomeric Abeta-Cu(II) complex in producing ROS. Other studies suggested that monomeric and fibrillar forms of Abeta does not generate any more reactive oxygen species (ROS) than controls of Cu(2+) and ascorbate. Rather hydroxyl radicals produced as a result of Fenton-Haber Weiss reactions of ascorbate and Cu(2+) rapidly react with Abeta; thus the potentially harmful radicals are quenched. Specific oxidation sites within the peptide were identified at the histidine and methionine residues [251]. EPR spectroscopy of ascorbate reduction of AβCu II under inert atmosphere and subsequent air oxidation of AβCu I to regenerate AβCu II suggested that O 2 oxidation of the AβCu I complex is kinetically sluggish, and Aβ damage is occurring following reoxidation of AβCu I by O 2 . it was hypothesized that Cu I is ligated by His13 and His14 in a linear coordination environment in Aβ, that Aβ may be playing a neuroprotective role, and that metal-mediated oxidative damage of Aβ occurs over multiple redox-cycles [252]. Tabner et al., 2005 [253] have shown that Aβ(1–40), Aβ(1–42) and Aβ(25–35) generate hydrogen peroxide which can be converted into hydroxyl radicals, via the Fenton reaction, upon addition of Fe(II). Hydrogen peroxide was not generated continuously throughout the aggregation process, but was formed as a short ‘burst’ comparatively early on during the peptide incubation period i.e., during the very early stages of protein aggregation, when protofibrils or soluble oligomers were present as revealed by atomic force microscopy. Mature Aβ fibrils lacked the ability to generate hydrogen peroxide. Aβ1-42 is a potent inhibitor of the terminal complex cytochrome c oxidase in a dose- dependent manner that was dependent on the presence of Cu 2+ and specific "aging" of the Aβ1-42 solution. Thus, Cu 2+ -dependent Aβ-mediated inhibition of cytochrome c oxidase may be an important contributor to the neurodegeneration process in Alzheimer's disease [254]. It appears that when the sensitive metal balance in the brain is sufficiently disrupted, it can lead to the self-perpetuating pathogenesis of Alzheimer’s disease. Maynard et al., 2005)[215]. Aβ is derived from intracellular proteolytic cleavage of amyloid precursor protein (APP). APP undergoes intramolecular cleavage by α-, β- and γ-secretases Aβ is a 39- 43-residue heterogeneous peptide derived from proteolytic processing of the β-amyloid precursor protein (APP) by β-secretase, the protease that cleaves at the amino-terminus, and γ-secretase, the protease that cleaves at the carboxy-terminus. Aβ1-40 is the major species found in cerebrospinal fuid [182-184]. Amyloid precursor protein (APP) is a major regulator of neuronal copper homeostasis via its copper binding domain, being acting as a neuronal Role of Reactivity of Transition Elements in Life 31 metallotransporter [256]. APP is able to bind Cu 2+ and reduce it to Cu + through its copper- binding domain. APP knockout mice have elevated cellular copper levels [257], whereas transgenic mice overexpressing the Swedish mutant of APP have reduced brain copper [258]. The interaction between Cu 2+ and APP leads to a decrease in Aβ production. On the other hand, lowering Cu concentrations can down regulate the transcription of APP, showing that APP and Aβ form part of the Cu homeostatic machinery in the brain [215]. APP possesses ferroxidase activity mediated by a conserved H-ferritin-like active site, which is inhibited specifically by Zn 2+ . Like ceruloplasmin, APP catalytically oxidizes Fe 2+ , loads Fe 3+ into transferring. Duce et al. [259] proposed that endogenous Zn 2+ originating from Zn 2+ -laden amyloid aggregates and correlating with Aβ burden can inhibit APP ferroxidase activity, inducing marked brain iron accumulation in Alzheimer’s disease. Metallothioneins (MTs) are the major endogenous zinc- and copper- binding protein within the brain. MT-1/2 can bind 7 divalent (Zn 2+ ) and up to 12 monovalent (Cu + ) metal ions in vivo through two distinct metal- thiolate clusters, termed the α- and β- domains [45, 260]. Metallothionein-3 (MT-3) binds with a high affinity essential monovalent and divalent d 10 metal ions Cu(I) and Zn(II). In cell cultures Zn 7 MT-3, protects neurons from the toxicity of Aβ. Zn 7 MT-3 scavenges free Cu 2+ ions through their reduction to Cu + and binding to the protein. In this reaction thiolate ligands are oxidized to disulfides concomitant with Zn 2+ release. Zn 7 MT-3 in the presence of ascorbate completely quenches the copper-catalyzed hydroxyl radical (OH· ) production [261]. MT-2A prevented the in vitro copper-mediated aggregation of Aβ 1–40 and Aβ 1–42 . This action of MT-2A appears to involve a metal-swap between Zn 7 MT-2A and Cu(II)-Aβ. Zn 7 MT-2A blocked Cu(II)-Aβ induced changes in ionic homeostasis and subsequent neurotoxicity of cultured cortical neurons [262]. Metals can also induce neurodegeneration via pathways independent of Aβ aggregation. Neurotrophins are an important family of neurotrophic factors e.g., nerve growth factor, brain derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5. They exert their effects by binding to and activating specific cell surface receptors of the Trk gene family. Activated receptors initiate a cascade of intracellular events, which ultimately induce gene expression and modify neuronal morphology and function [263]. The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth [264]. The transition metal cations Zn 2+ and Cu 2+ bind to histidine residues of nerve growth factor (NGF) and other neurotrophins (a family of proteins important for neuronal survival) leading to their inactivation. Cu 2+ has greater binding affnity to NGF than Zn 2+ at acidic conditions, consistent with the higher affnity of Cu 2+ for histidine residues [265]. METAL BRAIN LOWERING IN ALZHEIMER'S DISEASE Metal ligands such as clioquinol , DP-109 or pyrrolidine dithiocarbamate (PDTC) have shown promising results in animal models of AD and could have therapeutic benefits for Alzheimer’s disease. The 8HQ (8-hydroxyquinoline) derivative 5-chloro-7-iodo-8- hydroxyquinoline or clioquinol was shown to ‘dissolve’ plaques in vitro by removal of metals [266]. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 32 Figure 2. Clioquinol. A recent placebo-controlled trial in 36 patients with Alzheimer’s disease showed that clioquinol (250-750 mg daily) reduced plasma concentrations of Aβ 1–42 , raised plasma concentrations of zinc, and-in a subset with moderate dementia-slowed cognitive decline over 24 weeks [267]. In culture, cells over expressing APP when incubated with the metal ligand clioquinol and Cu 2+ or Zn 2+ ~ 85-90% reduction of secreted Abeta-(1-40) and Abeta-(1-42) was observed compared with untreated controls. The secreted Abeta were rapidly degraded through up-regulation of matrix metalloprotease (MMP)-2 and MMP-3 after addition of clioquinol and Cu 2+ . Metal ligands that inhibited Aβ induced metal-dependent activation of PI3K and JNK, resulted in JNK-mediated up-regulation of metalloprotease activity and subsequent loss of secreted Aβ [268]. Dithiocarbamates are metal chelating compounds. Pyrrolidine dithiocarbamate (PDTC) is a metal chelator and an inhibitor of nuclear factor-κB which increases the intracellular level of copper [269]. Oral therapy with PDTC prevented the decline in cognition in Alzheimer’s disease mice without altering β-amyloid burden or gliosis, increased the copper concentration in the brain, rescued cultured hippocampal neurons from the toxicity of oligomeric Aβ and reduced tau phosphorylation in the hippocampus of Alzheimer’s disease mice [270]. In Drosophila model of Alzheimer’s disease, treatment with clioquinol increased the lifespan of flies expressing Arctic Aβ 1–42 .[242]. Moreover, nicotine treatment of APP V717I (London mutant form of APP) transgenic mice led to significant reduction in the metal contents of copper and zinc in senile plaques and neuropil; effect that appears to be independent of the activation of nicotinic acetylcholine-receptor [271]. Lowering of copper concentrations in brain of patients with Alzheimer’s disease is thus an interesting therapeutic strategy. D-penicillamine, a copper chelating agent reduced extent of oxidative stress (though not the rate of cognitive decline) in these patients [272]. There are also data suggesting that copper deficiency markedly alters APP metabolism and can elevate Aβ secretion [273] making the situation more complex. In their study, Crouch et al. [274]found that in the brains of APP/PS1 transgenic AD model mice, the use of copper- bis(thiosemicarbazonoto) complexes to increase intracellular copper bioavailability, can restore cognitive function by inhibiting the accumulation of neurotoxic Aβ trimers and phosphorylated tau. Hung et al. [275]found that total cellular copper is associated inversely with lipid raft copper levels, so that under intracellular copper deficiency conditions, Aβ·copper complexes are more likely to form. This explains the paradoxical hypermetallation of Aβ with copper under tissue copper deficiency conditions in AD. Role of Reactivity of Transition Elements in Life 33 TRANSITION METALS AND PARKINSONS'S DISEASE Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer’s disease and is also a disease of the aging population in which the prevalence increases exponentially with age between 65 and 90 years. The mean age of onset is about 65 years and the overall age-adjusted prevalence is 1% worldwide. The clinical features of Parkinson's disease result from a progressive degeneration of dopamine-producing neurons in the substantia pars compacta (SNc) of the midbrain that project to the striatum. The SNC is one of five distinct subcortical interconnected nuclei whose primary function is the control of motor function. In Parkinson's disease there is slowness and difficulty with movement initiation "bradykinesia", muscular rigidity as well as tremor of the hands. Parkinsonian symptoms start to appear when 50–60% of SNc dopaminergic neuons and 70–80% of striatal nerve terminals are lost [276]. Apart from an idiopathic form, the disorder can be the result of vascular factors, brain trauma, manganese poisoning or drugs. Only ~5% of all cases are of genetic origin. The exact cause that leads to the the selective destruction of the nigrostriatal dopaminergic pathway has remained unknown but accumulating evidence suggests that it might represent the final outcome of interactions among multiple factors, including a signifi- cant genetic component for susceptibility to idiopathic Parkinson's disease, exposure to environmental toxin (s) and the occurrence of inflammation in the brain [277]. Several factors underlie the unduly high susceptibility of the brain tissue to oxidative stress. Owing to its high metabolic activity the brain has high oxygen consumption rate being ~ 20% of total oxygen consumption in adult human despite that it accounts for only a few percent of body weight. Hence it processes a lot of O 2 per unit tissue mass. The brain is also rich in highly oxidizable polyunsaturated fatty acids. Other factors causing increased oxidative burden are the metabolism of monoamine neurotramsmitters noradrenaline, serotonin and dopamine, yielding free radicals and brain iron content [176]. Dopamine Dopamine [2-(3,4-dihydroxyphenyl)-ethylamine] is a neurotransmitter that plays an important role in PD. When a solution of dopamine is exposed to air, after a while it turns pink due to oxidation to dopaminochrome even in the absence of metal ions. Finally the pink colour disappears to be replaced by a precipitate of the polymeric material melanine. The rate determining step is assumed to be hydrogen atom abstraction from the monodeprotonated species by O 2 .Addition of a small amount of acid inhibits this oxidation, unless metal ions such as Fe 3+ , Cu 2+ or VO 2+ are present. Although in acid solution added metal ions initially start an oxidation process, this soon comes to an end as the metal ions are efficiently removed from the solution by the melanine. The in vitro chemistry of dopamine reactions under the presence of Fe (III) and dioxygen showed that the reaction pathway essentially involved an FeL intermediate, which decomposes releasing Fe(II) and dopaminochrome which reacts further under involvement of both Fe (III) and dioxygen [279]. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 34 Figure 3. Dopamine and Dopaminochrome. The metabolism of dopamine can be a source of free radicals production via multiple pathways. Dopamine can auto-oxidize to produce free radicals particularly in the presence of iron and other heavy metals [280]. Dopamine forms quinones and semiquinones,which are themselves toxic and may lead to generation of reactive oxygen species [281]. In addition, the reduction of Cu 2+ to Cu 1+ and the formation of a peroxide lead to the oxidation of dopamine with formation of DNA adducts and oxidative base damage [282]E:\Documents and Settings\Lisa\Local Settings\Temporary Internet Files\Content.Outlook\9DAVGS4D\New Folder33\science.htm - en976560fn1. It has been suggested that increased turnover of dopamine in the early stages of PD should be associated with an oxidative stress derived from increased production of hydrogen peroxide with the subsequent formation of hydroxyl radical leading to dopaminergic cell death. The peroxide is formed during the oxidative deamination of dopamine by monoamine oxidase [283]. It has been shown that increased presynaptic metabolism of neurotransmitter alters the redox state of dopamine nerve terminals in the striatum. The H202 that is generated by MAO is scavenged by glutathione (GSH) peroxidase, leading to the formation of glutathione disulfide (GSSG). (1) (2) (3) Normally, GSSG is efficiently reduced by glutathione reductase. The ratio of oxidized to reduced glutathione reflects, in part, the redox state of the tissue [283]. We can conclude that the formation of singlet oxygen and the derives ractive oxygen species lead to the oxidation of thiol compounds to dimeric (GSSG). The alkaline medium prohibits the formation of GSH as can be seen from equation [3] which clarified that the transformation step usually takes place in an acidic medium. The liberation of ammonia inside the cells raises the pH value intracellularly to the alkaline region. This situation may lead to the precipitation of iron, copper and zinc which may alter the homeostasis of these transition elements in the brain. In addition, the high pH value enhances the reaction between hydrogen peroxide and sodium hypochlorite leading to formation of singlet oxygen which possesses a very stron damaging effect on different molecules forming the different cellular components (e.g., cell membrane, DNA) according to the following equation: he lin ac T un M pa Fi ox Fi su ot m NaOCl + H The above epatic precom nked to increa In addition ctivity increas he increased nchanged extr MAO-B is sig athogenesis of igure 4. Format xidation. In the igure 5. Metabo uperoxide anion Brain meta ther enzymes mitochondrial m Role o H 2 O 2 → 1 O 2 + is likely to ha ma where chan ased brain amm n, brain MAO ses with age, t MAO-B activ rasynaptosom gnificantly inc f PD. tion of free radi presence of tra olism of DA lea ns (O2·–), dopam abolism genera e.g., monoam membranes of of Reactivity o NaCl + H 2 O ave an importa nges in conscio monia level. O-B (involved thereby, expos vity in aging mal MAO-B.. creased by A cals from dopam ansition metals, ads to the forma mine–quinone s ates excess H 2 mine oxidases A f neurons and of Transition E ant implication ousness and n in the catabo sing cells to o is due to an There are al Al 3+ [285], thu mine (DA) by m H2O2 is conve ation of several species (SQ·) an 2 O 2 , not only v A and B, flav glia. They cat Elements in Li ns also in som neurobehaviou olism of dopam oxidative stres increased con so data show us implicating monoamine oxi erted to hydroxy cytotoxic mole nd hydroxyl rad via superoxide voprotein enzy alyze the reac ife me pathological ural alterations mine) (but no ss-mediated in ncentration of wing that the g this metal dase (MAO) or yl radical [286,2 ecules, including dicals (OH·)[28 e dismutases, ymes located i ction 35 l states like s are highly ot MAO-A) njury [284]. f otherwise activity of ion in the r auto- 287]. g 6,287]. but also by in the outer radical Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 36 and generate substantial H 2 O 2 in the brain [288]. DA quinone readily participates in nucleophilic addition reactions with sulfhydryl groups on free cysteine, glutathione, or and sulfhydryl groups in proteins [289-292]. The reaction between DA quinone and cysteine results in the formation of 5-cysteinyl-DA (Figure 1). Because cysteinyl residues are often found at the active site of proteins, the covalent addition of the catechol moiety to cysteine may inhibit protein function and possibly lead to cellular damage and/or cell death. In addition, DA quinone is able to react with the sulfhydryl group of cysteine in glutathione, which may decrease levels of this important antioxidant. The reactive quinones and free radicals produced by the oxidation of DA may contribute to the oxidative stress associated with PD. Figure 6. The oxidation of DA to DA quinine and the resultant conjugation with cysteine (5-Cys-DA). Oxidation of dopamine to an o-quinone and its subsequent product, aminochrome (2,3- dihydroindole-5,6-dione) may also result in redox cycling. Key reactions promoting the formation of reactive oxygen species, with a consequent prooxidant effect, include one- electron reduction of quinines catalysed by favoproteins, such as NADPH:cytochrome P-450 reductase, and the subsequent reaction between the formed semiquinone radical and dioxygen. One-electron reduction accompanied by autoxidation and redox cycling in the presence of dioxygen contributes greatly to the toxicity characterizing many quinines [293]. The human glutathione transferases (GSTs), in particular GST M2-2 (also in the substantia nigra of human brain), catalyse the formation of glutathione conjugates of o-quinones derived from physiologically important catecholamines. Glutathione conjugation of these quinones is a detoxication reaction that prevents redox cycling, thus indicating that GSTs have a cytoprotective role involving elimination of reactive chemical species originating from the oxidative metabolism of catecholamines [294]. Oxidized catecholamines can also induce modification of Cu,Zn-SOD that migkht induce the perturbation of cellular antioxidant systems and led to a deleterious cell condition. When Cu,Zn-SOD was incubated with the oxidized 3,4-dihydroxyphenylalanine (DOPA) or dopamine, the protein was induced to be aggregated. The deoxyribose assay showed that Role of Reactivity of Transition Elements in Life 37 hydroxyl radicals were generated during the oxidation of catecholamines in the presence of copper ion [295]. Neuromelanin Neuromelanin (NM) is a dark pigment polymer belonging to the family of melanins. which occupies a large proportion of the cytosol within certain catecholaminergic neurons in the human brain [296]. Melanised neurons are most abundant in the human SN and The dark appearance of the SN results from the presence of NM and for which it was named (lat. substantia nigra, black body) [297, 298]. Less neuromelanin is found in Parkinson's disease and depletion of this pigment results in pallor of the SN which is one of the most striking pathological features. Neuromelanin is synthesized from quinones and semiquinones produced by enzymatic or non-enzymatic oxidation of dopamine and noradrenaline in the SN and LC, respectively. In substantia nigra, dopamine is the major source. In the locus coeruleus, noradrenalin, and in the diffuse brain stem raphe system, serotonin is the chief precursor. The complex polymers contain also other oxidation metabolites of dopamine and L-DOPA, cysteinyl-DOPA [299], 5-S-cysteinyl-dopamine [300], proteinacious components and lipids [301,302. Neuromelanin also accumulates α-synuclein [303] as well as transition metals e.g., iron, copper and zinc [304]. The role of neuromelanin is a matter of debate. Neuromelanin has been proposed to play a protective role via trapping free radicals [302] as well as its ability to chelate transition metals, such as Fe Zn, Cu, Mn, Cr, Co, Hg, Pb, and Cd [301, 305, 306]. But the presence of neuromelanin in dopaminergic neurons of the SNc was also be taken as an indication that NM might in fact account for their vulnerability in Parkinson’s disease [307, 308]. Other researchers reported that neuromelanin, in contrast to synthetic dopamine melanin without iron, increased the oxidative stress and induces onset of oxidative stress in mitochondria. Superoxide dismutase and deferoxamine completely suppressed the increase, indicating that superoxide produced by an iron-mediated reaction plays a central role [309].Neuromelanin binds iron in the ferric form. Neuromelanin contains both high- and low-affinity iron binding sites and additional iron is added to existing iron clusters in NM, analogous to the formation and growth of the ferritin iron core [310]. neuromelanin is thought to be only partially saturated with iron in vivo, thus maintaining a residual chelating capacity to protect the substantia nigra against iron toxicity [311]. It was suggested that the increased brain iron content encountered in the SN of Parkinson's disease patients might saturate iron-chelating sites on NM, and a looser association between iron and neuromelanin may result in an increased, rather than decreased, production of free radical species (metal-ion binding capacity will be exceeded). This redox-active iron could be released and involved in a Fenton-like reaction leading to an increased production of oxidative radicals. The resultant radical-mediated cytotoxicity may contribute to cellular damage observed in PD [312]. It is likely that at low iron concentrations native neuromelanin does not induce cell damage but rather protects cells in culture from oxidative stress. This protective function appears to be lost at high iron concentrations where neuromelanin saturated with iron functions as a source of oxidative load, rather than an iron chelator. Changes to the structure of neuromelanin and tissue iron load in Parkinson’s disease may decrease the ability of the pigment to chelate iron, thus increasing the potential for cell damage [313]. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 38 In our opinion, the protective role of neuromelanin may arise from its ability to form metal-organic complexes with iron, Cu 2+ , which will prevent or reduce their involvement in formation of free radicals via the Fenton reaction. In addition, neuromelanin might form a stable free radicals which interact with potently oxidizing species (O 2 ·– , 1 O 2 ) thereby minimizing their effects on cellular molecules.this hypothesis is supported by the presence of neuromelanin in healthy persons and its decrease or even absence in individuals with Parkinson's disease. THE ROLE OF IRON Parkinson's disease is another neurodegenerative disorder in which transition metals and in particular Fe appear to have an important role. Owing to iron’s ability to donate electrons to oxygen, increased iron levels can lead to the formation of hydroxyl radicals and hydroxyl anions via the Fenton Reaction (Fe 2+ + H 2 O 2 → Fe 3+ + OH· + OH − ). Iron is found throughout the brain and important iron-containing proteins include cytochromes, ferritin, aconitases, non-heme iron proteins in the mitochondrial electron transport chain, cytochromes P450, and tyrosine and tryptophan hydroxylases [176]. The combination of high concentration of iron and the neurotransmitter, dopamine, may contribute to the selective vulnerability of the SNPc. Fe concentrations in SN values around 100–200 µg/g in normal subjects [301]. Increased Fe content in the SNc of patients with Parkinson's disease has been reported. There was a significant increase in total iron and iron (III) in substantia nigra of severely affected patients and a shift in the iron (II)/iron (III) ratio in favor of iron (III) with a significant increase in the iron (III)-binding protein, ferritin as well as a significantly lower glutathione content [314]. The increased iron content is mainly due to increased loading of ferritin [315]. High field strength MRI demonstrated SNC abnormalities consistent with increased iron content early in the disease [316]. It has been shown that the properties of the main iron-binding structure in human brain, the ferritin differ from those of ferritin in liver or spleen with the iron-cores of brain ferritin being significantly smaller than the iron-cores of liver ferritin. Also the ratio between the heavy and light subunits of the protein shell of ferritin (H/L) is different in liver and in brain structures, being the highest for hippocampus. Such differences in properties of brain ferritin may speak in favor of more rapid iron turn-over in brain compared to liver which might increase the possibility of oxidative stress [317]. Total iron intake was not associated with an increased risk of Parkinson's disease, but dietary nonheme iron intake from food was associated with a 30% increased risk of Parkinson's disease. This increase in risk was present in those who had low vitamin C intake [318]. Epidemiological studies suggest that exposure to pesticides, such as rotenone, paraquat or maneb, may contribute to the higher incidence of sporadic Parkinsonism among the population of rural areas [319, 320]. The combined environmental exposure to paraquat and Fe was shown to result in accelerated age-related degeneration of nigrostriatal dopaminergic neurons [321]. The divalent metal transporter 1 (a widely expressed mammalian ferrous ion (Fe 2+ ) transporter [18] appears to be a key regulator of brain iron accumulation in PD. A subtype containing iron response element (IRE) (DMT1+IRE) which is under control by iron regulatory proteins is increased in 6-hydroxydopamine-induced PD model along with elevation in iron uptake and oxidative stress [250, 322]. Role of Reactivity of Transition Elements in Life 39 Fe accumulation in the SNc of patients with Parkinson's disease is particularly important because iron is a redox-active metal, that can interact with molecular oxygen to generate superoxide anion (O 2 ·– ), which in turn, generates hydroxyl radical (_OH), a highly reactive oxygen specie (ROS). As a consequence of Fe 2+ reaction with O 2 , Fe 3+ is generated, that can trigger lipid oxidation through its reaction with lipid hydroperoxides normally present in biological systems. Finally, many neurotransmitters are auto-oxidizable molecules [323]. ROLE OF OTHER TRANSITION METALS Parkinson's disease is also characterized by the presence of proteinaceous deposits in the residual dopaminergic neurons of the SNc (Lewy bodies and Lewy neuritis). These consist mainly of aggregated forms of α-synuclein [324] which is a normally placed presynaptic protein involved in synaptic function and plasticity [325] (Clayton and George, 1998). The mechanisms underlying the gradual transition of soluble α-synuclein into virtually insoluble Lewy bodies or Lewy neurites are still unknown [326, 327]. Studies suggest that some metals can directly induce α-synuclein fibril formation. Uversky et al. [328] noted that several di- and trivalent metal ions caused significant accelerations in the rate of α-synuclein fibril formation. Aluminum was the most effective, along with copper(II), iron(III), cobalt(III), and manganese(II). The effectiveness correlated with increasing ion charge density. A correlation was noted between efficiency in stimulating fibrillation and inducing a conformational change, ascribed to formation of a partially folded intermediate. The potential for ligand bridging by polyvalent metal ions is proposed to be an important factor in the metal-induced conformational changes of α-synuclein. It seems that Al 3+ and Fe 3+ which are considered as hard acids posses a large probability to react with α-synuclein which can be considered in this case as hard or borderline base. Copper(II) also interacts with α-synuclein ands binds tightly near the N-terminus at pH 7 [329]. Cu(II) ions are effective in accelerating α-synuclein aggregation at physiologically relevant concentrations without altering the resultant fibrillar structures. By using numerous spectroscopic techniques (absorption, CD, EPR, and NMR), the primary binding for Cu(II) was delineated to a specific site in the N terminus, involving His-50 as the anchoring residue and other nitrogen/oxygen donor atoms in a square planar or distorted tetragonal geometry. The carboxylate-rich C terminus, originally thought to drive copper binding, is able to coordinate a second Cu(II) equivalent, albeit with a 300-fold reduced affinity. The NMR analysis of AS–Cu(II) complexes reveals the existence of conformational restrictions in the native state of the protein [330]. Cu 2+ binding of recombinant human α-synuclein was examined using Electron Paramagnetic Resonance (EPR) spectroscopy [331]. Wild type α-synuclein was shown to bind stoichiometric Cu 2+ via two N-terminal binding modes at pH 7.4. Electron spin−echo envelope modulation (ESEEM) studies of wild type α-synuclein confirmed the second binding mode at pH 7.4 involved coordination of His50 and its g and A parameters correlated with either {NH 2 , N − , β-COO − , N Im } or {N Im , 2N − } coordination observed in α-synuclein fragments. At pH 5.0, His50-anchored Cu 2+ binding was greatly Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 40 diminished, while {NH 2 , N − , β-COO − , H 2 O} binding persisted in conjunction with another two binding modes. Mn is another transition metal which has been linked to the development of a clinical entity simulating Parkinson's disease in humans. Mn2 may be oxidized to Mn3 , which is rather reactive and more toxic than Mn3 rapidly associates with Tf to form a stable complex. In tissues, Mn may exist primarily in the form of Mn2 . Mn-induced neurotoxicity from excess respiratory or dietary exposures has been well described. Oxidative stress is one of many factors implicated in Mn induced neurotoxicity [68]. The divalent manganese ions can interact with glutathione formaing a metal-organic complex which reduces the concentration of free GSH in the cell. Figure 7. Oxidative DNA damage induced by dopamine oxidation [332]. Dopamine oxidation by Mn is a potential mechanism for Mn-induced oxidative stress, especially since Mn preferentially accumulates in dopamine-rich brain regions (e.g., basal ganglia) [333]. Manganese toxicity has been suggested to relate to the formation of the trivalent cation, which contains four unpaired d-orbital electrons which are thermodynamically unstable compared to the three more favourably paired electrons present in the divalent cationic state. Production of ROS can result from impairment of mitochondrial function but may also be generated from the oxidation of dopamine in the presence of copper (Cu (II))[78]. Role of Reactivity of Transition Elements in Life 41 Figure 8. Manganese induced dopamine oxidation [334]. Vanadium compounds in high oxidation states can induce oxidative transformations. A recent study found that vanadium can exert neurotoxic effects in dopaminergic neuronal cells via caspase-3-dependent PKCdelta cleavage, suggesting that metal exposure may promote nigral dopaminergic degeneration [335]. Studies on rat liver mitochondria revealed that (VO(2+), VO(3)(-), VO(acac)(2) and VOcit (1-100microM) could induce mitochondrial swelling in a concentration dependent manner and disrupt mitochondrial membrane potential in a time dependent manner. Vanadium compounds thus induced oxidative stress on mitochondrial [336]. The oxidation stress of [VO] 1+ and [VO] 2+ may be ascribed to the ability of these cations to produce • OH radicals due to interaction with H2O2 in faintly or acidic medium. REFERENCES [1] Jeffcry G H, Basset J, Mendham J, and Dcnney RC. (1989). Text Book of Quantitative Chemical Analysis. Longman Group Limited, London, 5 th ed. [2] Nyle CB (1990). The Nature and the Properties of Soil", Macmillan Publishing Company, U.S.A., 10 th ed. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 42 [3] Wild A (1988). Soil Condition and plant growth. Longman group UK, Ltd, 11. [4] Coke GW (1975). Fertilizer for Maximun Yield. Granada publishing limited, Britain, 2 nd ed. [5] Sievers RE and Bailar JC (1962). Some metal chelates of ethylendiaminetetraacetic acid, diethylenetriaminepentaacetic acid and tri ethylentetraminethexaacetic acid. Inorg. Chem, 1, 174. [6] Wilson CJ, Apiyo D and Wittung-Stafshede P (2004). Role of cofactors inmetalloproteinfolding. Quarterly Reviews of Biophysics 37 (3/4): 285–314. [7] Robert J & Williams RJP (2006). The Biodistribution of Metal Ions. In Kraatz HB and Metzler-Nolte N (Eds), Concepts and Models in Bioinorganic Chemistry. Wiley-Vch Verlag GmbH & Co. [8] Roat-Malone RM (2002). Bioinorganic Chemistry: A Short Course. John Wiley & Sons, Inc. [9] Goyer R, Golub M, Choudhury H, Hughes M, Kenyon E, Stifelman M (2004). Issue paper on the human health effects of metals. [10] Solomons NW & Ruz M (1998). Trace element requirements in humans. An update. J. Trace Elem. Exp. Med. 11, 177-195. [11] Finney LA & O'Halloran TV (2003). Transition metal speciation in the cell: insights from the chemistry of metal ion receptors. Science 300, 931–936. [12] Stohs SJ & Bagchi D ( 1995 ). Oxidative mechanisms in the toxicity of metal ions . Free Radic. Biol. Med. 18, 321 – 336 . [13] Goyer RA ( 1997). Toxic and essential metal interactions . Annu. Rev. Nutr. 17, 37-50 . [14] O’Connor JM (2001). Trace elements and DNA damage. Biochemical Society Transactions, 29, 354–358. [15] Valko M, Morris H & Cronin MT (2005). Metals, toxicity, and oxidative stress. Curr.Med.Chem. 12, 1161–1208. [16] Halliwell B and Gutteridget JMC (1984). Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J. 219, 1-14. [17] Crichton R (2001). Inorganic Biochemistry of Iron Metabolism: From Molecular Mechanisms to Clinical Consequences. 2 nd ed. John Wiley & Sons, Ltd Baffins Lane, Chichester, West Sussex, England [18] Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997). Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature, 388 (6641), 482-488. [19] Bressler JP, Olivi L, Cheong JH, Kim Y, Maerten A & Bannon D (2007). Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities. Hum Exp Toxicol. 26(3), 221-9. [20] Kagi JH & Valee BL (1960). Metallothionein: a cadmium- and zinc-containing protein from equine renal cortex. J Biol Chem. 235, 3460-5. [21] Lieu PT, Heiskala M, Peterson PA, Yang Y. The roles of iron in health and disease (2001). The roles of iron in health and disease. Mol Aspects Med. 22(1-2), 1-87. [22] Andrews NC (1999). Disorders of iron metabolism. N Eng J Med. 341 (26), 1986- 1995.(1999) [23] Andrews NC (2000). Iron Metabolism: Iron Deficiency and Iron Overload. Ann Rev Genom and Hum Genet. 1, 75– 98. Role of Reactivity of Transition Elements in Life 43 [24] Conrad ME & Umbreit JN (2000). Iron absorption and transport: an update. Am J Hematol. 64, 287-298. [25] Broderick JB (2001). Coenzymes and Cofactors. In: Encyclopedia of Life Sciences. Nature Publishing Group / www.els.net pp.1-11 [26] Brown KE (2007). Normal iron metabolism. In: The Textbook of Hepatology: From Basic Science to Clinical Practice, 3rd Edition. By Joan Rodés, Jean-Pierre Benhamou, Mario Rizzetto. Wiley-Blackwell. pp.221-226. [27] Baker HM, Anderson BF & Baker EN (2003). Dealing with iron: common structural principles in proteins that transport iron and heme. Proc. Natl. Acad. Sci. USA, 100, 3579-3583. [28] Texel SJ, Xu X and Harris ZL (2008). Metal Metabolism: Transport, Development and Neurodegeneration. Biochem. Soc. Trans. 36, 1277–1281. [29] Wessling-Resnick M (2000). Iron transport. Annu Rev Nutr. 20, 129-151. [30] Moos T (2002). Brain iron homeostasis. Dan Med Bull. 49(4), 279-301. [31] Turnlund JR (1994). Copper. In: Shils ME, Olson JA, Shike M; Eds. Modern Nutrition in Health and Disease 8th Ed. Philadelphia: Lea and Febiger. [32] Turnlund JR, Keyes WR, Kim SK, Domek JM (2005). Long-term high copper intake: effects on copper absorption, retention, and homeostasis in men. Am J Clin Nutr. 81(4), 822-8. [33] Linder M (1991). Biochemistry of Copper. Plenum Press, New York. [34] Linder MC, Lomeli NA, Donley S, Mehrbod F, Cerveza P, Cotton S & Wooten L (1999). Copper Transport and Its Disorders in Advances in Experimental Medicine and Biology, ed. By A. Leone, J. F. B. Mercer, Kluwer Academic/Plenum Pub., New York, N.Y., pp. 1–16. [35] Linder MC (2001). Copper and genomic stability in mammals. Mut Res 475, 141-152. [36] Shike M (2009). Copper in parenteral nutrition. Gastroenterology137(5 Suppl), S13-7. Review. [37] Prohaska JR (1990). Biochemical changes in copper deficiency. J Nutr Biochem. 1, 452-461. [38] Culotta VC & Gitlin JD (2001). In: The Molecular and Metabolic Basis of Inherited Disease, eds Scriver CR, Beaudet AL, Sly WS, Valle D (McGraw–Hill, New York), pp 3105–3136. [39] Tümer Z & Møller LB (2010). Menkes disease. Eur J Hum Genet. 18(5), 511-8. [40] Hoogenraad TU. Monography: Wilson’s disease. In: Major Problems in Neurology. Vol 30, London: W.B. Saunders 1996. [41] Turnlund JR. (1988). Human whole-body copper metabolism A J Clin Nutri. 67, 960S- 964S. [42] Lutsenko S, Barnes NL, Bartee MY & Dmitriev OY (2007). Function and regulation of human copper-transporting ATPases. Physiol Rev. 87, 1011–1046. [43] Formigari A, Alberton P, Cantale V, De Nadal V, Feltrin M, Ferronato S, Santon A, Schiavon L & Irato P (2008). Relationship between metal transcription factor-1 and zinc in resistance to metals producing free radicals. Current Chemical Biology. 2, 256- 266. [44] Choi BS & Zheng W (2009). Copper transport to the brain by the blood-brain barrier and bBlood-CSF barrier. Brain Res. 1248, 14–21. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 44 [45] Coyle P, Philcox JC, Carey LC & Rofe AM (2002). Metallothionein: the multipurpose protein. Cell Mol Life Sci. 59, 627–647. [46] Vašák M (2005). Advances in metallothionein structure and functions. J Trace Elements Med and Biol. 19 (1), 13-17. [47] O'Halloran TV & Culotta VC (2000). Metallochaperones, an intracellular shuttle service for metal ions. J Biol Chem. 275(33), 25057-60. [48] Harrison MD, Jones CE, Solioz M & Dameron CT (2000). Intracellular copper routing: the role of copper chaperones. TIBS 25. [49] Gregory S. Kelner GS, Lee MH, Clark ME, Maciejewski D, McGrath D, Rabizadehi S, Lyonsi T, Bredesen D, Jenner P & Maki RA (2000). The copper transport protein Atox1 promotes neuronal survival. J Biol Chem. 275 (1), pp. 580–584. [50] Rae TD, Schmidt PJ, Pufahl RA, Culotta VC & O'Halloran TV (1999). Undetectable Intracellular Free Copper: The requirement of a copper chaperone for superoxide dismutase. Science 284 (5415), 805 – 808. [51] Rothstein JD, Dykes-Hoberg M, Corson LB, Becker M, Cleveland DW, Price DL, Culotta VC & Wong PC (1999). The copper chaperone CCS is abundant in neurons and astrocytes in human and rodent brain. Journal of neurochemistry 72(1), 422-9. [52] Doucette, Peter A., Potter, Soshanna Z., & Valentine, Joan S (2005). Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis; Annu. Rev. Biochem. 2005. 74:563–93 [53] Brewer GJ (2010). Risks of copper and iron toxicity during aging in humans. Chem. Res. Toxicol. 23 (2), 319–326. [54] Sarkar B and Roberts EA (2011) . The puzzle posed by COMMD1, a newly discovered protein binding Cu(II). Metallomics, 3, 20-27 [55] Cole MP, Chaiswing L, Oberley TD, Kiningham KK and St. Clair DK (2002). Mechanisms of cardiovascular aging. Advances in Cell Aging and Gerontology, 11, 233-281. [56] Schoonen MAA, Cohn CA, Roemer E, Laffers R, Simon SR & O’Riordan T (2006) Mineral-induced formation of reactive oxygen species. In: Sahai N, Schoonen MAA (eds) Medical Mineralogy and Geochemistry, Reviews in Mineralogy & Geochemistry, 64, 179-221 [57] Fubini B & Fenoglio I (2007). Toxic potential of mineral dusts. Elements, 3, 407-414 [58] Rizk SL & Sky-Peck HH (1984). Comparison between concentrations of trace elements in normal and neoplastic human breast tissue. Cancer Res, 44, 5390-4. [59] Kuo HW, Chen SF, Wu CC, Chen DR, & Lee JH (2002). Serum and tissue trace elements in patients with breast cancer in Taiwan. Biol Trace Elem Res. 89, 1-11. [60] Brewer GJ (2001). Copper control as an antiangiogenic anticancer therapy: lessons from treating Wilson's disease. Exp Biol Med (Maywood), 226, 665-73. [61] Theophanides T & Anastassopoulou J (2002). Copper and carcinogenesis. Crit Rev Oncol Hematol. 42, 57-64. [62] Yoshii J, H. Yoshiji, S. Kuriyama, Y. Ikenaka, R. Noguchi, H. Okuda, H. Tsujinoue, T. Nakatani, H. Kishida, D. Nakae, D. E. Gomez, M. S. De Lorenzo, A. M. Tejera & H. Fukui (2001). The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells. Int J Cancer. 94, 768-73. Role of Reactivity of Transition Elements in Life 45 [63] Ishida S, Lee J, Thiele DJ & Herskowitz I (2002). Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals. Proc Natl Acad Sci USA, 99, 14298-14302. [64] Ionescu JG, Novotny J, Stejskal V, Latsch A, Blaurock-Busch E, & Eisenmann-Klein M (2006). Increased levels of transition metals in breast cancer tissue. Neuroendocrinol Lett. 27(Suppl 1):36–39 [65] Qian ZM, Li H, Sun H & Ho K (2002). Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol. Rev. 54 (4), 561–87. [66] National Research Council Committee on Medical and Biological Effects of Environmental Pollutants: Manganese. Washington: National Academy of Sciences, (1973). pp. 1-191. [67] Graedel TE (1978). Inorganic elements, hydrides, oxides, and carbonates. In: Chemical compounds in the atmosphere. New York, NY, Academic Press, pp. 35–41, 44–49. [68] Aschner M (1997). Manganese neurotoxicity and oxidative damage. In: Connor, J.R. (Ed.), Metals and Oxidative Damage in Neurological Disorders. Plenum Press, New York, pp. 77–93. [69] Aschner JL & Aschner M (2005). Nutritional aspects of manganese homeostasis. Mol Aspects Med. 26(4-5), 353-62. [70] Santamaria AB & Sulsky SI (2010). Risk assessment of an essential element: manganese. J Toxicol Environ Health A. 73(2), 128-55. [71] National Academy of Sciences (NAS) (2001). Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Panel on Micronutrients, Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Available from: www.nap.edu/books/0309072794/html/. [72] Crossgrove J & Zheng W (2004). Manganese toxicity upon overexposure. NMR Biomed. 17, 544–553 [73] Hegsted BM (1976). Food fortification. In: Nutrition in the Community. McLaren, D.S., ED. John Wiley, N.Y. [74] Tuormaa TE (1996). The Adverse Effects of Manganese Deficiency on Reproduction and Health: A Literature Review. Journal of Orthomolecular Medicine, 11 (2), 69-79. [75] Hwang CS, Baek YU, Yim HS, Kang SO (2003). Protective roles of mitochondrial manganese-containing superoxide dismutase against various stresses in Candida albicans. Yeast. 20(11), 929-41. [76] Erikson KM, Thompson K, Aschner J & Aschner M (2007). Manganese neurotoxicity: a focus on the neonate. Pharmacol Ther. 113(2), 369-77. [77] Aschner M &, Aschner JL (1991) Manganese neurotoxicity: cellular effects and blood- brain barrier transport. Neurosci Biobehav Rev 15, 333–340. [78] Bagga S &Levy L (2007). Manganese Health Research Program: Overview of Research into the Health Effects of Manganese (2002-2007). The Institute of Environment and Health (IEH), Cranfield Health, Cranfield University, Silsoe, Bedfordshire, UK. http://www.silsoe.cranfield.ac.uk/ieh/ [79] Roth JA & Garrick MD (2003). Iron interactions and other biological reactions mediating the physiological and toxic actions of manganese. Biochem Pharmacol. 66(1), 1-13. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 46 [80] Erikson KM & Aschner M (2006). Increased manganese uptake by primary astrocyte cultures with altered iron status is mediated primarily by divalent metal transporter.. Neurotoxicology. 27(1), :125-30. [81] Garcia SJ, Gellein K, Syversen T & Aschner M (2007). Iron deficient and manganese supplemented diets alter metals and transporters in the developing rat brain. Toxicol Sci. 95(1), 205-14.. [82] Fitsanakis VA, Zhang N, Garcia S, Aschner M (2010). Manganese (Mn) and iron (Fe): interdependency of transport and regulation. Neurotox Res. 18(2), 124-31. [83] Misselwitz B, Mühler A & Weinmann HJ (1995). A toxicologic risk for using manganese complexes? A literature survey of existing data through several medical specialties. Invest Radiol. 30(10), 611-20. [84] Joint FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements. Vitamin and Mineral Requirements In Human Nutrition (1998). Second edition. Chapter 12. Zinc.pp.230-245). Bangkok, Thailand. [85] Yanagisawa H (2002). Clinical aspects of zinc deficiency. The Journal of the Japan Medical Association, 127(2), 261–268. [86] Ackland ML & Michalczyk A (2006). Zinc deficiency and its inherited disorders – A review. Genes & Nutrition 1 (1), 41-50. [87] Nriagu J (2007). Zinc Toxicity in Humans. Web-based Resources . 2007 Elsevier B.V. pp.1-7. [88] Bertini I, Luchinat C (1994). The reaction pathways of zinc enzymes and related biological catalysts. In Bioinorganic Chemistry. Edited by Bertini I, Gray HB. University Science Books Mill Valley, California. [89] Williams RJP (1987). The biochemistry of zinc. Polyhedron 6, 61–69. [90] Glusker JP, Katz AK & Bock CW (1999). Metal ions in biological systems. The Rigaku Journal. 16 (2), 8-16. [91] Fortescue JAC (1992). Landscape geochemistry: retrospect and prospect. Applied Geochemistry, 7, 1–53. [92] Hille R (1999). Molybdenum enzymes. Essays Biochem. 34, 125-37. [93] Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press; 2002. p. 420–41. [94] Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Molybdenum. SCF/SC/NUT/UPPERLEV/22. Brussels: Scientific Committee on Food, European Commission; 2000. p. 1–15. [95] Vyskocil A & Viau C (1999). Assessment of molybdenum toxicity in humans. J Appl Toxicol. 19(3), 185-92. [96] Turnlund JR, Weaver CM, Kim SK, Keyes WR, Gizaw Y, Thompson KH, & Peiffer GL (1999). Molybdenum absorption and utilization in humans from soy and kale intrinsically labeled with stable isotopes of molybdenum. Am J Clin Nutr. 69, 1217–23. [97] Novotny JA & Turnlund JR 92007). Molybdenum intake influences molybdenum kinetics in men. Nutr. 137, 37-42. [98] Johnson JL (2003). Prenatal diagnosis of molybdenum cofactor deficiency and isolated sulfite oxidase deficiency. Prenat Diagn. 23(1), 6-8. [99] Reiss J & Johnson JL (2003).Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH. Hum Mutat. 21(6), 569-76. Role of Reactivity of Transition Elements in Life 47 [100] Mendel RR & Hänsch R (2002). Molybdoenzymes and molybdenum cofactor in plants. J. Exp. Bot. 53 (375), 1689-1698. [101] Bogden JD, Klevay LM, eds. Clinical nutrition of the essential trace elements and minerals: the guide for health professionals. Totowa, NJ: Humana Press Inc. [102] Hille R (2002). Molybdenum and tungsten in biology. Trends in Biochemical Sciences, 27 (7), 360-367. [103] Buckel W & Golding BT (2008). Cobalamin Coenzymes and Vitamin B 12 . In: Encyclopaedia of Life Sciences, John Wiley & Sons, Ltd, online. [104] Scott JW (1998) Vitamin B12. In: Kroschwitz JI, Howe-Grant M (eds) Kirk-Othman encyclopedia of chemical technology, vol 25, 4th edn. Wiley, New York, pp 193–217. [105] Randaccio L, Geremia S, Demitri N & Wuerges J (2010). Vitamin B12: unique metalorganic compounds and the most complex vitamins. Molecules 15, 3228-3259; [106] Anderson RA (1997). Chromium as an essential nutrient for humans. Regul Toxicol Pharmacol. 26(1 Pt 2), S35-41. [107] Preuss HG & Anderson RA (1998). Chromium update: examining recent literature 1997-1998. Curr Opin Clin Nutr Metab Care. 1(6), 509-12. [108] Hummel M, Standl E & Schnell O (2007). Chromium in metabolic and cardiovascular disease. Horm Metab Res. 39(10), 743-51. [109] Wang ZQ & Cefalu WT. Current concepts about chromium supplementation in type 2 diabetes and insulin resistance. Curr Diab Rep. 10(2), 145-51. [110] Di Bona KR, Love S, Rhodes NR, McAdory D, Sinha SH, Kern N, Kent J, Strickland J, Wilson A, Beaird J, Ramage J, Rasco JF, Vincent JB (2011). Chromium is not an essential trace element for mammals: effects of a "low-chromium" diet. J Biol Inorg Chem. 16(3):381-90. [111] WHO (1987). Air quality guidelines for Europe. Copenhagen, World Health Organization Regional Office for Europe, 1987 (WHO Regional Publications, European Series, No. 23). [112] Rehder D (2003). Biological and medicinal aspects of vanadium. Inorganic Chemistry Communications, 6, 604–617. [113] Fallico R, Ferrante M, Fiore M, Madeddu A & Sciacca S (1998). Epidemiological research into the consequences of vanadium assimilated through diet and of its effects on human health following research carried out on people from the Etna massif. J Prev Med Hyg. 39, 74-79. [114] Air Quality Guidelines (2000). Second Edition Chapter 6.12 Vanadium WHO Regional Office for Europe, Copenhagen, Denmark. [115] INC (1986). Toxicology and Biological monitoring of metals in humans, including feasibility and need. Lewis publischers. [116] Sabbioni E, Kueera J, Pietra R, Vesterberg O (1996). A critical review on normal concentrations of vanadium in human blood, serum, and urine. The Science of The Total Environment, 188, 49-58. [117] IlicV, Bojanic V & Jovic B (2007). Epidemiological and pathogenetic aspects of nickel poisoning. Acta Medaca Medianae 46(2), 37-44. [118] Nielsen FH (1993). Is nickel nutritionally important? Nutrition today. 28 (1), 14-19. [119] Sabo-Attwood T, Ramos-Nino M & Mossman BT (2006). Environmental carcinogenesis. In: Oncology: An Evidence-Based Approach. Edited by Alfred E. Chang, Patricia A. Ganz, Daniel F. Hayes, and others. New York, Springer-Verlag. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 48 [120] Waalkes M( 1995). Metal carcinogenesis. In: Goyer RA & Klaassen CD, eds. Metal toxicology. New York: Academic Press, pp. 47-67. [121] Gold LS, Zeiger E, editors (1997). Handbook of Carcinogenic Potency and Genotoxicity Databases. New York, NY, USA: CRC Press. [122] Beyersmann D (2002). Effects of carcinogenic metals on gene expression. Toxicol Lett. 127(1–3), 63–68. [123] Cantor KP, Stewart PA, Brinton LA & Dosemeci M (1995). Occupational exposures and female breast cancer mortality in the United States. J Occup Environ Med. 37(3), 336-48. [124] Adachi S, Takemoto K, Ohshima S, Shimizu Y & Takahama M (1991). Metal concentrations in lung tissue of subjects suffering from lung cancer. Int Arch Occup Environ Health, 63, 193–197. [125] Ebadi M & Swanson S (1988). The status of zinc, copper and methallothionein in cancer patients. Prog Clin Biol Res. 259, 161–175. [126] Wang M, Dhingra K, Hittelman WN, Liehr JG, de Andrade M & Li D (1996). Lipid peroxidation-induced putative malondialdehye-DNA adducts in human breast tissue. Cancer Epidemiol Biomarkers Prev. 5, 705–710. [127] U.S. EPA (1985). United States Environmental Protection Agency. Health Assessment Document for Nickel. EPA/600/8-83/012F, pp. 3-3. [128] Nackerdien Z, Kasprzak KS, Rao G, Halliwell B & Dizdaroglu M (1991). Nickel(II)- and cobalt(II)-dependent damage by hydrogen peroxide to the DNA bases in isolated human chromatin. Cancer Res. 51, 5837-5842. [129] NTP (1994). National Toxicology Program. Technical Report on the Toxicology and Carcinogenesis Studies of Nickel Oxide in F344/N Rats and B6C3F1 Mice. NTP TR 451, NIH Publication No. 94-3363. U.S. Department of Health and Human Services. [130] Grimsrud TK & Peto J (2006). Persisting risk of nickel related lung cancer and nasal cancer among Clydach refiners. Occup Environ Med. 63, 365-366 [131] Chen H, Giri NC, Zhang R, Yamane K, Zhang Y, Maroney M & Costa M (2010). Nickel ions inhibit histone demethylase JMJD1A and DNA repair enzyme ABH2 by replacing the ferrous iron in the catalytic centers. J Biol Chem. 285, 7374-7383. [132] National Toxicology Program. NTP toxicology and carcinogensis studies of vanadium pentoxide (CAS No. 1314-62-1) in F344/N rats and B6C3F1 mice (inhalation). Natl Toxicol Program Tech Rep Ser. (507), 1-343. [133] Duffus JH (2007). Carcinogenicity classification of vanadium pentoxide and inorganic vanadium compounds, the NTP study of carcinogenicity of inhaled vanadium pentoxide, and vanadium chemistry. Regul Toxicol Pharmacol. 47(1), 110-4. [134] Assem FL & Levy LS (2009). A review of current toxicological concerns on vanadium pentoxide and other vanadium compounds: gaps in knowledge and directions for future research. J Toxicol Environ Health B Crit Rev. 12(4), 289-306. [135] Vanadyl binds readily to proteins, amino acids, nucleic acids, phosphates, phospholipids, glutathione, citrate, oxalate, lactate, ascorbate, edetate, etc. [134] (Nechay et al., 1986). [136] Ehrlich VA, Nersesyan AK, Atefie K, Hoelzl C, Ferk F, Bichler J, Valic E, Schaffer A, Schulte-Hermann R, Fenech M, Wagner KH, Knasmüller S (2008). Inhalative exposure to vanadium pentoxide causes DNA damage in workers: results of a multiple end point study. Environ Health Perspect. 116(12), 1689-93. Role of Reactivity of Transition Elements in Life 49 [137] Rodríguez-Mercado JJ, Alvarez-Barrera L & Altamirano-Lozano MA (2010). Chromosomal damage induced by vanadium oxides in human peripheral lymphocytes. Drug Chem Toxicol. 33(1), 97-102. [138] Rondini EA, Walters DM, Bauer AK (2010). Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner. Part Fibre Toxicol. 12, 7:9. [139] Shi X & Dalai NS (1993). Vanadate-mediated hydroxyl radical generation from superoxide radical in the presence of NADH: Haber-Weiss vs. Fenton mechanism. Arch. Biochem. Biophys. 3M, 336-341. [140] Langard S (1990). One hundred years of chromium and cancer: a review of epidemiological evidence and selected case reports. Am. J. Ind. Med., 17, 189–215. [141] Langard S (1993). Role of chemical species and exposure characteristics in cancer among persons occupationally exposed to chromium compounds. Scand. J. Work Environ. Health, 19 (suppl. 1), 81–89. [142] IARC (1990). Chromium, nickel, and welding. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 49, IARC, Lyon, 49–445. [143] Arslan P, Beltrame M & Tomasi A (1987). Intracellular chromium reduction. Biochim Biophys Acta, 931, 10–15. [144] Shi X, Chiu A, Chen CT, Halliwell B, Castranova V, Vallyathan V (1999). Reduction of chromium(VI) and its relationship to carcinogenesis. J. Toxicol. Environ. Health B Crit. Rev. 2, 87–104. [145] Shi XL, Dalal NS. (1989) Chromium (V) and hydroxyl radical formation during the glutathione reductase-catalyzed reduction of chromium (VI). Biochem. Biophys. Res. Commun., 163, 627–634. [146] Shi X, Mao Y, Knapton AD, Ding M, Rojanasakul Y, Gannett PM, Dalal N, Liu K. (1994) Reaction of Cr(VI) with ascorbate and hydrogen peroxide generates hydroxyl radicals and causes DNA damage: role of a Cr(IV)-mediated Fenton-like reaction. Carcinogenesis, 15, 2475–2478. [147] Luo H, Lu Y, Shi X, Mao Y, Dalal NS. (1996) Chromium (IV)-mediated fenton-like reaction causes DNA damage: implication to genotoxicity of chromate. Ann. Clin. Lab Sci., 26, 185–191. [148] Kawanishi S Inoue S & Sano S (1986). Mechanism of DNA cleavage induced by sodium chromate (VI) in the presence of hydrogen peroxide. J. Biol. Chem. 261, 5952- 5958. [149] Tamino G, Peretta L & Levis AG (1981). Effects of the trivalent and hexavalent chromium on the physicochemical properties of mammalian cell nucleic acids and synthetic polynucleotides. Chem Biol Interact 37, 309–319. [150] Arakawa H, Ahmad R, Naoui M & Tajmir-Riahi HA (2000). Acomparative study of calf thymus DNA binding to Cr(III) and Cr(VI) ions. Evidence for the guanine N-7- chromium-phosphate chelate formation. J Biol Chem. 275, 10150–10153. [151] Stearns DM, Courtney KD, Giangrande PH, Phieffer LS & Wetterhahn KE (1994). Chromium(VI) reduction by ascorbate: Role of reactive intermediates in DNA damage in vitro. Environ Health Perspect 102(Suppl 3), 21–25. [152] O'Brien TJ, Ceryak S, Patierno SR. (2003) Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms. Mutat. Res., 533, 3–36 Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 50 [153] Nickens KP, Patierno SR, Ceryak S (2010). Chromium genotoxicity: A double-edged sword. Chem Biol Interact. 188(2), 276-88. [154] Son YO, Hitron JA, Wang X, Chang Q, Pan J, Zhang Z, Liu J, Wang S, Lee JC, Shi X (2010).Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells. Toxicol Appl Pharmacol. 245(2), 226-35. [155] Mitochondrial ROS, specifically superoxide anion (O 2 ·– ), mediates Cr(VI)-induced apoptosis of human lung epithelial H460 cells [154](Azad et al., 2008). [156] Norseth T (1981). The carcinogenicity of chromium. Enviro Health Perspective, 40, 121-130. [157] Gibb HJ, Lees PS, Pinsky PF , Rooney BC (2000). Lung cancer among workers in chromium chemical production. Am J Ind Med. 38(2), 115-26. [158] Ammann RW, Müller E, Bansky J, Schüler G, Häcki WH (1980). High incidence of extrahepatic carcinomas in idiopathic hemochromatosis. Scand J Gastroenterol. 15(6), 733-6. [159] Stevens RG, Jones DY, Micozzi MS, Taylor PR (1988). Body iron stores and the risk of cancer. N Engl J Med. 319, 1047–1052. [160] Elmberg M, Hultcrantz R, Ekbom A, Brandt L, Olsson S, Olsson R (2003). Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology, 125, 1733–1741. [161] Okada S (1996). Iron-induced tissue damage and cancer: the role of reactive oxygen species and free radicals. Pathol Int. 46, 311–332. [162] Weinberg ED (1996). The role of iron in cancer. Eur J Cancer Prev. 5, 19–36. [163] Taetle R, Rhyner K, Castagnola J, To D, Mendelsohn J (1985). Role of transferrin, Fe, and transferrin receptors in myeloid leukemia cell growth. Studies with an antitransferrin receptor monoclonal antibody. J Clin Invest 75, 1061–7. [164] Hann HW, Stahlhut MW, Blumberg BS (1988). Iron nutrition and tumor growth: decreased tumor growth in iron-deficient mice. Cancer Res 48, 4168–70. [165] Carthew P, Nolan BM, Smith AG, Edwards RE (1997). Iron promotes DEN initiated GST-P foci in rat liver. Carcinogenesis. 18(3), 599-603. [166] Wu T, Sempos CT, Freudenheim JL, Muti, Smit E (2004 ). Serum iron, copper and zinc concentrations and risk of cancer mortality in US adults. Ann Epidemiol. 14(3), 195- 201. [167] Hughes R, Cross AJ, Pollock JR, Bingham S (2001). Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation. Carcinogenesis, 22, 199–202. [168] Senesse P, Meance S, Cottet V, Faivre J, Boutron-Ruault MC (2004). High dietary iron and copper and risk of colorectal cancer: a case-control study in Burgundy, France. Nutr Cancer, 49, 66–71. [169] Cross AJ, Gunter MJ, Wood RJ, Pietinen P, Taylor PR, Virtamo J, Albanes D, Sinha R (2006). Iron and colorectal cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study. Int J Cancer. 118(12), 3147-52. [170] Mello FA, Meneghini R (1984). In vivo formation of single-strand breaks in DNA by hydrogen peroxide is mediated by the Haber-Weiss-reaction. Biochem Biophys Acta. 781, 56 63. [171] Aust SD, Morehouse LA, Thomas CE (1985). Role of metals in oxygen radical reactions. J Free Radic Biol Med. 1, 3-25. Role of Reactivity of Transition Elements in Life 51 [172] Beyersmann D, Hartwig A (2008). Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol. 82(8), 493-512. [173] Bush AI (2003). The metallobiology of Alzheimer's disease. Trends Neurosci. 26(4), 207-14. [174] Crichton RR, Ward RJ (2006). Metal-based Neurodegeneration From Molecular mechanisms to Therapeutic Strategies, John Wiley and Sons, Chichester, pp. 227. [175] Alexander J, Kowdley KV (2009) HFE-associated hereditary hemochromatosis. Genet Med. 11, 307–313. [176] Hoogenraad TU (1996). Monography: Wilson’s disease. In: Major Problems in Neurology. Vol 30, London: W.B. Saunders. [177] Halliwell B (2006). Oxidative stress and neurodegeneration: where are we now?. Journal of Neurochemistry, 97, 1634–1658. [178] Khachaturian ZS (1985). Diagnosis of Alzheimer’s disease. Arch Neurol. 42, 1097– 105. [179] Filley CM (1995). Alzheimer’s disease: it’s irreversible but not untreatable. Geriatrics, 50, 18–23. [180] Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO (1989). Prevalence of Alzheimer’s disease in a community population of older persons: higher than previously reported. JAMA, 262 (18), 2551-6. [181] Probst A, Langui D, Ulrich J (1991). Alzheimer’s disease: a description of the structural lesions. Brain. Pathol. 1, 229-239 [182] Price DL, Sisodia SS (1998) Mutant genes in familial Alzheimer's disease and transgenic models. Annu Rev Neurosci 21, 479–505 [183] Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, et al. (1992) Isolation and Quantification of Soluble Alzheimers Beta-Peptide from Biological-Fluids. Nature, 359, 325–327. [184] Busciglio J, Gabuzda DH, Matsudaira P, Yankner BA (1993) Generation of Beta- Amyloid in the Secretory Pathway in Neuronal and Nonneuronal Cells. Proceedings of the National Academy of Sciences of the United States of America, 90, 2092–2096. [185] Selkoe DJ (2001). Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 81, 741–766. [186] Castellani RJ, Alexiev BA, Phillips D, Perry G and Smith MA (2007). Microscopic Investigations in Neurodegenerative Diseases. Modern Research and Educational Topics in Microscopy. Méndez-Vilas A and J. Díaz (eds) pp 171-182. [187] Iqbal K, Alonso Adel C, Chen S, Chohan MO, El-Akkad E, Gong CX, Khatoon S, Li, B, Liu F, Rahman A, Tanimukai H, Grundke-Iqbal I (2005). Tau pathology in Alzheimer’s disease and other tauopathies. Biochim. Biophys. Acta, 1739 (2-3), 198- 210. [188] Quintana C, Bellefqih S, Laval JY, Guerquin-Kern JL, Wu TD, Avila J, Ferrer I, Arranz R, Patino C (2006). Study of the localization of iron, ferritin, and hemosiderin in Alzheimer’s disease hippocampus by analytical microscopy at the subcellular level. J Struct Biol. 153, 42–54. [189] Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998). Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci. 158, 47-52. [190] Rossi L, Squitti R, Pasqualetti P, Marchese E, Cassetta E, Forastiere E, Rotilio G, Rossini PM, Finazzi-Agró A (2002). Red blood cell copper, zinc superoxide dismutase Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 52 activity is higher in Alzheimer's disease and is decreased by D-penicillamine. Neurosci Lett. 329(2), 137-40. [191] Danscher G, Jensen KB, Frederickson CJ, Kemp K, Andreasen A, Juhl S, Stoltenberg M, Ravid R (1997). Increased amount of zinc in the hippocampus and amygdala of Alzheimer's diseased brains: a proton-induced X-ray emission spectroscopic analysis of cryostat sections from autopsy material. J Neurosci Methods. 76(1), 53-9. [192] Cornett CR, Markesbery WR, Ehmann WD (1998). Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain. Neurotoxicology, 19(3), 339- 45. [193] Cornett CR, Ehmann WD, Wekstein DR, Markesbery WR (1998). Trace elements in Alzheimer's disease pituitary glands. Biol Trace Elem Res. 62(1-2), 107-14. [194] Dong J, Robertson JD, Markesbery WR, Lovell MA (2008). Serum zinc in the progression of Alzheimer's disease. J Alzheimers Dis. 15(3), 443-50. [195] Lovell MA, Smith JL, Xiong S, Markesbery WR (2005). Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease. Neurotox Res. 7(4), 265-71. [196] Lovell MA, Smith JL, Markesbery WR (2006). Elevated zinc transporter-6 in mild cognitive impairment, Alzheimer disease, and pick disease. J Neuropathol Exp Neurol. 65(5), 489-98. [197] Squitti R, Lupoi D, Pasqualetti P, Dal Forno G, Vernieri F, Chiovenda P (2002). Elevation of serum copper levels in Alzheimer’s disease. Neurol 59, 1153-61. [198] Sayre LM, Perry G, Harris PL, Liu Y, Schubert KA, Smith MA (2000). In situ catalysis by neurofibrillary tangles and senile plaques in Alzheimer’s disease: a central role for bound transition metals. J Neurochem. 74, 270-9. [199] Miller LM, Wang Q, Telivala TP, Smith RJ, Lanzirotti A, Miklossy J (2006). Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with β-amyloid deposits in Alzheimer’s disease. J Struct Biol. 155, 30– 37. [200] Squitti R, Bressi F, Pasqualetti P, Bonomini C, Ghidoni R, Binetti G, Cassetta E, Moffa F, Ventriglia M, Vernieri F, Rossini PM (2009). Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease. Neurology. 72(1), 50-5. [201] Salustri C, Barbati G, Ghidoni R, Quintiliani L, Ciappina S, Binetti G, Squitti R (2010). Is cognitive function linked to serum free copper levels? A cohort study in a normal population. Clin Neurophysiol. 121(4), 502-7. [202] Kessler H, Pajonk FG, Meisser P, Schneider-Axmann T, Hoffmann KH, Supprian T (2006). Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and ceruloplasmin in patients with Alzheimer’s disease. Neural Transm. 113, 1763-9. [203] Squitti R, Quattrocchi CC, Salustri C and Rossini PM (2008). Ceruloplasmin fragmentation is implicated in ‘free’ copper deregulation of Alzheimer’s disease. Prion 2:1, 23-27. [204] Gray EH, De Vos KJ, Dingwall C, Perkinton MS, Miller CC (2010). Deficiency of the Copper Chaperone for Superoxide Dismutase Increases Amyloid-β Production. J Alzheimers Dis. 21(4), 1101-5. [205] Strozyk D, Launer LJ, Adlard PA, Cherny RA, Tsatsanis A, Volitakis I, Blennow K, Petrovitch H, White LR, Bush AI 92009). Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid. Neurobiol Aging. 30(7), 1069-77. Role of Reactivity of Transition Elements in Life 53 [206] Finder VH, Glockshuber R (2007). Amyloid-beta aggregation. Neurodegener Dis. 4(1), 13-27. [207] Soto C (2003). Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci. 4(1), 49-60. [208] Shirwany NA, Payette D, Xie J, Guo Q (2007). The amyloid beta ion channel hypothesis of Alzheimer's disease. Neuropsychiatr Dis Treat. 3(5), 597-612. [209] McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, and Masters CL (1999). Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann. Neurol. 46, 860–866. [210] Yang X, Askarova S, Lee JC (2010). Membrane biophysics and mechanics in Alzheimer's disease. Mol Neurobiol. 41(2-3), 138-48. [211] Wu HY, Hudry E, Hashimoto T, Kuchibhotla K, Rozkalne A, Fan Z, Spires-Jones T, Xie H, Arbel-Ornath M, Grosskreutz CL, Bacskai BJ, Hyman BT (2010). Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation. J Neurosci. 30(7), 2636-49. [212] Chen T, Wang X, He Y, Zhang C, Wu Z, Liao K, Wang J, Guo Z (2009). Inorg Chem. Effects of cyclen and cyclam on zinc(II)- and copper(II)-induced amyloid beta-peptide aggregation and neurotoxicity. 48(13), 5801-9. [213] Huang XD, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD (1999). Cu(II) potentiation of Alzheimer A beta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. Journal of Biological Chemistry, 274, 37111– 37116. [214] Drochioiu G, Manea M, Dragusanu M, Murariu M, Dragan ES, Petre BA, Mezo G, Przybylski M (2009). Interaction of β-amyloid(1-40) peptide with pairs of metal ions: An electrospray ion trap mass spectrometric model study. Biophysical Chemistry, 144, 9–20. [215] Karr JW, Kaupp LJ, Szalai VA (2004). Amyloid-beta binds Cu2+ in a mononuclear metal ion binding site. J Am Chem Soc. 126(41), 13534-8. [216] Maynard CJ, Bush AI, Masters CL, Cappai R, Li QX (2005). Metals and amyloid-β in Alzheimer’s disease. Int J Exp Pathol. 86, 147–159. [217] Streltsov V (2008). X-ray absorption and diffraction studies of the metal binding sites in amyloid β-peptide. Eur Biophys J. 7, 257–263. [218] Streltsov VA, Titmuss SJ, Epa VC, Barnham KJ, Masters CL and Varghese JN (2008).The Structure of the Amyloid-β Peptide High-Affinity Copper II Binding Site in Alzheimer Disease. Biophys J. 95(7), 3447–3456. [219] Tõugu V, Karafin A, Palumaa P (2008). Binding of zinc(II) and copper(II) to the full- length Alzheimer's amyloid-beta peptide. J Neurochem. 104(5), 1249-59. [220] Dong J, Canfield JM, Mehta AK, Shokes JE, Tian B, Childers WS, Simmons JA, Mao Z, Scott RA, Warncke K, and Lyn DG (2007). Engineering metal ion coordination to regulate amyloid fibril assembly and toxicity. Proc Natl Acad Sci U S A. 104(33), 13313–13318. [221] Miura T, Suzuki K, Kohata N, Takeuchi H (2000). Metal binding modes of Alzheimer's amyloid beta-peptide in insoluble aggregates and soluble complexes. Biochemistry. 39(23), 7024-31. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 54 [222] Stellato F, Menestrina G, Serra MD, Potrich C, Tomazzolli R, Meyer-Klaucke W, Morante S (2006). Metal binding in amyloid beta-peptides shows intra- and inter- peptide coordination modes. Eur Biophys J. 35(4), 340-51. [223] Dong J, Atwood CS, Anderson VE, Siedlak SL, Smith MA, Perry G, Carey PR (2003). Metal binding and oxidation of amyloid-beta within isolated senile plaque cores: Raman microscopic evidence. Biochemistry, 42(10), 2768–73. [224] Smith DP, Smith DG, Curtain CC, Boas JF, Pilbrow JR, Ciccotosto GD, Lau TL, Tew DJ, Perez K, Wade JD, Bush AI, Drew SC, Separovic F, Masters CL, Cappai R, Barnham KJ (2006). Copper-mediated amyloid-beta toxicity is associated with an intermolecular histidine bridge. J Biolr Chem. 281(22), 15145-54. [225] Syme CD, Viles JH (2006). Solution 1H NMR investigation of Zn2+ and Cd2+ binding to amyloid-beta peptide (Abeta) of Alzheimer's disease. Biochim Biophys Acta. 1764(2), 246-56. [226] Miller Y, Ma B and Nussinov R (2010). Zinc ions promote Alzheimer Aβ aggregation via population shift of polymorphic states. Proc Natl Acad Sci U S A. 107(21), 9490– 9495. [227] Jun S, Gillespie JR, Shin BK, Saxena S (2009). The second Cu(II)-binding site in a proton-rich environment interferes with the aggregation of amyloid-beta(1-40) into amyloid fibrils. Biochemistry. 48(45), 10724-32. [228] Sarell CJ, Syme CD, Rigby SE, Viles JH (2009). Copper(II) binding to amyloid-beta fibrils of Alzheimer's disease reveals a picomolar affinity: stoichiometry and coordination geometry are independent of Abeta oligomeric form. Biochemistry. 48(20), 4388-402. [229] Curtain CC, Barnham KJ and Bush AI. Aβ metallobiology and the development of novel metal-protein attenuating compounds (MPACs) for Alzheimer's disease . Curr. Med. Chem. – Immun., Endoc. & Metab. Agents, 2003, 3, 309-315 [230] Cuajungco MP, Goldstein LE, Nunomura A, Smith MA, Lim JT (2000). Evidence that the beta-amyloid plaques of Alzheimer's disease represent the redox-silencing and entombment of A beta by zinc. J Biol Chem. 275, 19439–19442. [231] Suzuki K, Miura T, Takeuchi H (2001). Inhibitory effect of copper(II) on zinc(II)- induced aggregation of amyloid beta-peptide. Biochem Biophys Res Commun. 285(4), 991-6. [232] Yoshiike Y, Tanemura K, Murayama O, Akagi T, Murayama M, Sato S, Sun X, Tanaka N, Takashima A (2001). New insights on how metals disrupt amyloid beta-aggregation and their effects on amyloid-beta cytotoxicity. J Biol Chem. 276(34), 32293-9. [233] Karr JW, Akintoye H, Kaupp LJ, Szalai VA (2005). N-Terminal deletions modify the Cu2+ binding site in amyloid-beta. Biochemistry. 44(14), 5478-87. [234] Chen YR, Huang HB, Chyan CL, Shiao MS, Lin TH, Chen YC (2006). The effect of Abeta conformation on the metal affinity and aggregation mechanism studied by circular dichroism spectroscopy. J Biochem. 139(4), 733-40. [235] Dai X, Sun Y, Gao Z, Jiang Z (2010). Copper enhances amyloid-beta peptide neurotoxicity and non beta-aggregation: a series of experiments conducted upon copper-bound and copper-free amyloid-beta peptide. J Mol Neurosci. 41(1), 66-73. [236] Ha C, Ryu J, Park CB (2007). Metal ions differentially influence the aggregation and deposition of Alzheimer's beta-amyloid on a solid template. Biochemistry. 46(20), 6118-25. Role of Reactivity of Transition Elements in Life 55 [237] Ryu J, Girigoswami K, Ha C, Ku SH, Park CB (2008). Influence of multiple metal ions on beta-amyloid aggregation and dissociation on a solid surface. Biochemistry. 47(19), 5328-35. [238] Yang XH, Huang HC, Chen L, Xu W, Jiang ZF (2009). Coordinating to three histidine residues: Cu(II) promotes oligomeric and fibrillar amyloid-beta peptide to precipitate in a non-beta aggregation manner. J Alzheimers Dis. 18(4), 799-810. [239] House E, Mold M, Collingwood J, Baldwin A, Goodwin S and Exley C (2009). Copper Abolishes the β-Sheet Secondary Structure of Preformed Amyloid Fibrils of Amyloid- β 42 . J Alzheimers Dis. 18(4), 811–817. [240] Butterfield DA, Castegna A, Lauderback CM, Drake J (2002). Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death. Neurobiol Aging. 23(5), 655-64. [241] Abramov AY, Canevari L, Duchen MR (2004).Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase. J Neurosci. 24(2), 565-75. [242] De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, Klein WL (2007). Abeta oligomers induce neuronal oxidative stress through an N-methyl-D- aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem. 282(15), 11590-601. [243] Rival T, Page RM, Chandraratna DS, Sendall TJ, Ryder E, Liu B, Lewis H, Rosahl T, Hider R, Camargo LM, Shearman MS (2009), Fenton chemistry and oxidative stress mediate the toxicity of the beta-amyloid peptide in a Drosophila model of Alzheimer's disease. Eur J Neurosci. 29(7), 1335-47. [244] Tabner BJ, Turnbull S, El-Agnaf OM, Allsop D (2002). Formation of hydrogen peroxide and hydroxyl radicals from A(beta) and alpha-synuclein as a possible mechanism of cell death in Alzheimer's disease and Parkinson's disease. Free Radic Biol Med. 32(11), 1076-83. [245] Guilloreau L, Combalbert S, Sournia-Saquet A, Mazarguil H, Faller P (2007). Redox chemistry of copper-amyloid-beta: the generation of hydroxyl radical in the presence of ascorbate is linked to redox-potentials and aggregation state. Chembiochem. 8(11), 1317-25. [246] Mattson MP (2004). Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Ann N Y Acad Sci. 1012, 37-50. [247] White AR, Cappai R (2003).Neurotoxicity from glutathione depletion is dependent on extracellular trace copper. J Neurosci Res. 71(6), 889-97. [248] Bush AI (2002). Metal complexing agents as therapies for Alzheimer's disease. Neurobiol Aging. 23(6), 1031-8. [249] Jiang D, Men L, Wang J, Zhang Y, Chickenyen S, Wang Y, Zhou F (2007). Redox reactions of copper complexes formed with different beta-amyloid peptides and their neuropathological [correction of neuropathalogical] relevance. Biochemistry. 46(32), 9270-82. [250] Spasojević I, Mojović M, Stević Z, Spasić SD, Jones DR, Morina A, Spasić MB (2010). Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid. Redox Rep. 15(1), 29-35. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 56 [251] iang H, Song N, Xu H, Zhang S, Wang J, Xie J (2010). Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent. Cell Res 20, 345–356. [252] Nadal RC, Rigby SE, Viles JH (2008). Amyloid beta-Cu2+ complexes in both monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl radicals. Biochemistry. 47(44), 11653-64. [253] Shearer J and Szalai VA (2008). The amyloid-β peptide of Alzheimer's disease binds Cu I in a linear bis-His coordination environment: Insight into a possible neuroprotective mechanism for the amyloid-β peptide. J Am Chem Soc. 130(52), 17826–17835. [254] Tabner BJ, El-Agnaf OM, Turnbull S, German MJ, Paleologou KE, Hayashi Y, Cooper LJ, Fullwood NJ, Allsop D (2005). Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia. J Biol Chem. 280(43), 35789-92. [255] [254] Crouch PJ, Blake R, Duce JA, Ciccotosto GD, Li QX, Barnham KJ, Curtain CC, Cherny RA, Cappai R, Dyrks T, Masters CL, Trounce IA (2005). Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42. J Neurosci. 25(3), 672-9. [256] Barnham KJ, McKinstry WJ, Multhaup G, Galatis D, Morton CJ, Curtain CC, Williamson NA, White AR, Hinds MG, Norton RS, Beyreuther K, Masters CL, Parker MW, Cappai R (2003). Structure of the Alzheimer's disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis. J Biol Chem. 278(19), 17401-7. [257] Bellingham S, Ciccotosto G, Needham B, Fodero A, White A, Masters C, Cappai R. and Camakaris J (2004). Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2 increases cellular copper levels in primary mouse cortical neuron and embryonic fibroblasts. J. Neurosci. 91, 423–428. [258] Maynard C, Cappai, R, Volitakis I, Cherny R, White A, Beyreuther K, Masters C, Bush A and Li QX (2002). Overexpression of Alzheimer's disease amyloid-β opposes the age-dependent elevations of brain copper and iron. J. Biol. Chem. 277, 44670–44676 [259] Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI (2010). Iron- export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. Cell. 142(6), 857-67. [260] Kägi JH, Kojima Y (1987). Chemistry and biochemistry of metallothionein. Experientia Suppl. 52, 25–61. [261] Meloni G, Faller P, Vasák M (2007). Redox silencing of copper in metal-linked neurodegenerative disorders: reaction of Zn7metallothionein-3 with Cu2+ ions. J Biol Chem. 282(22), 16068-78. [262] Chung RS, Howells C, Eaton ED, Shabala L, Zovo K, et al. (2010) The native copper- and zinc- binding protein metallothionein blocks copper-mediated Aβ aggregation and toxicity in rat cortical neurons. PLoS ONE 5(8), e12030. [263] Bothwell M (1995). Functional interactions of neurotrophins and neurotrophin receptors. Annu Rev Neurosci. 18, 223–253. Role of Reactivity of Transition Elements in Life 57 [264] Milward EA, Papadopoulos R, Fuller SJ, Moir RD, Small D, Beyreuther K, Masters CL (1992). The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth. Neuron. 9(1), 129-37. [265] Ross GM, Shamovsky IL, Woo SB, Post JI, Vrkljan PN, Lawrance G, Solc M, Dostaler SM, Neet KE, Riopelle RJ (2001). The binding of zinc and copper ions to nerve growth factor is differentially affected by pH: implications for cerebral acidosis. J Neurochem. 78(3), 515-23. [266] Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, Barnham KJ, Volitakis I, Fraser FW, Kim Y (2001). Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron. 30, 665–676. [267] Doraiswamy PM, Finefrock AE (2004). Metals in our minds: therapeutic implications for neurodegenerative disorders. Lancet Neurol. 3(7), 431-4. [268] Caragounis A, Du T, Filiz G, Laughton KM, Volitakis I, Sharples RA, Cherny RA, Masters CL, Drew SC, Hill AF, Li QX, Crouch PJ, Barnham KJ, White AR (2007). Differential modulation of Alzheimer's disease amyloid beta-peptide accumulation by diverse classes of metal ligands. Biochem J. 407(3), 435-50. [269] Verhaegh GW, Richard MJ, Hainaut P (1997). Regulation of p53 by metal ions and by antioxidants: dithiocarbamate down-regulates p53 DNA-binding activity by increasing the intracellular level of copper. Mol Cell Biol. 17(10), 5699-706. [270] Malm TM, Iivonen H, Goldsteins G, Keksa-Goldsteine V, Ahtoniemi T, Kanninen K, Salminen A, Auriola S, Van Groen T, Tanila H, Koistinaho J (2007). Pyrrolidine dithiocarbamate activates Akt and improves spatial learning in APP/PS1 mice without affecting beta-amyloid burden. J Neurosci. 27(14), 3712-21. [271] Zhang J, Liu Q, Chen Q, Liu NQ, Li FL, Lu ZB, Qin C, Zhu H, Huang YY, He W, Zhao BL (2006).Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis. FASEB J. 20(8), 1212-4. [272] Squitti R, Rossini PM, Cassetta E, Moffa F, Pasqualetti P, Cortesi M, Colloca A, Rossi L, Finazzi-Agró A(2002). d-penicillamine reduces serum oxidative stress in Alzheimer's disease patients. Eur J Clin Invest. 32(1), 51-9. [273] Cater MA, McInnes KT, Li QX, Volitakis I, La Fontaine S, Mercer JF, Bush AI (2008). Intracellular copper deficiency increases amyloid-beta secretion by diverse mechanisms. Biochem J. 412(1), 141-52. [274] Crouch PJ, Hung LW, Adlard PA, Cortes M, Lal V, Filiz G, Perez KA, Nurjono M, Caragounis A, Du T, Laughton K, Volitakis I, Bush AI, Li QX, Masters CL, Cappai R, Cherny RA, Donnelly PS, White AR, Barnham KJ (2009).Increasing Cu bioavailability inhibits Abeta oligomers and tau phosphorylation. Proc Natl Acad Sci U S A. 106(2), 381-6. [275] Hung YH, Robb EL, Volitakis I, Ho M, Evin G, Li QX, Culvenor JG, Masters CL, Cherny RA, Bush AI (2009). Paradoxical condensation of copper with elevated beta- amyloid in lipid rafts under cellular copper deficiency conditions: implications for Alzheimer disease. J Biol Chem. 284(33), 21899-907. [276] Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973). Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci. 20(4), 415-55. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 58 [277] Jenner P, Olanow CW (1996) Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 47, S161–170. [278] Lev N, Melamed E (2001). Heredity in Parkinson's disease: new findings. Isr Med Assoc J. 3(6), 435-8. [279] Montgomery EB Jr (1995).Heavy metals and the etiology of Parkinson's disease and other movement disorders. Toxicology, 97(1-3), 3-9. [280] Olanow CW (1990). Oxidation reactions in Parkinson's disease. Neurology. 40(10 Suppl 3), suppl 32-7 [281] Lévay G., Ye Q and Bodell WJ (1997). Formation of DNA adducts and oxidative base damage by copper mediated oxidation of dopamine and 6-hydroxydopamine . Exp. Neurol. 146 (2), 570-574. [282] Spina MB, Cohen G (1989). Dopamine turnover and glutathione oxidation: implications for Parkinson disease. Proc Natl Acad Sci U S A. 86(4), 1398-400. [283] Oreland L, Gottfries CG (1986). Brain and brain monoamine oxidase in aging and in dementia of Alzheimer's type. Prog Neuropsychopharmacol Biol Psychiatry. 10(3-5), 533-40. [284] Zatta P, Zambenedetti P, Milanese M (1999). Activation of monoamine oxidase type-B by aluminum in rat brain homogenate. Neuroreport. 10(17), 3645-8. [285] Lotharius J, Brundin P (2002). Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. Nat Rev Neurosci. 3(12), 932-42. [286] Yuan H, Zheng JC, Liu P, Zhang SF, Xu JY, Bai LM (2007). Pathogenesis of Parkinson's disease: oxidative stress, environmental impact factors and inflammatory processes. Neurosci Bull. 23(2), 125-30. [287] Gal S, Zheng H, Fridkin M, Youdim MB (2005). Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases. In vivo selective brain monoamine oxidase inhibition and prevention of MPTP-induced striatal dopamine depletion. J Neurochem. 95(1), 79-8 [288] Graham DG (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14, 633– 643. [289] Graham DG, Tiffany SM, Bell Jr WR, Gutknecht WF (1978) Autoxidation versus covalent binding of quinones as a mechanism of toxicity of dopamine, 6- hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro. Mol Pharmacol 14, 644–653. [290] Fornstedt B, Rosengren E, Carlsson A (1986) Occurrence and distribution of 5-S- cysteinyl derivatives of dopamine, dopa and dopac in the brains of eight mammalian species. Neuropharmacology 25, 451-454 [291] Hastings TG, Zigmond MJ (1994). Identification of catechol-protein conjugates in neostriatal slices incubated with [3H]-dopamine: impact of ascorbic acid and glutathione. J Neurochem 63, 1126-1132. [292] Baez S, Linderson Y and Segura-Aguilar J (1995). Superoxide dismutase and catalase enhance autoxidation during one-electron reduction of aminochrome by NADPH- cytochrome P-450 reductase. Biochem. Mol. Med. 54 (1), 12-18. [293] Baez S, Segura-Aguilar J, Widersten M, Johansson AS, Mannervik B (1997). Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes. Biochem J. 324 ( Pt 1), 25-8. Role of Reactivity of Transition Elements in Life 59 [294] Kang, JH (2004). Modification of Cu,Zn-superoxide dismutase by oxidized catecholamines. J Biochem Mol Biol. 37(3), 325-9. [295] Dedov VN, Griffiths FM, Garner B, Halliday GM, Double KL (2007). Lipid content determines aggregation of neuromelanin granules in vitro. J Neural Transm Suppl. (72), 35-8. [296] Gerlach M, Deckert J, Double K, and Koutsilieri E, eds (2007). Neuropsychiatric Disorders An Integrative Approach. New York: SpringerWien. [297] Gerlach M, Double KL, Ben-Shachar D, Zecca L, Youdim MB, Riederer P (2003). Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic neurodegeneration underlying Parkinson's disease. Neurotox Res. 5(1-2), 35-44. [298] Odh G, Carstam R, Paulson J, Wittbjer A, Rosengren E, Rorsman H. Neuromelanin of the human substantia nigra: a mixed-type melanin (1994). J Neurochem. 62(5), 2030-6. [299] Zhang F, Dryhurst G (1994). Effects of L-cysteine on the oxidation chemistry of dopamine: new reaction pathways of potential relevance to idiopathic Parkinson's disease. J Med Chem. 37(8), 1084-98. [300] Zecca L, Tampellini D, Gerlach M, Riederer P, Fariello RG, Sulzer D (2001). Substantia nigra neuromelanin: structure, synthesis, and molecular behaviour. J Clin Pathol: Mol Pathol. 54, 414–418 [301] Zecca L, Zucca FA, Costi P, Tampellini D, Gatti A, Gerlach M, Riederer P, Fariello RG, Ito S, Gallorini M, Sulzer D (2003). The neuromelanin of human substantia nigra: structure, synthesis and molecular behaviour. J Neural Transm Suppl. (65), 145-55. [302] [303] Fasano M, Giraudo S, Coha S, Bergamasco B, Lopiano L (2003) Residual substantia nigra neuromelanin in Parkinson’s disease is cross-linked to alpha-synuclein. Neurochem Int. 42: 603–606 [303] Bridelli MG, Tampellini D, Zecca L (1999). The structure of neuromelanin and its iron binding site studied by infrared spectroscopy. FEBS Lett. 20, 457(1):18-22. [304] Zecca L, Pietra R, Goj C. Mecacci C, Radice D, and Sabbioni E. (1994). Iron and other metals in neuromelanin, substantia nigra and putamen of human brain. J. Neurochem. 62, 1097–1101. [305] Bolzoni F, Giraudo S, Bergamasco B, Lopiano L, Fasano M, Crippa PR (2002). Magnetic investigations of human mesencephalic neuromelanin. Biochim. Biophys. Acta, 1586, 210-218. [306] Hirsch E, Graybiel A, Agid Y (1988) Melanized dopamine neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature, 28, 345–348. [307] Kastner A, Hirsch EC, Lejeune O, Javoy-Agid F, Rascol O, Agid Y (1992) Is the vulnerability of neurons in the substantia nigra of patients with Parkinson’s disease related to their neuromelanin contents? J Neurochem 59: 1080–1089. [308] Shamoto-Nagai M, Maruyama W, Yi H, Akao Y, Tribl F, Gerlach M, Osawa T, Riederer P, Naoi M (2006). Neuromelanin induces oxidative stress in mitochondria through release of iron: mechanism behind the inhibition of 26S proteasome. J Neural Transm. 113(5), 633-44. [309] Double KL, Gerlach M, Sch€unemann V, Trautwein AX, Zecca L, Gallorini M, Youdim MBH, Riederer P, Ben-Shachar D (2003) Iron binding characteristics of neuromelanin of the human substantia nigra. Biochem Pharmacol. 66: 489–494. Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam et al. 60 [310] Shima T, Sarna T, Swartz H, Stroppolo A, Gerbasi R, Zecca L (1997) Binding of iron to neuromelanin of human substantia nigra and synthetic melanin: an electron paramagnetic resonance spectroscopy study. Free Radic Biol Med. 23: 110–119. [311] Gerlach M, Double KL, Ben-Shachar D, Zecca L, Youdim MB, Riederer P (2003). Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic neurodegeneration underlying Parkinson's disease Neurotox Res.;5(1-2):35-44. [312] Double KL (2006). Functional effects of neuromelanin and synthetic melanin in model systems. J Neural Transm 113, 751–756. [313] Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, Jellinger K, Youdim MB (1989). Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem. 52, 515–520 [314] Griffiths PD, Dobson BR, Jones GR and Clarke DT (1999).Iron in the basal ganglia in Parkinson's disease.An in vitro study using extended X-ray absorption fine structure and cryo-electron microscopy. Brain, 122(4), 667-673. [315] Martin WR, Wieler M, Gee M (2008).Midbrain iron content in early Parkinson disease.A potential biomarker of disease status. Neurology70 (16 Part 2), 1411-1417. [316] Galazka-Friedman J (2008). Iron as a risk factor in neurological diseases. J Hyperfine Interactions, 182 (1–3),31–44. [317] Logroscino G, Gao X, Chen H, Wing A, Ascherio A (2008). Dietary iron intake and risk of Parkinson's disease. Am J Epidemiol. 168(12), 1381-8. [318] Vanacore N, Nappo A, Gentile M, Brustolin A, Palange S, Liberati A, Di Rezzel S, Caldoral G, Gasparinil M, Benedetti F, Bonifatil V, Forastiere F, Quercia A, Mecol G (2002). Neurol. Sci. 23 (Suppl. 2), S119–S120. [319] Kamel F, Tanner C, Umbach D, Hoppin J, Alavanja M, Blair A, Comyns K, Goldman S, Korell M, Langston J, Ross G, Sandler D (2007). Am J Epidemiol. 165(4), 364-74. [320] Peng J, Peng L, Stevenson FF, Doctrow SR and Andersen JK (2007). Iron and paraquat as synergistic environmental risk factors in sporadic Parkinson's disease accelerate age- related neurodegeneration. J Neurosci. 27(26), 6914-6922. [321] Lee HP, Zhu X, Liu G, Chen SG, Perry G, Smith MA and Lee HG (2010). Divalent metal transporter, iron, and Parkinson's disease: A pathological relationship. Cell Res. 20, 397–399. [322] Verstraeten SV, Aimo L, Oteiza PI (2008). Aluminium and lead: molecular mechanisms of brain toxicity. Arch Toxicol. 82(11), 789-802. [323] Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) alpha- Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA. 95, 6469–6473. [324] Clayton DF and George JM (1998). The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci., 21, 249– 254. [325] Fornai F, Lenzi P, Gesi M, Ferrucci M, Lazzeri G, Natale G, Ruggieri S, Paparelli A (2003). Recent knowledge on molecular components of Lewy bodies discloses future therapeutic strategies in Parkinson’s disease. Curr. Drug. Target. CNS. Neurol. Disord. 2, 149–152. [326] Savitt JM, Dawson VL, Dawson TM (2006). Diagnosis and treatment of Parkinson disease: molecules to medicine. J. Clin. Invest. 116, 1744–1754. Role of Reactivity of Transition Elements in Life 61 [327] Uversky VN, Li J, Fink AL (2001). Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure. J Biol Chem. 276(47), 44284- 96. [328] Lee JC, Gray HB and Winkler JR (2008). Copper(II) Binding to α-Synuclein, the Parkinson’s Protein. J. Am. Chem. Soc. 130 (22), 6898–6899. [329] Rasia RM, Bertoncini CW, Marsh D, Hoyer W, Cherny D, Zweckstetter M, Griesinger C, Jovin TM, Fernández CO (2005). Structural characterization of copper(II) binding to alpha-synuclein: Insights into the bioinorganic chemistry of Parkinson's disease. Proc Natl Acad Sci U S A. 102(12), 4294-9. [330] Drew SC, Leong SL, Pham CL, Tew DJ, Masters CL, Miles LA, Cappai R, Barnham KJ (2008). Cu2+ binding modes of recombinant alpha-synuclein--insights from EPR spectroscopy. J Am Chem Soc. 130(24), 7766-73. [331] [332] Oikawa, S., Hirosawa, I., Tada-Oikawa, S., et al. (2006) Mechanism for manganese enhancement of dopamine-induced oxidative DNA damage and neuronal cell death. Free Radical Biology & Medicine, 41(5), 748-756. [332] Sloot WN, Korf J, Koster JF, DeWit LEA, Gramsbergen JBP (1996). Manganese- induced hydroxyl radical formation in rat striatum is not attenuated by dopamine depletion or iron chelation in vivo. Exp. Neurol. 138, 236–245. [333] Lloyd RV (1995). Mechanism of the manganese-catalyzed autoxidation of dopamine. Chem. Res. Toxicol. 8, 111–116. [334] Afeseh Ngwa H, Kanthasamy A, Anantharam V, Song C, Witte T, Houk R, Kanthasamy AG (2009). Vanadium induces dopaminergic neurotoxicity via protein kinase Cdelta dependent oxidative signaling mechanisms: relevance to etiopathogenesis of Parkinson's disease. Toxicol Appl Pharmacol. 240(2), 273-85. [335] Zhao Y, Ye L, Liu H, Xia Q, Zhang Y, Yang X, Wang K (2010). Vanadium compounds induced mitochondria permeability transition pore (PTP) opening related to oxidative stress. J Inorg Biochem. 104(4), 371-8. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 2 NONLINEAR OPTICAL PROPERTIES OF TRANSITION METAL NANOPARTICLES SYNTHESIZED BY ION IMPLANTATION Andrey L. Stepanov * Laser Zentrum Hannover, Hannover, Germany Kazan Federal University, Kazan, Russian Federation Kazan Physical-Technical Institute, Russian Academy of Sciences, Kazan, Russian Federation ABSTRACT Composite materials containing metal nanoparticles (MNPs) are now considered as a basis for designing new photonic media for optoelectronics and nonlinear optics. Simultaneously with the search for and development of modern technologies intended for nanoparticle synthesis, substantial practical attention has been devoted to designing techniques for controlling the MNP size. One of the promising methods for fabrication of MNPs is ion implantation. Review of recent results on ion-synthesis and nonlinear optical properties of cupper, silver and gold nanoparticles in surface area of various dielectrics as glasses and crystals are presented. Composites prepared by the low energy ion implantation are characterized with the growth of MNPs in thin layer of irradiated substrate surface. Fabricated structures lead to specific optical nonlinear properties for picosecond laser pulses in wide spectral area from UV to IR such as nonlinear refraction, saturable and two-photon absorption, optical limiting. The practical recommendations for fabrication of composites with implanted MNPs for optical components are presented. 1. INTRODUCTION The search for new nanostructured materials is one of the defining characteristics of modern science and technology [1-6]. Novel mechanical, electrical, magnetic, chemical, *E-mail:
[email protected] Andrey L. Stepanov 64 biological, and optical devices are often the result of the fabrication of new nanostructured materials. The specific interest of this review is recent advantages in optical science and technology, such as development of nonlinear optical random metal-dielectric and metal- semiconductor composites based on metal nanoparticles (MNP) synthesized by ion implantation. Simultaneously with the search for and development of novel technologies intended for nanoparticle synthesis, substantial practical attention has been devoted to designing techniques for controlling the MNP size. This is caused by the fact that the optical properties of MNPs, which are required for various applications, take place up to a certain MNP dimension. In this content, ion implantation nanotechnology allows one to fabricate materials with almost any MNP structures, types of metals and their alloys [7-9]; this opens new avenues in engineering nanomaterials with desired properties. Such composites possess fascinating electromagnetic properties, which differ greatly from those of ordinary bulk materials, and they are likely to become ever more important with a miniaturization of electronic and optoelectronic components. Nonlinear optics plays a key role in the implementation and development of many photonics techniques for the optical signal processing of information at enhanced speed. The fabrication of novel useful nonlinear optical materials with ultrafast time response, high resistance to bulk and surface laser damage, low two-photon absorption and, of course, large optical nonlinearities is a critical for implementation of those applications. In additional, nonlinear materials for optical switching should be manufactured by processes compatible with microelectronics technology. Nonlinear materials with such characteristics are interesting for waveguide applications. The earliest studies of optical analogs to electronicintegrated circuits – or integrated optics – were based on the recognition that waveguide geometries allowed the most efficient interaction of light with materials. Optoelectronic devices could be converted to all-optical configurations, with a number of technological advantages, by developing waveguide media with intensity-dependent refractive indices. Nonlinear optical switches must provide conversion of laser signal for pulse duration as short as from nano- to femtoseconds. The nonlinear properties of MNP- containing materials stem from the dependence of their refractive index and nonlinear absorption on incident light intensity. Giant enhancement of nonlinear optical response in a random media with MNPs is often associated with optical excitation of surface plasmon resonances (SPR) that are collective electromagnetic modes and they are strongly dependent on the geometry structure of the composite medium [4]. Therefore, MNP-containing transparent dielectric and semiconductor materials can be effectively applied in novel integrated optoelectronic devices. Although both classic and quantum-mechanical effects in the linear optical response of MNP composites have been studied for decades [4], the first experimental results on the nonlinear optical effects of MNPs in ruby-glass was obtained quite recently in 1985 by Ricard et al. [10]. Driven by the interest in creating nonlinear optical elements with MNPs for applications in all-optical switching and computing devices, variety of experimental and theoretical efforts have been directed at the preparation of composite materials. In practice, to reach the strong linear absorption of a composite in the SPR spectra region, attempts are made to increase the concentration (filling factor) of MNPs. Systems with a higher filling factor offer a higher nonlinear susceptibility, when all other parameters of composites being the same. Nonlinear Optical Properties of Transition Metal Nanoparticles … 65 MNPs hold great technological promise because of the possibility of engineering their electronic and optical properties through material design. The transition metals of choice are usually gold, silver, or copper, as these metals show SPR modes in the visible or near-infrared spectral range [4]. The advantages of devices based on MNP materials can be understood from the spectacular successes of quantum well materials [11, 12]. The capability of band gap engineering in these structures permits wavelength tuning, while their small size alters the electronic structure of these particles. This provides greater pumping efficiency for applications in optical limiting and switching. The potential advantages of MNP composites as photonic materials are substantial improvement in the signal switching speed. Up to 100 GHz repetition frequencies are expected in communication and computingsystems of the 21th century [11]. Figure 1 compares in graphical form the switching speed and switching energies of various electronic, optical materials and devices (adapted from [11, 13]). Within the broad range of parameters covered by “conventional semiconductor microelectronics”, current metal-oxide-semiconductor field-effect transistor devices made in silicon have low switching energies, but switching time in the nanosecond range. Photonic devices based on multiple quantum well (MQW) structures – SEED and GaAs MQW devices and Fabry-Perot (FP) cavities based on ferroelectric such as lithium niobate – have extremely low switching speed in comparison to MNPs [11, 12]. Figure 1. Plot of various photonic materials showing their switching energies and switching speed. Adapted from [11, 13]. Davenas et al.pioneered synthesis of MNPs in dielectrics by ion implantation in 1973 [14, 15], when nanoparticles of various metals (sodium, calcium, etc.) in ionic crystals of LiF and MgO were created. Late in 1975, noble metal nanoparticles such as Au and Ag were fabricated in silicate glasses by Arnold and Borders [16, 17]. As shown in reviews [7-9, 18- 23], now developments expanded from the metal implants to the use of compounds, including Andrey L. Stepanov 66 metal alloys and totally different composition precipitate inclusions. Implanted MNP were fabricated in various materials, as polymers, glass, artificial crystals, and minerals. Number of publications on nonlinear optical properties of MNPs fabricated in transparent dielectric and semiconductor matrix is increasing every year. There arereview articles observed partly this progress [11, 18, 19, 24, 25]. Unfortunately, some of this reviews are already quite old and do not reflect a modern knowledge of the field or restricted to numbers of selected publications only. However, as followed from a comprehensive list of publications presented in Table 1 by 2011 [26-118], the geography of interest to nonlinear properties of ion-synthesized MNPs covers all world continents. The data in Table 1 includes information on all known types of metal ions and transparent matrices, ion implantation conditions for fabrication of MNPs and for measurements of their optical properties. Nonlinear optical characteristics of composites such as nonlinear refraction (n 2 ) and absorption (β) coefficients, real (Re[χ (3) ]) and imaging (Im[χ (3) ])parts of third order nonlinear susceptibilities (χ (3) ) and saturation intensities (I sat ) are presented as well. As shown in Table 1, near one hundred articles were already published. It should be mention, that ion implantation technique was first used for ion-synthesis of MNPs in dielectrics to create nonlinear optical materials in 1991 to form copper and gold nanoparticles in silica glass [42, 100]. The present review focuses on advantages in nonlinear optical properties of MNPs fabricated generally by low- energy ion implantation and measured in wide spectral area from ultraviolet to infrared. 2. OPTICS OF METAL NANOPARTICLE COMPOSITES The nonlinear optical response of medium with MNPs can be described by expanding the i-th component of the polarization P induced by an applied optical field to third order in a power series in this electric field E = E 0 e lex [11, 12] P i = χ y (1) E j + j ∑ χ yk (2) E j E k + jk ∑ χ yki (3) E j E k E i + jki ∑ , (1) where the summation indices refer to Cartesian conditions in the material-dependent χ (q) and to the polarization of the applied optical field. The first-order susceptibility χ (1) is related to the linear refractive index n 0 and the linear (Lambert-Beer’s law) absorption coefficient α 0 through the following equation [13] n 0 = Re 1+ χ (1) ⎡ ⎣ ⎤ ⎦ and α 0 = ω n 0 c Im χ (1) ⎡ ⎣ ⎤ ⎦ , (2) where c – speed of the light, ω - the optical frequency. The value χ (3) of a centrosymmetric composite has an analogous relationship to the nonlinear coefficients n 2 and β[45] n 2 = 12π n 0 Re 1+ χ (1) ⎡ ⎣ ⎤ ⎦ and β = 96π 2 ω n 0 2 c 2 Im χ (1) ⎡ ⎣ ⎤ ⎦ . (3) Table 1. Types optically transparent dielectric and semiconductor matrixes with metal nanoparticles synthesized by ion implantation. Abbreviations: soda-lime silicate glass (SLSG), indium-tin oxide (ITO), degenerate four wave mixing (DFWM), pump-probe transient nonlinear spectroscopy (PPTNS), Z-scan and RZ-scan by reflection and vectorial self-diffraction (VSD) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm 2 , Current density (J), μA/cm 2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I 0 ), W/cm 2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n 2 ), cm 2 /W Absorption coef. (β), cm/W Satur. intensity (I sat ), W/cm 2 Re[χ (3) ], Im[χ (3) ], |χ (3) |, esu Authors Co SiO 2 E = 50 D = 4⋅10 16 J = 2 Z-scan λ = 770 τ = 0.13 ν = 76⋅10 9 I 0 = 11.4⋅10 9 n 2 = 1.8⋅10 -9 Cattaruzza et al. 1998 [26] Ni SiO 2 E = 100 D = 6⋅10 16 Z-scan λ = 770 τ = 0.13 ν = 76⋅10 9 I 0 = 9.8⋅10 9 n 2 = 1.7⋅10 -10 Falconieri et al. 1998 [27] Cattaruzza et al. 2002 [28] Cu Al 2 O 3 E = 40 D = (0.5 – 1.0)⋅10 17 J = 2.5 – 12.5 RZ-scan λ = 1064 τ = 55 ν = 2 I 0 = 7.7⋅10 9 n 2 = -(1.3 – 1.7)⋅10 -11 Re[χ (3) ] = -(1.0 – 1.4)⋅10 -9 Ganeev et al. 2005 [29] 2006 [30] Ryasnyanskiy et al. 2005 [31] Table 1. (Continued) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu Al 2 O 3 E = 60 Z-scan λ = 500 - 700 τ = 0.2 ν = 10 3 I 0 = 1.1⋅10 7 β 500-580 < 0 β 580-700 > 0 Plaksin et al. 2008 [32] Cu ITO E = 40 D = (0.5 – 7.5)⋅10 16 J = 4 Z-scan λ = 532 τ = 7.0⋅10 3 ν = 10 I 0 = (6.2 - 15.5)⋅10 9 n 2 = (5.2 – 8.3)⋅10 -8 Re[χ (3) ] = (5.4 – 7.4)⋅10 -6 β = -(3.5 – 3.6)⋅10 -3 Im[χ (3) ] = -(1.2 – 1.3)⋅10 -6 |χ (3) | = (5.5 – 7.5)⋅10 -6 Ryasnyanskiy et al. 2006 [33] Cu LiNbO 3 E = 60 D = (0.3 – 2.0)⋅10 17 J = 10 PPTNS λ = 574 τ = 0.2 ν = 10 3 P = 16 Bleaching absorption in 590 - 620 nm Takeda et al. 2002 [34-36] Kishimoto et al. 2003 [37] Plaksin et al. 2005 [38] 2006 [39] Cu MgAl 2 O 4 E = 60 D = 3.0⋅10 16 J = 10 DFWM λ = 532 |χ (3) | = (1.0 – 3.0)⋅10 -8 Kishimoto et al. 2000 [40] Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu MgO 2 ⋅Al 2 O 4 E = 60 D = 3.0⋅10 16 J = 1-100 PPTNS λ = 574 τ = 0.2 ν = 10 3 P = 16 Bleaching absorption in 590 - 620 nm Takeda et al. 2002 [34-36] 2001 [41] Cu SiO 2 E = 160 D = 6.0⋅10 16 J = 2 – 7.5 Z-scan λ = 532 τ = 100 ν = 76⋅10 9 I 0 = 5.0⋅10 6 n 2 = 2.0⋅10 -15 Becker et al. 1991 [42] Haglund et al. 1992 [43] Cu SiO 2 E = 160 D = 1.2⋅10 17 J = 2.5 Z-scan λ = 570 - 600 τ = 6 I 0 = 5.0⋅10 8 n 2 = (2.0 – 4.2)⋅10 -10 Re[χ (3) ] = 2.4⋅10 -8 β = -(0.1 – 1.0)⋅10 -6 Haglund et al. 1993 [44] 1994 [45] 1998 [46] Magruder et al. 1994 [47] Yang et al. 1994 [48] Table 1. (Continued) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu SiO 2 E = 160 D = 1.2⋅10 17 J = 0.7 – 7.5 DFWM λ = 532 τ = 10 and 35 n 2 = 2.0⋅10 -7 |χ (3) | = (2.4 – 7.3)⋅10 -8 Haglund et al. 1994 [45] 1998 [46] 1995 [42] Yang et al. 1994 [48] 1996 [49] [ Cu SiO 2 E = 160 D = 1.2⋅10 17 J = 2.5 Z-scan λ = 532 τ = 100 ν = 76⋅10 9 I 0 = 1.0⋅10 7 n 2 = (2.0 – 4.2)⋅10 -14 Re[χ (3) ] = 2.4⋅10 -8 β = -(3.0 – - 8.0)⋅10 -3 Magruder et al. 1994 [47] Cu SiO 2 E = 90 D = 6⋅10 16 Z-scan λ = 770 τ = 0.13 ν = 76⋅10 9 I 0 = 9.8⋅10 9 n 2 = 5.0⋅10 -11 Falconieri et al. 1998 [27] Cattaruzza et al. 2002 [28] Cu SiO 2 E = 2.0⋅10 3 D = (1.0 – 4.0)⋅10 17 J = 2.0 T = 1000, 1 h Z-scan λ = 532 and 555 - 600 τ = 4.5 ν = 76⋅10 9 I 0 = 8.8⋅10 9 n 2 = (4.0 – 6.8)⋅10 -19 |χ (3) | = (0.3 – 4.7)⋅10 -7 Ila et al. 1998 [50] Sarkisov et al. 1998 [51] Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu SiO 2 E = 60 D = 3.0⋅10 16 J = 1-100 DFWM λ = 532 and 561 τ = 7.0⋅10 3 I 0 = (0.1 – 1.0)⋅10 6 |χ (3) | = (0.2 – 2.2)⋅10 -8 Takeda et al. 1999 [52] 2000 [53] Cu SiO 2 E = 50 D = 8.0⋅10 16 J = 10 DFWM λ = 585 τ = 13 ν = 400 I 0 = 1.0⋅10 8 |χ (3) | = 1.0⋅10 -7 Olivares et al. 2001 [54] Cu SiO 2 E = 60 D = 3.0⋅10 16 J = 1-30 T = 800, 1 h PPTNS λ = 574 τ = 0.2 ν = 10 3 I 0 = 8.0⋅10 11 Bleaching absorption in 590 - 620 nm Takeda et al. 2002 [34-36, 55] 2001 [41] 2004 [56, 57] Cu SiO 2 E = 50 D = 8.0⋅10 16 J = 10 Z-scan λ = 354.7 τ = 55 ν = 2 I 0 = 4.1⋅10 9 n 2 = -0.6⋅10 -7 Re[χ (3) ] = -1.3⋅10 -8 β = -6.7⋅10 -6 Im[χ (3) ] = -2.9⋅10 -9 |χ (3) | = 1.4⋅10 -8 Ganeev et al. 2003 [58] 2004 [59] Table 1. (Continued) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu SiO 2 E = 50 D = 8.0⋅10 16 J = 10 Z-scan λ = 532 τ = 55 ν = 2 I 0 = 5.4⋅10 9 β = -6.0⋅10 -6 I sat = 4.3⋅10 8 Ganeev et al. 2003 [60] 2004 [61] Cu SiO 2 E = 50 D = 8.0⋅10 16 J = 10 Z-scan λ = 1064 τ = 35 ν = 2 I 0 = 1.0⋅10 10 n 2 = -1.4⋅10 -7 Re[χ (3) ] = -3.2⋅10 -8 β = -9.0⋅10 -6 Im[χ (3) ] = 6.5⋅10 -9 |χ (3) | = 3.3⋅10 -8 Ganeev et al. 2003 [62, 63] 2004 [64] Stepanov et al. 2003 [65] Cu SiO 2 E = 60 D = 1.0⋅10 17 J = 10 T = 800, 1 h Z-scan λ = 540 - 610 τ = 0.2 ν = 1 I 0 = 8.0⋅10 11 Re[χ (3) ] = -3.1⋅10 -9 Im[χ (3) ] = 1.7⋅10 -9 |χ (3) | = -(-1.6 - 3.1)⋅10 -8 Takeda et al. 2005 [66] Plaksin et al. 2008 [32] Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu SiO 2 E = 180 D = (0.5 - 2.0)⋅10 17 J = 1.5 T = 500 - 900, 1 h Z-scan λ = 790 - 800 τ = 0.15 ν = 76⋅10 9 I 0 = (8.0 – 14.5)⋅10 9 n 2 = -1.6⋅10 -10 Re[χ (3) ] = (0.9 – 1.4)⋅10 -7 β = -(1.6 - 9.0)⋅10 -6 Im[χ (3) ] = (0.8 – 1.7)⋅10 -7 |χ (3) | = (1.2 - 2.3)⋅10 -7 Ren et al. 2006 [67] Wang et al. 2006 [68, 69] Cu SiO 2 E = 100 -200 D = 3.0⋅10 16 T = 300 - 400, 1 h Z-scan λ = 533 τ = 7⋅10 3 ν = 0.1 I 0 = 0.9⋅10 9 n 2 = -3.7⋅10 -15 Re[χ (3) ] = 3.7⋅10 -12 β = (2.8 - 6.4)⋅10 -9 Im[χ (3) ] = 3.7⋅10 -14 |χ (3) | = 3.7⋅10 -12 I sat = (2.9 – 5.0)⋅10 7 Ghosh et al. 2007 [70] 2009 [71] Cu SiO 2 E = 2.0⋅10 3 D = 4.0⋅10 16 T = 900, 1 h VSD λ = 533 τ = 26 P = 16 n 2 = -1.1⋅10 -12 β = -2.0⋅10 -11 |χ (3) | = 8.4⋅10 -11 Torres-Torres et al. 2008 [72] Cu SiO 2 E = 2.0⋅10 3 D = 4.0⋅10 16 T = 900, 1 h VSD λ = 533 τ = 7⋅10 3 P = 16 n 2 = -1.2⋅10 -11 β = -2.0⋅10 -12 |χ (3) | = 8.8⋅10 -10 Torres-Torres et al. 2008 [72] Table 1. (Continued) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu SiO 2 E = 180 D = (0.5 – 1.0)⋅10 17 J = 1.5 Z-scan λ = 532 τ = 38 ν = 10 I 0 = 0.9⋅10 9 n 2 = -(1.3 – 0.6)⋅10 -10 β = -(458- 151)⋅10 -9 |χ (3) | = (2.1 - 0.8)⋅10 -7 Wang et al. 2009 [73] Wang et al. 2010 [74] Cu SiO 2 E = 180 D = (0.5 – 1.0)⋅10 17 J = 1.5 Z-scan λ = 1064 τ = 38 ν = 10 I 0 = 0.38⋅10 9 n 2 = -(1.1 – 0.6)⋅10 -10 |χ (3) | = (1.2 - 0.8)⋅10 -7 Wang et al. 2009 [73] Wang et al. 2010 [74, 75] Cu SLSG E = 50 D = 8.0⋅10 16 J = 10 Z-scan λ = 1064 τ = 35 ν = 2 I 0 = 3.0⋅10 10 n 2 = 3.6⋅10 -8 Re[χ (3) ] = 0.8⋅10 -8 β = -3.4⋅10 -6 Im[χ (3) ] = 2.5⋅10 -9 |χ (3) | = 0.9⋅10 -8 Ganeev et al. 2003 [62, 63] 2004 [64] Stepanov et al. 2003 [65] Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu SrTiO 3 E = 60 D = 3.0⋅10 16 J = 10 PPTNS λ = 574 τ = 0.2 ν = 10 3 Bleaching absorption in 605 - 690 nm and positive absorption in 516 - 506 nm Takeda et al. 2002 [35, 55] 2004 [76] Cu SrTiO 3 E = 60 D = 3.0⋅10 16 J = 10 T = 300, 1 h Z-scan λ = 540 - 610 τ = 0.2 ν = 1 I 0 = 6.0⋅10 11 Re[χ (3) ] = -(0.1 – 2.0)⋅10 -9 Im[χ (3) ] = -(0.2 – 1.2)⋅10 -9 |χ (3) | = (1.0 - 2.0)⋅10 -9 Takeda et al. 2006 [77] Cu SrTiO 3 D = (0.1 - 1.0)⋅10 17 DFWM Z-scan λ = 775 τ = 0.25 ν = 1 n 2 = (1.8 – 6.2)⋅10 -12 |χ (3) | = (1.6 - 5.33)⋅10 -10 Cetin et al. 2010 [77] Cu TiO 2 E = 60 D = 3.0⋅10 16 J = 10 PPTNS λ = 574 τ = 0.2 ν = 10 3 Bleaching absorption in 585 - 760 nm Takeda et al. 2002 [35] Cu ZnO E = 160 D = (0.1 - 1.0)⋅10 17 J = 20 Z-scan λ = 532 τ = 55 ν = 2 I 0 = 5.0⋅10 8 β = -(0.4 – 2.1)⋅10 -3 Stepanov et al. 2004 [79] Ryasnyansky et al. 2005 [80] Table 1. (Continued) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu ZnO E = 160 D = (0.1 - 1.0)⋅10 17 J = 20 Z-scan λ = 532 τ = 7.5⋅10 3 ν = 10 I 0 = 3.2⋅10 7 β = -(0.7 – 5.5)⋅10 -3 Ryasnyansky et al. 2005 [80] Ag Al 2 O 3 E = 30 D = 3.8⋅10 17 J = 3 – 10 RZ-scan λ = 1064 τ = 55 ν = 2 I 0 = 4.3⋅10 9 n 2 = (1.1 – 1.8)⋅10 -11 Re[χ (3) ] = (0.9 – 1.5)⋅10 -9 Ganeev et al. 2005 [29] 2006 [30] Ryasnyanskiy et al. 2005 [81] Ag LiNbO 3 E = 1.5⋅10 3 D = 2.0⋅10 16 T = 500, 1 h Z-scan λ = 555 - 600 τ = 4.5 ν = 76⋅10 6 I 0 = 8.8⋅10 7 n 2 = (0.8 – 1.3)⋅10 -8 Sarkisov et al. 1998 [51] Ag LiNbO 3 E = 1.5⋅10 3 D = 2.0⋅10 16 T = 500, 1 h Z-scan λ = 532 τ = 40 - 70 ν = 10 I 0 = 1.0⋅10 10 n 2 = 5.0⋅10 -10 Williams et al. 1999 [82] Sarkisov et al. 2000 [83] Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Ag SiO 2 E = 1.5⋅10 3 D = 4.0⋅10 16 J = 2 T = 500, 1 h Z-scan λ = 532 τ = 4.5 ν = 76⋅10 6 |χ (3) | = 5.0⋅10 -7 Ila et al. 1998 [50] Ag SiO 2 E = 60 D = 4.0⋅10 16 J = 10 Z-scan λ = 354.7 τ = 55 ν = 2 I 0 = 1.3⋅10 9 n 2 = -2.7⋅10 -7 Re[χ (3) ] = -6.0⋅10 -8 β = -1.4⋅10 -5 Im[χ (3) ] = -6.1⋅10 -9 |χ (3) | = 6.1⋅10 -8 Ganeev et al. 2003 [58] 2004 [63] Ag SiO 2 E = 60 D = 4.0⋅10 16 J = 10 Z-scan λ = 532 τ = 55 ν = 2 I 0 = (2.5 – 14)⋅10 9 n 2 = -(6.2 - -0.7)⋅10 -10 Re[χ (3) ] = -(3.5 - -0.4)⋅10 -8 β = -(3.6 - -0.5)⋅10 -5 Im[χ (3) ] = -(1.3 - -0.2)⋅10 -8 Ganeev et al. 2004 [84] Stepanov et al. 2010 [85] Ag SiO 2 E = 60 D = 4.0⋅10 16 J = 10 Z-scan λ = 1064 τ = 35 ν = 2 I 0 = 1.0⋅10 10 n 2 = 1.5⋅10 -8 Re[χ (3) ] = 2.5⋅10 -9 Ganeev et al. 2003 [62] 2004 [63] Ag SiO 2 E = (1.7 – 2.4)⋅10 3 D = (4.0 – 7.0)⋅10 16 J = 0.3 T = 500, 1 h Z-scan λ = 532 τ = 7.0⋅10 3 P = 0.14 Three-photon absorption Joseph et al. 2007 [86] Table 1. (Continued) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Ag SiO 2 E = 2.0⋅10 3 D = 7.0⋅10 16 T = 600, 1 h Z-scan λ = 527 τ = 0.233 ν = ⋅10 3 β = -(2.6 - 1.8)⋅10 -6 Im[χ (3) ] = 4.7⋅10 -10 I sat = (1.2 – 3.5)⋅10 7 Rangel-Rojo et al. 2009 [87] 2010 [88] Ag SiO 2 E = 200 D = 2.0⋅10 17 J = 2.5 Z-scan λ = 532 τ = 38 ν = 10 n 2 = -3.0⋅10 -11 Re[χ (3) ] = 3.0⋅10 -8 β = -7.0⋅10 -8 Im[χ (3) ] = 2.6⋅10 -8 |χ (3) | = 4.0⋅10 -8 Wang et al. 2009 [89] Ag SiO 2 E = 200 D = 2.0⋅10 17 J = 2.5 Z-scan λ = 1064 τ = 38 ν = 10 n 2 = -1.7⋅10 -10 Re[χ (3) ] = 1.8⋅10 -7 |χ (3) | = 1.8⋅10 -7 Wang et al. 2009 [89] Ag SLSG E = 60 D = 4.0⋅10 16 J = 10 Z-scan λ = 532 τ = 55 ν = 2 I 0 = (2.5 – 14)⋅10 9 n 2 = -(4.1 - -1.7)⋅10 -10 Re[χ (3) ] = -(2.4 - -1.4)⋅10 -8 β = -(6.7 - -1.7)⋅10 -5 Im[χ (3) ] = -(0.6 - 2.4)⋅10 -8 Ganeev et al. 2004 [84] Ag SiO 2 E = 60 D = 4.0⋅10 16 J = 10 Z-scan λ = 1064 τ = 35 ν = 2 I 0 = 3.0⋅10 10 n 2 = 3.5⋅10 -8 Re[χ (3) ] = 5.7⋅10 -9 Ganeev et al. 2003 [63] 2004 [64] Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Sn SiO 2 E = 400 D = 2.0⋅10 17 J = 1 DFWM λ = 460-540 τ = 5⋅10 3 I 0 = 3.0⋅10 10 |χ (3) | = 3.0⋅10 -6 Takeda et al. 1993 [90] 1994 [91] Sn SiO 2 E = 350 D = 8.0⋅10 17 J = 2 T = 200, 0.5 - 1 h Z-scan λ = 460-540 τ = 4.5 ν = 76⋅10 6 |χ (3) | = 1.5⋅10 -6 Ila et al. 1998 [50] Ta SiO 2 E = 60 D = 3.0⋅10 16 J = 0.3 T = 900, 1 h PPTNS λ = 574 τ = 0.2 ν = 10 3 Bleaching absorption in 502 - 605 nm Takeda et al. 2003 [92] Au Al 2 O 3 E = (2.75 – 3.0)⋅10 3 D = 2.2⋅10 16 T = 1100, 1 h DFWM λ = 532 τ = 35 – 40 ν = 10 I 0 = 1.0⋅10 9 |χ (3) | = 7.0⋅10 -9 White et al. 1993 [93] Au Al 2 O 3 E = 160 D = (0.6 – 1.0)⋅10 17 J = 10 T = 800 - 1100, 1 h RZ-scan λ = 1064 τ = 55 ν = 2 I 0 = (1.8 - 2.3)⋅10 9 n 2 = -(0.1 – 1.5)⋅10 -10 Re[χ (3) ] = -(0.8 – 1.2)⋅10 -8 Ganeev et al. 2005 [29] 2006 [30] Stepanov et al. 2005 [94] 2006 [95] Table 1. (Continued) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Au Al 2 O 3 E = 60 D = 2.0⋅10 17 J = 10 PPTNS λ = 568 τ = 0.2 ν = 10 3 Nonlinear dielectric functions Takeda et al. 2006 [96] 2007 [97] Au SiO 2 E = 2.75⋅10 3 D = (0.3 – 1.5)⋅10 17 T = 600 - 1100, 2.2 h DFWM Z-scan λ = 532 τ = 6 and 35 ν = 3.8 and 10 I 0 = 4.5⋅10 8 n 2 = (1.0 - 8.9)⋅10 -10 β = (3.7 - 4.8)⋅10 -5 |χ (3) | = (1.0 – 1.7)⋅10 -10 Haglund et al. 1994 [45] Yang et al. 1996 [49] Magruder et al. 1993 [98] White et al. 1994 [99] Au SiO 2 E = 1.5⋅10 3 D = 5.6⋅10 16 J = 0.7 T = 700 - 1200 DFWM λ = 532 τ = 5⋅10 3 I 0 = 1.0⋅10 9 |χ (3) | = (0.12 – 5.0)⋅10 -8 Fukumi et al. 1991 [100] 1994 [101] Au SiO 2 E = 3.0⋅10 3 D = 1.2⋅10 17 J = 2.0 T = 1200, 0.5-1 h Z-scan λ = 532 τ = 4.5 ν = 76⋅10 6 |χ (3) | = 6.5⋅10 -7 Ila et al. 1998 [50] Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Au SiO 2 E = 2.75⋅10 3 D = 1.5⋅10 17 T = 400 DFWM λ = 532 τ = 4⋅10 3 I 0 = 1.9⋅10 6 |χ (3) | = (0.3 – 1.3)⋅10 -7 Lepeshkin et al. 1999 [102] Safonov et al. 1999 [103] Au SiO 2 E = 60 D = (1.0 – 2.0)⋅10 17 J = 10 -17 PPTNS λ = 554 and 568 τ = 0.2 ν = 10 3 I 0 = (0.7 – 0.9)⋅10 9 Nonlinear dielectric functions, positive absorption in 500 – 650 nm Takeda et al. 2006 [96] 2007 [104] Au SiO 2 E = 2.0⋅10 3 D = 2.8⋅10 16 T = 1100, 1 h VSD λ = 532 τ = 7⋅10 3 P = 0.14 n 2 = -2.0⋅10 -8 Re[χ (3) ] = 1.9⋅10 -9 β = -5.0⋅10 -6 Im[χ (3) ] = -1.6⋅10 -9 |χ (3) | = 2.2⋅10 -9 Torrres-Torres et al. 2007 [105] Au SiO 2 E = 1.5⋅10 3 D = (0.3 - 1.0)⋅10 17 T = 400, 1 h Z-scan λ = 532 τ = 7⋅10 3 ν = 0.1 I 0 = 1.2⋅10 10 n 2 = -1.5⋅10 -11 Re[χ (3) ] = 1.5⋅10 -8 β = -(2.6 - 8.0)⋅10 -8 Im[χ (3) ] = -1.5⋅10 -10 |χ (3) | = 1.5⋅10 -8 I sat = (1.9 – 2.6)⋅10 7 Ghosh et al. 2008 [71] 2009 [106] Table 1. (Continued) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Au SiO 2 E = 250 - 300 D = 1.0⋅10 17 J = 2.5 Z-scan λ = 532 τ = 38 ν = 10 I 0 = 0.9⋅10 9 n 2 = -(1.2 – 1.4)⋅10 -10 Re[χ (3) ] = -1.2⋅10 -7 β = -(9.7 - 21.0)⋅10 -10 Im[χ (3) ] = -3.6⋅10 -8 |χ (3) | = (1.3 – 1.6)⋅10 -7 Wang et al. 2008 [107, 108] Au SiO 2 E = 250 - 300 D = 1.0⋅10 17 J = 2.5 Z-scan λ = 1064 τ = 38 ν = 10 I 0 = 3.8⋅10 8 n 2 = -0.4⋅10 -10 Re[χ (3) ] = -(4.3 - -1.2)⋅10 -8 |χ (3) | = (0.1 – 4.3)⋅10 -8 Wang et al. 2008 [107, 108] Cu-Ni SiO 2 E = 90 and 100 D = 6⋅10 16 and 6⋅10 16 Z-scan λ = 770 τ = 0.13 ν = 76⋅10 9 I 0 = 9.8⋅10 9 |χ (3) | = 6.8⋅10 -10 Falconieri et al. 1998 [27] Cattaruzza et al. 2002 [28] Cu-Ni SiO 2 E = 90 and 100 D = 6⋅10 16 and 6⋅10 16 Z-scan λ = 532 τ = 6 ν = 0.5 - 1 I 0 = 2.0⋅10 9 n 2 = 1.5⋅10 -10 |χ (3) | = 5.0⋅10 -12 Cattaruzza et al. 2002 [28] Battaglin et al. 2000 [109] Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Cu-Ag SiO 2 E = 160 and 305 D = 1.2⋅10 16 J = 1.3 - 3 Z-scan λ = 570 τ = 6 ν = 3.8⋅10 6 I 0 = 4.0⋅10 8 n 2 = (0.1 - 1.6)⋅10 -9 β = -(1.4 - -3.8)⋅10 -5 Magruder et al. 1994 [110] Cu-Ag SiO 2 E = 30 and 43 D = (1.0 – 2.0)⋅10 17 Z-scan λ = 790 τ = 0.15 ν = 76⋅10 9 I 0 = 8.8⋅10 9 n 2 = -(3.8 - 4.3)⋅10 -12 β = (1.0 - 2.2)⋅10 -6 |χ (3) | = (0.8 – 1.5)⋅10 -8 Wang et al. 2007 [111] Cu-Ag SiO 2 E = 180 and 200 D = (1.0 – 2.0)⋅10 17 J = 1.5 – 2.5 Z-scan λ = 1064 τ = 38 ν = 10 n 2 = (0.6 - 3.0)⋅10 -10 |χ (3) | = (0.6 – 2.1)⋅10 -7 Wang et al. 2008 [112] 2010 [113, 114] Ag-Au SiO 2 E = 130 and 190 D = 9.0⋅10 16 J = 2 T = 800, 1 h Z-scan λ = 572 τ = 5 ν = 1 I 0 = (1.6 -5.0)⋅10 9 n 2 = -1.6⋅10 -10 β = 1.3⋅10 -5 |χ (3) | = (0.9 – 1.7)⋅10 -8 Cattaruzza et al. 2003 [115] 2005 [116] Table 1. (Continued) Metal (Ion) Matrix Synthesis conditions: Energy (E), keV Dose (D), ion/cm2, Current density (J), μA/cm2 Annealing temper. (T), °C and time Study nonlinear optical method Laser parameters: Wavelength (λ), nm Pulse duration (τ), ps Repetition rate (ν), Hz Intensity (I0), W/cm2 Pulse energy (P), mJ Nonlinear parameters: Refract. coef. (n2), cm2/W Absorption coef. (β), cm/W Satur. intensity (Isat), W/cm2 Re[χ(3)], Im[χ(3)], |χ(3)|, esu Authors Ag-Au SiO 2 E = 130 and 190 D = 3.0⋅10 16 T = 800, 1 h Z-scan λ = 525 τ = 6 ν = 1 I 0 = 0.8⋅10 9 β = -(3.42 - -1.7)⋅10 -4 I sat = (0.1 – 3.2)⋅10 8 Cesca et al. 2010 [117] Ti-Au SiO 2 E = 320 and 1.1⋅10 3 D = (0.6 - 2.0)⋅10 16 T = 900, 2 h Z-scan λ = 532 τ = 6 ν = 3.8⋅10 6 I 0 = 4.0⋅10 8 n 2 = (0.6 - 1.2)⋅10 -9 β = 5.3⋅10 -6 Magruder et al. 1995 [118] For comparison some data for ion synthesized nontraditional MNPs are also presented. Nonlinear Optical Properties of Transition Metal Nanoparticles … 85 The susceptibility χ (3) is a fourth-rank tensor with eighty-one components; however, material symmetries often reduce the number of non-vanishing components substantially. For a MNP with a dielectric constant ε(ω) = ε 1 (ω)+iε 2 (ω) occupying a relative volume fraction (filling factor) p << 1in a host of dielectric constant ε h , the absorption can be presented as [45, 119] α 0 = ω n 0 c Im χ (1) (ω) ⎡ ⎣ ⎤ ⎦ = 9p ωε h 3/2 c ε 2 ε 1 +2ε h ( ) 2 +ε 2 2 = p ω n 0 c f 1 (ω) 2 ε 2 , (4) where the f 1 (ω) is the local-field enhancement factor. The absorption coefficient α 0 has a maximum at the SPR frequency [4] where ε 1 (ω)+2ε h (ω) = 0. The effective third-order nonlinear optical susceptibility of the dielectric medium with MNPs χ eff (3) can be derived by applying Maxwell’s equations to the first order in the electromagnetic field to yield [3, 120] χ eff (3) = p 3ε h ε 1 +2ε h 2 3ε h ε 1 +2ε h ⎛ ⎝ ⎜ ⎞ ⎠ ⎟ 2 χ met (3) = p f 1 2 f 1 2 χ met (3) , (5) where f 1 is the same local-field enhancement factor of the polarization describing the χ (1) . This equation shows that the nonlinearity of composites with MNPs comprises two factors: the nonlinearity due to the MNPs itself, and the enhancement contributed by the host matrix. Note that whereas the α 0 varies as ⎜f 1 ⎜ 2 , the χ eff (3) varies as ⎜f 1 ⎜ 2 f 1 2 . Hence, it is expected a significantly greater enhancement due dielectric nonlinearity in the χ eff (3) . 3. NONLINEAR OPTICAL PROPERTIES OF ION-SYNTHESIZED NANOPARTICLES NEAR IR-AREA (1064 NM) 3.1. Nonlinear Absorption of MNPs Studied by Z-Scan In numerous studies, the nonlinear optical characteristics of the composite materials with MNPs fabricated by various methods were generally studied using lasers operating at frequencies that correspond to the spectral range of the SPR in particles [120] and Table 1. One other hand, one should take into account that, when used in practice as optical switches, optical limiters, and so on, these nonlinear materials have to operate at the wavelengths of the most frequently used industry available lasers, such as Nd:YAG (λ = 1064 nm), Ti:Al 2 O 3 (λ = 800 nm), and so on. Hence, in order to create new materials promising for practical use in laser systems and integral optics and to optimize their characteristics, one should study the nonlinear optical properties of these materials not only in the SPR spectral region, but also at the frequencies specific for industrial lasers. Materials characterized with nonlinear properties in near IR are now searching for applications in the field of telecommunication. Here, recent results on nonlinear optical properties of copper and silver nanoparticles [62- 65], synthesized by ion implantation in glass host matrices studied by the classical Z-method Andrey L. Stepanov 86 [121, 122] at the wavelength of a picosecond mode-locked Nd:YAG laser (λ = 1064 nm) are presented. The used Z-scan setup is shown in Figure 2. Laser pulse duration was 35 ps, pulse energy 1 mJ and 2-Hz pulse repetition rate. The radiation had a spatial distribution close to Gaussian and was focused by a 25-cm focal length lens (1) onto the samples (2). The beam- waist diameter of the focused radiation was measured to be 90 μm using a CCD camera. The samples were transferred in steps of 2 mm along Z-axis when scanning focal region. The maximum laser intensity at the focal point was 3⋅10 10 W/cm 2 , whereas the intensities of optical breakdown were 6⋅10 10 W/cm 2 and 8⋅10 10 W/cm 2 for the glasses with copper and silver nanoparticles, respectively. The fluctuations of the laser energy from pulse to pulse did not exceed 10 %. The energy of single laser pulses was measured by a calibrated photodiode (3). The samples were moved by a translation stage (7) along the Z-axis. A 1-mm aperture (9) with 1 % transmittance was fixed at the distance of 100 cm from the focusing plane (closed- aperture scheme). A photodiode (5) was kept behind the aperture. The radiation energy registered by photodiode (5) was normalized relative to the radiation energy registered by photodiode (3) in order to avoid the influence of non-stability of laser parameters. The experimental data accepted as normalized transmittance T(z). The closed-aperture scheme allowed the determination a value of n 2 and the open-aperture scheme was used for the measurements a value of β. Figure 2. Z-scan setup. (1) focal length lens; (2) sample; (3) and (5) photodiodes; (4) and (6) digital voltmeters; (7) translation stage; (8) computer; (9) aperture. The samples with copper were prepared by Cu-ion implantation into amorphous SiO 2 and soda lime silicate glasses (SLSG) as described in details [65]. The energies of 50 keV and dose 8⋅10 16 ion/cm 2 and at a beam current density of 10 μA/cm 2 were used. The penetration depth of the MNPs in the glasses for given energy of implantation was not exceed 80 nm. Optical transmittance spectra of implanted samples Cu:SiO 2 and Cu:SLSG are presented in Figure 3. MNPs such as Cu in dielectric medium show optical absorption determined by SPR [4]. The spectra are maximized near 565 nm Cu:SiO 2 and 580 nm for Cu:SLSG that gives evidence for formation of the Cu nanoparticles in the glasses. Depending on the ion implantation conditions, the incorporation of accelerated ions into silicate glasses leads to the generation of radiation-induced defects, which can initiate reversible and irreversible tr di am fr in ra U ob Fi ex U M in ex Fi en co th co in sp ap av N ransformations ifferent types, morphization, rom implanted ncrease in its v adiation-induc UV fundament bserved in th igure 3. It sho xposure of the UV spectral ran MNPs and gla nterband transi xperimental re igure 3. Transm nergy of 50 keV Figure 4 sh ontaining copp he measureme oefficient β. S ntensities. It c pecific feature pproached an veraging over Nonlinear Opti s in the glas such as the g the formation d ions, etc. In volume and th ced defects are al absorption he short-wave ould be noted t e samples to la nge of the lin asses. For thi itions and rad esults. mittance spectra V and dose of 8⋅ hows the exp per nanopartic ents carried o Silicate glasse can be seen f es inherent in d reaches a m r the values m ical Properties s structure [6 generation of e n of a new pha n particular, th he generation e responsible f edge in the sp length range that, presented aser radiation near absorption is reason, in iation-induced a of (1) SiO 2 a 10 16 ion/cm 2 (2 erimental dep cles in the Z-s out in this sch es did not dem from Figure 4 n nonlinear ab minimum at Z measured for s of Transition 6]. This can extended and p ase either from he formation o of internal st for an increas pectrum of the of the optica d here nonline at a waveleng n attributed to what follow d defects will and (3) SLSG b 2) Cu:SiO 2 and pendences of scan scheme w heme make it monstrate the 4 that the ex bsorption: the Z = 0. Each p 40 pulses. So n Metal Nanop result in stru point defects, m atoms involv of MNPs in th resses within e in the absor e glass. In our al transmittan ear optical stud gth of 1064 nm o the SPR and ws, the contrib be eliminated before and after (4) Cu:SLSG [6 the T(z) me with an open a t possible to nonlinear abs xperimental de e T(z) decreas point in the g ome distributi particles … uctural imperf local crystall ved the glass s he glass bring an implanted rption in the ra r case, this ef nce spectra di dy were perfo m, which lies f d interband tra butions assoc d from the ana r Cu-ion implan 65]. asured for bo aperture [65]. determine the sorption at ap ependences T ses as the foc graphs was o ion of the ex 87 fections of ization and structure or gs about an layer. The ange of the ffect can be isplayed in ormed upon far from the ansitions in ciated with lysis of the ntation with oth glasses Recall that e nonlinear pplied laser T(z) exhibit cal point is btained by xperimental 88 po pa Fi co w 35 re [1 op lig q( re w is 8 oints in the gr art, by the tim igure 4. Norm omposites in th with energy of 4 5 ps [65]. The nonli elationship for 122, 123] T(z) = q(z) - Here, q(z) ptical path wit ght passed thr (z) describes elationship hol 1/q(z) = 1/G where G(z) = z[ s the diffracti raphs is cause me instabilities malized transmi he z-scan schem 40 keV and dose near coeffici r the T(z), whi -1 ln(1+q(z)). = βI(z)L eff is th MNPs in th rough the sam the propagat lds G(z)-2λΔφ/πw [1+z 0 2 /z 2 ]is th ion length of Andre ed, to some e of laser radiat ittance as a f me with an ope e of 8⋅10 16 ion/ ient βof com ich, in the case the laser beam he sample, Lis mple as a funct tion of the la w 2 -iλ/πw 2 , e radius of the f the beam, k ey L. Stepano extent, by the tion. function of the en aperture. Sa /cm 2 .Laser inten mposite mater e of the schem m parameter, the sample th tion of its pos aser beam in e wave front c k= 2π/λis the v energy instab e Z-position o amples fabricate nsity is 8⋅10 9 W rials can be me with an ope L eff = (1−e α hickness, and I sition along th the material, curvature in th wave vector bilities and, fo of Cu:SiO 2 and ed by Cu-ion i W/cm 2 and pulse e determined en aperture, is α 0 L ) / α 0 is th I(z) is the inten he Z-axis. The , because the he Z-direction, r, Δφ = ΔΦ 0 /( or the most d Cu:SLSG implantation e duration is from the s written as (6) he effective nsity of the e parameter e following (7) , z 0 = kw 2 /2 (1+ z 0 2 /z 2 ), Nonlinear Optical Properties of Transition Metal Nanoparticles … 89 ΔΦ 0 = (2π/λ)n 2 I 0 L eff - phase shift of frequency gained by the radiation passed through the sample, w(z) = w 0 (1 + z 0 2 /z 2 ) 2 is the beam radius at the point Z, and w 0 is the beam radius at the focal point (at a level of 1/e 2 ). At Z = 0 (focal plane), the parameter q(0) = q 0 is defined by the expression q 0 = βI 0 L eff , (8) where I 0 = I(0) – intensity at the focal point. Using formulas (6) and (8), it is possible to write T 0 = q 0 -1 ln(1+q 0 ), (9) where T 0 is the minimum of T(z) in the focal plane in the scheme with an open aperture. Expression (9) permits to determine the nonlinear absorption coefficient β. The values of βcalculated in this way from the experimental data for the Cu:SiO 2 and Cu:SLSG composites are equal to 9.0⋅10 –6 and 3.42⋅10 –6 cm/W, respectively (Table 2). Table 2. Nonlinear optical parameters of silicate glasses with ion-synthesized copper and silver nanoparticles measured at the wavelength of 1064 nm Sample n 2 , 10 -8 esu β, 10 -6 cm/W Reχ (3) , 10 -9 esu Imχ (3) , 10 -9 esu ⎜χ (3) ⎜, 10 -8 esu Cu:SiO 2 -13.7 9 -32.0 6.5 3.28 Cu:SLSG 3.6 3.42 8.3 2.5 0.87 Ag:SiO 2 1.5 2.5 Ag:SLSG 3.5 5.7 SLSG 8.1⋅10 -6 1.4⋅10 -6 1.4⋅10 -6 As can be seen, the nonlinear coefficients β for these composites differ by a factor of 2.63. However, to compare correctly the coefficients β for the Cu:SiO 2 and Cu:SLSG, it is necessary to take into account the individual linear coefficients α 0 for layers with copper nanoparticles in different glasses ( α 0 SiO 2 = 9340 and α 0 SLSG = 5800 cm –1 ). By assuming that the thicknesses of the layers with MNPs in the implanted glasses are virtually identical (~80 nm) [124], the nonlinear coefficient β to the linear coefficient α 0 for the relevant composite (U = β/α 0 ) can be normalized. As a result, the normalized values of U SiO 2 = 9.64·10 –10 and U SLSG == 6.73·10 -10 cm 2 /W, which differ by a factor of 1.432, were obtained. To account for this discrepancy between the parameters U for different samples, proper allowance must be made not only for the difference in the linear absorption coefficients but also for the specific features in the location of the SPR peaks attributed to copper nanoparticles. As can be seen from Figure 3, the SPR peaks assigned to MNPs is observed at 565 nm (ω p = 17699.1 cm –1 ) for the Cu:SiO 2 composite and at 580 nm (ω p = 17241.4 cm –1 ) for the Cu:SLSG composite. In such MNP systems a two-photon resonance related to the SPR Andrey L. Stepanov 90 can be assumed [3, 11]. On the other hand, it is known that, in the range of excitations and their associated transitions in nonlinear medium, the optical nonlinearities become more pronounced with a decrease in the detuning of the frequency from the resonance (in a case, two-photon) excitation [125]. In present experiment, the frequency detuning should be treated as the difference between the SPR frequency and the frequency of two photons of the laser radiation used ω 20 = 18797 cm –1 (532 nm). The difference in the location of the SPR peaks for copper nanoparticles in the SiO 2 and SLSG composites can be estimated from the following ratio: M = ω 20 −ω p Cu:SiO 2 ( ) −1 / ω 20 −ω p Cu:SLSG ( ) −1 =1.42 . (10) This value is in qualitative agreement with a ratio of 1.432 between the nonlinear coefficients βnormalized to the linear coefficients α 0 for different glasses. The most interesting feature in the nonlinear optical properties of glasses with copper nanoparticles irradiated at a wavelength of 1064 nm is the fact that the doubled frequency of the laser radiation is close to the SPR peak frequency of copper particles. This is illustrated by the diagram in Figure 5, which shows the spectral positions of the SPR peaks of the MNPs in the samples studied and the spectral positions of the fundamental and doubled frequencies of the laser radiation [63, 64]. Thus, from the above date, it can draw the following conclusions: (1) In the near-IR range, the large nonlinear absorption coefficients determined experimentally for glasses containing copper nanoparticles are explained by the SPR in MNPs; (2) The efficient nonlinear absorption in the composites with copper nanoparticles considered is associated with both the linear absorption of the material and the effect of two- photon resonance at the SPR frequency for copper nanoparticles, which leads to the two- photon transition at the wavelength 1064 nm. The theoretical realization of two-photon absorption associated with the SPR of colloidal metal (silver) particles in a solution was previously discussed in [126, 127], but in these experiments the authors were difficult to analyze this possibility due to the experimental problems related to the efficient aggregation of colloidal silver under laser irradiation, which changed the nonlinear optical properties of the samples in time. When analyzing the results presented here, it is expedient to dwell on the possible fields of practical application of the studied composites. As is known, media with nonlinear (in particular, two-photon) absorption are very promising as materials for optical limiters, which can serve, for example, for the protection of eyes and highly sensitive detectors against intense optical radiation [128]. Early, the majority of studies in this field have been performed using nanosecond laser pulses. In this case, the main mechanisms responsible for nonlinear effects are associated with the reverse saturable nonlinear absorption (fullerenes and organic and metalloorganic compounds) and nonlinear scattering (solutions of colloidal metal aggregates). Picosecond and subpicosecond laser pulses have been used only to examine the optical limiting in media belonging primarily to semiconductor materials (two-photon absorption and strong nonlinear refraction). Since two-photon absorption at a wavelength of 1064 nm is observed in the Cu:SiO 2 and Cu:SLSG samples, it is of interest to investigate the optical limiting effect in these composites in the scheme with an open aperture. Here, it was assumed that the sample is located in the re T 10 co in co co se pr Fi na 3 Fi ap fe su im re ch de co w M be N egion correspo he nonlinear 0 11 W/cm 2 [6 oefficients, the n Figure 6. It omposite is ch omposite exhi erve as nonlin referable from igure 5. Diagram anoparticles [63 .2. Nonlinea Consider th igure 7 shows perture. Each eature of the ubstrate glass mplantation co egion (the no haracterized b emonstrate a s To recogni opper nanopa wavelength of MNPs synthesi e considered w Nonlinear Opti onding to a m absorption w 2, 63]. With e dependences can be seen haracterized b ibits an approx ear materials f m the practical m of the SPR fr 3, 64]. ar Refractio he nonlinear o s the T(z) dep point on the samples with s demonstrat onditions. From onlinearity si by self-defocu self-focusing e ize the reason articles, the the laser rad ized by the im within the fra ical Properties minimum trans was studied ex the use of t s of the norma n from Figure by an approxim ximately three for optical lim standpoint. requencies for t on of MNPs optical refract pendences of plot correspon h copper nan te opposite m the position ign), it can using of the effect (n 2 > 0) for the differ observed sel diation used in mplantation [6 amework of th s of Transition mittance, i.e., xperimentally the linear and alized T(z) on e 6 that, at th mately fifteen e-fold limiting miting. It is cle the glasses with Studied by tion of Cu:SiO the samples nds to a value noparticles is signs of no n of the T(z) p be can conc laser beam ( . rent signs of n f-action effec n this study 6, 9], the optic he effective m n Metal Nanop , in the focal p at an operati d nonlinear ( the laser radi he maximum n-fold limiting g. Consequent ear that the Cu h implanted copp y Z-Scan O 2 and Cu:SL in the Z-scan e averaged ov that the plot nlinear refra peak in the pos clude that th (n 2 < 0), while nonlinear refra cts has to b considerably cal properties medium theory particles … plane of a bea ing intensity (two-photon) iation intensity m intensity, th g, whereas the tly, these comp u:SiO 2 compos per and silver SG composite n scheme wit ver 40 pulses. s for differen ction under sitive or negat he Cu:SiO 2 s e the Cu:SLS action in the g by analyzed. exceeds the s of the nanopa y [4]. Such an 91 am (Z = 0). from10 7 to absorption y presented he Cu:SiO 2 e Cu:SLSG posites can site is more es [63, 65]. th a closed A specific nt types of the same tive Z-scan sample are SG sample glasses with Since the size of the articles can n approach 92 al pr Fu C re el re de co re no el fr ne ab tr co 2 llows to cons resence of MN ug. 6. Calculate u:SLSG compo In general, efractive inde lectronic resp esonance trans epending on ontributions to esonance inte onlinear index lectromagnetic requency of th egative only f bove the two-p For a hom ransitions, on orresponding e sider the com NPs in them. ed curves T(z) a osites [62]. , among nonli x, it should ponse of atom sitions in the the type o o the n 2 of su eractions invo x n 2 is determ c laser wave he material (ω for frequencie photon resona mogeneous con ne can consid equation for th Andre mposites as o as a function of inear optical p be taken into ms and molec medium [129 of interaction uch medium a olving one-ph mined from th ω 10 (or a mu ω p in the case es that are slig ances [130]. ndensed medi der the stand he nonlinear in ey L. Stepano ptically homo the incident rad processes con o account the cules [125] a 9]. The nonlin n (resonance as glasses are hoton or two he difference b ultiple freque of MNPs). In ghtly below t ium character dard two-lev ndex n 2 will h v ogeneous mat diation intensity ntributing to t e optical Ker and associated near index n 2 e or nonreso usually positi o-photon proc between the f ency ω i0 ) and n particular, t the one-photo rized by the o vel energy m have the form terials, disreg y for (1) Cu:SiO the nonlinear rr effect, caus d with the p 2 may vary co onance). Non ive [130]. In t cesses, the si frequency of a the intrinsic the nonlinear n resonances occurrence of model [125]. garding the O 2 and (2) part of the sed by the presence of onsiderably nresonance the case of ign of the an incident resonance index n 2 is or slightly f resonance Then, the w re ac na n 2 Δ de an w co ph Fi sc do m fo sa Si ph N n 2 = −2π where ω p and ω espectively; th ctive excitatio anoparticles in As follows 2 (the sign of t Δ i0 . Keeping in etermining the sgn Re ⎡ ⎣ nd analyze it o which lies in th onsidered the hotons and the igure 7. Depend cheme with a cl ose of 8⋅10 16 ion As was me maxima for MN or the Cu:SLS amples lies ne iO 2 and SLSG hoton excitati Nonlinear Opti πN μ i 0 n 0 η(ω io ω i0 correspond he subscript i d on centers c n the sample); from equation the nonlinearit n mind that χ e sign of the n χ (3) ⎡ ⎣ ⎤ ⎦ ∝−(ω only for the fre he vicinity of t effect that th e SPR frequen dence of the cur ose aperture. Sa n/cm 2 . Laser int entioned (Figu NPs in glass h SG samples is ear 565 nm. Su G (Figure 5) a ion of the la ical Properties 0 4 −ω p ) 3 , d to the frequ denotes one- a considered to and μ i0 is the n (11), N and ty), which is d χ (3) depends li nonlinearity as ω 20 −ω p ) − equency ω 20 , i the SPR of the he frequency d ncy exerts on n rves T(z) for (a) amples fabricat tensity is 8⋅10 9 ure 7) the sam host matrices o s in the vicini ubstituting the and the freque ser radiation s of Transition uencies of the and two-photo be dipoles transition dip μ i0 have no ef determined on inearly on n 2 −3 = −sgnΔ i.e., for the do e samples with detuning betw nonlinear optic ) Cu:SiO 2 and (b ted by Cu-ion im W/cm 2 and pul mples show di of different ty ity of 580 nm e frequencies ency ω 20 ~ 18 used) into eq n Metal Nanop SPR of MNP on processes; N (virtually eq pole moment a ffect on the sig nly by the detu [125], it can Δ i 0 , oubled frequen h copper partic ween the sum cal processes. b) Cu:SLSG co mplantation wit se duration is 3 ifferent spectr ypes. For exam m, while the SP of the SPR of 8797 cm –1 (th quation (12), particles … P and the laser N is the conce qual to the n at the frequenc gn of the nonli uning from the be written th ncy of the lase cles. In other w frequencies o omposites in the th energy of 40 5 ps [65]. ral positions o mple, the SPR PR peak of th f copper nanop he frequency o a negative s 93 (11) r radiation, entration of number of cies ω i0 . inear index e resonance he relation (12) er radiation, words, it is f two laser e Z-scan keV and of the SPR R maximum he Cu:SiO 2 particles in of the two- sign of the Andrey L. Stepanov 94 detuning is obtained, which points to a negative contribution to the nonlinear susceptibility for the matrices of both types. These conditions correspond to the self-defocusing of laser radiation, which was experimentally observed for the Cu:SiO 2 sample (Figure 7a). Thus, the two-level model used in this paper gives the proper sign of nonlinearity in the Cu:SiO 2 system excited by laser radiation at a frequency lying outside the SPR region of its particles, namely, at a frequency about two times lower than the SPR frequency. A noticeable contribution to the n 2 can also be made by the thermal effect, i.e., by the heat transfer from MNPs and defects of a dielectric host matrix heated by laser radiation [131]. The rise time τ rise of n 2 variations is determined by τ rise = R beam /V s , where R beam is the beam-waist radius and V s is the sound velocity in the lattice.In present case (R beam = 75 μm, V s ≈ 5500 m/s) the time necessary for both the distribution of the density of a material and its n 2 to reach their stationary values — t relax ~ 13–15 ns — is three orders of magnitude longer than the pulse duration (35 ps). This allows one to exclude from consideration the influence of the thermal effect on the nonlinear optical properties of the composites at present experimental conditions and regard the electronic optical Kerr effect in MNPs as the main factor. On the other hand, for the Cu:SLSG sample, the self-focusing of the laser radiation (Figure 7b) was observed [63], which contradicts the conclusions derived from equation (12). To reveal the reasons for the different self-action effects in the glasses, it is necessary to consider the influence of the substrate on the nonlinear optical properties of the composites. For this purpose, the dependences of the T(z) for both types of glasses without MNPs was measured. The SiO 2 substrate shows no noticeable changes in the character of the T(z) under irradiation with the intensities used in this study; i.e., this glass does not demonstrate nonlinear refraction and the nonlinearities observed in the Cu:SiO 2 samples are evidently caused by the copper nanoparticles. At the same time, the SLSG matrix exhibits a self-focusing effect (Figure 8). To estimate the contribution of the glass substrate to the optical refraction of the Cu:SLSG sample, it was determined and compared the values of χ (3) for the SLSG and Cu:SLSG samples. In the general case, when a material simultaneously exhibits both nonlinear refraction and nonlinearabsorption, the nonlinear susceptibility is a complex quantity χ (3) = Re χ (3) ⎡ ⎣ ⎤ ⎦ +iIm χ (3) ⎡ ⎣ ⎤ ⎦ (13) where the real part is related to the nonlinear index n 2 and the imaginary part is related to the nonlinear coefficient β. As was mentioned the used glasses, contrarily to the samples with nanoparticles, have no nonlinear absorption and, hence, χ (3) for the SLSG substrates is directly real-valued and can be expressed in terms of n 2 as Re χ (3) ⎡ ⎣ ⎤ ⎦ = n 0 3π n 2 . (14) This parameter can be experimentally estimated using the known Z-scan relations [122] w m ph Fi su pa ob w pa su to el N ΔT m−v = where ΔT m-v i measured T(z), hotodiode. igure 8. Depend Applying r ubstrate, a val arameter was btained that, f while Re[χ (3) ] f Taking into arameter, who Im χ (1) ⎡ ⎣ ⎤ ⎦ Using equa usceptibility is Since the R o such nonlin liminate the in Nonlinear Opti 0.404(1− S s the differen , Sis the perc dence of the cur relations (15) lue of n 2 = 8. detected to be for SLSG, wh for Cu:SLSG i o account tha ose imaginary ⎤ ⎦ = n h ε h c 2 ω β ation (13) and s |χ (3) | = 8.7⋅10 Re[χ (3) ] is respo near parameter nfluence of bo ical Properties S) 0.25 ΔΦ 0 nce between ent of radiati rves T(z) for SL ) to the expe 1⋅10 –14 esu w e of n 2 = 3.6⋅1 hich shows no is equal to 8.3⋅ at the nonline part is expres β . d the value of 0 –9 esu (Table onsible for the rs (Table 2) f oth the linear s of Transition the maximum ion passing th LSG in the z-sca erimental data was estimated, 10 –8 esu. Usin nonlinear abs ⋅10 –9 esu (Tab ar susceptibil sed via the no f Im[χ (3) ] for t 2) [63]. e nonlinear ref for the SLSG absorption an n Metal Nanop m and the m hrough the ap an scheme with a (Figure 8) , while for th ng relation (14 sorption, |χ (3) |i ble 2). lity in Cu:SLS onlinear coeffi the given med fraction in a m G and Cu:SLS nd the differen particles … minimum (vall perture and re a close apertur obtained for he Cu:SLSG s 4) for the Re[χ is equal to 1.4 SG is a comp cient β as dium, then the material, it was SG samples. I nce in the thic 95 (15) ley) of the eaching the re [63]. the SLSG sample this χ (3) ], it was 4⋅10 –14 esu, plex-valued (16) e nonlinear s compared In order to cknesses of Andrey L. Stepanov 96 the samples, in practice, one does not compare directly the values of Re[χ (3) ], but rather their normalized values Re[χ (3) ]L eff (in this case, L eff includes a correction for the linear absorption). Using L eff of the wavelength 1064 nm for the samples of both types, it is possible to getRe[χ (3) ] L eff = 4.92⋅10 –14 esu⋅cm for Cu:SLSG,Re[χ (3) ] L eff = 3.45⋅10 –15 esu⋅cm for SLSG. Therefore, the nonlinear parameters of pure SLSG are lower by an order of magnitude than the same parameters for the glasses containing nanoparticles. Discussing the reasons for the self-focusing observed in the experiment (Figure 7), i.e., the reasons for the positive contribution to the nonlinear susceptibility of Cu:SLSG, it should be take into account the considerable (~30%) linear absorption of SLSG in the spectral region ofthe laser radiation (Figure 3). If a material exhibits the effect of saturation at the laser wavelength, the total absorption will decrease upon the laser irradiation. However, if a material is characterized by nonlinear absorption, the total absorption will increase, as is observed for the glasses with nanoparticles. The nonlinear absorption of Cu:SLSG causes an additional decrease in the intensity of the transmitted light in the focal plane by approximately 10–12%, while for Cu:SiO 2 , whose linear absorption is ~15%, this value is equal to 18%. Irrespective of the conditions of the laser radiation which was choose here, the increase in the total absorption of Cu:SLSG can be caused by the nonlinear thermal effect predicted early [132], and observed in [133] for silicate glasses containing radio-frequency sputtered copper nanoparticles with size of 2.2±0.6 nm irradiation at the wavelength 1064 nm, when positive nonlinear susceptibility was recorded using trains of picosecond pulses (100 pulses in a train). Consider nonlinear refraction of glass containing silver nanoparticles. The composites with silver were prepared by Ag-ion implantation into amorphous SiO 2 and soda lime silicate glasses (SLSG) as described [23]. The energies of 60 keV and dose 4⋅10 16 ion/cm 2 and at a beam current density of 10 μA/cm 2 were used. The penetration depth of the MNPs in the glasses for given energy of implantation did not exceed 80 nm [124]. Optical transmittance spectra of implanted samples Ag:SiO 2 and Ag:SLSG are presented in Figure 9. MNPs such as Ag in dielectric medium show optical absorption determined by SPR with maximum near 415 - 440 nm [4]. Figure 10 shows the experimental dependences of the T(z) of the samples Ag:SiO 2 and Ag:SLSG during Z-scanning in the scheme with a closed aperture. As follows from Figure 10, both types of glasses with silver nanoparticles demonstrate self-focusing of laser radiation. The values n 2 and Re[χ (3) ] are presented in Table 2. The nonlinear absorption was not detected for these samples. Estimate the nonlinear optical contributing to both the magnitude and the sign of the nonlinear susceptibility χ (3) . Similarly to the case of sample with copper nanoparticles, the spectral positions of the SPR bands in the glasses with silver nanoparticles depend on the type of substrate (Figure 9). The SPR maximum lies at about 415 nm (ω p = 24096.4 cm –1 ) for the Ag:SiO 2 and at 440 nm (ω p = 22727.3 cm –1 ) for the Ag:SLSG samples. As can be seen from the diagram in Figure 5, the frequency of the sum of two photons of the laser radiation is lower than the SPR frequency for nanoparticles in either matrix, which corresponds to a positive sign of the detuning and, as a consequence, leads to a positive contribution to the nonlinear susceptibility. Hence, no two-photon absorption occurs in the samples with silver nanoparticles. Fi en Fi sc do 3 m [1 N igure 9. Transm nergy of 60 keV igure 10. Depen cheme with a cl ose of 4⋅10 16 ion .3. RZ-Scan There are materials, for e 137], Z-scan [ Nonlinear Opti mittance spectra V and dose of 4⋅ ndence of the cu ose aperture. Sa n/cm 2 . Laser int n Technique different appr example, dege 121, 122]). As ical Properties of (1) SiO 2 and 10 16 ion/cm 2 (3 urves T(z) for (a amples fabricat tensity is 8⋅10 9 e roaches for th enerate four-w s was mention s of Transition d (2) SLSG befo 3) Ag:SiO 2 and a) Ag:SiO 2 and ted by Ag-ion im W/cm 2 and pul he study of no wave mixing [ ned the latter t n Metal Nanop ore and after Ag (4) Ag:SLSG [2 (b) Ag:SLSG c mplantation wit se duration is 3 onlinear optic 136], nonlinea technique allo particles … g-ion implantat 23]. composites in th th energy of 60 5 ps [63]. cal properties ar optical inte ows determinin 97 ion with he Z-scan keV and of various erferometry ng both the Andrey L. Stepanov 98 value and the sign of nonlinear optical indexes n 2 and β. There are several modifications of the Z-scan technique, such as transmission Z-scan (TZ-scan) [121, 122], eclipsing Z-scan [138], two-beams [139], reflection Z-scan (RZ-scan) [140-142], time-resolved Z-scan [143], etc. The RZ-scan has an advantage with comparing to the others that allows studying the optical nonlinearities of materials with a limited optical transparency. This technique is based on the analyze of the surface properties of materials, whereas the others are used for theinvestigation of bulk characteristics of media. The application of RZ-scan was firstly presented in [14], where the nonlinear refraction of gallium arsenide was studied in at a wavelength of 532 nm at which this semiconductor is fully opaque. On the other hand, this technique can also be applied for transparent materials and can be used for the comparison with conventional TZ-scan. Ricently, the RZ-scan technique was applied for measurement of nonlinear characteristics of low-transparency dielectric layers with MNPs beyond the region of the SPR absorption of particles [29, 94]. Consider some examples with composites based on dielectric with copper, silver and gold nanoparticles synthesized by ion implantation. As a substrate for such model composites an artificial sapphire (Al 2 O 3 ) was used. Whose surface of the sapphire opposite to the implanted surface was frosted, because of which the sample was almost nontransparent in visible and IR-spectral area. Ion implantation was performed with Ag + , Cu + and Au + [95, 144]. Experimental conditions of ion implantation used for fabrication of MNPs in Al 2 O 3 are shown in Table 3 [30]. Table 3. Ion implantation conditions and nonlinear optical parameters of Al 2 O 3 with ion-synthesized silver, copper and gold nanoparticles measured at the wavelength of 1064 nm. * - thermal annealing [30] Sample No. Energy, keV Current density, μA/cm 2 Ion dose, 10 17 ion/cm 2 I 0 , 10 9 W/cm 2 n 2 , 10 -11 cm 2 /W Re[χ (3) ], 10 -9 esu Ag:Al 2 O 3 1 30 3 3.75 4.3 3.40 0.94 Ag:Al 2 O 3 2 30 6 3.75 4.3 3.89 1.07 Ag:Al 2 O 3 3 30 10 3.75 4.3 5.36 1.48 Cu:Al 2 O 3 4 40 2.5 0.54 7.7 -3.75 -1.04 Cu:Al 2 O 3 5 40 12.5 1.0 7.7 -4.96 -1.38 Au:Al 2 O 3 6 160 10 0.6 2.3 -28.15 -7.77 Au:Al 2 O 3 7* 160 10 0.6 2.8 -32.68 -10.0 Au:Al 2 O 3 8 160 10 1.0 2.3 -38.76 -10.7 Au:Al 2 O 3 9* 160 10 1.0 2.8 -44.30 -12.2 The RZ-scan setup for measurement of nonlinear refraction is presented in Figure 11. The Nd:YAG laser (λ = 1064 nm, τ = 55 ps) operated at a 2 Hz pulse repetition rate was applied. Laser radiation was focused by a 25-cm focal length lens (1). The maximum intensity and the beam waist radius in the focal plane were measured to be I 0 = 7·10 9 W/cm 2 and 72 μm, respectively. The sample (2) was fixed on the translation table (7) and moved along the Z- axis. The angle of incidence of laser radiation on the surface of sample was 30°. A part of radiation was reflected from the beam splitter (9) and measured by photo-diode (3) to control th th ra ra Fi vo ex no re ap (t th ex be no R fo po gr a fe ab w N he energy of la he mirror (10) adiation by ph atio R(z) betwe igure 11. RZ-sc oltmeters; (7) tr In the case xample, see [ onlinearities a esponsible for perture before that are the su he influence of The princip xperiment thro eam change onlinear effec (z) of the ref ocal plane, the ositive nonlin rowth of R(z). decrease of R eature will be bout the sign o The expres written in the fo I R z ( )= Nonlinear Opti aser pulses. T ) and than col hoto-diode (5). een the reflect can setup. (1) fo ranslation stage e of RZ-scan [145]). In TZ and the apert r the amplitud e the detector ubject of prese f phase change ples of RZ-sc ough the foca due to the in cts appear whe flected and inc e laser intensit ear refraction After crossin R(z) down to p observed with of n 2 from the ssion for the in orm [140-142] I 0 R 0 V 0 −1 ( ( ical Properties he radiation r llected by the . To decrease t ted signal and ocal lens; (2) sam ; (8) computer; the refractive Z-scan scheme ture is neede de changes of r. The measur ent studies) we es caused by n can can be de al plane of fo nfluence of n en the sample cident laser ra ty becomes hi (n 2 > 0), the m ng the focal pla previous value h the valley ap R(z) depende ntensity of rad ] z ( )+ R 1 θ ( ) s of Transition eflected from lens (11) tha the influence the incident o mple; (3) and (5 (9) beam splitt e nonlinearitie e, the phase ed in this ca f reflected rad rements of the ere carried ou nonlinear abso escribed as fo cusing lens. T nonlinear refra is positioned adiation is co igher and the movement of ane the nonlin e. In the case o ppearing in th nce. diation reflecte ) n 2 − ik 2 ( ) I n Metal Nanop the surface o at allowed reg of the instabil one was accep 5) photodiodes; ter; (10) mirror; es are measure changes are ase. The refra diation so the e refractive n ut without an a orption. ollows. The sa The amplitude action and no d far from the onstant. When nonlinear effe sample close near refraction of self-defocus he R(z) depend ed from the su I z ( )V 1 −1 z ( ) particles … f sample was gistering all th lity of laser rad ted. ; (4) and (6) dig (12) lens. ed without ap produced by active nonline ere is no need nonlinearities aperture, thus ample moves e and phase o onlinear abso focal plane, s n the sample a ects occur. In to the focus l n diminishes th sing (n 2 < 0) th dence. One ca urface of a sam ) 1− ix' ( ) ) 2 99 directed to he reflected diation, the gital perture (for absorptive earities are d to use an of samples neglecting during the of reflected orption. No so the ratio approaches the case of leads to the hat leads to he opposite an conclude mple can be 2 . (17) Andrey L. Stepanov 100 Here, k 2 is the coefficients of nonlinear extinction; R 0 is the linear reflection coefficient, V m (z) = g(z) – id/d m , g(z) = d/d 0 x, d is the distance from the sample to the far-field aperture; d m = kω 2 m0 /2, ω 2 m0 = ω 2 (z)/(2m+1), ω 2 (z) = ω 2 (1+x 2 ), x = z/z 0 , z 0 = kω 2 0 /2 is the diffraction length of the beam; ω 0 is the beam waist radius; z characterizes the sample position: R 1 θ ( ) = 2n 0 3 cos(θ) − 4n 0 cos(θ)Sin 2 (θ) n 0 4 cos 2 (θ) − n 0 2 + sin 2 (θ) n 0 2 −sin 2 (θ) [ ] −1 2 , (18) and θ is the angle of incidence of the beam [145]. Substituting into equation (17) the parameters given above, it will be obtained the following expression for the normalized reflection: R z,θ ( )= 1− 4R 1 θ ( )/ R 0 ( )I 0 k 2 x' x' 2 + 9 ( ) x' 2 +1 ( ) + 2R 1 θ ( )/ R 0 ( )I 0 n 2 (x' 2 + 3) x' 2 + 9 ( ) x' 2 +1 ( ) + R 1 θ ( )/ R 0 ( ) 2 I 0 2 (n 2 2 + k 2 2 ) x' 2 + 9 ( ) x' 2 +1 ( ) . (19) Here, the first expression on the right-hand side is responsible for the nonlinear absorption, the second expression describes the nonlinear refraction, and the third expression characterizes their joint effect. It should be noted that equation (18) was derived without taking into account the effect of thermal processes, which are characteristic of nanosecond pulses [131] or of radiation with a high pulse repetition rate [131]. To determine the real part of the third-order nonlinear susceptibility, the expression (14) was used. For practical purpose the R(z) power could be presented as follows [144] : P(z) =1+2Re R(n 2 +ik 2 ) [ ] E(ρ, z) 4 ρ dρ 0 ∞ ∫ E(ρ, z) 2 ρ dρ 0 ∞ ∫ , (20) where ρ the radial coordinates, and E(ρ,z) is the incident beam amplitude. This equation describes the general case, when both nonlinear refraction and nonlinearabsorption appear simultaneously during the reflection from the sample. However, the application of open-aperture RZ-scan allowed neglecting the influence of nonlinear absorption for the measurements of nonlinear refraction [146]. 3.3.1. RZ-Scan Study of Ag:Al 2 O 3 The spectra of linear optical reflection for both virgon Al 2 O 3 and Ag:Al 2 O 3 composites obtained by ion implantation under different conditions presented in Figure 12. Samples 1 - 3 Ag:Al 2 O 3 were implanted at fixed doses and energies but at different ion current densities, which increases with the sample number (Table 3). The thickness of a substrate layer containing silver nanoparticles was about 50 nm [124]. Fi do ar ba ob na sh fr A im (M ir io re SP sh Si po im di at N igure 12. Reflec ose of 3.75⋅10 17 As is seen re characterize and with a m btained at hig anoparticles in harp increase romapproxima Al 2 O 3 matrix an As was sh mplantation of MNPs) in the rradiated by hi ons and thus t esult in an inc PR absorption hould be relat ince the spec ossible to conc mplantation in imensions, wh The experi t the waveleng Nonlinear Opti ctance spectra o 7 ion/cm 2 and di from Figure 1 ed by the pres maximum nea gher ion curre n the implante e in the refle ately 380 nm ( nd by interban hown recentl f silver ions i sample. This igh ion curren their more ef crease both in n of MNPs. T ed to a larger ctral positions clude that an i nto Al 2 O 3 res hich would im imental R(z) d gth 1064 nm a ical Properties of Al 2 O 3 before ifferent current 12, in contrast sence in the vi ar 460 nm, w ents. This refle ed Al 2 O 3 and ection intensi (beyond the SP nd transitions i ly [147], an into SiO 2 lead is explained nts and, hence fficient incorp the number o Therefore, the portion of m s of the SPR increase in the sults in a hig mmediately cau dependences f at the laser rad s of Transition and after Ag-io densities (1) 3; t to nonimplan isible spectral whose intensity ection band a corresponds t ity in the sh PR band) is ca in metal NPs. increase in ds to an incre by an increas , by a higher poration into M of MNPs and rising in the etallic silver i band maxim e ion current d gher concentr use a spectral s for the Ag:Al 2 diation intensi n Metal Nanop on implantation (2) 6 and (3) 1 nted Al 2 O 3 , al l region of a b y is slightly appears due to to the SPR abs horter wavele aused by the a the ion curr ase in the por se in the temp diffusion mob MNPs. In the in their sizes, SPR reflectio in Al 2 O 3 impl ma almost do density under t ration of MN shift of the SP 2 O 3 samples m ty I 0 = 4.3⋅10 9 particles … n with energy of 0 μA/cm 2 [30]. ll the implante broad selective higher for th o the formatio sorption in M ength region absorption of l rent density rtion of the m perature of the bility of impla e general case which leads on intensity in anted at highe not change, h these condition NPs rather tha PR reflection m measured by RZ 9 W/cm 2 are p 101 f 30 keV, . ed samples e reflection he samples on of silver NPs [4]. A beginning light by the during the metal phase e dielectric anted silver e, this may to a higher n Figure 12 er currents. hence it is ns of silver an in their maximum. Z-scanning presented in 10 Fi up to cu in ar op ou va of hi Fi do is 3. pr M na an la im 02 igure 13. Dep pward, symme ops of the be urrents, i.e., fo Virgin Al 2 ntensity up to re caused by ptical nonline utside the SPR Using mod alues of n 2 and f the results sh igher values o igure 13. Depen ose of 3.75⋅10 17 4.3⋅10 9 W/cm 2 .3.2. RZ-Scan The second revious series MNPs was var anoparticles (s nd a low ion arger dose (1 mplantation w endences R(z) etrical with re ell-shaped dep or the samples 2 O 3 shows no the optical br the presence earities of silv R absorption o deled R(z) dep d Re[χ (3) ] in ea hows that the of n 2 and Re[χ ( ndence of the cu 7 ion/cm 2 and di 2 and pulse dura n Study of Cu d type of sam s of Ag:Al 2 O ried by using sample 4) was current (2.5 μ 10 17 ions/cm 2 ) as equal to 40 Andre ) for all the sa espect to Z = 0 pendences are s with a higher o such optical reakdown. Thu of silver nan ver particles of the MNPs. pendences (Fig ach sample we samples with (3) ]. urves R(z) for A ifferent current ation is 55 ps. S u: Al 2 O 3 mples is the A 3 samples (1– different ion s obtained by μA/cm 2 ), whil ) and a hig 0 keV for both ey L. Stepano amples have th 0, and by the p e higher for t r content of m l nonlinearity us, the nonline noparticles in are observed gure 13) and f ere estimated a a higher conc Ag:Al 2 O 3 compo densities (1) 3; olid line is a fit Al 2 O 3 with cop –3) presented current densi implantation w le the other sa gher current samples (Tab v he shape of a b positive n 2 . It the samples i etallic silver. y in experime ear optical eff Al 2 O 3 . It is at laser irrad fitting by them and presented centration of s osites implanted (2) 6 and (3) 1 tting [30]. pper nanopart in Table 3, i ities, one of t with a small d ample (sampl (12.5 μA/cm 2 ble 3). bell with the to should be not implanted at ents with lase fects shown in also interestin diation at a w m the experim in Table 3. T silver nanopar d with energy o 0 μA/cm 2 . Lase ticles. In cont in which the the samples w dose (0.54·10 1 e 5) was imp 2 ). The energ op directed ted that the higher ion er radiation n Figure 13 ng that the wavelength mental data, he analysis rticles have of 30 keV, er intensity trast to the content of with copper 7 ions/cm 2 ) planted at a gy of ion al in lin w co ~ sa of fo Fi an an in (i it op ob se in w na op al N The choice llowed to obta n particular, w near reflection whose maxima opper nanopa 650 nm) than ample 5 [21, 1 f MNPs also orsample 5 is n igure 14. Reflec nd different par nd 12.5 μA/cm 2 The experi n Figure 15. S n particular, in was chosen ptical propert btained are als elf-focusing in n contrast to t which clearly t anoparticles, ptical properti lso observed Nonlinear Opti e of ion impl ained samples with different s n spectra of C take clearly d articles, exhib n sample 4 (~ 148]. A pronou manifests its noticeably hig ctance spectra o ameters: dose o 2 (3) [147]. imental and ca Since the effic n films, wires a somewhat h ties I 0 = 7.7·10 so bell-shaped n the Cu:Al 2 O the case with testifies to the i.e., to a neg ies of Ag:Al 2 in transmissi ical Properties lantation regim with a notice sizes of MNP Cu:Al 2 O 3 with different positi bits the band ~ 610 nm), w unced differen self in the int gher than that f of Al 2 O 3 before of 0.54·10 17 ions alculated depe ciency of the , etc.) is know higher intensi 0 9 W/cm 2 (Ta d and symmetr O 3 samples due h Ag:Al 2 O 3 , w e self-defocus gative n 2 (Tab 2 O 3 and Cu:A on Z-scan m s of Transition mes (Table 3) eably different s. This is illu h the SPR ab ions. Sample 5 at a longer which points nce in the port tensity of the for sample 4. (1) and after C s/cm 2 and 2.5 μ endences R(z) electronic SPR wn to be notice ity of laser ra able 3) than f rical with resp e to the presen when the tops sing of the las ble 3). Such a Al 2 O 3 samples easurements n Metal Nanop ) in the case t filling factor strated in Figu bsorption band 5, which has a wavelength to the presen tion of the me SPR bands. u-ion implantat μA/cm 2 (2) and ) for the Cu:A R excitation i eably lower th adiation for m for Ag:Al 2 O 3 . pect to the poi nce of copper of the bells ser beam in t a different be (a difference at the same w particles … of copper na r of the metal ure 14, which ds of copper N a higher conce (with the ma nce of larger etal phase and The reflectio tion with energy dose of 1.0⋅10 17 Al 2 O 3 samples in copper nan han in silver pa measuring their . The R(z) de nt Z = 0, whic nanoparticles are directed d the samples w ehavior of the in the signs wavelength o 103 anoparticles phase and, h shows the NPs [148], entration of aximum at r MNPs in d in the size on intensity y of 40 keV 7 ion/cm 2 are shown nostructures articles [4], r nonlinear ependences ch points to . However, downward, with copper e nonlinear of n 2 ) was of 1064 nm 10 in C pr (s Fi (1 cu is 3. na re 0. [9 su nu so (T Fi of Fi im 04 nSiO 2 with silv Cu:Al 2 O 3 by sim resented in T sample 5) has igure 15. Depen 1) dose of 0.54 urrent density o a fitting [30]. .3.3. RZ-Scan Samples (6 anoparticles, w egion. As in .1·10 17 ions/cm 94, 95]. Since ubsurface laye ucleation of M ome of sampl Table 3) [94, 9 The spectra igure 16. The f SPR reflectio igure 16), obt mplantation do ver and coppe mulating the R able 3. It is f higher |n 2 | and ndence of the c 4·10 17 ions/cm 2 of 12.5 μA/cm 2 . n Study of Au 6–9) described which are also the case with m 2 , but high e, at such hig er of the irradi MNPs accumu les 7 and 9 w 95]. a of linear op formation of on bands peak ained directly ose (sample 8 Andre er nanoparticle R(z) dependen found that the d |Re[χ (3) ]|. curves R(z) for and current de . Laser intensity u:Al 2 O 3 d in Table 3 o characterized h copper ion er irradiation gh energies, ated dielectric ulates over a l were annealed ptical reflectio gold nanopart ked at about 6 y by ion impla 8) results in a ey L. Stepano es (Table 2). E nces and comp e sample with Cu:Al 2 O 3 com ensity 2.5 μA/c y is 7.7⋅10 9 W/c are the Al 2 d by efficient ns, two differe n energies, 1 the implanted c [124], the im longer time. In d in a furnac n from the Au ticles by ion im 10 nm. Compa antation, it is p slight shift of v Estimated val paring them wi h a higher con mposites implan cm 2 and (2) dos cm 2 and pulse d 2 O 3 containin SPR absorptio ent implantat 60 keV (sam d impurity ac mpurity concen n order to inc e for 1 h at a u:Al 2 O 3 samp mplantation is aring samples possible to se f the maximu ues of n 2 and ith experimen ntent of the m ted with energy se of 1.0⋅10 17 i duration is 55 p ng ion-synthe on in the visib tion doses, 0. mples 6 and 8 ccumulates in ntration necess crease the size a temperature ples 6–9 are p s proved by th 6 and 8 (curv ee that an incr um of the SPR d Re[χ (3) ] in ntal data are metal phase y of 40 keV ion/cm 2 and ps. Solid line sized gold ble spectral .6·10 17 and 8, Table 3) n a thicker sary for the e of MNPs, e of 800°C resented in he presence ves 1 and 3, rease in the R reflection (t in hi of le re 7, re m ob Fi cu Sa na fo fo pr th re ch pr N to ~ 620 nm), nthe previous igher filling fa f these sample eads to a shar eflection shou , curve 2 in F edistribution o material and, he bserved in exp igure 16. Reflec urrent density o amples anneale At present, anoparticles in or Au:Al 2 O3 w or samples 6 resents the de hermal treatme espect to the haracterized b resented in Ta Nonlinear Opti which is acco case with the actor of the m es almost doe rp increase in lder (sample 9 Figure 16) ap of the metal p ence, with the periments with ctance spectra o f 10 μA/cm 2 wi d after ion impl , there are no n a solid matri were given in and 7, which ependences for ent. As is seen point Z = 0, by self-defocus able 3. ical Properties ompanied by e implantation metal phase in s es not change n the reflectio 9, curve 4 in F ppearing near hase in the di e formation of h fractal aggre of Al 2 O 3 before ith different dos lantation during data in the li ix in the near- [94, 95] and p h were obtain r samples 8 a n, the R(z) de , with the to sing, which co s of Transition a noticeable i n with copper sample 8 (Au: the positions on in the long Figure 16) or the SPR refl ielectric volum f aggregates of egates of silver and after Au-io ses of 0.6·10 17 i g 1 h at tempera iterature on th -IR region (10 presented in F ned directly by and 9, obtained pendences ha ops directed orresponds to n Metal Nanop increase in the r ions (sample :Al 2 O 3 ). Subse of the maxim g-wavelength even an addit lection bands me due to the f MNPs. Simil r particles but on implantation ions/cm 2 (3, 4) a ature of 800ºC ( he nonlinear o 064 nm). The f igure 17. Figu y ion implant d by ion impl ve a bell-like downward. T a negative n 2 a particles … e intensity. Th es 4 and 5), p equent therma ma of the SPR spectral range tional maximu can be assoc high tempera lar spectral be t in solutions [ n with energy of and 1.0⋅10 17 ion (2, 4) [94, 95]. optical propert first experime ure 17a shows tation, while lantation and shape symme Thus, sample and Re[χ (3) ] wh 105 his fact, as points to a al treatment R bands but e. A broad um (sample ciated with ature of the ehavior was 149]. f 160 keV, n/cm 2 (1, 2). ties of gold ental results s the curves Figure 17b subsequent etrical with s (6-9) are hich values 10 Fi w di im 1 lin 06 igure 17. Depen with doses 0.6·10 ifferent doses o mplantation (1, 3 h at temperatur ne is a fiting [94 ndence of the cu 0 17 ions/cm 2 (1, f 0.6·10 17 ions/c 3) and samples re of 800ºC (2, 4 4, 95]. Andre urves R(z) for A 2) and 1.0⋅10 17 cm 2 (3, 4) and 1 created by ion 4). Laser intens ey L. Stepano Au:Al 2 O 3 compo 7 ion/cm 2 (3, 4) 1.0⋅10 17 ion/cm 2 n implantation w sity is 2.3⋅10 9 W v osites implanted at current dens 2 (1, 2). Sample with subsequent W/cm 2 and pulse d with energy o ity of 10 μA/cm es created by ion t thermal anneal duration is 55 p of 160 keV m 2 with n ling during ps. Solid Nonlinear Optical Properties of Transition Metal Nanoparticles … 107 3.3.4. Nonlinear Refraction of MNPs Studied by RZ-Scan For the composites based on Al 2 O 3 , the frequencies ω p are equal to 22222 cm –1 (~ 450 nm, Figure 12) for silver nanoparticles, 16393 – 15384 cm –1 (~ 610 – 650 nm, Figure 14) for cupper nanoparticles, and 16129 cm –1 (~ 620 nm, Figure 16) for gold nanoparticles. Consider relation (12) for the case of a one-photon process (i = 1), i.e., for the frequency ω 10 = 9398 cm –1 (λ = 1064 nm), which is the fundamental frequency of the laser radiation used. Substituting the values of ω 10 and ω p into relation (12), positive values of Re[χ (3) ] and a negative detuning Δ 10 for all the samples can be obtained. The positive Re[χ (3) ] and n 2 correspond to the self-focusing of the laser radiation in the sample, which was observed experimentally for the Ag:Al 2 O 3 samples (samples 1–3, Table 3). On the other hand, the positive values of the signs of Re[χ (3) ] and n 2 contradict the self- defocusing experimentally detected in the samples with cupper and gold nanoparticles (Figures 15 and 17). Hence, the description of nonlinear processes in the approximation of one-photon excitation for the Cu:Al 2 O 3 and Au:Al 2 O 3 systems is incorrect. Therefore, consider the case of two-photon excitation for all the composite systems studied using again expression (12) but with the doubled frequency of the laser radiation, ω 20 = 18797 cm –1 (λ = 532 nm). This frequency lies in the vicinity of the SPR frequencies of MNPs in Cu:Al 2 O 3 and Au:Al 2 O 3 . Determine the signs of Δ 20 for composites and see how they correlate with the nonlinear optical processes observed experimentally. In this case, the signs of Re[χ (3) ] for the Cu:Al 2 O 3 and Au:Al 2 O 3 systems are negative, which agrees with the self-defocusing detected in experiments and suggests the occurrence of two-photon absorption in these samples. For the Ag:Al 2 O 3 samples, this sign turns out to be positive again, as in the case of one-photon excitation, and correlates with the self-focusing observed in experiments. However, for silver nanoparticles in Al 2 O 3 , it is difficult to choose between the one-photon and two-photon excitation mechanisms. Probably, the two mechanisms are simultaneously realized in this type of MNPs and their manifestation depends on the dominant frequency of laser excitation. Thus, the two-level model correctly predicts the sign of the nonlinearity in the Cu:Al 2 O 3 and Au:Al 2 O 3 systems in the case of excitation by laser radiation at a frequency divisible by the doubled SPR frequency. As was mention a change in n 2 of a composite material can be caused by the thermal effect due to heat transfer from MNPs or defects of the dielectric host matrix heated by laser radiation [131]. Despite the duration of laser pulses used was rather short (τ = 55 ns), the influence of the thermal effect on the nonlinear refraction can be analyzed. Estimate how large a change in the refractive indexof crystalline sapphire Δn Al 2 O 3 caused by heating can be. The change in the refractive index due to the thermal effect can be represented in the form [131] Δn(r, z, t) = 1 C h p h dn dT ΔΕ(r, z, t) , (21) where C h and ρ h are, respectively, the heat capacity and the density of the host matrix with MNPs (in the case of sapphire, C h = 0.419 J/g⋅K and ρ h = 3.97 g/cm 3 ); dn/dT is the thermo- optic coefficient, equal to 13.7⋅10 –6 1/K; and ΔE(r, z, t) is the energy of the radiation absorbed Andrey L. Stepanov 108 in a unit volume of the material over a time t. The thermo-optic coefficient for sapphire is positive, and, hence, the thermal effect should lead to the self-focusing of laser radiation in all the samples. Since the self-focusing of laser radiation was experimentally observed only for the samples with silver nanoparticles the thermal effect for such samples were analyzed using present experimental conditions of nonlinear measurements [94, 95]. Thus, in the case of Ag:Al 2 O 3 , the energy of the absorbed radiation is 3.87⋅10 –6 J. For the layer with silver nanoparticles of 50 nm thickness and the beam waist radius 72 μm, the analyzing volume is 4.88⋅10 –10 cm 3 . In this case, the energy ΔE(r, z, t) is 7.92⋅10 3 J/cm 3 . Substituting these values into equation (21), the value of Δn(r, z, t) ≈ 6.53⋅10 –2 will be obtained. In same time, the experimental values are from 4.33⋅10 –2 to 6.83⋅10 –2 . Hence, the thermal effect may manifest itself in the case of samples with silver nanoparticles. However, as it was mentioned the time τ rize necessary for a change in the medium density and a corresponding change in the refractive index is determined by the ratio of the beam waist radius to the speed of sound. Taking into account our experimental conditions (ω 0 = 72 μm at the wavelength 1064 nm and V s ~ 5000– 5500 m/s), τ rize ≈13–15 ns will be again estimated. This time is three orders of magnitude longer than the pulse duration used (55 ps), and, hence, the thermal effect caused by the propagation of an acoustic wave can be excluded from consideration in our case. In conclusion, RZ-scan method is suited for study of nonlinear refraction of samples based on dielectrics with MNPs. Although the sensitivity of the RZ-scan method is slightly lower than that of the classical transmission Z-scan, the RZ-scan method allows one to extend the spectral range of study to the region of low transparency of composite materials. The sign of the Re[χ (3) ] is analyzed on the basis of the two-level model, and it is shown that Re[χ (3) ] of the samples with copper and gold nanoparticles are determined by the two-photon process. It is difficult to make similar conclusion for samples with silver nanoparticles. 4. NONLINEAR OPTICAL ABSORPTION OF ION-SYNTHESIZED SILVER NANOPARTICLES IN VISIBLE RANGE The silver nanoparticles doped in different dielectrics demonstrate variable nonlinear optical properties in visible range [120]. The interest on such structures is based on the prospects of the elaboration of optical switchers with ultrafast response, optical limiters, and intracavity elements for mode locking. Silver nanoparticles have an advantage over another metal nanoparticles (i.e., gold and copper) from the point of view that the surface plasmon resonance energy of silver is far from the interband transition energy. So, in the silver nanoparticle system it is possible to investigate the nonlinear optical processes caused solely by SPR contribution. It should be noted that previous studies of nonlinear optical parameters of silver nanoparticles-doped glasses were mostly focused on determination of third-order nonlinear susceptibility χ (3) . The saturated absorption in silicate glasses doped with ion-synthesized Ag nanoparticles at wavelength of 532 nm and their dependence on laser radiation intensity are considered at present review. As was shown the ion-synthesized silver nanoparticles in Ag:SLSG and Ag:SiO 2 demonstrate the SPR band with minimum transmission in the range of 410–440 nm (Figure 9). Early, it was predicted that glasses with silver-doped nanoparticles could possess a Nonlinear Optical Properties of Transition Metal Nanoparticles … 109 nonlinear saturated absorption [150]. The spectral dispersion of the imaginary part of susceptibility Im[χ (3) ] of such glass was detected as negative value in the spectral SPR range of 385 – 436 nm. The nonlinear coefficient β is also negative in the case of saturated absorption. The T(z) dependences of Ag:SLSG and Ag:SiO 2 samples measured using open aperture Z-scan scheme at laser radiation intensity of I 0 = 2.5·10 9 W/cm 2 and pulse duration of 55 ps is presented in Figure 18 [84]. The transmission of samples was increased due to nonlinear saturated absorption as they approached close to the focal plane. Experimentally estimated nonlinear parameters of the β are -6.7·10 -5 cm/W in Ag:SLSG and -3.6·10 -5 cm/W in Ag:SiO 2 . Note that the coefficient β can be presented as β = α/I s whereI s is saturated intensity. Then the values of I s are 1.1·10 9 and 1.4·10 9 W/cm -2 and the Imχ (3) are -2.4·10 -8 and -1.3·10 -8 esu in Ag:SLSG and Ag:SiO 2 , respectively. Figure 18. Normalized transmittance Ag:SLSG (1) and Ag:SiO 2 (2) samples at laser radiation intensity of I 0 = 2.5·10 9 W/cm 2 . Solis lines show is a fittings [84]. In Figures 19 and 20 values of β in dependence of laser intensity varied from 10 9 to 2·10 10 W/cm 2 are presented. As seen from the figures there are a decrease βof for higher intensities. In particularly, a 21- and 12-fold decrease of β was measured at I 0 = 1.15·10 10 W/cm 2 for Ag:SLSG and Ag:SiO 2 , respectively, compared to β detected at I 0 = 1·10 9 W/cm 2 . The variations of nonlinear transmission in MNP structures in dielectrics were early attributed in some cases to the fragmentation, or fusion of nanoparticles following the their photothermal melting [151, 152]. It was reported about the alteration of the sign of nonlinear refractive index of small Ag clusters embedded in SLSG [153]. They noted that thermal Andrey L. Stepanov 110 effects could change the properties of nanoclusters. The transparency in these samples was associated with oxidation of Ag nanoparticles. However, no irreversible changes of transmittance were observed in present experiments. Figure 19. Coefficient β of Ag:SLSG in dependence of laser intensity. Figure 20. Coefficient β of Ag:SiO 2 in dependence of laser intensity. Nonlinear Optical Properties of Transition Metal Nanoparticles … 111 The reverse saturated absorption can be responsible for the decrease of negative nonlinear absorption of Ag nanoparticles and it could be assume that in the case of picosecond pulses the reverse saturated absorption starting to play an important role in the overall dynamics of nonlinear optical transmittance of MNPs contained compounds, taking into account the saturation of intermediate transitions responsible for saturated absorption.Thus, saturated absorption in Ag:SLSG and Ag:SiO 2 was dominated at small intensities and decreased with the growth of intensity due to influence of competing effects, whereas the selfdefocusing at low intensities was changed to self-focusing at high intensities. The possible mechanism of the decrease of Im[χ (3) ] is the influence of nonlinear optical processes with opposite dependences on laser intensity, also such as two-photon absorption [122]. The wavelength range corresponded to the interband transitions in Ag is located below 320 nm, so the two- photon absorption connected with interband transitions can be involved in the case of 532 nm radiation. The possibility of two-photon absorption due to interband transition of photoexcited electrons was previously demonstrated for Ag particles [154]. The three-photon absorption connected with interband transition for Ag nanoparticles was analysed in (Kyoung et al., 1999). Thus, saturated absorption in Ag:SLSG and Ag:SiO 2 was dominated at small intensities and decreased with the growth of intensity due to influence of competing effects, whereas the self-defocusing at low intensities was changed to self-focusing at high intensities. ACKNOWLEDGMENTS I wish to thank my partners and co-authors from different countries D. Hole, P.D. Townsend, I.B. Khaibullin, V.I. Nuzhdin, V.F. Valeev, Yu.N. Osin, R.A. Ganeev, A.I. Ryasnyanskiy, T. Usmanov, M.K. Kodirov, V.N. Popok, and U. Kreibig, Also, I grateful to the Alexander von Humboldt Foundation and the DAAD in Germany, Austrian Scientific Foundation in the frame of Lisa Meitner Fellowship and the Royal Society in UK for financial support. This work was partly supported by the Ministry of Education and Science of the Russian Federation (FTP “Scientific and scientific-pedagogical personnel of the innovative Russia” No. 02.740.11.0779). REFERENCES [1] Zhang, J. Z. Optical properties and spectroscopy of nanomaterials; Wold Sci. Pub.: London, 2009. [2] Optical properties of nanostructured random media; Shalaev, V. M.; Ed,: Springer: Berlin, 2002. [3] Flytzanis, C.; Hache, F.; Klein, M. C.; Ricard D.; Rousignol P. Nonlinear optics in composite materials; Elsevier Science: Amsterdam, 1991. [4] Kreibig, U.; Vollmer, M. Optical properties of metal clusters; Springer: Berlin, 1995. [5] Stepanov, A. L. In High-power and Femtosecond Lasers: Properties, Materials and Applications; Barret, P.-H.; Palmer M.; Eds., NOVA Sci. Publ.: New York, 2009, pp. 27-70. Andrey L. Stepanov 112 [6] Townsend P. T.; Chandler P. J.; Zhang, L. Optical effects of ion implantation; Cambridge Univ. Press: Cambridge, 1994. [7] Stepanov, A. L. In Metal-Polymer Nanocomposites; Nicolais, L.; Carotenuto, G.; Eds.; John Wiley & Sons Publ: London, 2004; pp. 241-263. [8] Gonella, F.; Mazzoldi, P. In Handbook of nanostructured materials and nanotechnology; Nalwa, H. S.; Ed.; Academic Press: London, 2000. [9] Stepanov, A. L. Ion-synthesis of metal nanoparticles and their optical properties; NOVA Sci. Publ.: New York, 2011. [10] Ricard, D.; Roussignol, P.; Flytzanis, C. Opt. Lett. 1985, 10, 511-513. [11] Haglund Jr., R. F. In Handbook of optical properties. Vol. II. Optics of small particles, interfaces, and surfaces; Hummel, R. F.; Wismann, P.; Eds.; CRC Press: London, 1997; pp. 198-231. [12] Haglund Jr., R. F.; Osbone, D. H.; Magruder III, R. H.; White, C. W.; Zuhr, R. A.; Hole, D. E.; Townsend; P. D. Proc. Conf. Science and technology of atomically engineered materials; Jena, P.; Khanna, S. N.; Rao B. K.; Eds.; World Sci.: Singapure, 1995; pp. 411-418. [13] von Neumann, J. In Fundamentals of photonics, Saleh B. E. A.; Teich, M. C.; Eds.; Wiley: New York, 2001; p. 856-903. [14] Davenas, J.; Perez, A.; Thevenard, P.; Dupuy, C. H. S. Phys. Stat. Sol. A. 1973, 19, 679-686. [15] Treilleux, M.; Thevenard, P.; Ghassagne, G.; Hobbs, L. H. Phys. Stat. Sol. A. 1978, 48, 425-430. [16] Arnold, G. W. J. Appl. Phys. 1975, 46, 4466-4473. [17] Arnold, G. W.; Borders, J. A. J. Appl. Phys. 1977, 48, 1488-1496. [18] Mazzoldi, P.; Arnold, G. W.; Battaglin, G.; Bertoncello, R.; Gonella, F. Nucl. Instr. Meth. Phys. Res. B. 1994, 91, 478-492. [19] Mazzoldi, P.; Arnold, G. W.; Battaglin, G.; Gonella, F.; Haglund Jr., R. F. J. Nonlinear Opt. Phys. Mater. 1996, 5, 285-230. [20] Chakraborty, P. J. Mater. Sci. 1998, 33, 2235-2249. [21] Stepanov, A.; Khaibullin, I. B. Rev. Adv. Mater. Sci. 2005, 9, 109-129. [22] Meldrum, A.; Lopez, R.; Magruder III, R. H.; Boatner, L. A.; White, C. W. In Material science with ion beam; arnes, H.; Ed.; Springer: Berlin, 2010; pp. 255-285. [23] Stepanov, A.L. Rev. Adv. Mater. Sci. 2010, 26, 1-29. [24] Ganeev, R. A. J. Opt. A.: Pure Appl. Opt. 2005, 7, 717-733. [25] Ganeev, R. A.; Usmanov, T. Quant. Electr. 2007, 37, 605-622. [26] Cattaruzza, E.; Gonella, F.; Mattei, G.; Mazzoldi, P.; Gatteschi, D.; Sangregorio, S.; Falconieri, M.; Salvetti, G.; Battaglin, G. Appl. Phys. Lett. 1998, 73, 1176-1778. [27] Falconieri, M.; Salvetti, G.; Cattarruzza, E.; Gonella, F.; Mattei, G.; Mazzoldi, P.; Piovesan, M.; Battaglin, G.; Polloni, R. Appl. Phys. Lett. 1998, 73, 288-290. [28] Cattaruzza, E.; Battaglin, G.; Gonella, F.; Polloni, R.; Mattei, G.; Maurizio, C.; Mazzoldi, P.; Sada, C.; Montagna, M.; Tosello, C.; Ferrari, M. Phil. Mag. B. 2002, 82, 735-744. [29] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Marques, C.; da Silva, R. C.; Alves, E. Opt. Comm. 2005, 253, 205-213. [30] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T.; Marques, C.; da Silva, R. C., Alves, E. Opt. Spectr. 2006, 101, 615-622. Nonlinear Optical Properties of Transition Metal Nanoparticles … 113 [31] Ryasnyanskiy, A. I. Nonlin. Opt. Quant. Opt. 2005, 33, 17-28. [32] Plaksin, O.; Takeda, Y.; Amekura, H.; Kishimoto, N.; Plaksin, S. J. Appl. Phys. 2008, 103, 114302-1 - 114302-5. [33] Ryasnyansky, A. I.; Palpant, B.; Debrus, S.; Khaibullin, R. I.; Stepanov, A. L. J. Opt. Soc. Am. B. 2006, 23, 1348-1352. [34] Takeda, Y.; Lee, C. G.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2002, 191, 422- 427. [35] Takeda, Y.; Lee, C. G.; Bandourko, V. V.; Kishimoto, N. Proc. SPIE, 2002, 4628, 46- 54. [36] Takeda, Y.; Bandourko, V. V.; Lee, C. G.; Kishimoto, N. Mater. Trans. 2002, 43, 1057-1061. [37] Kishimoto, N.; Takeda, Y.; Umeda, N.; Okubo, N.; Faulkner, R.G. Nucl. Instr. Meth. Phys. Res. B. 2003, 206, 643-638. [38] Plaksin, O. A.; Takeda, Y.; Kono, K.; Umeda, N.; Fudamoto, Y.; Kishimoto, N. Mat. Sci. Eng. B. 2005, 120, 84-87. [39] Plaksin, O.A.; Kishimoto, N. Phys. Solid State, 2006, 48, 1933-1939. [40] Kishimoto, N.; Takeda, Y.; Umeda, N.; Gritsyna, T.; Lee, C. G.; Saito, T. Nucl. Instr. Meth. Phys. Res. B. 2000, 166-167, 840-844. [41] Takeda, Y.; Umeda, N.; Gritsyna, V. T.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2001, 175-177, 463-467. [42] Becker, K.; Yang, L.; Haglund Jr., R. F.; Magruder III, R. H.; Weeks, R. A.; Zuhr, R. A. Nucl. Instr. Meth. Phys. Res. B. 1991, 59-60, 1304-1307. [43] Haglund Jr., R.F.; Magruder III, R.H.; Morgen, S.H.; Henderson, D.O.; Weller, R.A.; Yang, L.; Zuhr, R. A. Nucl. Instr. Meth. Phys. Res. B. 1992, 65, 405-411. [44] Haglund Jr., R. F.; Yang, L.; Magruder III, R. H.; Wittig, J. E.; Becker, K.; Zuhr, R. A. Opt. Lett. 1993, 18, 373-375. [45] Haglund Jr., R. F.; Yang, L.; Magruder III, R. H.; Wittig, C. W.; Zuhr, R. A.; Yang, L.; Dorsinville, R.; Alfano, R. R. Nucl. Instr. Meth. Phys. Res. B. 1994, 91, 493-504. [46] Haglund Jr., R. F. Mat. Sci. Eng. A. 1998, 253, 275-283. [47] Magruder III, R. H.; Haglund Jr., R. F.; Yang, L.; Wittig, J. E.; Zuhr, R. A. J. Appl. Phys. 1994, 76, 708-715. [48] Yang, L.; Becker, K.; Smith, F. M.; Magruder III, R. H.; Haglund Jr., R. F.; Yang, L.; Dorsinville, R.; Alfano, R. R.; Zuhr, R. A. J. Opt. Soc. Am. B. 1994, 11, 457-461. [49] Yang, L.; Osbone, D. H.; Haglund Jr., R. F.; Magruder III, R. H.; Wittig, C. W.; Zuhr, R.A.; Hosono, H. Appl. Phys. A. 1996, 62, 403-415. [50] Ila, D.; Williams, E. K.; Sarkisov, S.; Smith, C. C.; Poker, D. B.; Hensley, D. K. Nucl. Instr. Meth. Phys. Res. B. 1998, 141, 289-293. [51] Sarkisov, S.; Williams, E. K.; Curley, M.; Ila, D.; Venkateswarlu, P.; Poker, D. B.; Hensley, D. K. Nucl. Instr. Meth. Phys. Res. B. 1998, 141, 294-298. [52] Takeda, Y.; Gritsyna, V.T.; Umeda, N.; Lee, C. G.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 1999, 148, 1029-1033. [53] Takeda, Y.; Zhao, J. P.; Lee, C. G.; Gritsyna, V. T.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2000, 166-167, 877-881. [54] Olivares, J.; Requejo-Isidro, J.; del Coso, R.; de Nalda, R.; Solis, J.; Afonso, C. N.; Stepanov, A. L.; Hole, D.; Townsend, P. D.; Naudon, A. J. Appl. Phys. 2001, 90, 1064- 1066. Andrey L. Stepanov 114 [55] Takeda, Y.; Lee, C. G.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2002, 190, 797- 801. [56] Takeda, Y.; Lu, J.; Plaksin, O. A.; Amekura, H.; Kono, K.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2004, 219-220, 737-741. [57] Takeda, Y.; Lu, J.; Okubo, N.; Plaksin, O. A.; Suga, T.; Kishimoto, N. Vacuum, 2004, 74, 717-721. [58] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Phys. Stat. Sol. B. 2003, 238, R5-R7. [59] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Phys. Solid State, 2004, 46, 351-356. [60] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Quant. Electr. 2003, 33, 1081-1084. [61] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Phys. Stat. Sol. B. 2004, 241, R1-R4. [62] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Phys. Solid State, 2003, 45, 1355-1359. [63] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Kodirov, M. K.; Usmanov, T. Opt. Spectr. 2003, 95, 967-975. [64] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Phys. Stat. Sol. B. 2004, 241, 935-944. [65] Stepanov, A. L.; Ganeev, R.; Ryasnyanskiy, A. I.; Usmanov, T. Nucl. Instr. Meth. Phys. Res. B. 2003, 206, 624-628. [66] Takeda, Y.; Plaksin, O. A.; Kono, K.; Kishimoto, N. Surf. Coat.Technol. 2005, 196, 30- 33. [67] Ren, F.; Jiang, C. Z.; Wang, Y. H.; Wang, Q. Q.; Wang, J. B. Nucl. Instr. Meth. Phys. Res. B. 2006, 245, 427-430. [68] Y.H. Wang, C.Z. Jiang, F. Ren, Q.Q. Wang, D.J. Chen D.J. Fu Physica E. 33 (2006) 444-248. [69] Wang, Y. H.; Ren, F.; Wang, Q. Q.; Chen, D. J.; Fu, D. J.; Jiang, C. Z. Phys. Lett. A. 2006, 357, 364-368. [70] Ghosh, B.; Chakraborty, P.; Mohapartra, S.; Kurian, P. A.; Vijayan, C.; Deshmukh, P. C.; Mazzoldi, P. Mat. Lett. 2007, 61, 4512-4515. [71] Ghosh, B.; Chakraborty, P.; Singh, B. P.; Kundu, T. Appl. Surf. Sci. 2009, 256, 389- 394. [72] Torres-Torres, C.; Reyes-Esqueda, J. R.; Cheng-Wong, J. C.; Crespo-Sosa, A.; Rodriguez-Fernandez, L.; Oliver, A. J. Appl. Phys. 2008, 104, 14306-1 -14306-5. [73] Wang, Y. H.; Wang, Y. M.; Lu, J. D.; Ji, L. L.; Zang, R. G.; Wang, R. W. Physica B. 2009, 404, 4295-4298. [74] Wang, Y. H.; Wang, Y. M.; Lu, J. D.; Ji, L. L.; Zang, R. G.; Wang, R. W. Opt. Comm. 2010, 283, 486-489. [75] Wang, Y. H.; Wang, Y. M.; Han, C. J.; Lu, J. D.; Ji, L. L. Physica B 2010, 405, 2664- 2667. [76] Takeda, Y.; Lu, J.; Plaksin, O. A.; Kono, K.; Amekura, H.; Kishimoto, N. Thin Solid Films, 2004, 464-456, 483-486. [77] Takeda, Y.; Plaksin, O. A.; Lu, J.; Kono, K.; Amekura, H.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2006, 250, 372-376. Nonlinear Optical Properties of Transition Metal Nanoparticles … 115 [78] Cetin, A.; Kibar, R.; Hatipoglu, M.; Karabulut, Y.; Can, N. Physica B. 405 (2010) 2323-2325. [79] Stepanov, A. L.; Khaibullin, R. I.; Can, N.; Ganeev, R. A.; Ryasnyanski, A. I.; Buchal, C.; Uysal, S. Tech. Phys. Lett. 2004, 30, 846-849. [80] Ryasnyanskiy, A. I.; Palpant, B.; Debrus, S.; Ganeev, R.; Stepanov, A. L.; Can, N.; Buchal, C.; Uysal, S. Appl. Opt. 2005, 44, 2839-2845. [81] Ryasnyanskiy, A. I. J. Appl. Spect. 2005, 72, 712-715. [82] Williams, E. K.; Ila, D.; Darwish, A.; Poker, D. B.; Sarkisov, S. S.; Curley, M. J.; Wang, J.-C.; Svetchinkov, V. L.; Zandbergen, H. W. Nucl. Instr. Meth. Phys. Res. B. 1999, 148, 1074-1078. [83] Sarkisov, S. S.; Curley, M. J.; Williams, E. K.; Ila, D.; Svetchinkov, V. L.; Zandbergen, H. W.; Zykov, G. A.; Banks, C.; Wang, J.-C.; Poker, D. B.; Hensley, D. K. Nucl. Instr. Meth. Phys. Res. B. 2000, 166-167, 750-757. [84] Ganeev, R.; Ryasnyanskiy, A. I.; Stepanov, A. L.; Usmanov, T. Opt. Quant. Electron. 2004, 36, 949-960. [85] Stepanov, A. L. In Silver nanoparticles; Perez, D.P.; Ed.; In-tech: Vukovar, 2010; p. 93- 120. [86] Joseph, B.; Suchand Sandeep, C. S.; Sekhar, B. R.; Mahapatra, D. P.; Philip, R. Nucl. Instr. Meth. Phys. Res. B. 2007, 265, 631-636. [87] Rangel-Roja, R.; McCarthy, J.; Bookey, H. T.; Kar, A. K.; Rodriguez-Fernandez, L.; Cheang-Wong, J.-C.; Crespo-Soso, A.; Lopez-Suarez, A.; Oliver, A.; Rodriguez- Iglesias, V.; Silva-Pereryra, H. G. Opt. Comm. 2009, 282, 1909-1912. [88] Rangel-Roja, R.; Reyes-Esqueda, J. A.; Torres-Torres, C.; Oliver, A.; Rodriguez- Fernandez, L.; Crespo-Soso, A.; Cheang-Wong, J. C.; McCarthy, J.; Bookey, H. T.; Kar, A. K. In Silver nanoparticles, Perez, D.P.; Ed.; In-tech: Vukovar, 2010; p. 35-62. [89] Wang, Y. H.; Peng, S. J.; Lu, J. D.; Wang, R. W.; Cheng Y. G.; Mao, Y. I. Vacuum, 2009, 83, 412-415. [90] Takeda, Y.; Hioki, T.; Motohiro, T.; Noda, S. Appl. Phys. Lett. 1993, 63, 3420-3422. [91] Takeda, Y.; Hioki, T.; Motohiro, T.; Noda, S.; Kurauchi, T. Nucl. Instr. Meth. Phys. Res. B. 1994, 91, 515-519. [92] Takeda, Y.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2003, 206, 620-623. [93] White, C. W.; Thomas, D. K.; Hensley, D. K.; Zuhr, R. A.; McCallum, J. C.; Pogany, A.; Haglund Jr., R. F.; Magruder III, R. H.; Yang, L. Nanostruct. Mat. 1993, 3, 447- 457. [94] Stepanov, A. L.; Marques, C.; Alves, E.; da Silva, R. C.; Silva, M. R.; Ganeev, R.; Ryasnyanskiy, A. I.; Usmanov, T. Tech. Phys. Lett. 2005, 31, 702-705. [95] Stepanov, A. L.; Marques, C.; Alves, E.; da Silva, R. C.; Silva, M. R.; Ganeev, R.; Ryasnyanskiy, A. I. Tech. Phys. 2006, 51, 1474-1481. [96] Takeda, Y.; Plaksin, O. A.; Wang, H.; Kono, K.; Umeda, N.; Kishimoto, N. Opt. Rev. 2006, 13, 231-234. [97] Takeda, Y.; Plaksin, O. A.; Wang, H.; Kishimoto, N. Nucl. Instr. Meth. Phys. Res. B. 2007, 257, 47-50. [98] Magruder III, R. H.; Yang, L.; Haglund Jr., R. F.; White, C. W.; Yang, L.; Dorsinville, R.; Alfano, R. R. Appl. Phys. Lett. 1993, 62, 1730-1772. [99] White, C. W.; Zhou, D. Z.; Budai, J. D.; Zhur, R. A.; Magruder III, R. H.; Osbone, D.H. Mat. Res. Soc. Proc. 1994, 316, 499-507. Andrey L. Stepanov 116 [100] Fukumi, K.; Chayahara, A.; Kadono, K.; Sakaguchi, T.; Horino, Y.; Miya, M.; Fujii, K.; Hayakawa, J.; Satou, M. Jpn. J. Appl. Phys. 1991, 30, L742-L744. [101] Fukumi, K.; Chayahara, A.; Kadono, K.; Sakaguchi, T.; Horino, Y.; Miya, M.; Fujii, K.; Hayakawa, J.; Satou, M. J. Appl. Phys. 1994, 75, 3075-3080. [102] Lepeshkin, N. N.; Kim, W.; Safonov, V. P.; Zhu, J. G.; Armstrong, R. L.; White, C. W.; Zuhr, R. A.; Shalaev, V. M. J. Nonlin. Opt. Phys. Mat. 1999, 8, 191-210. [103] Safonov, V. P.; Zhu, J. G.; Lepeshkin, N. N.; Armstrong, R. L.; Shalaev, V. M.; Ying, Z. C.; White, C. W.; Zuhr, R. A. Proc. SPIE, 1999, 3788, 34-41. [104] Takeda, Y.; Plaksin, O. A.; Kishimoto, N. Opt. Express, 2007, 10, 6010-6018. [105] Torres-Torres, C.; Khomenko, A. V.; Cheang-Wong, J. C.; Rodriguez-Fernandez, L.; Crespo-Soso, A.; Oliver, A. Opt. Express, 2007, 15, 9248-9253. [106] Ghosh, B.; Chakraborty, P.; Sundaravel, B.; Vijayan, C. Nucl. Instr. Meth. Phys. Res. B. 2008, 266, 1356-1361. [107] Wang, Y. H.; Lu, J. D.; Wang, R. W.; Peng, S. J.; Mao, Y. I.; Cheng, Y. G. Physica B. 2008, 403, 3399-3402. [108] Wang, Y. H.; Lu, J. D.; Wang, R. W.; Mao, Y. I.; Cheng, Y. G. Vacuum, 2008, 82, 1220-1223. [109] Battaglin, G.; Calvelli, P.; Cattaruzza, E.; Polloni, P.; Borsella, E.; Cesa, T.; Mazzoldi, P. J. Opt. Soc. Am. B. 2000, 17, 213-218. [110] Magruder III, R. H.; Osbone, D. H.; Zuhr, R. A. J. Non.-Cryst. Solids, 1994, 176, 299- 303. [111] Wang, Y. H.; Jiang, C. Z.; Ren, F.; Wang, Q. Q.; Chen, D. J.; Fu, D. J. J. Mat. Sci. 2007, 42, 7294-7298. [112] Wang, Y. H.; Jiang, C. Z.; Xiao, X. H.; Cheng, Y. G. Physica B 2008, 403, 2143-2147. [113] Wang, Y. H.; Wang, Y. M.; Han, C. J.; Lu, J. D.; Ji, L. L.; Wang, R. W. Physica B. 2010, 405, 2848-2851. [114] Wang, Y. H.; Wang, Y. M.; Han, C. J.; Lu, J. D.; Ji, L. L.; Wang, R. W. Vacuum, 2010, 85, 207-210. [115] Cattaruzza, E.; Battaglin, G.; Gonella, F.; Calvelli, P.; Mattei, G.; Maurizio, C.; Mazzoldi, P.; Padovani, S.; Polloni, R.; Sada, C.; Scremin, B. F.; D’Acapito, F. Composites Sci. Technol. 2003, 68, 1203-1208. [116] Cattaruzza, E.; Battaglin, G.; Gonella, F.; Calvelli, P.; Mattei, G.; Maurizio, C.; Mazzoldi, P.; Polloni, R.; Scremin, B. F. Appl. Surf. Sci. 2005, 247, 390-395. [117] Cesca, T.; Pellegrini, G.; Bello, V.; Scian, C.; Mazzoldi, P.; Calvelli, P.; Battaglin, G.; Mattei, G. Nucl. Instr. Meth. Phys. Res. B. 2010, 268, 3227-3230. [118] Magruder III, R. H.; Zuhr, R. A.; Osbone, D. H. Nucl. Instr. Meth. Phys. Res. B. 1995, 99, 590-593. [119] Mie, G. Ann. Phys. 1908, 25, 377-420. [120] Palpant B. In Non-Linear optical properties of matter; Papadopoulos, M. G.; Ed.; Springer: Amsterdam, 2006; pp. 461-508. [121] Sheik-Bahae, M.; Said, A. A.; van Stryland, E. W. Opt. Lett. 1989, 14, 955-957. [122] Sheik-Bahae, M.; Said, A. A.; Hagan D. J.; van Stryland, E. W. IEEE J. Quan. Elect. 1990, 26, 760-769. [123] Kwak, C. H.; Lee, Y. L.; Kim, S. G. J. Opt. Soc. Am. 1999, 16, 600-604. [124] Stepanov, A. L.; Zhikharev, V. A.; Hole, D. E.; Townsend, P. D.; Khaibullin, I. B. Nucl. Instr. Meth. Phys. Res. B. 2000, 166-167, 26-30. Nonlinear Optical Properties of Transition Metal Nanoparticles … 117 [125] Reintjes, J. F.Nonlinear-optical parametrical processes in liquids and gases; Academic: Orlando, 1984. [126] Karpov, S. V.; Popov, A. K.; Slabko V. V. JETP Lett. 1997, 66, 106-111. [127] Ganeev, R. A.; Ryasnyansky, A. I.; Kamalov, S. R.; Kodirov, M. K.; Usmanov, T. J. Phys. D: Appl. Phys. 2001, 34, 56-61. [128] Tutt, L. W.; Boggess, T. F. Prog. Quant. Electr. 1993, 17, 299-338. [129] Shen, Y. R. The principles of nonlinear optics; Wiley: New York, 1989. [130] Owyoung, A. IEEE J. Quant. Electr. 1973, 9, 1064-1069. [131] Mehendale, S. C.; Mishra, S. R.; Bindra, K. S.; Laghate, M.; Dhami, T. S.; Rustagi, K. C. Opt. Comm. 1997, 133, 273-272. [132] Falconieri, M. J. Opt. A: Pure Appl. Opt. 1999, 1, 662-667. [133] Battaglin, G.; Calvelli, P.; Cattaruzza, E.; Gonella, F.; Polloni, R.; Mattei G.; Mazzoldi, P. Appl. Phys. Lett. 2001, 78, 3953-3955. [134] Mizrahi, V.; DeLong, K. W.; Stegeman, G. I.; Saifi, M. A.; Andejco, M. J. Opt. Lett. 1989, 14, 1140-1142. [135] Rangel-Rojo, R.; Kosa, T.; Hajto, E.; Ewen, P. J. S.; Owen, A. E.; Kar, A. K.; Wherrett, B. S. Opt. Comm. 1994, 109, 145-150. [136] Fribers, S. R.; Smith, P. W. IEEE J. Quant. Electr. 1987, 23, 2089-2096. [137] Moran, M. J.; She, C. Y.; Carman, R. L. IEEE J. Quant. Electr. 1975, 11, 259-263. [138] Xia, T.; Hagan, D. J.; Sheik-Behae, M.; van Stryland, E. W. Opt. Lett. 1994, 19, 317- 319. [139] Ma, H.; Gomes, A. S. L.; de Araujo, C. B. Appl. Phys. Lett. 1991, 59, 2666-2668. [140] Petrov, D. V.; Gomes, A. S. L.; de Araujo, C. B. Appl. Phys. Lett. 1994, 65, 1067-1069. [141] Petrov, D. V.; Gomes, A. S. L.; de Araujo, C. B. Opt. Comm. 1996, 123, 637-641. [142] Petrov, D. V. J. Opt. Soc. Am. 1996, 13, 1491-1498. [143] Kawazoe, T.; Kawaguchi, H.; Inoue, J.; Haba, O.; Ueda, M. Opt. Comm. 1999, 160, 125-129. [144] Stepanov, A. L. Rev. Adv. Mater. Sci. 2003, 4, 45-60. [145] Martinelli, M.; Gomes, L.; Horowicz, R. J. Appl. Opt. 2000, 39, 6193-6196. [146] Ganeev, R. A.; Ryasniansy, A. I. Phys. Stat. Sol. A. 2005, 202, 120-125. [147] Stepanov, A. L.; Popok, V. N. Surf. Sci. 2004, 566-568, 1250-1254. [148] Stepanov, A. L.; Kreibig, U.; Hole, D. E.; Khaibullin, R. I.; Khaibullin, I. B.; Popok, V.N. Nucl. Instr. Meth. Phys. Res. B. 2001, 178, 120-125. [149] Karpov, S. V.; Popov, F. K.; Slabko, V. V. Izv. Akad. Nauk SSSR Ser. Fiz. 1996, 60, 42-49. [150] Hamanaka, Y.; Hayashi, N.; Nakamura, A.; Omi, S. J. Luminesc. 2000, 87-89, 859-861. [151] Link, S.; Burda, C.; Mohamed, M. B.; Nikoobakht, B.; El-Sayed, M. A. J. Phys. Che. A. 1999, 103, 1165-1170. [152] Mafune, F.; Kohno, J.-Y.; Takeds, Y.; Kondow, T. J. Phys. Chem. B. 2002, 106, 7576- 7577. [153] Osbone Jr., D. H.; Haglund Jr., R. F.; Gonella, F.; Garrido, F. Appl. Phys. B. 1998, 66, 517-521. [154] Kyoung, M.; Lee, M.; Opt. Comm. 1999, 171, 145-148. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 3 SELF-ORGANIZATION OF THE NANOCRYSTALLINE STRUCTURE AND RADIATION RESISTANCE OF STRUCTURAL MATERIALS V. P. Kolotushkin * and A. A. Parfenov JSC ”VNIINM ” A.A. Bochvar, Moscow, Russia ABSTRACT Radiation resistance of structural materials depends on the ability of their structure to reduce the rate of accumulation of secondary radiation defects. The introduction of interstitial or substitutional atoms into the matrix, increasing the density of dislocations and other external factors, can accelerate the recombination of primary point defects. We have studied the use of internal structural factors in recombination accelerating of vacancies and interstitials. The principal difference between the two approaches lies in the next. In the proposed metastable alloys the traps of point defects forms the matrix itself but not embedded in a matrix artificial species. The crystal lattice distortions arising in synergistic effect of neutron irradiation and short-range ordering become the traps of vacancies and interstitials. Distortions capture vacancies and interstitials, thus occurs a self-organization of the crystal structure of material. 1. INTRODUCTION Structural materials of reactor cores are simultaneously impacted the neutron radiation, high temperatures, and the temperature gradient across the thickness of products, mechanical stress and chemical interaction with the environment. Under these conditions the materials must provide the strength of the reactor equipment units, the stability of their geometric shapes and sizes throughout the campaign [1]. The most important damaging factor is the neutron irradiation. When impacted into the metal atom a neutron with energy of 1 MeV can * Email:
[email protected] V. P. Kolotushkin and A. A. Parfenov 120 transfer energy to 50 keV sufficient to displace the atom from the lattice site (20-50 eV). The destruction of the crystal lattice and the mixing of atoms in the displacement cascade alter the qualitative structure of the metal. The size of a cascade is ∼ 10 nm. In this region is released an energy of primary knock-on atom. Although most of this energy is released as heat in the process of Frenkel pair’s recombination, much of them remain creating a microstructure changes that lead to changes in the phase diagram [2]. Typical values of activation energy of migration of vacancies and interstitials are respectively E mV = 1 eV and E mi = 0.4 eV. At temperatures around 800 K both types of defects are mobile. Due to the supersaturating of lattice vacancies and interstitials there are the clusters of these defects. Accumulation of vacancies leads to the formation of vacancy pores as well as clusters of interstitial atoms form an additional extra planes bounded by edge dislocations. These secondary radiation defects (clusters) determine the change in material properties. Behavior of point defects imposed into the metal during irradiation depends mainly on the temperature and material structure. In this case unlike the case of thermal diffusion vacancies and interstitials are introduced into the material in equal amounts during irradiation. It is clear that depending on the temperature the effect of irradiation will be different. The low temperature irradiation can freeze almost all input defects which in subsequent annealing start migrating and interact with each other and with the available material sinks. Analysis of experiments shows that due much higher mobility the interstitial atoms are quickly assembled into clusters and form dislocation loops which rather rapidly grow to noticeable size in process of irradiation. The formation of vacancy clusters and loops runs more slowly. This process is temperature dependent; usually the formation of vacancy-type defects with other things being equal occurs at higher temperatures and these defects are smaller than the defects of interstitial type. In order to maintain a stable structure and high mechanical characteristics of materials it is necessary to create the structure conditions for reducing the rate of accumulation of secondary radiation defects (dislocation loops, vacancy pores, excess phases, etc.). Accumulation of secondary radiation defects is determined by the rate of appearance and recombination of vacancies and interstitials [3]. The morphology of the multiphase structure under irradiation, ultimately, determined counteraction of dissolution in the displacements cascades and the phase formation due to freely migrating radiation point defects [4]. Investigations show that the interstitial or substitution atoms doping of austenitic steels and alloys accelerates the recombination of radiation point defects [5]. On the other hand it has been found that in the number of transition metal alloys for the increasing of the radiation resistance it is need not stabilize the structure by means of certain doping, but on the contrary, to create an unstable, metastable structure, prone to the formation of short-range order [6]. Such alloys showed the functional properties exceeding the analogues properties [7]. In these alloys at the stage of short-range order nucleation occur crystal lattice distortions, which are the traps for the vacancies and interstitials and accelerate their recombination [8]. It was also found that formation of the cluster sub lattice of short-range order with the period ≤ 5 nm in the solid solution during neutron irradiation is the most effective mechanism for the enhance of radiation resistance of alloys at temperatures of 573-623 K [9]. Thus on improving the structure and mechanical properties of materials under neutron irradiation as follows from [3, 10] affects the no equilibrium metastable character of alloys Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 121 original structure. Studies of the metastable alloys of nickel - chromium basis showed extremely high radiation resistance of Ni-42Cr-1Mo alloys. Such alloys are not susceptible to radiation swelling; changes of their mechanical properties are minimal [11]. These features are caused by the fact that during the formation of short-range order in their structure arise domains of tension and compression [8], which are lattice distortions and act as centers of attraction for the vacancies or interstitials, depending on the sign of distortion. The analysis shows that the reactor structural materials, having transitional from the ordering to the bundle structure, with near-zero enthalpy of mixing, can be developed on the basis of transition metal alloys for a number of systems: Fe-Cr, Ni-Cr, Ni-V, Ni-Cr-V, V-Ti, and V-Ti-Cr etc. Working temperature of alloys of Ni-Cr can be temperature ≤ 623 K, for alloys of the Fe-Cr ≤ 823 K, for alloys V-Ti-Cr ≤ 1023 K, respectively. Despite the huge number of works devoted to the physics of radiation damage and the explaining of the behavior of structural materials under neutron irradiation, a complete understanding of the nature of radiation damage, as well as the mechanisms and the ways of its reducing does not exist. This makes it impossible to effectively decide the tasks of reactor material science. However, lately there have been data that allow us to hope that this situation can be corrected with the appropriate formulation of tasks. Such a problem is the establishment of the stability and metastability of materials interrelation. Changes in the structure of metastable alloys during irradiation is directed toward stability, but this change stops without a phase transition at the stage of formation of short range order nanodomains in size ∼ 2.5 nm [9]. It is known that the nanodomains (clusters) represent the intermediate link between elementary particles (atoms and molecules) and bulk solids. Due to the discrete structure of energy levels and a large value of the surface ratio to a volume the properties of clusters differ from the properties of individual atoms and the properties of bulk substance. Clusters with the number of particles N ≥ 102 represent the nanoparticles [12]. During irradiation of nanoobjects as well as coarse-grained materials are formed cascades of atomic displacements, i.e. are formed as the single vacancies and interstitials as their complexes in the form of loops and vacancy nanopores. If the size of nanoobjects is comparable with the diffusion way of defects to sinks we can expect a higher radiation resistance of nanomaterials in comparison with their coarse counterparts that actually observed in most studies [13]. The exceptional interest that represents the formation of short-range order nanodomains, stems from the fact that the difference in volume and the electronic subsystems of the component atoms creates during irradiation the ordered static distortions and dimensional effect whose value is determined by the degree of short-range ordering and can change not only the mobility of vacancies and interstitials but also the mechanism of their annihilation. The development of approaches to the creation of radiation-resistant nanocrystalline materials is a promising problem of metal science. It will allow creating a new class of materials. Such materials will have a neutron irradiation stable structure and properties and elevated service life. This paper is devoted to the development and detailing of the phenomenological model of self-organization of the nanocrystalline structure ensuring the stability of properties of structural materials of nuclear power plants. V. P. Kolotushkin and A. A. Parfenov 122 2. EXPERIMENTAL PROCEDURE In this paper we study the structure, composition and properties of steels and alloys based on iron and nickel-based alloys with chromium and molybdenum in the states before and after neutron irradiation (electrons). To study the dependence of radiation damage of austenitic steel on the parameters of niobium carbonitrides the samples have been prepared in the form of rings 10 mm high for structural studies and 2.5 mm for mechanical testing. The samples were annealed in vacuum horizontal furnace at 1300°C, 1 h. Extent of deformation of the samples was about 67 %. The deformed specimens were subjected to recrystallization annealing at temperatures of 800- 1250°C for 1 h and additional annealing at 680°C for 2 h. After the annealing the containers with the samples was cooled in water. Then the samples were irradiated in a reactor «MIR» with neutrons up to ~ 1.5 dpa at ∼ 330°C. In order to calculate the concentration of the niobium carbonitrides the particles were divided by size into 6 groups (from the < 50 nm to ~ 300 nm). In each size group was determined the number of particles K i . Concentration of particles (the parameters of the dislocation loops are calculated the same way) related to a given size group was determined by the formula ρi=[К i М 2 ]/[S(t + d i )], where M - the picture increase, equal to the product of instrumental increase the photographic, S - area of the image, on which were count the particles, t - thickness of the foil, d i - size of particles in size group. The total concentration of particles was determined as the sum of the particle concentrations in all size groups ρ=Σρ i . The average particle size was calculated using the expression: (d = (Σd i ρ i )/ρ. The volume fractions of excess phase particles of each size group were as follows: (ΔV/V) i = 4/3πr i 3 ρ i 100 % = ~ 0,52 d 3 ρ i 100 %. The total volume fraction of particles of excess phase equals the sum of volume fractions of particles of all size groups ΔV/V=Σ(ΔV/V) i . From here was calculated amount of the niobium, carbon and nitrogen as part of the niobium carbonitrides: α = (4 ΔV)/V яч A, β = (2 ΔV)/V яч A. Here α and β - volume fractions respectively of the niobium and carbon (nitrogen), ΔV - volume of particles Nb (CN) in 1 m 3 , Vяч - unit cell volume of Nb (CN), equal to 0.087366 nm 3 , A - number of atoms in 1 m 3 of austenite, which equals 8,65х10 28 м -3 . The study of structural phase changes in Ni-Cr alloys was carried out on experimental nonstoichiometric nickel alloys with chromium 32-47 wt% containing additional ~ 1.3 wt% molybdenum. Experimental samples were manufactured from metal open-induction melting. Ingots weighing 10 kg were reformed into billets of thickness 40 mm followed by hot rolling to a thickness of 5 mm at 1100 - 1250°C. Hot-rolled plates were subjected to cold rolling to a thickness of 2 mm. From these sheets were produced the specimens for testing and research. The starting processing of the samples of alloys Ni-Cr-Mo was annealing in an argon atmosphere at temperatures from 1050 to 1220°C for 30 min to obtain a homogeneous solid solution. Annealed specimens were quenched in water. Samples of steel of type Fe-18Cr-20Ni and some of the samples of the alloy Fe-20Cr- 40Ni-5Mo-Nb were irradiated with neutrons in the reactor 27-BM. Other steels and alloys based on iron were irradiated in the reactor BOR-60 with neutron dose of 10 dpa. Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 123 In BOR-60 were also irradiated specimens of the alloy Ni-42Cr-1Mo with a diameter of working part 3 mm and 15 mm long and the ring specimens of the alloy Ni-47Cr-1Mo. At the bottom of the ampoules the temperature was equal to the temperature of sodium at the reactor inlet. With the rise of the sodium temperature increased, reaching 350º C in the middle of the ampoule in height. Alloys were exposed to ~ 32 dpa. As the objects for electron microscopic studies were used the disks diameter of 3 mm, obtained of foil, rings, and of tensile samples. Major investigations of the material microstructure were carried out under an electron microscope EM-301. Thinning of the samples was carried out in installation of jet electro polishing "Struers" in solution of 4-10 % vol. perchloric acid and 90-96 % vol. icy acetic acid at ~ -10°C and a voltage of 65 V. The diffractograms were recorded on a DRON-4, on the copper Cu Kα radiation using a pyrographite crystal - monochromator. The shooting mode is "on points", the time is 10 s to a point, step 0.05° of 2θ. The samples of the size 15x8x2 mm were subjected to electrochemical polishing in a solution of 60 % phosphoric acid and 40 % glycerol to remove the surface layer of 10-20 microns. Profile analysis of reflections was performed to estimate the physical broadening of the reflections of structural imperfections in the phases. In order to determine the hardware profile of the diffractometer the standard sample of powder monocrystal Ge were used for the measurements. The measurements of the density alloys were performed by hydrostatic weighing in water with preliminary evacuation of air, thermostatic, and after adjusting for buoyancy force of the suspension and the temperature correction of the water density. The total error in determining of the density is ± 0.01 g/cm 3 . 3. EXPERIMENTAL RESULTS 3.1. Influence of Carbide-Forming Elements on the Formation of Secondary Radiation Defects in the Steels and Alloys under Neutron Irradiation up to ~10 dpa In order that a structural reactor material maintained its performance it is necessary that the amount accumulated in the structure of radiation defects did not exceed the critical value at which the change in the shape of the material becomes more than acceptable, or there is destruction. It means that it is necessary in the initial material to create non-equilibrium structure in which the accumulated during neutron irradiation the vacancies and interstitial atoms are forced to recombine. There are a number of different mechanisms that provide such an opportunity. First we estimate the dependence of the formation of point radiation defects complexes from the state of the metal solid solution, which is due to the dissolution of the niobium carbonitrides enriched in the process of initial thermomechanical treatments with the interstitial atom. V. P. Kolotushkin and A. A. Parfenov 124 3.1.1. Features of Radiation Damage of Austenitic Steel, Depending from the Thermomechanical Treatment at a Dose of Radiation Damage ~1.5 dpa The standard treatment of steels and alloys as the structural reactor materials involves the processes of cold deformation and heat treatments. The purpose of the final annealing is to create a material structure with a certain grain size and excess phases. The atoms, which create an excess phase in the present case niobium carbonitrides, may be dissolved into matrix or incorporated into large or small particles. Depending on the position of interstitial atoms, their influence on the irradiated with neutrons material will vary. Investigation of the structure of Fe-16Cr-15Ni-3Mo-Nb-0.021C steel (Table 1) was performed before and after irradiation in the reactor «MIR» with neutron dose ∼ 1.5 dpa at ∼330ºС. Table 1. Chemical composition of the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C in wt% C Si Mn Cr Ni Mo Nb N Fe Al 0.021 0.080 0.79 16.35 15.30 2.67 0.39 0.010 осн. 0.03 The content of carbon and nitrogen in the solid solution was changed as follows: particles of Nb (CN) were dissolved in the matrix by homogenizing annealing at 1300°C for 1 h. The samples were then deformed at room temperature for 67 % (Fig. 1). Cold deformation increased the dislocation density to ≤ 1x10 16 m -2 , formed multiple slip planes and micro twins. After deformation, specimens were subjected to recrystallization annealing at temperatures 800 - 1250°С. Figure 1. Structure of the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C after cold deformation (the deformation ratio is 67 %). With increasing the temperature of recrystallization annealing the number of remaining in solid solution C and N atoms was increased, and after annealing at 1250°C almost all the atoms of Nb, C and N were in the solid solution. The lattice period of solid solution as the Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 125 result of raising the temperature of recrystallization annealing and the amount of carbon and nitrogen in the matrix increased from 0.35943 to 0.35949 nm. The study showed that during the recrystallization annealing at temperatures 800-900ºC the largest number of the niobium carbonitrides was formed. A maximal concentration of particles Nb (CN) has been found after annealing at 800ºC (Fig. 2). In structure of these samples along with recrystallized grains are preserved and deformed grains with a high concentration of particles Nb (CN). In the recrystallized grains behind the front recrystallization the particle size and concentration are, respectively, ~ 7 nm and ~ 2х10 21 m -3 . In the deformed grains are allocated the fine particles Nb (CN) of a higher concentration (average particle size of ~ 3 nm, the concentration ~4х10 21 m -3 ). The volume fractions of particles of Nb (CN) are, respectively, 0.05 and 0.005 % in the recrystallized and deformed regions. It follows that the passage of the front recrystallization leads to a more intensive release of particles Nb (CN) from the solid solution and the greater its purification by carbon, nitrogen and niobium. Figure 2. Particles Nb (CN) in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C after recrystallization annealing at 800°C. Dispersed particles of the niobium carbonitrides after recrystallization annealing at 800ºC are located mainly on the footsteps of the slip planes of the deformed grains (Fig. 2). Chains of the niobium carbonitrides often pass through the boundary of adjacent grains. Similar processes occurred at temperatures of 850 and 900ºC. Rising of recrystallization annealing temperature to 1000ºC and above led to a decrease in the number of particles of Nb (CN) and the enlargement (Fig. 3). It should be noted that the distribution of precipitated particles of Nb (CN) sufficiently no uniform, for example, after recrystallization annealing at 1000° C particles are arranged with an interval from ∼ 30 to ∼ 300 nm. Depletion of the solid solution of steel Fe-16Cr-15Ni-3Mo-Nb-0.021C of the interstitial atoms during annealing at 800 and 1000°C occurs in different ways. At 800° C the solubility of the atoms Nb, C and N into the recrystallization front boundary is higher than in the V. P. Kolotushkin and A. A. Parfenov 126 matrix, so most of the dissolved in the matrix atoms Nb, C and N swept out the recrystallization front. On the boundary of the front there is an accumulation of atoms. High diffusion mobility in the bulk of the moving front recrystallization boundary promotes the nucleation and growth of Nb (CN). Growing particles inhibit the movement of the front of recrystallization, but upon reaching a certain critical particle size of Nb (CN) curved boundary of recrystallization front separates from them (Fig. 2). Behind the boundary remains depleted on the Nb, C and N matrix, which are interspersed with small and large particles of Nb (CN). Figure 3. Particles Nb (CN) in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C after recrystallization annealing at 1000°C. When the annealing temperature increases, the solubility of Nb, C and N in solid solution also increases. Therefore, at 1000°C much of the interstitial atoms are not enjoys the front of the recrystallization, but remains in solid solution. Therefore, an additional annealing at 680°C, 2 h following the recrystallization annealing at 1000°C, even more clean matrix, binding the atoms of Nb, C and N in the smallest particles of Nb (CN). Due to differences in the volume fraction of particles of Nb (CN) in the original samples and the corresponding difference in the enrichment of solid solution of C and N atoms under neutron irradiation the accumulation of radiation defects in the samples of steel Fe-16Cr- 15Ni-3Mo-Nb-0.021C differed. Irradiation at ∼ 330°C led to the formation in the solid solution mainly of prismatic dislocation loops (Fig. 4) and, in the some states, vacancy pores. The distribution of dislocation loops in the matrix is fragmented, apparently in accordance with inhomogeneity of chemical composition and distribution in the matrix of C and N atoms and particles Nb (CN). In the various sample grains concentration of loops sometimes differed by 2-3 times. The size of the loops varies from 1 to 50 nm. The main part of dislocation loops has a size of less than 10 nm. Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 127 Figure 4. Dislocation loops in irradiated alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C. On the histogram of the dislocation loops distribution in size in irradiated samples of Fe- 16Cr-15Ni-3Mo-Nb-0.021C steel is clearly seen that the temperature increasing of recrystallization annealing entails an increase in the number of loops (Fig. 5). It is caused by the increasing an enrichment of solid solution with carbon and nitrogen atoms, which poison the dislocation loops slowing their growth. Preferential absorption of interstitials by dislocation loops decreases, respectively, decreasing the growth rate of loops. Figure 5. Dislocation loop size distribution in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C irradiated at ∼ 330°C. The sharp difference in the concentration of dislocation loops in the samples after recrystallization annealing and the samples after additional annealing at 680°C is formed mainly due to the dislocation loops with the size of ≤ 10 nm. The concentration of such loops in the samples with additional annealing is much lower. The difference in the concentration of larger loops is less significant. In the Fig. s is clearly seen that in the samples not annealed at V. P. Kolotushkin and A. A. Parfenov 128 680°C (Fig. 6a), dislocation loops are smaller, and their concentration is accordingly higher than in samples with an additional annealing (Fig. 6b). Thus, additional purification of the matrix from carbon and nitrogen reduces the possibility of poisoning of dislocation loops and promotes their growth in the process of neutron irradiation at ∼ 330ºC. Figure 6. Dislocation loops in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C: a) irradiation following the recrystallization annealing 1000°C, b) irradiation following the recrystallization annealing 1000°C plus an additional annealing 680°C. With the release from the solid solution of steel Fe-16Cr-15Ni-3Mo-Nb-0.021C the niobium carbonitrides particles is linked another mechanism of reduction the radiation damage. Particles Nb (CN) create in the lattice during separating from the solid solution the zones of structural distortions due to lattice period mismatch of the phase and of the matrix. In relation to point defects such distortions in the initial period of Nb (CN) particle formation may be the regions of compression or tension, which can serve as traps for vacancies or interstitials. Fixing of point defects in the neighborhood of distortion zones accelerates their recombination. As a consequence, the growth of dislocation loops and the formation of vacancy pores slow. Effectiveness of the latter mechanism is clearly visible when comparing the concentration of dislocation loops in samples of 1000°C and 1000°C +680°C (Fig. s 5 and 6). In the structure of steel Fe-16Cr-15Ni-3Mo-Nb-0.021C samples recrystallized at 800 - 950°C and additionally annealed at 680°C, after irradiation were found the vacancy pores (Fig. 7). The pores are distributed in the matrix unevenly like the dislocation loops. The pore size does not exceed ∼ 10 nm; the total relative swelling was less than 0.02 %. Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 129 Figure 7. Vacancy pores in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C: a) irradiation following the recrystallization annealing 850°C plus an additional annealing 680°C, b) irradiation following the recrystallization annealing 800°C plus an additional annealing 680°C. The analysis shows that the formation of vacancy pores in the steel Fe-16Cr-15Ni-3Mo- Nb-0.021C samples correlated with depletion of the original solid solution the atoms Nb, C and N. For example, in the structure of the sample after recrystallization annealing at 800°C plus an additional annealing at 680°C vacancy pores were found only in areas with the recrystallized structure, depleted the atoms Nb, C and N. In the deformed grain the pores are not revealed. Thus, the experiments show that depletion of the matrix with carbon nitrogen and niobium during the passage of the front recrystallization results in the growth of dislocation loops and reducing their concentration as well as the appearance of vacancy pores. Taking into account that the degree of solid solution depletion with carbon, nitrogen and niobium after recrystallization annealing at 800 and 1000°C is different, and the neutron irradiation was conducted under the same conditions it may be concluded: decrease in the amount of carbon and nitrogen in solid solution increases the preferential absorption of interstitials by dislocation loops. The confirmation of this was found in specimens after recrystallization annealing at 1000°C, plus an additional annealing 680°C. But there is appears to be a certain critical concentration of carbon and nitrogen in solid solution. It is created by recrystallization annealing at 800-850°C plus an additional annealing 680°C. At the lower concentration than critical the dislocation loops absorb a higher proportion of interstitials. As a result, the matrix sate by vacancies, the rate of recombination of point defects is reduced, and vacancy swelling begins. These experimental results underscore the importance of considering the content of interstitial impurities in the solid solution of austenitic steels, and ensuring uniformity of their structure-phase state. 3.1.2. Effect of Interstitial Atoms on the Accumulation of Radiation Defects in Steels and Alloys Under Neutron Irradiation to 10 dpa Described in section 3.1.1 results have shown a qualitative dependence of structure changes of Fe-16Cr-15Ni-3Mo-Nb-0.021C steel after neutron irradiation at ~ 330°C from the V. P. Kolotushkin and A. A. Parfenov 130 initial processing and content in solid solution of atoms niobium, carbon and nitrogen. In the present section the quantitative evaluation of the influence of carbide-forming elements in solid solution of iron-based steels and alloys (Table 2) on radiation damage of materials under neutron irradiation of higher damage dose is conducted. Table 2. Chemical composition of materials studied in wt% Materials C Si Mn Cr Ni Mo Nb N Fe-16Cr-15Ni-3Mo-Nb- 0.020C 0.020 0.08 0.94 16.99 15.45 2.73 0.37 0.010 Fe-16Cr-15Ni-3Mo-Nb- 0.026C 0.026 0.31 0.51 16.00 14.97 2.68 0.39 0.040 Fe-20Cr-25Ni-Nb 0.013 0.05 1.48 20.1 24.60 - 0.72 0.008 Fe-20Cr-25Ni-Nb-Si 0.012 0.92 1.80 20.1 24.80 - 0.79 0.008 Fe-20Cr-40Ni-5Mo-Nb 0.014 0.09 1.68 19.80 40.80 4.73 0.57 0.020 Initial state of material structure changed during recrystallization annealing (Table 3). The volume fraction of particles of excess phase varied in accordance with the final heat treatment. With increasing annealing temperature, as seen from the table, the number of atoms of carbide-forming elements in solid solution grows, and the volume fraction of niobium carbonitrides is reduced. A higher content of carbon and nitrogen in the matrix corresponds to annealing at higher temperature. Table 3. Distribution of Nb, C and N in the structure of alloys in the initial state Materials Operation of recrystallizat ion annealing Parameters of the niobium carbonitrides The content of elements in the matrix in wt% Number density (m -3 ) Size (nm) Volume fraction, % Nb C + N Fe-16Cr-15Ni- 3Mo-Nb- 0.020C 800°С, 1 ч 3х10 20 20 0.15 0.17 0.012 900°С, 30’ 1х10 21 10 0.1 0.29 0.018 1200°С,1 ч - - <0.01 0.37 0.030 Fe-16Cr-15Ni- 3Mo-Nb- 0.026C 950°С, 30’ 1х10 21 180 0.43 0.09 0.010 Fe-20Cr-25Ni- Nb 1000°С, 30’ 2х10 18 150 0.45 0.34 <0.010 Fe-20Cr-25Ni- Nb-Si 1000°С, 30’ ≤1х10 19 40 0.05 0.70 0.015 Fe-20Cr-40Ni- 5Mo-Nb 800°С, 1 ч 2х10 19 60 0.20 0.34 0.010 1000°С, 1 ч 1х10 18 30 0.01 0.54 0.032 Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 131 The samples of steels and alloys were irradiated in the BOR-60 reactor with neutrons up to ~ 10 dpa at ∼ 350°C. In the process of irradiation the phase composition of steels and alloys has not changed. The results of determining the parameters of secondary radiation defects are shown in Table 4. These results show a significant effect of changing the quantity of carbide-forming elements in the solid solution: of niobium, carbon and nitrogen on the recombination of point radiation defects. In the structure of materials under neutron irradiation were formed, as a rule, the dislocation loops. In some specimens in addition to dislocation loops have appeared and the vacancy voids. Dislocation loops were mostly perfect prismatic loops of embedded type. In specimens of steels and alloys with higher content in solid solution of atoms Nb, C and N the concentration of dislocation loops was greater and the average size of loops is less. Table 4. Parameters of secondary radiation defects in the alloys after irradiation in BOR-60 reactor with neutrons up to ~ 10 dpa at 350°C Materials Annealing temperature, °C / Contents (C+N) in the matrix in wt% Parameters of the vacancy pores Parameters of the dislocation loops ρ (10 21 m -3 ) d (nm) Swelling, % ρ (10 21 м -3 ) d (nm) Fe-16Cr-15Ni- 3Mo-Nb- 0.020C 800 / 0.012 - - - 12 20 900 / 0.018 - - - 15 15 1200 / 0.030 - - - 20 10 Fe-16Cr-15Ni- 3Mo-Nb- 0.026C 950 / 0.010 3 10 0.20 4 40 Fe-20Cr-25Ni- Nb 1000 / <0.010 0,3 13 0.04 4 30 Fe-20Cr-25Ni- Nb-Si 1000 / 0.015 - - - 10 20 Fe-20Cr-40Ni- 5Mo-Nb 800 / 0.010 3 9 0.10 9 30 1000 / 0.032 - - - 30 8 In the samples of Fe-16Cr-15Ni-3Mo-Nb-0.020C steel the temperature raise of recrystallization annealing increases the amount of niobium, carbon and nitrogen in the matrix (Table 3). After neutron irradiation, as seen from Table 4, in accordance with the enrichment of solid solution with atoms of Nb, C and N the concentration of dislocation loops increases, and their average size decreases. On the structure and phase composition of steel Fe-16Cr-15Ni-3Mo-Nb-0.026C of electroslag remelting in the initial state appears to be influenced the peculiarities of its creation that is the composition (Table 2), the smelting and the processing. Samples were subjected to recrystallization annealing at a lower temperature of 950°C, compared with the standard annealing temperature of 1050°C. As a result of this annealing, niobium, carbon and nitrogen were significantly linked in the particles of niobium carbonitrides (Fig. 8a). In this case, the total content of carbon and nitrogen in solid solution was decreased to the level of V. P. Kolotushkin and A. A. Parfenov 132 0.01 wt%. Apparently due to the fact that during exposure in the depleted by interstitial impurities matrix the interstitials mainly went to major (≥ 40 nm) dislocation loops, in the solid solution formed an excess of vacancies, which formed the vacancy pores (Fig. 8b). Figure 8. Structure of the alloy Fe-16Cr-15Ni-3Mo-Nb-0.026C: a) initial state, b) irradiation to ∼10 dpa at 350°C. In the samples of steel Fe-20Cr-25Ni-Nb with a silicon content of 0.05 wt% in the process of recrystallization annealing of the initial samples the carbide-forming elements of niobium, carbon and nitrogen were mostly linked in the particles of niobium carbonitrides Nb (CN) (Fig. 9a). Solid solution of these samples was depleted on carbon and nitrogen to <0.010 wt%. Therefore under neutron irradiation to 10 dpa in clean from introduction impurities solid solution a separate vacancy pores were formed (Fig. 9c). In samples of steel Fe-20Cr-25Ni-Nb (Fig. 9b) which had increased silicon content (Table 2), the solid solution after the recrystallization annealing was enriched in carbon and nitrogen resulting from the substitution these elements with silicon at the grain boundaries and in solid solution. Enrichment of solid solution on carbon and nitrogen (0.015 wt%) probably contributed to the increasing the recombination rate of vacancies and interstitials and the nucleation of vacancy pores has not been detected (Fig. 9d). Recrystallization annealing of the alloy Fe-20Cr-40Ni-5Mo-Nb at 800º C for 1 h (Fig. 10a) caused extensive appearance of carbonitrides of niobium and led to the depletion of the solid solution on carbon and nitrogen. Subsequent neutron irradiation created in the pure on introduction impurities the solid solution vacancy pores and large dislocation loops (Fig. 10). Their emergence and rapid growth are due to a decrease in the rate of recombination of point defects in the equilibrium matrix. The temperature rise of recrystallization annealing of the alloy Fe-20Cr-40Ni-5Mo-Nb up to 1000ºC (Fig. 10b) led to a more than threefold (0.032 wt%) enrichment of the matrix on carbon and nitrogen. As a result the neutron irradiation increased the concentration of smaller dislocation loops. At the same time the rate of recombination of point defects on the equilibrium distortions of the solid solution increased, and the vacancy voids during irradiation were not revealed (Fig. 10d). Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 133 Figure 9. Structure of the alloy Fe-20Cr-25Ni-Nb: a, b) initial state: melting with 0,05 and 0,92 % Si, respectively; c, d) irradiation of 10 dpa at ~ 350 ° C: melting with 0,05 and 0,92 % Si, respectively. Moreover all the chromium-nickel steels and alloys behave practically identically. In all materials there is an accumulation of Frenkel pairs to the level of > 10 25 m -3 that is 1 - 20 % of the quantity of Frenkel pairs in the cascade of displacements which equal ∼10 27 м -3 . Summarizing the experimental results obtained on effect of interstitial atoms carbon and nitrogen on the process of recombination of vacancies and interstitials in neutron irradiation of steels and alloys based on iron it is possible to come to such conclusion: if the solid solution of steels and alloys is depleted by carbon and nitrogen in the initial heat treatment to a level ≤ 0,01 wt% (≤ 500 ppm at) there is a stabilization of the structural state of alloy, the disequilibrium decreases. The location of the structural distortions of the solid solution with an average linear spacing of more than 12 interatomic distances does not create enough of traps or sinks for point defects. Therefore the rate of recombination is reduced and neutron irradiation to 10 dpa at a temperature of ∼ 350°C causes the formation of the vacancy pores and the large dislocation loops in the solid solution. V. P. Kolotushkin and A. A. Parfenov 134 Figure 10. Structure of the alloy Fe-20Cr-40Ni-5Mo-Nb: a, b) in its original condition after recrystallization annealing at: a) 800°C, b) 1000°C, c, d) after neutron irradiation to ~10 dpa at 350°C: c) 800°C, d) 1000°C. 3.1.3. The Influence of Oversized Substitutional Atoms on the Acceleration of the Recombination of Radiation Defects Examined in the previous section, the mechanism of influence of carbide-forming elements on the radiation damage of steels and alloys outlined the important role of carbon and nitrogen atoms in a change in the rate of the point defects recombination. If the carbon and nitrogen atoms there are in the solid solution, they accelerate the recombination of vacancies and interstitials. Upon binding of carbon and nitrogen in niobium carbonitrides particles their effect on recombination is reduced. When considering the mechanism of the effect of carbide-forming elements on the radiation-damage susceptibility was not separately accounted for the influence of so-called "oversized" atoms of niobium and molybdenum. The radius of the niobium atoms (the Goldschmidt) by 15%, and molybdenum atoms by 10% larger than that of iron atoms. When replacing the main on the oversized atoms in the Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 135 crystal lattice there are distortions that can serve as traps for vacancies and to accelerate the recombination of point defects. The influence of oversized substitution atoms on the recombination of point defects was evaluated in the study [5] of the samples of high purity steel Fe-18Cr-20Ni (Fig. 11a) and complex doped alloy Fe-20Cr-40Ni-5Mo-Nb (Fig. 12a). Figure 11. Structure of the alloy Fe-18Cr-20Ni: a) initial state, b) irradiation with neutrons with a fluence of 4.6x10 24 n/m 2 , E > 0.8 MeV. The steel Fe-18Cr-20Ni in the initial state after recrystallization annealing has a homogeneous structure of the solid solution. In the structure there is no excess phase and oversized atoms. The total concentration of carbon and nitrogen in solid solution is about 0.015 wt%. Alloy Fe-20Cr-40Ni-5Mo-Nb, unlike steel Fe-18Cr-20Ni, has an additional 5 wt% oversized atoms of molybdenum and niobium, so the structure of the alloy Fe-20Cr- 40Ni-5Mo-Nb (Fig. 12a) contains also particles of niobium carbonitrides Nb (CN), concentration and average size equal to ~ 2x10 18 m -3 and 0.2 microns. The samples of steel Fe-18Cr-20Ni and the alloy Fe-20Cr-40Ni-5Mo-Nb were irradiated with neutrons in a reactor 27VM at 320-340°C for 7400 h up to 1 dpa. After neutron irradiation up to 1 dpa change in phase composition of materials was not observed (Fig. s 11b, 12b). In the structure of steel and alloy formed prismatic dislocation loops, the average size and the concentration, as well as the numbers of displaced atoms in the loops are shown in Table 2.9. From the results of exposure can be seen that the concentration of dislocation loops in steel Fe-18Cr-20Ni with an increase in the neutron fluence rapidly reaches saturation. Already after the fluence 4x10 24 n/m 2 concentration of loops remains practically unchanged as the number of displaced atoms in the loops. V. P. Kolotushkin and A. A. Parfenov 136 Figure 12. Structure of the alloy Fe-20Cr-40Ni-5Mo-Nb: a) initial state, b) neutron irradiation with a fluence of 6.2 x10 24 n/m 2 , E > 0.8 MeV. Table 5. Parameters of dislocation loops in neutron-irradiated samples of the alloys Fe- 18Cr-20Ni and Fe-20Cr-40Ni-5Mo-Nb Alloys Флюенс (10 24 n/m 2 , Е>0,8 MeV) Parameters of dislocation loops Mean size (nm) Number density (10 22 m -3 ) Number of atoms in the loops (10 24 m -3 ) Fe-18Cr-20Ni 4.0 4.6 6.3 4.0 6.0 5.0 3.2 3.0 3.2 9.0 16.0 14.0 Fe-20Cr-40Ni- 5Mo-Nb 1.4 4.9 6.2 6.0 6.0 6.5 0.1 0.7 2.0 0.5 3.2 11.0 In the complex doped alloy Fe-20Cr-40Ni-5Mo-Nb the development and accumulation of dislocation loops in the initial stages of irradiation is much slower than in steel Fe-18Cr-20Ni. However, upon reaching the neutron fluence of ~ 5x10 24 n/m 2 and the hereinafter concentration of dislocation loops and the number of displaced atoms in the loops in the alloy increases rapidly and almost reach the level of damage to the steel Fe-18Cr-20Ni in the studied range of irradiation. The average size of dislocation loops in the alloy Fe-20Cr-40Ni- 5Mo-Nb in the course of irradiation changes little. The resulting dependence of the accumulation rate of secondary radiation defects on the amount of impurities in the solid solution shows that the increase in the number of interstitial atoms in solid solution, especially after the neutron irradiation of small fluences, accelerates the formation of dislocation loops. A longer incubation period of accumulation of dislocation loops in the alloy Fe-20Cr-40Ni-5Mo-Nb can, apparently due to the fact that oversized substitutional atoms Mo and the Nb in solid solution create a traps for the displaced atoms and the vacancies, accelerating their recombination. However, the difference in the Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 137 concentration of dislocation loops and the number of displaced atoms in the loops is almost eliminated with increasing the neutron fluence up to ~ 6.2x10 24 n/m 2 , i.e. at a dose of damage ≤ 1 dpa. Furthermore the presence in the solid solution of steel Fe-18Cr-20Ni a comparatively large amount of carbon and nitrogen promotes more intensive poisoning of dislocation loops. In the alloy Fe-20Cr-40Ni-5Mo-Nb significant part of the carbon and nitrogen was bound with niobium, so poisoning of the loop was smaller. As a consequence the dislocation loops in the alloy Fe-20Cr-40Ni-5Mo-Nb are larger and have a smaller concentration. It should be noted that the width of the histogram loop size is much larger in the alloy than in the steel. For example, in neutron-irradiated to a fluence of 6.3x10 24 n/m 2 (E> 0.5 MeV) samples of steel Fe-18Cr-20Ni were observed the loop of maximum size 10 nm, and in irradiated at similar conditions the samples of the alloy Fe-20Cr-40Ni-5Mo -Nb correspondingly 15 nm. Analysis presented in the last sections of the results displays comparatively higher efficiency of the influence of carbon and nitrogen atoms on the acceleration of recombination vacancies and interstitials in steels and alloys. Heat treatments of chromium-nickel steels and alloys, creating a depletion of the solid solution on the carbon and nitrogen to the level of ≤ 0.01 wt% contribute to the development of during neutron irradiation of vacancy porosity. When the total content of carbon and nitrogen is > 0.01 wt% vacancy pores are not formed at the dose of 10 dpa. Thus, the combined impact of carbide forming and oversized atoms and interstitial atoms (carbon and nitrogen) increases the duration of the incubation period of radiation damage by more than one order of magnitude compared with the effect only oversized substitution atoms. The traps created by oversized atoms, the interstitial atom in the excess phases or in the form of interstitial impurities can affect the change in flows of point defects in the incubation period, but are not the unsaturated traps, i.e. do not possess sufficient effectiveness to provide a continuous recombination of vacancies and interstitials. The most important shortcoming in the conduct of such traps in steels and alloys is the change in their morphology and composition during neutron irradiation. The phase particles, formed during the initial thermomechanical treatments are destroyed in the displacement cascade and as a result of radiation-induced segregation become radiation-stable phase. Turning into the stable formations, they lose the ability to be the traps of point defects. Thus, it can be assumed that the methods of accelerating the recombination of point radiation defects with the help of a homogeneous and uniform decay of particles of excess phases, and thereby increasing their radiation resistance, apparently, are not effective. 3.2. Effect of Short-Range Order on Recombination Accelerating of Radiation Point Defects Accumulated to date data on the impact of various factors on the radiation damage of chromium-nickel steels and alloys have highlighted the crucial role of recombination accelerating of point radiation defects. To understand the changes in the behavior of steels and alloys under neutron irradiation it is necessary to understand the influence of non- equilibrium structure on the kinetics of these changes. V. P. Kolotushkin and A. A. Parfenov 138 Structural disequilibrium in metals occurs if the rate of cooling after recrystallization annealing is so high that the diffusion processes in the solid solution did not have time to go, and quenching structure is fixed. In the basis of their origin virtually all types of non- equilibrium structures have changing the solubility of the components with temperature changes. The disequilibrium of structure depends mainly on the doping, quenching rate, the presence of impurities, etc. The structure with no uniform chemical composition acquire during the rapid cooling all the construction materials used in nuclear energy sector. In this connection it is interesting to consider the communication nature of the damage, which develops in metals during irradiation with the disequilibrium of the structure. In studying the mechanical properties of the alloy Ni-42Cr-1Mo, irradiated in BOR-60 reactor with neutrons up to 32 dpa, it was surprisingly found that with the accumulation the dose the mechanical properties and especially the relative total and uniform elongation of the alloy at temperatures of irradiation and test up to 350°C virtually unchanged. At the same time in austenitic stainless steels the total elongation becomes < 3 % for neutron irradiation of lower dose (Fig. 13). This means that the alloy Ni-42Cr-1Mo significantly less susceptible to radiation damage as compared to austenitic stainless steels [11]. Figure 13. Effect of irradiation on the mechanical properties of the austenitic alloys of type 316, 304 and alloy Ni-42Cr-1Mo. Studies of the structure of materials whose properties are shown in Fig. 13 using electron microscopy showed that the size of dislocation loops in the alloy Ni-42Cr-1Mo irradiated with neutrons up to ∼ 32 dpa, was 2-3 times more, and concentration of loops - one order of magnitude lower than in austenitic steel Fe-16Cr-15Ni-3Mo-Nb-0.026C (Fig. 14a). The concentration of dislocation loops in the alloy is ~ 3x10 21 m -3 (Fig. 14b), and in the steel ~ 3x10 22 m -3 . It should be noted at the same time that the steel Fe-16Cr-15Ni-3Mo-Nb-0.026C was irradiated by neutrons in the order of lower dose compared with the alloy. Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 139 Figure 14. Structure of alloys after neutron irradiation at ∼ 350°C: a) Fe-16Cr-15Ni-3Mo-Nb-0.026C, ∼ 2.5 dpa, b) Ni-42Cr-1Mo, ∼32 dpa. Larger dislocation loops with a low concentration in the alloy Ni-42Cr-1Mo impede dislocation motion weaker; therefore the effect of radiation hardening in the alloy respect of the steels is weak. In the turn, lowering the concentration of secondary radiation defects in the alloys of Ni-Cr type of Ni-42Cr-1Mo can be, apparently, associated with acceleration of recombination of vacancies and interstitials in the process of neutron irradiation. Radiation damage of structural materials under the action of neutron flux begins with the appearance in the structure of vacancies, interstitials and the formation of their clusters. Gathering of point defects in complexes: dislocation loops, vacancy pores, the participation of point defects in segregation processes that alter the phase composition of materials and mechanical properties, means a change in the stability of the structure and deterioration of the radiation resistance. Thereby, one of the ways of improving the stability of the structure material is the recombination accelerating of vacancies and interstitials and lowering the rate of accumulation of radiation defect. Therefore the principal goal of this paper was to investigate the possibilities of creating in the construction-traditional materials such original structure, which accelerates the recombination of vacancies and interstitials. 3.2.1. Features of Radiation Damage of of Ni-Cr Alloys Alloys of the system Ni-Cr, which showed significant benefits in neutron irradiation have been investigated in the connection with the need creation of the material, the complex match to the requirements of high radiation and corrosion resistance, high mechanical properties and structural stability at temperatures of 300-350°C. In studying of alloys of the system nickel-chromium were obtained the first experimental data on the significant influence of metastable structure on the recombination of point defects. In the particular, it was found that the concentration of dislocation loops in the alloy Ni-42Cr- 1Mo after irradiation by neutrons up to ∼ 32 dpa at 350°C was almost one order of magnitude smaller than in the alloy Ni-47Cr-1Mo [3]. V. P. Kolotushkin and A. A. Parfenov 140 The alloys Ni-42Cr-1Mo and Ni-47Cr-1Mo (Table 6) after quenching have FCC lattice based on nickel. Volume fraction of particles of excess α - phase in the alloy Ni-42Cr-1Mo (Fig. 15) did not exceed 0.05 %. In the solid solution of tension samples of the alloy Ni- 47Cr-1Mo were remained not dissolved in holding for quenching globular particles of α - phase based on chromium BCC and inhomogeneously distributed titanium carbide particles of size ~ 100 nm and the concentration of ~ 8 x 10 18 m -3 . Volume fraction of particles α - phase in the alloy was ∼ 0.1 %, the dislocation density ~ 1x10 13 m -2 . Table 6. Chemical composition of alloys Ni-Cr-Mo in wt% Alloys C Si Mn S P Cr Mo Al Fe Ti Ni-42Cr-1Mo 0.003 0.05 0.05 0.001 0.003 41.65 1.01 0.21 0.23 0.21 Ni-47Cr-1Mo 0.013 0.15 <0.05 0.007 0.007 46.69 1.36 0.23 0.24 0.25 Figure 15. Structure of the Ni-42Cr-1Mo alloy after quenching from a temperature of 1100°C. Under irradiation in BOR-60 at ~ 350°C by neutrons dose of 10 dpa in the tensile samples of the alloy Ni-47Cr-1Mo were formed dislocation loops, vacancy pores and the linear dislocations (Fig. 16). In addition to the globular precipitates of α - phase in the structure were observed the titanium carbide particles (Fig. 16a) with the lattice constant 0.435 nm, the size of 100 nm and the concentration ≤ 8x10 18 m -3 . Concentration of dislocation loops reached ~ 2x10 21 m -3 , the average size of ~ 16 nm. Vacancy pores (Fig. 16b) had a size of ~ 9.5 nm and a concentration of ~ 3x10 21 m -3 and the swelling was ~ 0.14 %. There were near the grain boundaries depleted zones in the pores of a width of 100 nm. Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 141 Figure 16. Structure of the alloy Ni-47Cr-1Mo samples after neutron irradiation to ~ 10 dpa at ~350°С: a) α - phase and titanium carbides, b) dislocation loops, voids and linear dislocations. In the ring samples of the alloy Ni-47Cr-1Mo after irradiation in BOR-60 reactor at a temperature of 350ºC by neutrons dose of ~ 32 dpa vacancy pores were not detected. Concentration of dislocation loops was ~ 3x10 22 m -3 (Fig. 17a), the average size of loops - 7.5 nm. In the structure were observed the linear dislocations, carbides of titanium and randomly distributed particles α - phase (Fig. 17b). Figure 17. Structure of the alloy Ni-47Cr-1Mo samples after neutron irradiation to ~ 32 dpa at ~350ºС: a) dislocation loops and line dislocations, b) α - phase and titanium carbides. Analysis of the structural features of the irradiated samples of the alloy Ni-47Cr-1Mo shows that his damage is analogous to by neutrons damage of austenitic steels and alloys (Section 3.1.2). In the samples in tension of this alloy during the initial hot repartition the solid solution was depleted of interstitial impurities. Therefore under neutron irradiation dose of 10 dpa interstitial atoms are arranged in the large size of dislocation loops and dislocation V. P. Kolotushkin and A. A. Parfenov 142 network, as well vacancy - in the pores. In the ring samples irradiated up to ~ 32 dpa, interstitials are located in the higher concentration dislocation loops (~ 3x10 22 m -3 ) and the smaller size, as well vacancies are located in the vacancy loops d < 10 nm, ρ ~2x10 22 m -3 . In such a way, the radiation damage of the alloy Ni-47Cr-1Mo affects the content of interstitial impurities in solid solution. Reducing the number of carbon atoms in solid solution reduces the decorating of the dislocation loops, which increase in size by absorbing the interstitials. As a result, the recombination rate of Frenkel pairs slows down. The concentration of radiation-induced vacancies in the matrix increases and causes the appearance of porosity in the samples in tension of the alloy Ni-47Cr-1Mo. Under the carbon content in the ring samples of the alloy Ni-47Cr-1Mo at the level of the original concentration the dislocation loops are screened by carbon, the growth of loops slows down. The increased amount of interstitial atoms in the matrix accelerates the recombination of point defects. Not exchanged radiation vacancies can be united into vacancy dislocation loops. In the samples for tensile of the alloy Ni-42Cr-1Mo, irradiated in the BOR-60 at ∼ 350°C by neutrons dose of ~ 32 dpa, dislocation loops were formed and the linear dislocations (Fig. 18). The volume fraction of particles of excess phase (Fig. 18a) does not exceed 0.05 %. Diffraction contrast of the matrix has a tweed structure (Fig. 18b) showing the homogeneous formation of the short-range ordering. Homogeneous short-range ordering in the alloy matrix manifested brighter after heating of the irradiated samples for mechanical testing: in the electron diffraction patterns - in the form of diffuse streaks around the main reflections (Fig. 19a) as well in the microphotographs in the form of clusters of dark spots, whose concentration was ≤ 10 24 m -3 . An increase the sizes of short-range ordering regions is not large (∼ 2 nm, Fig. 19b) due to the short duration of heating of samples for tensile testing. Figure 18. Structure of the alloy Ni-42Cr-1Mo after neutron irradiation to ~ 32 dpa: a) the grain boundary, and b) the dislocation structure. A tendency to developing of short-range order means that in conditions of neutron irradiation the atoms of a disordered after quenching solid solution are rebuilt to form clusters of the ordered structure. Occurring during the nucleation of clusters the lattice distortions increase the probability of recombination of vacancies and interstitials. Accelerating of the Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 143 recombination of vacancies and interstitials reduces the amount of secondary radiation defects including dislocation loops and vacancy pores. After irradiation under identical conditions, the concentration of dislocation loops in the disposed to the short-range ordering alloy Ni- 42Cr-1Mo was several times lower than in the alloy Ni-47Cr-1Mo. Accordingly, uniform and total elongation of the alloy Ni-42Cr-1Mo after neutron irradiation dose of 32 dpa ∼ was 2 - 3 time higher. Figure 19. Short-range ordering in the alloy Ni-42Cr-1Mo, irradiated at ~ 350ºС to ~ 32 dpa after mechanical tests: a) electron diffraction pattern, b) structure after tensile testing at 500ºС. Now we shall return to the problem of different radiation damage of austenitic stainless steel Fe-16Cr-15Ni-3Mo-Nb-0.026C and alloy Ni-42Cr-1Mo, which had been irradiated by neutrons in a factor of 10 the higher fluence and at the same time had a factor by 10 smaller concentration of dislocation loops than steel. In this connection there appeared one more unexpected experimental fact. Alloy Ni-47Cr-1Mo alloy was different from the Ni-42Cr-1Mo only the fact that had the content of chromium in ∼ 5 % more (Table 6). However under neutron irradiation a dose of 32 dpa this alloy has accumulated secondary radiation defects, not as a nickel alloy with ∼ 42 % chromium, but as austenitic steel Fe-16Cr-15Ni-3Mo-Nb- 0.026C. Despite the slight differences in chemical composition, the concentration of dislocation loops in the nickel alloy with 42 % chromium was an order of magnitude smaller and the number of not recombine defects - 3 times less. The recombination rate, the concentration of dislocation loops, longer incubation period of damage show that the structure of the alloy Ni-42Cr-1Mo under neutron irradiation is changed according to some different mechanism than in austenitic stainless steels and alloys and nickel alloy with 47 % chromium. Study of the mechanisms and laws of point defects recombination accelerating in alloys of the system Ni-Cr is discussed in the next section. 3.2.2. The Short-Range Ordering Nanodomains of the Ni-Cr System To elucidate the mechanism of accelerating of point defects recombination in the alloy Ni-42Cr-1Mo under neutron irradiation were carried out comprehensive studies of the V. P. Kolotushkin and A. A. Parfenov 144 structure, resistivity, lattice parameters, density and other features of the experimental alloys of the Ni-Cr system (supplemented with. ∼ 1 at% Mo, table 7 ) in the initial state and after thermal and radiation exposure. Table 7. Chemical composition of experimental alloys Ni-Cr-Mo in wt% Alloys C Ni Cr Cr* Mo S Ni-32Cr-1Mo 0.027 осн. 32.11 34.94 1.28 0.006 Ni-38Cr-1Mo 0.027 осн. 37.85 40.90 1.30 0.005 Ni-39Cr-1Mo 0.022 осн. 38.90 42.00 1.30 0.005 Ni-41Cr-1Mo 0.028 осн. 41.35 44.49 1.30 0.005 Ni-43Cr-1Mo 0.025 осн. 43.06 46.24 1.30 0.005 Ni-44Cr-1Mo 0.026 осн. 44.48 47.69 1.30 0.005 * at%. The starting state for the alloys investigated [7] is the state after quenching from the single-phase γ - region of state diagram. Alloys for the investigations were quenched from the single-phase γ - region of state diagram, and then annealed at temperatures of 300-450°C (points on the graph show the position of alloy before quenching and with aging, Fig. 20). The typical structure of alloys in the initial state is shown in Fig. 21. The structure is a homogeneous solid solution of nickel. Significant differences in the structural-phase state of alloys after the quenching occur with increasing chromium content of more than 38 wt%. In the body of grains of alloys with such a chromium content remain did not dissolved by annealing for quenching particles of α - phase of chromium with the volume fraction ≤ 0,1 % (Fig. 21a. At the grain boundaries are observed seldom selections of chromium carbides M 23 C 6 (Fig. 21b). Figure 20. The alloys investigated in the phase diagram of the system Ni-Cr. Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 145 Figure 21. Structure of the alloy Ni-41Cr-1Mo after quenching: body (a) and grain boundary (b). In the microstructure of quenched alloys is observed diffraction tweed contrast (Fig. 22a. Tweed contrast becomes sharper detected after the annealing at 450°C for 9 000 h (Fig. 22b). Oscillation period of the fragments of contrast is ∼ 5 nm. Study of the kinetics of structural features in the annealing process at 300 - 450°C for up to about 40 000 hours spent on the experimental samples of nickel alloys with chromium, has shown that annealing in the temperature range 300 - 400°C did not cause significant structural and phase changes which are practically not detected by electron microscopy [14]. At 450°C in the alloys there are structural-phase changes in accordance with the chromium content in the matrix. The increase in chromium content stimulates grain boundary precipitation of α - phase, especially if the chromium content > 41 wt% (Fig. 23). In the alloys with 32 and 38 wt%. of chromium on the high-angle grain boundaries were formed chromium carbides type M 23 C 6 [6]. In the alloy Ni-38Cr-1Mo having a larger amount of chromium the grain-boundary processes were developed more intensively. Further increase in amount of chromium (alloy Ni-39Cr-1Mo) is even more intensified phase transformation at grain boundaries. There were formed the plates of M 23 C 6 carbides and the plates of α - phase that is the beginning of discontinuous disintegration. Apparently due to the chemical no uniformity the phase decomposition at the grain boundaries occurs uneven. On some sections of the grain boundaries were formed carbides M 23 C 6 ; on the others - there was the beginning of discontinuous disintegration. V. P. Kolotushkin and A. A. Parfenov 146 Figure 22. Tweed contrast in the alloy Ni-42Cr-1Mo: a) after quenching, b) after quenching and annealing at 450°С, 9 000 h. Figure 23. Structure of grain boundaries in alloys of Ni-Cr-Mo after annealing at 450°С, 40 000 h. In the alloy Ni-41Cr-1Mo at the grain boundaries is observed occasional precipitation of carbides M 23 C 6 and plates α - phase. Increasing the chromium content to 43 wt% leads at 450°C to intensive phase decomposition of frontier regions of the alloy Ni-43Cr-1Mo emitting chromium-rich particles. There is the development of discontinuous disintegration and precipitation of carbides M 23 C 6 . In the alloys with more than 43 wt% chromium the discontinuous disintegration covers most of the grain body. Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 147 Fine structure of alloys at long (40 000 h) annealing varies in accordance with the equilibrium phase diagram. Fig. 24 shows that in the alloy near the stoichiometric composition at 450°C for 40 000 h were formed Ni 2 Cr domains of superstructure with a concentration > 7x10 21 m -3 and the size of 4 - 10 nm. In the electron diffraction pattern in addition to the matrix reflections are present reflections from the superstructure, in the light of which was shown dark-field image of long-range ordering domains. Long-range order develops in the whole volume of the matrix. In the alloy Ni-38Cr-1Mo concentration and size of the domains of the superstructure constitute respectively 1.2x10 23 m -3 and 1-2 nm. Closer to the grain boundaries, on which is allocated the phase based on chromium, the amount of long-range ordering domains more, and their concentration is lower ( d ≥2 nm, ρ = 5x10 22 m -3 . The smaller size of the long-range order domains, which according to their size have been called "nanodomains", in the alloy Ni- 38Cr-1Mo, apparently due to lower nickel content. Figure 24. Structure of the alloys Ni-Cr-Mo (32, 38 and 39 wt% Cr) after annealing at 450°С, 40 000 h. With increasing chromium content up to ~ 39 wt% intensity of superstructure precipitation is reduced (Fig. 24). In the matrix of the alloy Ni-39Cr-1Mo, as in the matrix of alloy Ni-38Cr-1Mo homogeneous nucleation of superstructure nanodomains Ni 2 Cr occurs. Their concentration and size constitute are 1.4x10 23 m -3 and 1-2 nm, respectively. The parameters of phases after the aging at 450°C show that increase in the chromium content with increasing distance from the stoichiometric gradually lowers the amount of long- range ordering superstructure. The intensity of the reflections from the superstructure Ni 2 Cr V. P. Kolotushkin and A. A. Parfenov 148 nanodomains in the electron diffraction patterns decreases. And finally, in the alloy with content of chromium ∼ 41 wt% during aging at 450°C appears to be formed only the short- range order. Reflections from the superstructure Ni 2 Cr nanodomains in the electron diffraction patterns of the alloy Ni-41Cr-1Mo did not detected (Fig. 25). In such a way, in the fine structure of the alloy with 41 wt% of chromium after the prolonged aging at 450°C occurs only the short-range order, phase transitions are not observed. In the kinetics of transformation of the solid solution of the alloy Ni-44Cr-1Mo at 450°C was clearly demonstrated the effect of chromium. At the grain boundaries were formed the fields of discontinuous decomposition (Fig. 25) size up to 5 microns. The precipitation of chromium carbides M 23 C 6 was observed at grain boundaries. In the alloys with 43 and especially 44 wt% chromium the discontinuous disintegration with the formation of α - phase of chromium in the form of plates occurs very rapidly, at the same time due to of enrichment in nickel the matrix adjacent to the - α phase domains forms large domains of the superstructure Ni 2 Cr. The domains of superstructure have a size of 2 nm far away from grain boundaries to 70 nm closer to precipitates, which are enriched with chromium. Figure 25. Structure of the alloys Ni-Cr-Mo (41, 43 and 44 wt% Cr) after annealing at 450°С, 40 000 h. An important feature of the restructuring of the atoms of nickel and chromium at the long range ordering of FCC solid solution by type Ni 2 Cr lies in the fact that after formation of a superstructure Ni 2 Cr the slip planes {111} become structurally not equivalent. The Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 149 arrangement of atoms in the two systems {111} planes corresponds to planes of type I (Fig. 26), in two other systems - planes of type II. Figure 26. Location of atoms in different planes {111} of superstructure Ni 2 Cr [8]. Another important aspect in the formation of domains and the nucleation of the superstructure nanodomains is a distortion of values of the matrix lattice parameters. In the crystal lattice of the matrix (Fig. 27) the lattice parameters in the directions [110] [111] increase while in the directions [311] and [331] decrease as compared with the original cubic lattice parameters. At the same time in the crystal lattice of the matrix appear tetragonal distortions. Figure 27. The unit cell of superstructure Ni 2 Cr in the fcc lattice based on nickel [15]. The crystal lattice spacings of experienced alloys of the system Ni-Cr calculated from the reflections [111] and [331] are shown in Fig. 28. It is seen that the lattice spacings of all the alloys determined from the reflection of [111] is greater, as well from reflection of [331] - smaller than the spacing of the original cubic lattice а cube (Table 8). V. P. Kolotushkin and A. A. Parfenov 150 Figure 28. The lattice spacings of Ni-Cr alloys after aging at 450°C, 40 000 h, calculated from the main reflections (111) and (331). The values of changes of the matrix lattice parameters for different basic reflections compared with the parameters of the original cubic lattice, also shown in Table 8. Table 8. Changes in the lattice parameters of Ni-Cr alloys as a result of short-and long- range ordering during annealing 450°C, 40 000 h Alloys Changes of lattice parameters upon annealing (d 450 - d cube )/ d 450 , % The lattice period of initial alloys а cube (nm) Δd 220 Δd 111 Δd 311 Δd 331 Ni-32Cr-1Mo +0.07 % +0.07 % -0.19 % -0.27 % 0.35726 Ni-38Cr-1Mo +0.11 % +0.11 % -0.14 % -0.11 % 0.35860 Ni-39Cr-1Mo +0.11 % +0.12 % -0.08 % -0.05 % 0.35888 Ni-41Cr-1Mo +0.04 % +0.21 % -0.05 % -0.05 % 0.35927 Ni-43Cr-1Mo +0.09 % +0.06 % -0.08 % -0.02 % 0.35948 Ni-44Cr-1Mo -0.03 % +0.03 % -0.08 % -0.05 % 0.36010 With the results of structural studies agree well the changes in the mechanical and physical properties of experimental alloys of the system Ni-Cr. So, the occurrence of tetragonal distortions in the solid solution due to the long-range order decreases the maximum impact strength in exactly those alloys in which there is the highest degree of long-range order - in the alloys with 35 and 48 at% chromium (Fig. 29). Fig. 29 also shows that when the aging time is ≤ 10 000 h the toughness of alloys with elevated chromium content (~ 43 and ~ 44 wt%) is higher than that in alloys with lower chromium content (~ 38 and ~ 39 wt%), but after exposure 40 000 h the situation is reverse. It is connected, apparently, with the formation the regions of long-range ordering around of precipitates the α - phase. Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 151 Figure 29. Dependence of impact strength Ni-Cr alloys from chromium content after annealing at 450°C [6]. Character of the electrical resistivity changes of the system Ni-Cr alloys also confirms the results of electron microscopic studies [16], which showed that the no equilibrium state of the system Ni-Cr alloys manifests itself during aging in different ways. If in the alloys with 32 and 44 wt% chromium at 450°C occur drastic structural changes, in the alloys with ∼ 41 wt% chrome like as if nothing happened. To elucidate the structural transformations have been conducted experimental determinations of the electrical resistivity of alloys in the initial state and after aging at 450°C for 4000, 10000 and 40000 h [17]. Electrical resistivity was measured at room temperature for the same samples before and after aging. The results of electrical resistance measurements are shown in Fig. 30. The analysis shows that the electrical resistivity is in good agreement with the structural features of alloys Ni-Cr-Mo. The higher after quenching in comparison with other alloys electrical resistivity of the alloy Ni-32Cr-1Mo is connected, apparently, with higher degree of short-range ordering. In accordance with this assumption in solid solution of the alloy Ni-32Cr-1Mo should be more pairs of unlike atoms after quenching than in the alloys with higher amounts of chromium. The significant and monotonic decrease in the electrical resistivity with increasing of aging time at 450°C of the alloy Ni-32Cr-1Mo is caused by increasing the long-range order extent in solid solution. V. P. Kolotushkin and A. A. Parfenov 152 Figure 30. Resistivity of alloys Ni-Cr-Mo after quenching and aging at 450°C [17]. As far as the distance from the stoichiometric Ni 2 Cr grows the character of electrical resistivity changes in the system Ni-Cr alloys is complicated by competition between short- and long-range ordering and discontinuous decomposition with the formation of α - phase. Long-range order of alloys with approaching to the boundary of the «cupola» of ordering in the process of aging is becoming less and less intensive, and in these alloys occurs only short- range order. In the alloys outside the "cupola" of ordering apparently due to the changes the mechanism of disintegration of solid solution, the course of the electrical resistivity curves is more complicated. A significant role in the changes of the electrical resistivity starts to play the decomposition. The elucidation more details of these changes is not the purpose of this study. One can only note a few facts. Reduction of resistivity in the alloys with higher chromium content is due to intensive precipitation α - phase and the subsequent nucleation of long-range order domains in interlamel space. Somewhat unexpected increase in the values of resistivity in the alloy Ni-44Cr-1Mo for the first 10 000 h of aging may be caused by short- range ordering connected with the intense precipitation α - phase. In further with increasing the aging time up to 40 000 h the resistance of the alloy Ni-44Cr-1Mo decreases during the formation of the Ni 2 Cr superstructure in the interlamel space. For further investigation, it should be noted that the degree of long-range order, which was estimated on the decrease of electrical resistivity, is minimal in the alloys, which are on the content of chromium are close to the right boundary of the "cupola" ordering on phase diagram of the system Ni-Cr. Significance and meaning of this phenomenon will be clarified during the discussion the results of further research. The changes of the electrical resistivity (Fig. 31) associated with structural changes at 450°C, are apparently caused by dependence of the electron density of the system Ni-Cr alloys from chromium content. In alloy, which is close to stoichiometric, electrical resistivity during the aging has dropped after 4 000 h of exposure due to long-range ordering. In alloys with higher chromium content character of changes of the electrical resistivity is more Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 153 complicated because it is influenced by several factors, in particular, the need a more prolonged exposure for the beginning of long-range ordering. Annealing time: ♦ - 4 000 h, ■ - 10 000 h, Δ - 40 000 h Figure 31. Relative change of alloys Ni-Cr-Mo resistivity after aging at 450°C. In the paper [18] have been suggested that the change in electrical resistance with the formation of alloys based on transition metals is determined by the redistribution of electrons between atoms. According to this hypothesis, the chromium atoms give a portion of their conduction electrons, which pass to d - subshells of nickel atoms. Such a transition should lead to an increase in the binding energy of atoms. During the short-range ordering in solid solution increases the number of pairs of unlike atoms. The free energy of the electron cloud decreases due to the transfer of electrons in a stable state, this is accompanied by the release of energy ΔH mix <0. Number of conduction electrons decreases, as well the electrical resistivity increases. If we increase the content of chromium in the alloys, then due to increasing tendency of alloys to the disintegration with the formation of pairs of like atoms, the relative amount of chromium, transferred their valence electrons to the nickel atoms is reduced. Accordingly, the number of conduction electrons increases as well the electrical resistivity of the alloy decreases. In the process of long-range ordering in solid solution alloys Ni-Cr-Mo is formed not a pairs of Ni-Cr, but superstructure, based on its triad of Ni-Ni-Cr. In this case, the number of atoms of chromium, referred from solid solution to the superstructure is less than during the formation of short-range ordering. In this case, respectively, the number of conduction electrons increases and the electrical resistivity of alloys decrease. V. P. Kolotushkin and A. A. Parfenov 154 Decrease in the electrical resistivity due to aging at 450°C for 40 000 h was found in all the experimental alloys Ni-Cr-Mo, but the minimum relative change in the electrical resistivity occurs in alloys with chromium content in the interval ∼ 38 - 41 wt%. So the results of structural studies and the definition of the electrical resistivity showed in the good agreement with the hypothesis of exchange interaction of electrons of the nickel and chromium atoms the minimum relative structural and physical changes in alloys with chromium content in the interval ∼ 38 - 41 wt%. 3.2.3. Crystal Lattice Distortions and Recombination of Point Defects Since the purpose of this study is to understand the role of changes in the structure in improving of radiation resistance of materials, as well as the causes and mechanisms that cause such an increase it is necessary to clarify the changes of physical properties with the peculiarities which arise with rearrangement of atoms in the crystal lattice. The appearance of tetragonal distortions in the crystal lattice of the Ni-Cr alloys in the process of prolonged annealing at 450°C have been reliably confirmed by X-ray studies of structure and measuring the density of alloys. First of all, it was found that the absolute values of the lattice constant in all the alloys after annealing at 300° C have higher values than after aging at 450° C (Fig. 32 [8]). This means that in all the studied alloys of the system Ni-Cr, which more or less display a tendency to short-range ordering and long-range ordering in the process of the formation of order there is a decrease of the atomic volume or the lattice contraction. The difference of the lattice periods after annealing at 300 and 450° C is maximal for close-stoichiometric alloys and decreases with increasing chromium content up to ∼ 42 at%. ▲ - matrix, aging at 300 °C; ◆,■ - the matrix, aging at 450 °C; × - superstructure Ni 2 Cr Figure 32. The lattice periods of alloys Ni-Cr-Mo. Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 155 Aging at 300°C for 40 000 h of studied alloys Ni-Cr-Mo, as was shown in [3, 6], practically does not change their phase composition as compared to the state after quenching. Was found only the initial γ - phase. However, in the solid solution of alloys, apparently in connection with the annealing of quenched vacancies, there were the signs of short-range ordering [8], as indicated by the comparison of the Bragg peaks (331) for the alloy Ni-41Cr- 1Mo at two temperatures (Fig. 33). It is seen that the lattice parameter of the alloy as a result of short-range ordering at 450°C decreased Δd/d ≈ (4x10 -4 ) and the width of the reflections increased (∼ 20 %). Qualitatively such changes manifest themselves in all other samples. Figure 33. Comparison of the alloy Ni-41Cr-1Mo (331) reflections after annealing at 300 and 450°C, 40 000 h. The lattice compression was also discovered [19] by hydrostatic weighing in water with preliminary evacuation the air, thermostatting, and with correction for buoyant force of the suspension and the temperature correction to the density of water. The total error of determining the density is ± 0,01 g/cm 3 . The density of experimental alloys after quenching and after prolonged aging was determined (Table 9). In the alloys with chromium content from 41 to 44 wt% the density increase due to short- and long range ordering was compensated by its decrease due to precipitation of α - phase. Effect of annealing temperature on the density is observed more clearly in alloys with 32 and 39 wt% Cr (Table 9). In the Ni-32Cr-1Mo alloy located near the stoichiometric phase Ni 2 Cr the raising of annealing temperature from 300 to 450°C led to a significant increase in density due to the formation of a superstructure Ni 2 Cr. In the alloys with 43 and especially 44 wt% chromium discontinuous disintegration of solid solution occurs at the grain boundaries. At the first stage of disintegration in some parts of the grain boundaries there is a formation of α - phase in the form of plates. The plates of α - phase are formed to the discontinuous disintegration cell. The formation of cells occurs very rapidly, and in adjacent with plates of α - phase enriched by nickel interlamel space the particles of phase Ni 2 Cr are formed. V. P. Kolotushkin and A. A. Parfenov 156 Table 9. Density of Ni-Cr alloys after annealing at 300-450°C, 40 000 h Alloys Annealing temperature, °С Sample Weight in air (g) Alloy density ρ (g/cm 3 ) Никель - - 8.91 Хром - - 7.20 Ni-32Cr-1Mo 300 0.47505 8.22 400 1.15615 8.23 450 0.58670 8.34 Ni-39Cr-1Mo 300 0.58625 8.09 400 0.59115 8.11 450 0.45520 8.13 Ni-41Cr-1Mo 300 0.36330 8.08 400 0.95355 8.02 450 0.52045 8.00 Ni-44Cr-1Mo 400 0.45730 7.99 450 0.44530 8.00 Increasing the chromium content from ~ 32 to ~ 44 wt% in the investigated alloys is accompanied during annealing at 300 and 450° C uniform increasing in the lattice parameter (Fig. 32. An increase the parameter is accompanied by decrease in the density because the density of chromium less than the density of nickel (Table 9), and the size of chromium atom by about 2.4 % larger than the size of the nickel atom. Figure 34. Dependence of relative changes in density and lattice constants of alloys Ni-Cr-Mo on the content of chromium with increasing aging temperature from 300 to 450°C, 40 000 h. With increasing chromium content from about 32 to ∼ 41 wt% the propensity of alloys Ni-Cr-Mo to long range ordering decreases [3, 6, 8]. Simultaneously with the decrease in the Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 157 propensity to long range ordering increases the propensity to the disintegration of solid solution with the formation of α - phase. Character of change in the lattice parameter and the density of alloys Ni-Cr-Mo with aging (Fig. 34) confirm these trends. The increase in the density (Δρ > 0) due to the formation of long-range ordering domains, with increasing chromium content decreases and becomes minimum at short-range order alloys. Since the beginning of the selection α - phase the density become lower than the initial (Δρ <0). At the simultaneous formation of discontinuous disintegration cells and concomitant formation of long-range ordering domains in the transition from ordering to disintegration region in which long-range order does not occur, i.e. stage of short-range ordering is not transferred to the stage of the long-range ordering the change in density close to zero. Thus, the chromium content in the range ~ 39 - 41 wt% for alloys of Ni-Cr at ∼ 450°C is a transition or critical. Within this interval, at reasonable times of aging there is only short- range ordering. In the microstructure of these alloys is observed only diffraction tweed contrast which is evidence of short-range order. At this stage, oscillation period of the fragments of contrast, i.e. zones of enrichment and depletion of nickel in the matrix is ∼ 5 nm. It is known that in solid solutions, whose formation is accompanied by the increase in the number of unlike pairs of atoms, i.e. ordering, there is the release of heat (negative deviations from Raoult's law). In solid solutions whose formation is accompanied by a decrease in the number of unlike pairs i.e. disintegration of solid solutions, there is the heat absorption (positive deviations from Raoult's law). For this reason, the enthalpy of mixing H mix is sometimes called the enthalpy of ordering if it is negative or enthalpy of decomposition if it is positive. In the critical range of the chromium content the enthalpy of mixing H mix should be close to zero. The aging process at a temperature of ~ 450°C in alloys with chromium content ~ 39 - 41 wt% stops at the stage of formation of crystalline domains size ∼ 2.5 nm i.e. at the stage that is intermediate between the homogeneous and micro domain short-range order. This step should be to call, according to the size of areas, "nanodomain short-range order". A characteristic feature of the nanodomain short-range order is close to zero enthalpy of mixing H mix . The nanodomain short-range order should have a positive impact on improving the radiation resistance of alloys by increasing the recombination of vacancies and interstitials in the border zones of the nanodomains. This also implies that with a glance the heterogeneity of chemical composition, the alloys in the concentration range of ~ 39-41 wt% chromium are in a no equilibrium metastable state. Solid solution of these alloys has the concentration and density of components fluctuations, availability and the development of which is crucial for increasing radiation resistance of materials. To determine the effect of short-and long-range order on the recombination of point defects was conducted 5 MeV electron irradiation [20] of nickel alloy with 32 wt% chromium in the states after quenching (short-range order) and after annealing at 450°C for 40 000 h (long-range order). In analyzing the structure was used the method of positron annihilation by measuring the angular distribution of annihilation photons. Changes in the shape of the spectra due to the capture of positrons by defects were characterized by standard S - and W - parameters. S - and W - parameters were determined as the ratio of the coincidence rate sum in the angle range of θ from 0 to 3.5 mrad and 10 to 20 mrad to the total rate of coincidences, respectively. When positrons are trapped by vacancy-type defects or dislocations, the value of V. P. Kolotushkin and A. A. Parfenov 158 S - parameter increases and W decreases, i.e. increases the probability of annihilation of positrons with conduction electrons, and decreases the probability of annihilation with the electrons of the ion core. Fig. 35 shows the dependence of parameter S, proportional to the number of vacancies in the matrix of the irradiated alloy from the electron fluence. ○ - long-range ordering ■ - short-range ordering [20] Figure 35. Effect of short-and long-range ordering on the accumulation of vacancies in the irradiated at 200° C 5 MeV electrons alloy Ni-32Cr-1Mo: It is seen that with increasing electron fluence the number of vacancies in which the positrons annihilate is increased. However for the alloy in a state of short range ordering at a fluence of ~ 2x10 22 m -2 the growth of S - parameter is slowing, and the values of S - parameters reach saturation. This means that the emerging vacancies during irradiation of the alloy in a state of short-range ordering recombine with the interstitial atoms. At the same time for the alloy in a state of long-range ordering the growth of values S - parameter at irradiation continues, i.e. vacancies in the matrix continues to accumulate. This experiment shows that the tetragonal distortions that occur in the matrix during the formation of short-range order nanodomains are effective traps for point defects. From this experiment should also be an important conclusion: when the alloy is given in a stable state, for example by long-range ordering, the alloy can not provide the high recombination of vacancies and interstitials. At the same time the recombination accelerating of vacancies and interstitials is observed, as determined by the study of experienced Ni-Cr alloys in no equilibrium metastable alloys, removed from the composition of the stoichiometric phase Ni 2 Cr and having approximately the same inclination as to ordering and to phase separation, i.e. near to zero enthalpy of mixing of solid solution. Due to nonstoichiometric of composition and near- Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 159 zero enthalpy of mixing in the structure of these alloys during neutron irradiation does not occur long-range ordering and is observed only short-range order. Study of physical mechanisms of radiation damage of materials and the ways of increasing resistance to embrittlement and swelling is the most important problem of radiation material science, and in this regard, understanding of dependence the recombination of point defects on the effects of short-range ordering is of considerable interest. In the process of the study of ordering alloys of system Ni-Cr with near-zero enthalpy of mixing was found that their evolution during neutron irradiation is stopped at the stage of formation of tweed contrast with the period of oscillation of zones nickel enriched ∼ 5 nm. It is known that due to the high surface energy such small particles have high catalytic activity [21]. The number of constituent atoms in an isolated metal particle is small, so the distance between the energy levels of electrons δ = E F /N (E F — Fermi energy, N — the number of atoms in a particle) comparable to the thermal energy k B Т. Activity of small metal particles begins to appear when δ in size close to k B Т. This allows us to estimate the size for which show catalytic properties of the particle. In accordance with the algorithm proposed in [22], were determined for metals used in nuclear industry (Table 10), parameters for calculating the number of atoms in a particle: the number of electrons in 1см 3 A Z n m ρ 24 10 6022 , 0 ⋅ = (1), where Z - number of conduction electrons, ρ m - bulk density (g/cm 3 ), А - relative atomic mass; radius of a sphere whose volume is equal to the amount paid for a conduction electron 3 1 4 3 ⎟ ⎠ ⎞ ⎜ ⎝ ⎛ = n r S π (2) and the Fermi energy of metals ( ) 2 0 1 , 50 a r эВ E S F = (3), where а 0 - Bohr radius = 0.529 Å. Table 10. Initial data for calculating the number of atoms in the particle [9] Element Z ρ (g/cm 3 ) n, 10 22 cm -3 r s , Å r s / а 0 Е F , eV Ti 2 4.51 11.34 1.28 2.42 8.55 V 2 6.1 14.42 1.18 2.23 10,07 Cr 1 7.19 8.33 1.42 2.68 6.98 Fe 2 7.87 16.97 1.12 2.12 11.15 Ni 2 8.9 18.26 1.09 2.06 11.81 V. P. Kolotushkin and A. A. Parfenov 160 Calculating the number of atoms N = E F /k B T in the isolated metal particle from the atoms of transition elements gives, in accordance with the Fermi energy, defined by (3), the values shown in Table 11. Table 11. Assessment of the number of atoms for some transition metals in accordance with the catalytic activity The number of atoms in a particle (at temperature*, °C), = E F / k B T Temperature* 20 100 200 300 400 500 600 700 800 E l e m e n t Ti 342 267 214 174 147 128 114 102 93 V 423 330 264 216 182 158 141 126 115 Cr 279 218 174 142 120 104 93 83 76 Fe 446 348 279 228 192 166 149 133 121 Ni 472 369 295 241 204 176 157 141 128 With such quantity of the atoms a linear particle size is 2 - 4 nm and, therefore, in this size range should significantly change the physical and the catalytic properties of small particles of these atoms. The evaluation shows that short-range order nanodomains with an average size ∼ 2 -3 nm formed in alloys of nickel and chromium under irradiation with neutrons are the particle of size at which is actively manifest catalytic properties. Short-range order nanodomains form homogeneously distributed in the matrix system or a sub lattice of the catalytically active sites that interact with vacancies and interstitials. With the linear size of the nanodomains ∼ 2 - 3 nm, the number of the atoms in them in the system Ni-Cr amounts 150 - 250 for a temperature of 600 K [9]. One can assume that consolidation of point defects in the zone of influence of nanodomains short-range ordering is an effective factor in the recombination accelerating and increasing radiation resistance of the alloys. 4. DISCUSSION: SELF-ORGANIZATION OF THE NANOCRYSTALLINE STRUCTURE OF TRANSITION METALS Now back to the unusual results of the experiment on neutron irradiation, in which was discovered a more long incubation period to maintain a stable structure of the alloy Ni-42Cr- 1Mo compared with other materials. On the diagram state of the system Ni-Cr figurative point of radiation-resistant alloy Ni-42Cr-1Mo is located in the region of metastable alloys, which have enthalpy of mixing close to zero (H mix ∼ 0). Due to this the alloy Ni-42Cr-1Mo affects only short-range order during prolonged radiation and thermal aging. Less radiation resistant alloy Ni-47Cr-1Mo alloy lies in the region of alloys which subjected to discontinuous disintegration at exposed to prolonged thermal aging and therefore in conditions of the reactor are more inclined to transition to stable structural condition. Over the stabilization of the structure there should be accelerated accumulation of dislocation loops. Mechanism of the recombination accelerating in alloys of system Ni-Cr of type Ni-42Cr- 1Mo with near-zero enthalpy of mixing is as follows. In the alloys with the structure of short- range order (38 - 41 wt% Cr) the changes in the displacement cascade of the composition of Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 161 matrix entails the formation of the local areas short-range ordering. If in the local region begins short-range ordering, then the adjacent areas of the matrix are enriched with chromium. In the chromium-enriched areas begins to form discontinuous disintegration. In this case, the surrounding matrix is enriched with nickel. In these areas begins to form short- range ordering, etc. Short-range ordering and the short-range disintegration help each other, and the as a result no one phase is not formed, which corresponds to the spinodal condition. This mechanism suggests that the processes in the metastable structure, leading to the appearance of nuclei of new phases are competing. However, it seems obvious that if for the nucleation of short-range order is necessary only tendency to minimize of the system free energy, for the formation of clusters should be further upward diffusion. From this point of view, the formation of clusters (zones of Guinier - Preston) are less likely than the emergence of short-range order nanodomains, since during the nucleation of short-range order nanodomains the energy gain will be greater.. However, the tetragonal distortions move over the matrix due to the fact that in the displacement cascades the formed nanodomains of short-range ordering and disintegration are destroyed and re-formed in another place. As a result of differences in lattice constant and the density of the FCC phase and the nanodomains short-range order in the alloys appear the mobile local distortions that significantly accelerate the recombination of the surrounding radiation-induced point defects. Ordered arrangement of the short-range order nanodomains with an interval of ∼ 5 nm allows evaluate them as an ordered structure of traps of vacancies and interstitials. The short-range order nanodomains form crystalline structure, but do not have time to form long-range order domains of the superstructure due to failure in displacement cascades and the near-zero enthalpy of mixing. During the formation of nanodomains the surrounding volume is depleted with one of the components, creating a periodic change in chemical composition. Such zones are constantly shuffled and placed on a matrix, which ultimately ensures the presence of traps and recombination of point defects in any point of the matrix, where the formation of displacement cascade would not have happened with the corresponding appearance of an excess concentration of vacancies and interstitials. In these processes, the dynamic equilibrium of ordering and disordering is the decisive factor that controls the structural transformations. Such is the concept of maximal radiation resistance of the metastable alloys. It is known that in the presence of distortions in the crystal lattice the interstitial atoms tend to get into the stretched spaces, and vacancies on the contrary, in tight. Therefore, existing and emerging after quenching and aging in the alloys Ni-Cr-Mo fluctuations of concentration and density represent a system or sub lattice of short-range order nanodomains - traps for vacancies and interstitials. In the process of neutron irradiation the primary knocked atoms destroy the integrity of the nanodomains, takes place a process similar to hardening of the alloy - there is a local disordering. Alloy tends to decrease the free energy and again is locally ordered; then again in the displacement cascade is destroyed etc. Thus, the behavior of the atomic structure of the alloy under neutron irradiation becomes in the local points the character of the continuous reversible change from ordering to disordering and vice versa, i.e. the character of dynamic equilibrium. The orientation and shift of the dynamic equilibrium of the metastable alloy in the direction of the order or disorder is determined by the alloy composition, i.e. electron density V. P. Kolotushkin and A. A. Parfenov 162 and other physical characteristics, as well as the parameters of an open system. With the change in the physical characteristics of the alloy appears to be changed the effectiveness of interaction of vacancies and interstitials with the crystal lattice. We can assume that the rate of ordering of the alloy must be equal to the rate of disorder in the neutron field or be a few below it. Such a preponderance of the rate of disorder in the neutron field is required in order to prevent the transformation of the metastable solid solution through the ordering in the stable. Calculating the number of displaced atoms in the dislocation loops according to the formula N=0,141d 2 ρ, where d - the average size of dislocation loops, ρ - the average concentration showed: in the alloy Ni-42Cr-1Mo after neutron irradiation dose of ~ 32 dpa the number of displaced atoms in the loops, i.e. the number of the not recombined interstitials was approximately two times less than in the alloy Ni-47Cr-1Mo. One can with certainty assume that the advantages of alloys of Ni-42Cr-1Mo, as a stable during neutron irradiation material, are based on the metastability of the structure derived from a tendency to short-range order. The above analysis also suggests that the development of the traps associated with the short-range ordering nanodomains, is the most effective mechanism for improving radiation resistance at temperature of 350°C. Thus, the analysis of the results of neutron and electron irradiation clearly demonstrates that the alloys in a metastable state having a tendency to the short-range order much more slowly accumulate radiation damages compared to the more stable alloys in the state of long- range ordering, and especially in comparison with the austenitic steels. The obtained experimental facts indicate that in assessing the number of secondary radiation defects must be taken into account as the conditions for the appearance of point defects and the effectiveness of the conditions for their recombination. The higher the rate of the creation the displacements in the core, the greater number of vacancies and interstitials per unit of time are created in the crystal lattice of the alloy. And, in its turn, the higher the rate of ordering of the structure, the greater amount of point defects recombines in a time unit. The equality of these rates will provide the dynamic equilibrium of the structure during neutron irradiation. The analysis of own and literature data shows that the established mechanism of accelerated recombination of point defects is effective not only in radiation-resistant alloys system of Ni-Cr, but also in the alloys with the others system components. The use of radiation-resistant alloys of different systems is predetermined by operating temperature range in which in structure of the alloy are formed the short-range order nanodomains. Different classes of materials of active zones have the different temperature ranges of use. For example, alloys based on nickel-chromium are suitable to ∼ 400°C, iron-based alloys with the chromium - approximately 550°C. At higher temperatures, are perspective ternary alloys based on vanadium with titanium and chromium, which can provide a more stringent operating conditions arising from the 2 - 3-fold reduce the amount of the core of fast reactors per unit of installed capacity. Thus in accordance with the proposed phenomenological model the alloys that are resistant to neutron irradiation in a specific temperature range necessary to select in the range of compositions with the enthalpy of mixing, which is close to zero. This implies that the alloys have the metastable structure of short-range ordering and about the same penchant for Self-Organization of the Nanocrystalline Structure and Radiation Resistance … 163 ordering and phase separation, i.e. structure that as the swing periodically inclined then to ordering then to the disintegration. The distinctive feature of short-range ordering nanodomains as the traps for vacancies and interstitials is that they are formed from atoms of the components of the matrix, however, such atoms can be either in the a disordered state or in a state of short-range order. And the transition from one state to another in the open system of neutron irradiation is carried out continuously. Under the influence of the temperature the matrix is ordered, creating the traps and under the influence of the neutron flux - becomes disordered, losing the traps. And these "the swing" is working as long as the active zone works. This feature of the behavior of solid solution of the metastable alloys with the near-zero enthalpy of mixing we call "the self- organization of the nanocrystalline structure" of transition metal alloys under the influence of temperature and radiation. CONCLUSION The analysis of experimental results of the study the structure-phase state of the austenitic steels, nickel-based alloys after quenching and aging, neutron irradiation at temperatures of 300 - 350°C and by electrons with the 5 MeV allows us to make the following conclusions. 1) The formation in the solid solution of nickel-based alloys of the short-range order nanodomains as the traps of vacancies and interstitials with the period ∼ 5 nm and concentration ≥ 10 24 m -3 is the most effective way to ensure the radiation resistance. 2) The crystal structure of the short-range order nanodomains is formed in the process of the neutron irradiation under the influence of radiation enhanced temperature, while under the influence of irradiation is destroyed. 3) The effect of "the self-organization of the nanocrystalline structure" of alloys, inclined to short-range ordering during neutron irradiation consists in the permanent formation in the solid solution of the short-range order nanodomains, being destroyed in the displacement cascades. 4) In accordance with the proposed phenomenological model the alloys that are resistant to neutron irradiation in the specific temperature range should be selected in the range of compositions with the enthalpy of mixing which is close to zero. This implies that the alloys have the metastable structure of short-range order and about the same penchant to the ordering and phase separation. 5) A necessary condition for the minimal accumulation of secondary radiation-induced defects in the alloys is the lagging speed of short-range ordering from the rate of disorder in the neutron field, which prevents the formation of stable phases and the shift of the solid solution state to the stability. 6) The choice of alloy components with the metastable structure for the operation in conditions of specific open system should be determined by its parameters, that is the temperature and intensity of irradiation, as well as the relevant physical characteristics of the material. V. P. Kolotushkin and A. A. Parfenov 164 REFERENCES [1] S. N. Votinov, V. I. Prokhorov, and Z. E. Ostrovskii, Irradiated Stainless Steels (Nauka, Moscow, 1987) [in Russian]. [2] Russell K.C. //Acta Met. (1978). Vol. 26, 1615-1630. [3] V. P. Kolotushkin, //Fiz. Met. Metalloved. (2004) 97 (2), 63–73; Phys. Met. Metallogr. 97, 177–187 (2004)]. [4] H. Wollenberger //Journ. of Nucl. Mater. (1991) Vol. 179-181, Part 1, 76-80. [5] V. P. Kolotushkin and S. N. Votinov //Metalloved. Term. Obrab. Met. (2006) 10(616), 27–31. [6] V. P. Kolotushkin, V. P. Kondrat’ev, A. V. Laushkin, and V. N. Rechitskii //Metalloved. Term. Obrab. Met. (2003) 11, 7–10. [7] V. P. Kolotushkin, V. P. Kondrat’ev, and V. N. Rechitskii //Perspektivnye Materialy, (2004) 1, 36–45. [8] V. P. Kolotushkin, A. A. Chernyshev, and A. A. Veligzhanin //Materialovedenie, (2006) 1, 18–24. [9] V.P. Kolotushkin, A.A. Parfenov //Russian Metallurgy (Metally) (2010) 3, pp. 197– 206. [10] V. P. Kolotushkin and V. N. Rechitskii //Vopr. At. Nauki Tekh., Ser. Materialoved. Nov. Mater. (2004) 1(62), 131–138. [11] M. I. Solonin, V. P. Kondrat’ev, S. N. Votinov, V. N. Rechitskii, Yu. I. Kazennov, A. B. Alekseev, and V. P. Kolotushkin //Vopr. At. Nauki Tekh., Ser. Materialoved. Nov. Mater. (1995) 1 (52), 13–20. [12] G.N. Makarov //Uspekhi Fizicheskikh Nauk. (2008) 178, No 4, 337-376. [13] R.А. Andrievskii // Fiz. Met. Metalloved, (2010) 110, No 3, 243-254. [14] V. P. Kolotushkin, V. P. Kondrat’ev, A. V. Laushkin, and V. N. Rechitskii //Vopr. At. Nauki Tekh., Ser. Materialoved. Nov. Mater. (2005) 1(64), 348–353. [15] Yu. A. Bagaryatskii //Dokl. Akad. Nauk SSSR (1958) 122 (5), 806–809. [16] V. P. Kolotushkin, V. N. Rechitskii, O. B. Ermolova, and A. V. Laushkin //Vopr. At. Nauki Tekh., Ser. Materialoved. Nov. Mater. (2003) 1(61), 94–104. [17] S. N. Votinov and V. P. Kolotushkin //Metalloved. Term. Obrab. Met. (2006) 1(607), 33–37. [18] I. Ya. Dekhtyar //Dokl. Akad. Nauk SSSR (1952) 85 (3). [19] V. P. Kolotushkin, S. N. Votinov, and V. I. Sorkoin //Materialovedenie, (2007) 6(123), 40–46. [20] A.P. Druzhkov, V.P. Kolotushkin, V.L.Arbuzov et al. //The Physics of Metals and Metallography, (2006) 101, No. 4, 369-378. [21] A.I. Gusev. Nanomaterials, Nanostructures, and Nanotechnologies. – Moscow: FIZMATLIT, 2005. [22] N. Ashcroft and N. Mermin, Solid State Physics (Holt, New York, 1976; Mir, Moscow, 1979). In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 4 TRANSITION METAL COMPLEXES OF SCHIFF BASE LIGANDS OF 3-FORMYLSALICYLIC ACID: SYNTHETIC PATHWAYS AND USEFUL PROPERTIES Saikat Sarkar 1 and Kamalendu Dey 2 1 Department of Chemistry, Santipur College, Santipur, Nadia, West Bengal, India 2 Department of Cheistry, University of Kalyani, Kalyani, Nadia, West Bengal, India ABSTRACT The contributions of transition metal complexes of 3-formylsalicylic acid and varieties of Schiff base ligands based on it have been vividly reviewed and discussed. The mode of reactions along with the structural topologies with such variety of ligands having a wide range of donor atoms such as N, S, O, P are typically commented. The metal complexes of such ‘privileged ligands’ show many interesting polymeric / supramolecular coordination architectures involving different weak forces e.g. C-H….π, π….π etc. interactions. The synthesis and practical properties of the complexes of various nuclearities of the Schiff bases derived from 3-formylsalicylic acid with monoamines, diamines, polyamines and substituted amines are discussed systematically. Such transition metal coordination complexes, due to their intriguing topologies, have found their applications in magnetism, catalysis, biological activities, solid state properties, charge transfer and useful materials. A few non-transition metal complexes have also been disussed for comparison. 1 E-mail addresses:
[email protected] (S. Sarkar) 2 Email address:
[email protected] (K.Dey) Former Professor of Chemistry and UGC Emeritus Fellow. Saikat Sarkar and Kamalendu Dey 166 1. INTRODUCTION In 1864 Hugo Schiff [1] first described the reaction between an aldehyde and an amine lead to a condensation product called Schiff base according to his name. Modern chemists still prepare Schiff bases, and now-a-days active and well-designed Schiff bases are being prepared. Schiff bases may also act as ligands to form metal complexes coordinating metal centres through imine nitrogen(s) and other groups usually linked to aldehyde, and they can also stabilize them in various oxidation states, enabling the use of such complexes for a large variety of useful catalytic transformations and recently they are considered as “privileged ligands” [2]. Many simple organic aldehydes were used to react with variety of amines to produce a large number of Schiff base ligands. 3-Formylsalicylic acid (Figure 1.1), first synthesized by Duff and Bills [3], has been extensively utilized as an efficient precursor for the synthesis of numerous multidentate Schiff base ligands. 3-Formylsalicylic acid, itself, may also act as a ligand for the synthesis of many metal complexes. Figure 1.1. 2. METAL COMPLEXES OF 3-FORMYLSALICYLIC ACID 3-Formylsalicylic acid, owing to the presence of three different binding groups (viz. - COOH, -CHO and -OH) may act as monobasic bidentate (like salicylaldehyde), dibasic bidentate (like salicylic acid) or dibasic phenoxy oxygen bridged tridentate ligand [4-6]. Dey et al. [6] had synthesized anionic complexes of V(IV)O and V(V)O with H 2 fsa of the types (NH 4 ) 2 [VO(fsa) 2 ].2H 2 O and NH 4 [VO(fsa)(OH) 2 (H 2 O)]. The IR spectra [4,7] of the complexes suggest that both OH and COOH groups participate in chelate formation after deprotonation and the ligand behaves as a dibasic bidentate fashion. The electronic spectra of the V(IV)O and V(V)O have been measured and compared with the previously reported low-symmetry oxovanadium complexes [8,9] of hydroxy acids. Qualitative band assignments suggest that the geometry of these V(IV)O and V(V)O complexes are intermediate between square pyramid and bi-pyramid. Binuclear Cu(II) complexes of the types Cu 2 Cl 2 (fsa)H 2 O, Cu 2 Cl 2 (Hfsa) 2 H 2 O, Cu 2 (CH 3 COO) 2 (Hfsa) 2 .H 2 O and Cu 2 (fsa) 2 .3H 2 O were prepared and characterized by Dey and coworkers [10]. Binuclear Ni(II) complexes of H 2 fsa are also known [11]. Encapsulation of metal complexes inside microporous supports has emerged as a general technique to increase and control selectivity of catalysis [12]. Zeolites can play as effective and attaractive supports for encapsulation as they are thermally and chemically stable having Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 167 a regular, crystalline framework. Besides, because of their similarities with the metalloenzymes, the encapsulated complexes are expected to mimic enzyme active site for catalytic reactions such as oxidation [13,14], hydrogenation [15], dehalogenation [16], etc. Considering the above characteristics Xavier et al. [17] synthesized and characterized Y zeolite encapsulated Co(II), Ni(II) and Cu(II) complexes of 3-formylsalicylic acid which were used as a novel solid catalysts for the partial oxidation of benzyl alcohol and ethyl benzene. Encapsulated Cu(II) complexe has been found to be more efficient than the other two complexes for the oxidation reaction. However, thorough investigations on the metal complexes of H 2 fsa are yet to be done. 3. METAL COMPLEXES OF LIGANDS DERIVED FROM 3-FORMYLSALICYLIC ACID The formyl group (-CHO) of H 2 fsa can easily be condensed with different monoamines, aminoalcohols, aminophenols, aminothiol, aminothiophenol, suphanilamides, diamines and polyamines leading to different types of Schiff bases. Most of these Schiff bases were synthesized and their versatility as ligands has been investigated over the past several years by different group of workers. The accounts of which are given below under appropriate headings covering the salient features of the topics. 3.1. Mono-, Bi- And Polynuclear Complexes of the Schiff Base Ligands Derived by the Condensation of 3-Formylsalicylic Acid with Monoamines, Aminoalcohols, Aminoacids, etc. Condensation reactions of appropriate amino compounds and 3-formylsalicylic acid (1:1 molar ratio) lead to the formation of corresponding Schiff base ligands (Scheme 1.1). Scheme 1.1. Saikat Sarkar and Kamalendu Dey 168 Depending on the nature of R, the Schiff base ligands can act as a monobasic bidentate (Figure 1.2), dibasic tridentate (Figure 1.3) and phenoxo-bridged dibasic tridentate (Figure 1.4) ligand. Most of the transition and non-transition metals form these types of complexes [18-23]. Figure 1.2. Figure 1.3. Figure 1.4. Magnetic moment values of the Fe(II) and Fe(III) complexes of H 2 fsaan and H 2 fsaana show that the complexes belong to the ionic or outer-level covalent category [7]. Some V(IV)O and V(V)O complexes of dibasic tridentate Schiff bases, H 3 fsagly and H 2 fsaana have also been prepared and characterized [9]. The complexes synthesized are of the types, [(Hfsagly)VO(H 2 O)], [(Hfsagly)VO(H 2 O)(Py)], [(Hfsaana)VO(H 2 O)], [(Hfsaana)VO(H 2 O) (OH)] and [(Hfsagly)VO(OH)] 2 . The structures of the complexes have been discussed on the basis of elemental analyses, magnetic moments and spectroscopic (IR, UV-Vis.) data. The V(IV)O complexes are paramagnetic with magnetic moment ranging from 1.77-1.81 B.M., which is close to the spin-only value of 1.73 B.M. for a d 1 system. A square-pyramidal geometry has been assigned to the [(Hfsagly)VO(H 2 O)] and [(Hfsaana)VO(H 2 O)] complexes and their electronic spectra are interpreted using the ordering of vanadium d orbitals, i.e. d xy <d xz , d yz <d x 2 -y 2 <d z 2 proposed by Vanquickenborne and McGlynn [11,24]. The other Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 169 complexes found to be diamagnetic. The electronic spectrum of the dimeric compound in nujol mull shows one broad band around 17000 cm -1 which may be considered as metal ligand charge transfer [18,25]. Dey et al. [10] reported the synthesis and characterization of Cu(II) complexes of H 2 fsama, H 2 fsaan and H 2 fsaeao. All of these complexes except one are binuclear with subnormal magnetic moments at room temperature. Using g av = 2.2 and a value of 6 x 10 6 c.g.s. units for TIP (temperature independent paramagnetism), the energy separation between singlet and triplet states, i.e. –2 J, have been calculated using Bleaney and Bowers equation [19,26] which support the occurrence of strong antiferromagnetic spin-exchange interaction between the two Cu(II) centres. Similar Cu(II) complexes have also been described by Tanaka et al. [11,27]. Sugar borne Schiff bases and their metal complexes can play wide variety of roles in different fields like, metal-base affinity chromatography materials [28], chiral homogeneous catalysts [29], metal chelators for clinical use [30], etc. Inspite of the above facts, the field of sugar-metal chemistry is still unexplored vividly. Keeping the facts in mind, Adam and Hall synthesized a new sugar containing Schiff base ligand and its Cu(II) complex [31]. Methyl 3,4,6-tri-o-actyl-2-amino-2-deoxy-β-D-glucopyranoside hydrobromide on condensation with H 2 fsa gives the Schiff base which on reaction with copper(II) acetate afforded Cu(II) complex in alcoholic solution. From detail study of mass spectrometry and ESR spectra it has been concluded that the complex has binuclear Cu(II) structure. The overall reactions are shown in Scheme 1.2. Scheme 1.2. Saikat Sarkar and Kamalendu Dey 170 Other complexes of this type with first and second row transition metal ions have also been synthesized. Some boron derivatives of this ligand are also known [32]. Amine containing polysaccharides on reaction with such aldehydes also produce Schiff base which on treatment with the metal salts also give metal complexes [33]. 3-Formylsalicylic acid (H 2 fsa) on reaction with 2-aminothiophenol in methanol yielded benzothiazoline [34-36], (H 2 chpbzn) which remains in equilibrium with its corresponding Schiff base form, H 3 mpcsalim, in solution (Figure 1.5). However, in the solid state the benzothiazoline structure has been suggested from the infrared spectroscopic data. The absence of ν CHO , ν C=N and ν SH at 1660 cm -1 , ~1600 cm -1 and ~2600 cm -1 respectively support the benzothiazoline structure [37]. Figure 1.5. Some complexes of Cu(II), Ni(II), Zn(II), Pd(II) and U(VI)O 2 have been synthesized by the treatment of the benzothiazoline solution with the corresponding metal salts [34]. In these complexes, the Schiff base actually functions as a tridentate NSO donor ligand. Based on physico-chemical data the authors proposed following monomeric structures for Zn(II) and U(VI)O 2 complexes (Figure 1.6) but sulphur-bridged dimeric structures for Cu(II), Ni(II) and Pd(II) complexes (Figure 1.7) [34]. Crystallographic studies of such complexes will be of much interest. Figure 1.6. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 171 Figure 1.7. Scheme 1.3. Scheme 1.4. Recently Dey et al. synthesized many new metal complexes and organometallic compounds by the reaction of benzothiazoline (H 2 chpbzn) with (π-C 5 H 5 ) 2 TiCl 2 , (π-C- 5 H 5 ) 2 ZrCl 2 , CrCl 3 .6H 2 O, FeCl 3 , VOSO 4 .2H 2 O, VOCl 3 , Ni(OAc) 2 .4H 2 O, Na 2 PdCl 4 , Me 2 TlCl, Ph 2 TlCl, BiCl 3 and SbCl 3 under varied reaction conditions [36]. During complexation, the Saikat Sarkar and Kamalendu Dey 172 Schiff base (H 3 mpcsalim) involves in its dianionic form utilizing NSO donor set of atoms, except in case of Bi(III) and Sb(III), where the benzothiazoline acts as a unidentate neutral N- donor ligand. Such Lewis basic behaviour of benzothiazoline is very rarely encountered in literature [35,38-40]. The reactions are summarized in the Schemes 1.3-1.5. Scheme 1.5. Scheme 1.6. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 173 As proposed by Nag et al. [34] sulphur-bridged dimeric structures have been proposed for Ni(II), Pd(II) and V(IV)O complexes. Corresponding molybdenum (III, IV, V, VI) complexes are also known [41]. The reaction of [(Hmpcsalim)Ti(π-C 5 H 5 ) 2 Cl] with Me 3 SiE (where E stands for SMe, NMe 2 , N 3 and C≡CPh) affording new organotitanium(IV) compounds have also been discussed (Scheme 1.6). Due to immense importance of benzothiazoline type of ligand in coordination chemistry, Dey and co-workers [42] have shown interest to synthesize a new benzothiazolidine compound and studied similar types of reactions with different metal salts. The reaction of 3- formylsalicylic acid with 2-aminoethanethiol produces the thiazolidine (H 2 chptz) compound which shares equilibrium in solution with its corresponding Schiff base form (H 3 mcsalim) (Figure 1.8). Figure 1.8. The reaction of this thiazolidine with Me 2 SnCl 2 is very interesting. It gives NSO chelated organotin(IV) compound having trigonal bipyramidal geometry (Figure 1.9). Similar type organotin(IV) complex with benzothiazoline (Figure 1.10) has also been reported. Figure 1.9. Saikat Sarkar and Kamalendu Dey 174 Figure 1.10. The 1 H NMR spectra of organotin(IV) complex [(Hmcsalim)SnMe 2 ] (Figure 1.9) displays the Sn-CH 3 protons as one sharp singlet at δ 0.89 ppm. The observed 3 J ( 119 Sn-CH 3 ), 2 J ( 117 Sn-CH 3 ) and 3 J ( 119 Sn-N=CH + ) values (74.5, 72.1, 38.8) respectively are within the ranges reported for other trigonal bipyramidal (CH 3 ) 2 Sn(IV) chelate complexes with two methyl groups in the cis-configuration [43]. The dimeric Cu(II) complex also draws our attention. The ESR data of the complex in polycrystalline and solution phase (DMF) at room temperature (300 K) exhibits four lines ( 63 Cu, I = 3/2) slightly anisotropic spectra at higher magnetic field. At liquid nitrogen temperature (77 K) the spectrum shows axial type with g ║ (2.280) and g ┴ (2.091) with respect to DPPH marker. The trend g ║ > g ┴ > g e (2.0048) suggests that the unpaired electron is localized in d x 2 -y 2 [44,45]. The cyclic voltammogram (CV) of the Cu(II) complex exhibits one quasi-reversible redox couple at E 1/2 = 0.16 V (∆E p = 150 mv) and an irreversible peak at 0.8 V vs. SCE. First response is reductive due to Cu II → Cu I and the second one is oxidative Cu II → Cu III . Dey et al. [46] very recently synthesized a new hydrazone ligand, 3-carboxy-2- hydroxybenzaldehydemorpholine N-thiohydrazone (H 2 chbmth) by the condensation of H 2 fsa and morpholine N-thiohydrazide (Hmth) and studied its reactions with 3d and 4d transition metal salts. The thiohydrazone ligand remained as thioketo form in the solid state. However, in solution, thioketo and small amount of thiolo tautomeric forms (H 2 chbmth and H 3 chbmthol respectively) may remain in equilibrium (Figure 1.11). Depending on the pH’s of the reaction medium and the nature of the metal salts used, the ligand is found to act as monobasic tridentate, dibasic tridentate, monobasic bidentate and neutral bidentate fashion. Figure 1.11. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 175 The dimeric Cu(II) complex, [Cu(Hchbmthol)] 2 (scheme 1.7) is found to show low magnetic moment (1.44 B.M.) which might be due to spin-coupling resulting from super exchange through the bridging sulphur (oxygen) atom or metal-metal bonding as observed earlier on similar such complexes [47-49]. The decrease in the magnetic moment with the decrease in the temperature indicates the presence of antiferromagnetic coupling between the two centres. Scheme 1.7. Using the idea of an easy route for the synthesis of immobilized transition metal complexes by the reaction of polymer-anchored ligand with metal ions, recently, Syamal et al. [50,51] have reported the synthesis and characterization of Cu(II), Ni(II), Co(II), Fe(III), Zn(II), Cd(II), Mn(II), Mo(VI), Zr(IV) and U(VI)O 2 complexes of polystyrene supported resin containing Schiff base derived by the reaction of chloromethylated polystyrene, 3- formylsalicylic acid and ethanolamine (Scheme 1.8). The reaction of PS-Cl and H 2 fsa in 1:4 molar ratio leads to the 100 % conversion to PS- FSal, which does not contain any chlorine. But the same reaction in the ratio 1:<4 always resulted the product containing chlorine. These types of polymer-assisted complexes might have wide range of applications [52-54] based on their physico-chemical properties. The same group of workers extended their idea to synthesize polystyrene-anchored mixed Schiff bases and their coordination complexes [55,56,57] in view of their numerous applications in organic synthesis [58], biological systems [53], catalysis [59] and analytical chemistry [60]. They designed the mixed Schiff base having H 2 fsa as one component fixed which are shown in Scheme 1.9. Scheme 1.8. Saikat Sarkar and Kamalendu Dey 176 Scheme 1.9. The Maurya group of researchers also synthesized many polymer bound Schiff base metal complexes and studied their immense catalytic applications [61-64]. Schiff bases have been derived by the condensation reaction of 3-formylsalicylic acid with 2-aminoethanol, 3- aminoethanol, 2-amino-2-methylpropanol, β-alanine, D,L -alanine, L -isoleucine and o- hydroxybenzylamine. Then, the polymer bound oxovanadium, oxomolybdenum and copper complexes have been synthesized, characterized and employed as efficient catalysts in various oxidation reactions. The recycling studies also indicated the reusability of such catalysts for atleast three times without any significant loss in their potential catalytic activity. Recent research of Maurya et al. has shown a new gateway for the desulfurization of various organo-sulfur compounds to their corresponding sulfones using polymer bound oxovanadium(IV) and oxovanadium(V) complexes [65]. The desulfurization process is deadly required in petroleum industry. The general mechanism (Scheme 1.10) of oxidation has also been proposed based on UV-Vis, EPR, 51 V NMR and DFT study. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 177 Scheme 1.10. Scheme 1.11. The immobilization of H 2 fsa on the surface of amino group containing silica gel phases and the use of such phases for the extraction of different metal ions from aqueous solution using batch equilibrium has been reported by Mahmoud et al. [66,67]. The synthesis of silica gel bound H 2 fsa has been shown in the Scheme 1.11. The selectivity of the different phases is evaluated by atomic absorption spectroscopy and found with highest exchange capacity of 0.95-0.96 mmol/g for Fe(III) ion. A method for the recycling of immobilized silica gel after metal extraction has also been demonstrated for practical utility. Saikat Sarkar and Kamalendu Dey 178 The synthesis and reactivity of a Cu(II) complex of N-4-acetophenyl-3-carboxy- salicylaldimines (Figure 1.12) has been studied [68] to build up a hierarchy for similar type metal complexes of N-substituted salicylaldimine. Figure 1.12. Further condensation of the ketone parts of the Schiff base and its Cu(II) complex generates new ketimine center which leads to transamination reaction. The reaction involves exchange of amine parts in the Schiff bases with the added amines and in situ complexation of the freshly generated Schiff bases with Cu(II) ion present in solution. Mononuclear complexes of Co(II), Ni(II) and Cu(II) with the Schiff base derived from H 2 fsa and hydroxylamine hydrochloride have been characterized by infrared spectra, thermal analysis and molar conductance studies [69]. The Co(II) and Cu(II) complexes are found to be paramagnetic while Ni(II) exhibits diamagnetism. The Schiff base ligand formed by the condensation of H 2 fsa and 2- (aminomethyl)pyridine have been first investigated by Coppola et al. [70] by fast atom bombardment mass spectrometry and metastable ion studies. Monomeric [Cu(Hfsagly)].2H 2 O and trimeric [Cu 3 (fsagly) 2 ].6H 2 O are prepared by the reaction of CuCl 2 .2H 2 O, H 2 fsa, gycine and Na 2 CO 3 in Cu: H 3 fsagly as 1:1 and 2:1 ratio respectively. The spectroscopic (IR, UV-Vis.) and magnetic studies proposed the trimeric Cu(II) complex as [Cu(H 2 O) 6 ][Cu 2 (fsagly) 2 ] with uncoordinated glycinato ‘O’. A strong antiferromagnetic coupling is observed in [Cu 2 (fsagly) 2 ] 2- unit with J = -185 cm -1 [71]. The coordination chemistry of alkaline earth metals with such ligands received far less attention than that with transition metal ions. Keeping this in view Erxleben and co-workers [72,73] tried to synthesize Mg (3s 2 ) complex with the Schiff base ligand, H 3 fsagly. The Mg(II) complex is prepared by the substitution reaction of the corresponding Zn(II) complex in DMSO. It is found that Zn(II) is susceptible to substitution by Mg(II) when DMSO is used as the non-aqueous solvent. But the presence of small amount of water decrease the yield of the Mg-complex mainly owing to the high affinity of Mg(II) for aqua ligand. The whole observation (Scheme 1.12) has been monitored by 1 H NMR spectroscopy. Presently the homo- and heteropolymetallic complexes are of much interest due to their unique physico-chemical properties associated with metal-metal interactions [74,75]. Several synthetic routes have been proposed for their synthesis, one being consists of the ingenious use of compartmental ligands. The newly synthesized unsymmetrical polydentate Schiff base, 3-[N-2-(pyridylether)fomimidoyl]salicylic acid (H 2 fsapea), derived by the reaction of H 2 fsa and 2-(2-aminoethyl)pyridine in ethanol in 1:1 molar ratio, belonging to this compartmental behaviour category, is used to synthesize a series of bi-[76-79] and tri-nuclear [77,78] Cu(II) complexes. The 3d-4f hexanuclear cluster compounds [76] are also cited using dinuclear species as precursor. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 179 Scheme 1.12. In all these complexes ligand utilizes two different adjacent coordination sites, N 2 O and O 2 and favours the formation of polymetallic systems containing phenoxo groups as exogenous bridges. Variable temperature magnetic susceptibility measurements for the chloro- bridged dicopper complex, [Cu(Hpefdsa) 2 Cl 2 ], show the presence of very weak ferromagnetic coupling between the Cu(II) ions with J = 0.15 cm -1 . But the antiferromagnetic coupling between the two Cu(II) centres is observed in [Cu 2 (pefdsa) 2 ] (J = -617 cm -1 ) and trimeric Cu(II) complex [Cu 3 (pefdsa) 2 ](ClO 4 ) 2 with J = -228 cm -1 . The Scheme 1.13 shows synthetic routes for preparation of some of the bi- and tri-nuclear complexes. But to explain the magnetic behaviour of the hexanuclear clusters {Cu 4 Ln 2 }, the clusters may be taken as two individual {Cu II Ln III Cu II } triads. A weak antiferromagnetic Cu(II)-Cu(II) interaction through the closed shell rare earth ion is noticed for {Cu 4 La 2 } complex having J CuCu = -3.13 cm -1 . Inspite of antiferromagnetic coupling, the {Cu 4 Gd 2 } complex shows ferromagnetic Gd(III)-Cu(II) interaction with J GdCu = 6.0 cm -1 , which is attributed to the coupling between the Gd(III)Cu(II) ground configuration and the Gd(III)Cu(II) charge- transfer excited configuration in which the electron is transferred from the slightly occupied 3d type copper orbital towards an empty 5d type gadolinium orbital. The Gd(III)-Cu(II) interaction is quite peculiar in the sense that owing to the contraction of 4f orbitals, the usual mechanisms involving 4f-3d overlap densities are inoperative [76,77]. In this connection the work of Tuna et al. [79] may be mentioned, who for the first time reported a pentanuclear complex of {Cu II Cu II Mn II Cu II Cu II } moiety with the ligand H 2 fsapea having novel magnetic properties. The IR spectrum of the complex shows two bands at 1564 and 1439 cm -1 , attributed to the ν COO stretching modes, which are characteristic of the bridging carboxylate groups. The variable temperature magnetic susceptibility measurements indicate the presence of antiferromagnetic interactions within the {Cu II Cu II Mn II Cu II Cu II } pentanuclear entity. The bridging capability of the phenolic oxygen between the Cu(II) and Mn(II) ions in {Cu 4 Mn} system might be responsible for the most probable exchange pathway for the antiferromagnetic coupling. On the basis of the above discussion and considering the electronic spectra the following structure for the pentanuclear complex may be proposed (Figure 1.13). However, only x-ray structure can say the last word. Saikat Sarkar and Kamalendu Dey 180 Scheme 1.13. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 181 Figure 1.13. In continuation of this study, a new oxalato bridged dinuclear Cu(II) complex of the same ligand, H 2 fsapea (Figure 1.14), and phenolato bridged dinuclear Cu(II) complex of the ligand derived from H 2 fsa and N,N-dimethyl-1,3-propanediamine (Figure 1.15) has been reported [80]. Both the complexes are crystallographically characterized and show strong antiferromagnetic coupling interaction between the two Cu(II) centres. Figure 1.14. Figure 1.15. Two dinuclear Zn(II) complexes (Figure 1.16) of unsymmetrical binucleating Schiff base ligand 3-{N-[2-(dimethylamino)ethyl]iminomethyl}salicylic acid (H 2 fsadmen) (Figure 1.17) have been synthesized by the reaction of ZnX 2 (X = NO 3 - , CH 3 COO - ) with H 2 fsa and N,N- Saikat Sarkar and Kamalendu Dey 182 dimethylethylenediamine at neutral or slightly acidic pH [81]. In the nitrate complex, [Zn 2 (Hfsadmen) 2 (H 2 O) 2 ](NO 3 ) 2 .2H 2 O the centrosymmetric Zn(II) ions are bridged by two phenolato oxygens. Further coordination sites of the ligand are the imine nitrogen and carboxylate oxygen, while the amino nitrogens of the ligand side arms are protonated. The basic structure of the acetato analogue, [Zn 2 (Hfsadmen) 2 (CH 3 COO) 2 ].6H 2 O is identical to that of nitrate complex except the water ligands coordinated to Zn(II) ions in the former have been replaced by acetate ion in the later. Figure 1.16. Figure 1.17. On dissolution in DMSO or DMF these dizinc complexes are converted into mononuclear species [Zn(Hfsadmen)] + and the cleavage is accompanied by migration of the ammonium proton to the carboxylate group and coordination of the amino nitrogen to zinc. Reaction of [Zn 2 (Hfsadmen) 2 (CH 3 COO) 2 ].6H 2 O with 1(N) NaOH at pH 9.9 produces yellow cubes of tetranuclear zinc complex, [Zn 4 (fsadmen) 4 ].6.5H 2 O that is found to show asymmetry in coordination around the four zinc centres having N 2 O 3 and N 2 O 4 coordination environments and located at the corners of a nearly square-planar rectangle. In contrast to H 2 fsadmen the Schiff base 3-[N-(2-pyridylmethyl)iminomethyl]-salicylic acid (H 2 fsapma) (Figure 1.18) (formed by H 2 fsa and 2-picolylamine) forms the mononuclear complex with zinc in acid medium (Figure 1.19). The ligand H 2 fsapma bind Zn(II) via Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 183 deprotonated phenolic oxygen, the imine nitrogen and pyridine nitrogen while the carboxylate group remains free. Figure 1.18. Figure 1.19. When a solution of the above zinc complex is brought to pH 8.9 with 0.5(N) NaOH, deprotonation of the carboxyl (-COOH) group results to form a tetranuclear compound [Zn 4 (fsapma) 4 ].4.5H 2 O with a cubane like {Zn 4 (o-phenolato) 4 } core situated around a crystallographic two-fold axis of symmetry. Two tetranuclear Cu(II) assembly complexes comprised of one dimetallic di(3- iminomethylsalicylato)dicopper(II) core and two monometallic Cu(II) auxiliaries attached to the imino nitrogens of the dinuclear core through an alkane chain have been reported [82]. The synthetic route to the preparation is shown by the Scheme 1.14. One Cu(II) complex, [Cu 4 (LigA)](PF 6 ) 4 .2CH 3 CN.3H 2 O has one di(2-pyridylethyl)amine copper(II) as the monometallic auxiliary and the other Cu(II) complex [Cu 4 (LigB)](ClO 4 ) 4 .CH 3 OH has 1,4,8,11-tetraazacyclotetradecanecopper(II) as the monometallic auxiliary. The cryomagnetic property suggests that the bimetallic core and the monometallic auxiliaries are magnetically independent of each other, and a strong antiferromagnetic interaction operates within the bimetallic core to achieve a perfect coupling above 100 K. This is also supported by the previous magnetic studies of the similar complexes [83]. [Cu 4 (LigA)](PF 6 ) 4 .2CH 3 CN.3H 2 O in acetonitrile shows a two-electron reduction at –0.08 V (vs. SCE) followed by a one electron reduction at –0.42 V. Together with EPR studies for electrolyzed solutions, it is shown that the two monometallic auxiliaries are reduced at –0.08 V, followed by an intramolecular electron transfer from one of the reduced auxiliaries to the bimetallic core and by the second reduction at the resulting monometallic Cu(II) centre at – 0.42 V: {Cu(II)-Cu 2 (II,II)-Cu(II)}/ {Cu(I)-Cu 2 (II,II)-Cu(I)}→{Cu(I)-Cu 2 (I,II)-Cu(II)}/ Saikat Sarkar and Kamalendu Dey 184 {Cu(I)-Cu 2 (I,II)-Cu(I)}. The cyclic voltammogram (CV) of [Cu 4 (LigB)](ClO 4 ) 4 .CH 3 OH in DMSO shows two couples at–0.68 and –0.99 V attributable to the stepwise reduction: {Cu(II)-Cu 2 (II,II)-Cu(II)}/{Cu(II)-Cu 2 (I,II)-Cu(II)}/{Cu(I)-Cu 2 (I,II)-Cu(I)}. The tetranuclear complex, [Cu 4 (LigA)](PF 6 ) 4 is reduced with ascorbic acid to {Cu(I)-Cu 2 (I,II)-Cu(I)} species, whereas [Cu 4 (LigB)](ClO 4 ) 4 does not undergo reduction with ascorbic acid. Scheme 1.14. The syntheses and structure determination of mixed valence pentanuclear manganese complex [{Mn II Mn III (fsatren)} 2 Mn II (H 2 O) 4 ].n(sol) where, H 6 fsatren is tris-[(2-hydroxy-3- carboxybenzylidene)aminoethyl]amine and ‘sol’ is H 2 O or MeOH and hexanuclear cobalt complex [Co 4 II Co 2 III (fsaea) 2 (OMe) 4 (NO 3 ) 2 (OAc) 2 (MeOH) 2 ] where, H 3 fsaea is 3-[N-(2- hydroxyethyl)formimidoyl]salicylaldehyde by T. Shiga and H. Oshio is also worth mentioning [84]. It is clear from the crystal structure that [Mn 3 II Mn 2 III ] complex has a linear pentanuclear core bridged by phenoxo and carboxyl group and [Co 4 II Co 2 III ] complex has a Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 185 face shared incomplete tetra cubane core bridged by μ 3 -MeO - , phenoxo, alkoxo and carboxyl groups. An antiferromagnetic interaction between the Mn(II) ions in [Mn 3 II Mn 2 III ] complex and a ferromagnetic interaction between Co(II) ions in [Co 4 II Co 2 III ] complex have been proved by magnetic susceptibility studies. The structures of both the complexes are show below (Figure 1.20). Figure 1.20. The technique ‘complex as a ligand’ was also successfully used by R-J. Tao et al. [85] to synthesize a 1D chain coordination polymer having chemical formula {[Cu 4 L 2 (H 2 O)].H 2 O} n where, H 4 L is 2-hydroxy-3-[(E)-({2-[(2-hydroxybenzoyl)imino]ethyl}imono)methyl]benzoic acid. The polymer has been synthesized by the assembly reaction of precursor complex K 2 CuL. 1.5 H 2 O and Cu(CH 3 COO) 2 . H 2 O in 1:1 molar ratio. The x-ray crystal structure has shown that the polymeric chain structure has been formed by dissymmetrical tetranuclear units and the Cu-Cu antiferromagnetic interactions have also been observed. Double stranded monohelical complexes with exclusive M-helicity of divalent iron, nickel, cobalt and zinc have been synthesized from an unsymmetrical chiral Schiff base ligand, prepared by a two-step reaction of 3-formylsalicylic acid and (1R, 2R)- diaminocyclohexane in alcoholic solvents [86]. The 1:1 condensation product was shown to exist as a zwitterion in the solid state having pleated weak hydrogen bonding interactions. The chiral ligand behaves as a monobasic tridentate donor system having carboxylic acid group remains free in all the complexes. But the same ligand reacts in distinctly different way to bind with divalent copper, in which the ligand was shown to be transformed into a symmetric tetradentate ‘salen’ type ligand with uncoordinated carboxylic acid groups. Another most interesting diazine tetratopic helicand ligand (H 4 L) was synthesized by the condensation of 3-formylsalicylic acid and hydrazine and the ligand was used to synthesize a novel chiral coordination polymer which was built up from tetranuclear helicates connected by Na ions [87]. The anionic helicates results from the self-assembly process involving the heterotopic helicand and Co(II) and Fe(III) ions. It was reported that the tetratopic helicand offers two different types of binding domains: one with only oxygen donor atoms and the other one with N and O donor atoms. The two metal ions were connected by the phenoxo bridging oxygen atoms which belong to the two chelating moieties and the oxygen of the carboxyl group helps to build the helical motif through subsequent coordination to a third Saikat Sarkar and Kamalendu Dey 186 metal ion. The crystal structure of the coordination polymer shows that the polymer consists of triple-stranded dianionic helicates, [L 3 Co 2 II Fe 2 III ] 2- , and the three ligands twisted along N-N single bonds. The variable temperature magnetic moment values indicate the spin states of different metals ions. The perspective view [Figure 1.21 (a)] and the space-filling representation [Figure 1.21 (b)] of the coordination polymer with M helicity is shown below. Figure 1.21. 3.2. Binuclear Complexes of 3-Formylsalicylic Acid Oxime Metal condensed compounds are of much interest due to their physico-chemical properties arise from the interaction of the metal centres in close proximity. Generally complex ligands having one or more sites capable of donating other metal ions are used to synthesize metal-condensed compounds. Complex ligands with cis-dioximate groups within the molecular framework are of particular interest [88-99] because the dioximate-bridge is known as a good magnetic mediator between a pair of metal ions. 3-Formylsalicylic acid oxime (H 3 fsaox) is obtained [100] by the reaction of 3- formylsalicylic acid and hydroxylamine hydrochloride in presence of NaHCO 3 . The ligand H 3 fsaox on reaction with Cu(II) and Ni(II) salts gives the following binuclear complexes [Cu 2 (Hfsaox) 2 ]0.5H 2 O, Na[Cu 2 (Hfsaox)(fsaox)].3H 2 O, [Ni 2 (Hfsaox) 2 ].2.5H 2 O, [Ni 2 (Hfsaox) 2 (H 2 O) 4 ].8H 2 O. The x-ray structure shows that Na[Cu 2 (Hfsaox)(fsaox)].3H 2 O has a cis-arrangement of the two ligands providing dissimilar {CuN 2 O 2 } and {CuO 4 } chromophores sharing the two phenolic oxygen atoms. The N 2 O 2 cavity has a hydrogen- bonded N-O …. H …. O-N linkage as the lateral chain and the Cu(II) in this site has a square- Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 187 pyramidal geometry with a water molecule at the axial site. The Cu(II) at O 4 cavity has a planar geometry. [Ni 2 (Hfsaox) 2 ].2.5H 2 O has a trans- configuration with respect to its two ligands and each Ni(II) has a six-coordinate geometry with two H 2 O molecules at the axial sites. The interconversion among the dinuclear Cu(II) and Ni(II) complexes have been established by pH adjustment (Scheme 1.15 & 1.16). Scheme 1.15. Scheme 1.16. 3.3. Mononuclear Complexes of the Schiff Base Ligands Derived by the Condensation of 3-Formylsalicylic Acid with Diamines 3-Formylsalicylic acid (H 2 fsa) on reaction with diamines in 2:1 molar ratio produces different types of Schiff base ligands as shown in the Scheme 1.17. Saikat Sarkar and Kamalendu Dey 188 Scheme 1.17. These Schiff bases are capable of acting as dibasic tetradentate ligands having N 2 O 2 donor with –COOH groups being remained free in the complexes except in the complexes of U(VI)O 2 and Eu(III) ions. For these ions the ligands generally act as a tetrabasic tetradentate O 2 O 2 donor system. Such ligands form numerous numbers of mononuclear complexes with different transition, non-transition and lanthanide metal ions [101-117]. The corresponding disodium salt has also been reported [118]. The general structures have been shown below in the Figures 1.22-1.25. Figure 1.22. Figure 1.23. Figure 1.24. Figure 1.25. The complexes have been characterized by the help of elemental analyses, molecular weights, magnetic moments, and molar conductance, UV-Vis., IR, ESR, CD and 1 H NMR spectral data [119-156]. The x-ray crystal structures of some of the complexes have also been determined [157-160]. Mononuclear complexes of Cu(II), Ni(II) and U(VI)O 2 with the Schiff base, H 4 fsadmtp, derived by the condensation H 2 fsa and 1,5-diamino-3-thiapentane (dmtp) have been Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 189 synthesized and properly characterized. In the complexes, Ni(II) and Cu(II) lie in inner N 2 SO 2 site while U(VI)O 2 takes the outer O 2 O 2 site. It is interesting to mention here that Kahn and co-workers [161,162] studied some spin crossover, high-spin, low-spin Co(II) complexes with Schiff base derived from H 2 fsa and ethylenediamine (en). The magnetic behaviour of [Co(H 2 fsaen)L] [161,162] and [Co(H 2 fsaen)L 2 ] [161,163] species clearly suggests that, in both kinds of compounds, the lowest high-spin (S = 3/2) and low-spin (S = 1/2) states are very close in energy. Indeed, though the χ M .T products (χ M = molar magnetic susceptibility) related to [Co(H 2 fsaen)(EtOH)] and [Co(H 2 fsaen)(4-t-BuPy)] (where, 4-t-BuPy is 4-tert-butylpyridine) follow, in a wide temperature range, a Curie-law characteristic of low-spin form, the slight increase of χ M .T with temperature that is observed above ~200 K for the former complex and ~250 K for the later seems to indicate the beginning of an occupation of excited high-spin levels. Likewise in the six-fold coordinated complexes, the ligand field appeared to approximate the conditions suitable for the pairing of electrons: in [Co(H 2 fsaen)(3-MePy) 2 ], Co(II) is found to retain an essentially high-spin state from 300-4 K, while in [Co(H 2 fsaen)( Py) 2 ] and [Co(H 2 fsaen)(H 2 O)] it exhibited thermally induced quartet ↔ doublet spin transitions. It is worth nothing that these transitions are very abrupt, in contrast to the previously reported for other Co(II) complexes, which are generally of the continuous type [164-173]. Again Thuery and Zarembowitch show the influence of the apical Lewis bases on the spin state of the metal ion in order to forecast the nature of the L ligands that would likely to spin-crossover compounds [174]. The Co(II) complexes of the type [Co(H 2 fsaen)L n ] (where L is a substituted pyridine) shows a wide range of magnetic properties . The Five-coordinate (n =1) species with L = 2-MePy recognized a spin-quartet ground state, and its magnetic property was described using a rhombic spin Hamiltonian ((D 2 + 3E 2 ) 1/2 = 16.7 cm -1, g = 2.04) with additional temperature independent paramagnetism (N α = 211 x 10 -6 cm 3 mol -1 ). The L = 3-OHPy adduct has undergone a kinetically controlled S = 3/2 ↔ S = 1/2 crossover, while retaining an essentially high-spin character and the cobalt complex with L = 4-MePy is in the low-spin state even at room temperature. The six-coordinate species (n = 2) with L = 3-MePy, 3-NH 2 Py and 3,5-Me 2 Py present a predominant high-spin character. The effect of the nature of the apical ligands on the spin- state of Co(II) is discussed in terms of σ-donor ability, orientation of the pyridine ring and steric requirements [173,175-180]. Recently Tuna et al. [181] has reported a five-coordinate Co(II) complex containing a photosensitive ligand which displays a thermally-induced S = 1/2 ↔ S = 3/2 conversion at high temperature. The schematic representation of the preparation of the complex is shown (Scheme 1.18). The coordination of trans-1-(4-methylphenyl)-2-(4-pyridyl)ethene (t-MeSPy) is proved by electronic spectral data which corresponds to the t-MeSPy π-π* absorption in the room temperature around 315 nm (~31750 cm -1 ) [182,183]. Like other transition metal ions [112] a stable Hg(II) complex of the ligand H 4 fsapnol has been formed by the reaction of HgCl 2 solution with the corresponding Schiff base H 4 fsapnol. But the elemental anlyses show metal-ligand ratio as 2:1. This 2:1 complex, further on treatment with KI solution, a transient red colouration is formed which ultimately gives a greenish-yellow solution (with excess of KI solution) with the separation of a yellow crystalline compound, identified as [Hg(H 2 fsapnol)] [19]. Saikat Sarkar and Kamalendu Dey 190 Scheme 1.18. The above observation may be explained by assuming that each Schiff base molecule in these metal chelates is also associated with one HgCl radical by displacing a hydrogen atom in the free hydroxyl group. The Hg-O bond thus formed in the 2:1 complex is not so strong as Hg-N bond [184,185] and as such the (>CHO.HgCl) group may easily be effected by KI solution producing K 2 HgI 4 and [Hg(H 2 fsapnol)] (Scheme 1.19). Scheme 1.19. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 191 H 4 fsaen may act as compartmental ligand; the inner compartment consists of N 2 O 2 and outer compartment O 2 O 2 donor atoms. For transition elements it uses generally the inner N 2 O 2 coordination site while for lanthanoids (e.g. Eu(III)) it can form complexes using outer O 2 O 2 site [113,186]. Recently both Cu(II) and Eu(III) complexes have been investigated [186] by photo-acoustic (PA) and fluorescence spectroscopy. The ‘outside’ and ‘inside’ coordination sphere shows different ligand field strength. The emission spectrum of [Eu(H 2 fsaen)(H 2 O) 2 ]Cl.H 2 O (Figure 1.26) shows four characteristic emissions of Eu(III) (λ = 594, 614, 650 and 701 nm) attributable to the 5 D 0 to 7 F 1 , 7 F 2 , 7 F 3 and 7 F 4 transitions respectively. Figure 1.26. The Schiff bases derived from 3-formylsalicylic acid and diamines also formed heterochelates [106], involving quadridentate Schiff base ligands and bidentate ligands (L-L) of the type, [M(Lig)(L-L)] (where M = Co(III), Cr(III) or Mn(III) and L-L = acac - , gly - , etc.) (Scheme 1.20). The same workers also reported some mixed ligand complexes of Co(III) of the type [Co(H 2 fsaen)L 2 ]X.2H 2 O. All the mixed ligand complexes were characterized with the help of elemental analyses, molar conductances, magnetic moment values, UV-Vis., IR and 1 H NMR spectroscopic data [187-202]. From the above observations it may be concluded that the reaction of [Co(H 2 fsaen)] with bidentate chelating agents and oxygen to give Co(III) mixed ligand chelates in which the dibasic quadridentate Schiff base has been rearranged from a planar to a twisted conformation by the displacement of only one oxygen atom from equatorial plane to the planar isomer. The Schiff bases H 4 fsaen and H 4 fsatn do not give any mixed ligand complex with Co(II) ions, instead they produce square planar Co(II) chelates of the type Na 2 [Co(fsaen)] and Na 2 [Co(fsatn)] respectively. These compounds are characterized with help of elemental analyses, magnetic moment value and spectroscopic data [203-206]. Saikat Sarkar and Kamalendu Dey 192 Scheme 1.20. The Schiff bases have been employed to synthesize varieties of oxomolybdenum (V and VI) complexes. Detailed characterization data are also available [207-213]. Non-planar configurations of the quadridentate Schiff bases are also observed in the Mo(VI)O 2 complexes (Figure 1.27) as discussed above. Figure 1.27. The tendency of the group MoO 2 to assume a cis-configuration forced the essentially planar ligand to occupy the non-planar geometry. This aspect had been discussed earlier [209,214]. The 1 H NMR spectral data also support this view [209-214]. 3-Formylsalicylic acid (H 2 fsa), on treatement with boric acid, formed 3-formylsalicylato salt [215]. Thus the Schiff bases H 4 fsaen and H 4 fsatn yielded tri-coordinated boron complexes [216]. These complexes might have some importance in view of their industrial utility [217], biological uses [218] and activities [219-221]. The syntheses are depicted in the Scheme 1.21. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 193 Scheme 1.21. The compound as shown above is interesting in the sense that it has potentiality of being used as a precursor for further novel syntheses. Thus it smoothly reacts with Ph 2 BCl (1:1 molar ratio) in thf at around 5 o C in di-nitrogen atmosphere and yielded a new organo boron derivative (Scheme 1.22). Scheme 1.22. The compound on reaction with Ni(OAc) 2 .4H 2 O in thf at room temperature, yielded another novel organoboron derivative containing Ni(II) (Scheme 1.23). The study of the reaction of Ni(II) complex with lanthanide ions will be of much interest. Scheme 1.23. Saikat Sarkar and Kamalendu Dey 194 Analogously Pd(II) and Pt(II) derivatives were also synthesized [222]. The corresponding compound [Na(H 2 fsatn)B(OH) 2 ] had also been prepared (Figure 1.28). Figure 1.28. All these compounds are solid and coloured. They are stable in air and also in their solutions. However, the aqueous solutions of the complexes are hydrolysed on prolonged standing and the solution turned strongly basic probably due to liberation of NaOH upon hydrolysis. Scheme 1.24. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 195 Scheme 1.25. The low values of molar conductance for boron chelates in the solvents suggest their non- electrolytic nature. However, the conductance value in water, measured after 2 h of dissolution, increased sufficiently indicating thereby extensive hydrolysis. The electronic absorption spectral band positions and their molar extinction co-efficients, when compared with the spectra of the ligands, suggest for complex formation [220,223]. The complex [Ni(fsaen){B(OH) 2 BPh 2 }] is characterized with the help of elemental analyses, magnetic moment, UV-Vis., IR and 1 H NMR spectroscopic data [224-231]. Dey and Nandi [232] have successfully synthesized a new 1,2,3 trisubstituted benzene derivative by using mononuclear Ni(II) complex of the Schiff base ligand, H 4 fsaen. Here metal ions play the vital role in protecting the reactive groups. Dey et,al. [233,234] and Dilworth et al. [235] have synthesized lithio and silyl- derivatives of several quadridentate Schiff base ligands and also studied their reactions leading to new synthesis of coordination complexes, organo-derivatives of boron, titanium, zirconium, tin and organo-oxoderivatives of phosphorus (see later discussion). Saikat Sarkar and Kamalendu Dey 196 Lithio or silyl derivative of mononuclear complex, N,N'-ethylenebis{(3- carboxy)salicylideneiminato}nickel(II) is easily converted to different organic compounds and are shown in the following scheme (Scheme 1.24): The free carboxylic acid group of mononuclear complex [Ni(H 2 fsaen)] had also been converted to the corresponding acyl chloride functionality, which on Fridel-Craft acylation with suitable substrates followed by normal work-up produced different organic compounds which is shown in the Scheme 1.25. 3.4 Organoderivatives of the Schiff Base Ligands Derived From 3- Formylsalicylic Acid and Diamines Cobalt-carbon σ-bond [236,237] is found in vitamin B 12 -coenzyme. The Co(III) ion containing a coordinated carbanion [238] in such organometallic complexes stimulated the interests to synthesize and characterize a wide variety of organocobalt complexes with other ligands [239-242]. Organoderivatives of dibasic tetradentate ligand with different metal ions are also known [102,105]. Dey et al. synthesized organotin(IV) [102] and organocobalt(III) complexes [105] of dibasic tetradentate ligands H 4 fsaen and H 4 fsapnol having general formula shown below (Figure 1.29). Figure 1.29. The organoderivatives are hydrolyzed easily with aqueous mineral acids, and the light remarkably accelerates this. This ‘photo lability’ represents connection between the present complexes and that of the corrinoids [243,244]. All the diamagnetic Co(III) complexes are characterized by elemental analyses, thermogravimetric analysis, magnetic moments and spectroscopic (electronic and IR) data [102,105,245-247]. 3.5 Electrochemical Behaviour of the Complexes of Schiff Base Derived From 3-Formylsalicylic Acid and Diamine Complexes in which a ligand can bind two metal centres in close proximity are of much interest in particular in electrochemical field. Such complexes have attracted growing attention because of their ability to illuminate the redox properties of such complexes, which, for instance are connected with the function of metalloenzymes incorporating two metal ions in close proximity to the active site. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 197 The electrochemical behaviour of a series of mononuclear and dinuclear complexes of Ni(II), Cu(II) and U(VI)O 2 ions have been studied with the Schiff base H 4 fsaen. The hexadentate H 4 fsaen ligand has an outer O 2 O 2 and an inner N 2 O 2 coordination site. The redox properties of the metal ions in these two different and adjacent chambers have been investigated [248]. It is observed that the reduction of metal centre in the N 2 O 2 compartment is greater than that of in the O 2 O 2 compartment. The redox properties of such complexes have also been compared with the ligand H 4 aapen derived by the condensation of o-acetoacetylphenol and ethylenediamine and it has been seen that the H 4 fsaen complexes are in general easier to reduce than the corresponding H 4 aapen complex [249,250]. 3.6. Binuclear Complexes of the Schiff Base Ligands Derived from 3-Formylsalicylic Acid and Diamines The chemistry of polymetallic Schiff base complexes is subject of considerable interest. Ligands derived from the reaction of 3-formylsalicylic acid (H 2 fsa) and different diamines have one inner N 2 O 2 core and outer O 2 O 2 coordination site capable of binding two similar or dissimilar metal ions in these two closely placed chambers. Such homo- or heterobimetallic complexes are useful in homogeneous catalysis [251] and biochemical field [252,253], particularly in connection with metalloenzymes which involve two metal ions at their active site [254]. Specially, the recognition that super oxide dismutase [255] and cytochrome oxidase [256] contain two kinds of metal ions has stimulated an interest in heterodinuclear complexes. Two magnetic centres whenever brought into close proximity our natural inclination is to assume that, like bar magnets, they will arrange themselves so that they couple antiferromagnetically, and thus reduce the overall magnetism of the dimer. This spin- exchange phenomenon is thus common to such bimetallic complexes [74]. Another interest in heterodinuclear complexes is to find new reactivities or functions associated with such hetero centres where distinct features of the constituting metal ions are accumulated or amplified to give rise to unprecedented cooperative effects [257,258]. The potential of this polynuclear area can be gauged from the appearance of many reviews in the literature [259-261]. All these considerations have led the investigators to investigate the synthesis and characterization of polynuclear metal complexes with special emphasis on hetero-polynuclear complexes. The hydrolysis of bis(p-nitrophenyl phosphate) (BNPP) and p-nitrophenyl phosphate (NPP) was observed to be catalyzed by the heterodinuclear Cu(II)-La(III) complex in 50% aqueous DMSO at 35 °C [262]. It was also reported that the Cu(II)-La(III) complex exhibited a relatively higher catalytic function on NPP hydrolysis, while the hydrolysis of BNPP was slightly more efficient in the presence of mononuclear La(III) complex. The Schiff base H 4 fsaen and its homologous ligands having two dissimilar coordination sites, N 2 O 2 and O 2 O 2 can form dinuclear complexes [11,263-272] sharing the bridging phenolic oxygens [11,263]. When only transition metal ions participate in the heterodinuclear complex, then those transition metal ions, which are higher in the Irving-Williams order, occupy the N 2 O 2 site and those metal ions that are lower in that series occupy the outer O 2 O 2 site [265-272]. Further, during the synthesis of heterodinuclear complexes containing Saikat Sarkar and Kamalendu Dey 198 transitions metal ions and lanthanoids, the O 2 O 2 site prefer to bind with the lanthanoids [273,274]. The synthesis of Co-Ln [275] complexes (Ln = La, Nd or Gd) has been carried out by a step-wise reaction, that is mono-nuclear Co(II) complex is isolated as [Co(H 2 fsaen)(Py) 2 ] and subject to reaction with a Ln(III) ion. The Co(II)-Ln(III) complexes are [CoLa(fsaen)(CH 3 OH)(NO 3 )], [CoNd(fsaen)(H 2 O) 2 (NO 3 )], [CoGd(fsaen)(H 2 O)(NO 3 )]. In these complexes the cobalt ion is bound at the N 2 O 2 -site and the lanthanoid ion at the O 2 O 2 site. All these complexes are quite stable in air and fully characterized with the help of elemental analyses, molar conductivity, UV-Vis. and IR spectroscopic data [276-285]. At liquid nitrogen temperature the configuration around the cobalt is dependent upon the nature of the base. It is suggested that substrates possessing N- and O-donor groups such as 2- aminoethanol is specifically bind at the cobalt-lanthanoid centre via 'N' to the cobalt and 'O' to the lanthanoid ion. Cu(II) salts also give Cu(II)-Ln(III) hetero-binuclear complexes (Ln = La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb or Lu) with the Schiff base ligands such as H 4 fsaen and H 4 fsapn [273] . These complexes have also been fully characterized with the help of physico- chemical and spectroscopic data [27,286-292]. The frequencies of ligand field bands, due to Cu(II) ion bound to the N 2 O 2 site i.e. [CuN 2 O 2 ] chromophore, on forming a binuclear complex with a lanthanide ion at the coordination site O 2 O 2 , are higher than those of mono-nuclear complexes of Cu(II) with same ligand [263]. Such a blue shift of the d-d band may be attributed to the enhanced planarity of the [CuN 2 O 2 ] chromophore on forming a binuclear complex with a lanthanoid ion at the coordination site. When the complexes are dissolved in Py, DMSO or DMF, the d-d band frequency decreases in order of the solvent DMSO>DMF>Py for the binuclear complexes where- as it decreases in order of DMF>DMSO>Py for mononuclear complexes [273]. These trends is due to the different affinities of solvent molecules for Cu(II) and Ln(III) ions. The absorption spectra and circular dichroism (C.D.) spectra of Cu(II)-Gd(III) [282, 293] hetero-binuclear complexes suggest that substrates with a nitrogeneous and oxygeneous groups (amino alcohols, amino acids, 8-quinolinol, amino acid esters) were specifically bound to Cu(II)-Gd(III) centre, with the nitrogen to the copper and with the oxygen to the gadolinium. The V(IV)O also gives different binuclear complexes with rare earth(III) ions with the Schiff base ligand H 4 fsaen [294]. The general formula of these complexes is [VOLn(fsaen)(NO 3 )(H 2 O) n ](m-n)H 2 O. where Ln = La, Pr, Eu, Gd, Tb. The V(IV)O ion and Eu(III) ion in the respective mono-nuclear complexes is bound at the O 2 O 2 site of the ligand, where as in the V(IV)O-Ln(III) complexes V(IV)O ion is bound at the N 2 O 2 site and Ln(III) ion at the O 2 O 2 site because Ln(III) ion is more hard than V(IV)O ion, strongly prefers oxygen donor atoms. Dinuclear Cu(II)-M(II) (where M = Co, Ni, Cu, Zn, Mg, Ca and Ba) and Cu(II)-Fe(III) heterodinuclear complexes [287] of N,N'-bis(3-carboxysalicylidene)-1,1-dibenzyl- ethylenediamine, (H 4 fsadb) have been prepared and characterized [26,195, 264,265,269,295]. Other complexes of the series are also known. e.g. [CuM(fsadb].nH 2 O where M = Co, Ni, Cu, Zn, Mg, Ca, Ba and [CuFe(fsadb)].3/2H 2 O. The magnetic susceptibilities, measured in the temperature range 78-300K, indicate antiferromagnetic spin-exchange interactions operating Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 199 between metal ions. The Cu(II/I) redox potentials of the hetero metal complexes are much lower as compared to that of [Cu(H 2 fsadb)H 2 O]. The binucleating ligand H 4 fsaen has formed Cu(II)-Me 2 Sn(IV) and Co(II)-Me 2 Sn(IV) complexes of the type [MSn(CH 3 ) 2 (fsaen)] (M = Cu, Co), where the Cu(II) or Co(II) ion is bound at the inner N 2 O 2 site and the Sn(IV) ion at the outer O 2 O 2 site with two methyl groups at the axial positions. Both complexes are fairly stable towards atmospheric moisture in the solid state but decomposes into a mononuclear complex [M(H 2 fsaen)] by a trace amount of water when dissolved in solution. Spectroscopic investigations on the Cu-Sn complex in pyridine reveals that the coordination of pyridine to the Cu(II) is sterically hindered by the methyl groups attached to the neighbouring Sn(IV) ion. In the case of Co-Sn complex such a steric effect of methyl groups is not pronounced enough to hinder the coordination of pyridine to the axial site of the Co(II). ESR spectra at liquid nitrogen temperature reveals that the Co(II) ion adopts a penta-coordinate structure at room temperature and a hexa-coordinate structure near liquid nitrogen temperature with pyridine molecule at the axial site [296]. Recently a side-off septadentate Schiff base ligand has been synthesized by the reaction of H 2 fsa and bis(2-aminophenyl)disulphide (apds) [297]. Though the ligand contains eight donor atoms (N 2 S 2 O 4 ), it, however, acts as a septadentate side-off ligand leaving one disulphide sulphur atom. Thio-ether is not a good ligand to bind class ‘a’ metal ions [298] and in this ligand it is located in an internal position within the complexing side chains as shown in the Scheme 1.26. Scheme 1.26. This ligand forms several complexes with the inner N 2 SO 2 with copper ions and outer O 2 O 2 site having transition/non-transition metal ions. The dinuclear copper complex exhibits subnormal magnetic moment due to spin-exchange. The complexes have been characterized by the usual physico-chemical methods and the proposed structures are given in the Figures 1.30 to 1.32. Figure 1.30. Saikat Sarkar and Kamalendu Dey 200 Figure 1.31. Figure 1.32. Nag et al. [299] has also synthesized some mono and heterodinuclear transition metal complexes with a polydentate Schiff base ligand derived from H 2 fsa and 1,2-bis(o- aminophenylthio)ethane. The complexes [CoMn(fasen)(Py) 3 ], [CoMn(fsapn)(Py) 3 ] and [CoFe(fsapn)(Py) 3 ] [Figure 1.33] have been synthesized and characterized [268]. Cryomagnetic data indicate no spin- exchange interaction operating between the low-spin Co(II) and the high-spin Mn(II) or Fe(II) ions. Figure 1.33. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 201 Scheme1.27. Dey et al. have shown that [Ni(H 2 fsaen)] has been successfully silylated or lithiated [224] to get [Ni{(SiMe 3 ) 2 fsaen}] and [{(Li) 2 fsaen}] which in turn react with R 2 MX 2 (R = CH 3 , C 6 H 5 , π-C 5 H 5 ; M = Sn, Ti; X = Cl), R 2 BCl (R = C 6 H 5 ), RPCl 2 (R = CH 3 , C 6 H 5 ) and POCl 3 to yield the complex of the type [Ni(M) 2 R 2 fsaen], [Ni(BR 2 ) 2 fsaen], [Ni(PR)fsaen] and [Ni(POCl)fsaen] (Scheme 1.27). All the complexes have been properly characterized. Similarly mononuclear complexes of Ni(II), Pd(II) and Sn(IV) upon silylation coupled with desilylation and reaction with R 2 SnCl 2 afforded many new organotin(IV) complexes [300] (Figure 1.34). Figure 1.34. A magnetically important Cu(II)-V(IV)O heterodinuclear complex [CuVO(fsaen)CH 3 OH] has been synthesized and confirmed by molecular structure [301]. In this complex copper ion Saikat Sarkar and Kamalendu Dey 202 is five-fold coordinated to two nitrogens, two phenolic oxygens and the oxygen of methanol molecule and the vanadium ion is also five-fold coordinated to two phenolic oxygens, two carboxylic oxygens and the oxygen of the vanadyl group. The metallic ions and the oxygen of the methanol and of the vanadyl group are in a mirror plane σ for the two square-pyramids CuN 2 O 3 and VO 5 . These pyramids point in the same direction. The nature of intramolecular interaction has been explained easily by the orthogonality of the magnetic orbitals centered on Cu(II) and V(IV)O metallic ions, antisymmetric and symmetric respectively, with regard to mirror plane σ. The magnetic behaviour of the complex is studied in the temperature 4-300 K which reveals an intramolecular ferromagnetic coupling characterized by a ground triplet state separated by around J = 118 cm -1 from the excited singlet state. The magnitude of the ferromagnetic interaction is interpreted from considerations of overlap density between the magnetic orbitals (Figure 1.35). Figure 1.35. Casellato et al. has reported [302] the synthesis and characterization of a new heptadentate compartmental Schiff base ligand (H 4 fsadmtp) synthesized by the condensation of H 2 fsa and 1,5-diamino-3-thiapentane (dmtp) in methanol. The ligand contains an inner N 2 SO 2 and an outer O 2 O 2 sites and gives homo- and heterodinuclear complexes with Cu(II), Ni(II) and U(VI)O 2 . The syntheses of the complexes have been shown in the Scheme 1.28. Perovskite type oxides (La x MO y ) are known to be efficient in catalysis for oxidation reactions [303-307]. Initially, they have been synthesized by grinding a stoichiometric mixture of rare earth oxide and a metal oxide, and heating subsequently at 800-1000 ºC [308]. Unfortunately, this method generates highly heterogeneous solids with a poorly controlled stoichiometry. An improvement for the synthesis of such perovskite compounds has been observed by using the process of thermal decomposition of heterodinuclear complexes with Schiff base as a ligand [309]. Cations of the heterodinuclear complexes of the type [LaM(fsaen)]NO 3 .H 2 O (M = Ni(II), Co(II), Fe(II)) is first exchanged with the interlamellar cation of montmorillonite, and subsequent thermal decomposition of the derivative under oxygen at ca. 500-600 ºC produces a clay-perovskite oxide (La x MO y ) type nano-composite [310-312]. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 203 Scheme1.28. 3.7. Mono- and Binuclear Complexes of the Schiff Base Ligands Derived by the Condensation of 3-Formylsalicylic Acid with Polyamines Cassellato et al. [21,313] have reported the synthesis of some new potentially heptadentate compartmental ligands by the reaction of 3-formylsalicylic acid (H 2 fsa) with diethylenetriamine (H 4 fsadien) (Figure 1.36) or bis-3-aminopropylphenylphosphine (H 4 fsaappp) (Figure 1.37). Saikat Sarkar and Kamalendu Dey 204 Figure 1.36. Figure 1.37. Both the ligands form mononuclear, homo- and heterodinuclear complexes with some metal salts. The schematic representations of the preparation of such metal complexes with H 4 fsadien are given below (Scheme 1.29 & 1.30). The potentially heptadentate H 4 fsaappp ligand contains an inner N 2 O 2 P and outer O 2 O 2 coordination sites which can bind two similar or dissimilar metal ions in close proximity. This Schiff base ligand forms mononuclear complexes with Ni(II) while analogous compounds of Cu(II) and U(VI)O 2 are not formed. But in any case the binuclear species have been obtained. The structures of the homo- and heterodinuclear complexes are shown in Figures 1.38 and 1.39. Weak and strong antiferromagnetic spin-exchange has been observed in homodinuclear Ni 2 and Cu 2 complexes respectively. The homodinuclear Cu 2 complexes have also been employed in the oxidation of 3,5-di-t-butylcatechol (3,5-DTBC) to 3,5-di-t-butylquinone (3,5- DTBQ). The electrochemical behaviour of the homo- and heterodinuclear complexes has also been recorded. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 205 Scheme 1.29. Dey et al. [314] synthesized and studied some mononuclear complexes of some oxo- cations like U(VI)O 2 , V(IV)O and V(V)O with the Schiff base ligand H 4 fsadien. All the V(IV)O complexes are paramagnetic with the μ eff ranging from 1.67-1.73 B.M., which are quite close to spin-only value for one unpaired electron with no significant interaction between the neighbouring vanadium ions [315,316]. On the contrary V(V)O and U(VI)O 2 are found to be diamagnetic as expected for these ions having d 0 configuration [315,316]. Saikat Sarkar and Kamalendu Dey 206 Scheme 1.30. Figure 1.38. Figure 1.39. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 207 The U(VI)O 2 complex, [(H 4 fsadien)UO 2 (NO 3 ) 2 ] is non-conducting in DMSO (Λ M = 5.8 ohm -1 cm 2 mol -1 ) but on prolonged standing (about 3 days) the molar conductance value is increased and attained value of 58.5 ohm -1 cm 2 mol -1 . This is rationalized by the following equation and it shows the formation of a 1:2 electrolyte in solution. From these observations the structure of the V(IV)O and U(VI)O 2 complexes have been proposed as in Figures 1.40 and 1.41. Figure 1.40. Figure 1.41. Recently the same group of researchers thoroughly discussed the formation of mononuclear [317], homo- and heterodinuclear [318] complexes with the same Schiff base ligand H 4 fsadien. It has been observed that the reaction of H 4 fsadien with CoCl 2 .6H 2 O, Ni(OAc) 2 .4H 2 O, Cu(OAc) 2 .H 2 O, Zn(OAc) 2 .2H 2 O, Na 2 MoO 4 .2H 2 O, WO 2 (acac) 2 , (NH 4 ) 2 [MoOCl 5 ], (PyH) 2 [Mo(SCN) 6 ], FeSO 4 .7H 2 O and FeCl 3 .6H 2 O under varied reaction conditions led to the formation of mononuclear complexes. On the basis of elemental analyses, molecular weights, magnetic moment values, molar conductances and spectroscopic (IR, UV-Vis. and 1 H NMR) data the structure of the complexes of [(H 2 fsadien)M] has been proposed as shown in Figure 1.42. Figure 1.42. Saikat Sarkar and Kamalendu Dey 208 The presence of cis-MoO 2 /WO 2 moiety in the complexes [(H 2 fsadien)MoO 2 ] and [(H 2 fsadien)WO 2 ] (Figure 1.43) is confirmed by the presence of bands around 910-940 cm -1 and 900-930 cm -1 region respectively in the IR spectrum [319]. Figure 1.43. The formation of homo- and heterodinuclear complexes has been achieved by reacting the mononuclear Co(II) complex, [(H 2 fsadien)Co] as precursor with suitable metal salts. The silylation and lithiation of the complex [(H 2 fsadien)Co] having two free COOH groups with Me 3 SiCl or trimethylsilyl N,N / -diphenylurea (TDPU) and LiOH yielded disilylated and dilithiated product which then smoothly reacts with (π-C 5 H 5 ) 2 TiCl 2 , (π- C 5 H 5 ) 2 ZrCl 2 , Me 2 SnCl 2 , Ph 2 SnCl 2 and MX 2 .nH 2 O (where, M = Ni(II), Cu(II), Co(II), Pd(II), V(IV)O and X = Cl - or CH 3 COO - ) leading to the formation of some homo- and heterodinuclear complexes including some organo-derivatives. The reaction of H 4 fsadien with FeCl 3 .6H 2 O and Co(NO 3 ) 2 .6H 2 O in access of oxygen also yields diiron and dicobalt complexes. In all the mononuclear complexes the ligand functions either as dibasic tetradentate (N 2 O 2 donor) or pentadentate (N 3 O 2 donor) ligand. On the other hand, in the homo- and hetero-dinuclear complexes the ligand functions either as dibasic hexadentate (N 2 O 2 inner and O 2 O 2 outer compartment) ligand. The Scheme 1.31 shows the sequences of the reactions. Coordination supramolecules of Mn(II), Ni(II) and Cd(II) with a new symmetrical N 4 O 2 hexadentate Schiff base ligand has been reported by Sarkar et al. [320]. The hexadentate ligand was synthesized by the condensation of 3-formylsalicylic acid and triethylenetetramine in 2:1 molar ratio and the metal complexes was synthesized using in situ condensation reaction. The crystal structures shows that the 1D, 2D and 3D supramolecules have been formed by different weak force interactions like H-bonding, π….π stacking and C-H….π interactions. Solid-state properties (e.g. electrical conductivity at different temperatures and optical properties) of the Ni(II) and Mn(II) complexes have also been studied and depending on the temperature, the conductivity of the complexes is found to be insulating and semiconducting (intrinsic and extrinsic) in nature. The optical band gap (E gd ) of Mn(II) and Ni(II) complexes was found to be 2.57 and 2.30 eV, respectively. The representative 1D and Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 209 2D crystal structures and the perspective view of the Mn(II) complex are shown below [Figure 1.44, 1.45 and 1.46]. Scheme 1.31. Figure 1.44. Saikat Sarkar and Kamalendu Dey 210 Figure 1.45. Figure 1.46. Some other mononuclear transition and non-transition metal complexes have also been synthesized and reported by the same group of researchers [321]. The Schiff base ligand and most of the complexes have been screened in vitro to judge their antibacterial (Escherichia coli and Staphylococcus aureus) and antifungal (Aspergillus niger and Pencillium chrysogenum) activities and was found as efficient agent. ACKNOWLEDGMENT S.S. is thankful to UGC, ERO, Kolkata for providing financial assistance (No. F. PSW- 107/09-10 (ERO) dt. 08-10-09.) and K.D is thankful to the UGC, New Delhi for awarding Emeritus Fellowship and Financial grants. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 211 REFERENCES [1] H. Schiff, Ann. Suppl., 3 (1864) 343. [2] T.P. Yoon, E.N. Jacobsen, Science, 299 (2003) 1691. [3] J.C. Duff, E.J. Bills, J. Chem. Soc., (1932) 1987. [4] D.M.H. Bovey, E.R. Clark, J. Inorg. Nucl. Chem., 29 (1969) 755. [5] K. Dey, R.K. Maiti, Indian J. Chem., 14A (1976) 602. [6] K. Dey, R.K. Maiti, A.K. Sinha Roy, Indian J. Chem., 22A (1983) 580. [7] M.S.C. Flett, J. Chem. Soc., (1951) 962. [8] J. Selbin, L. Morpurgo, J. Inorg. Nucl. Chem., 27 (1965) 673. [9] N.D. Chasteen, R.L. Belford, I.C. Paul, Inorg. Chem., 8 (1969) 408. [10] K. Dey, S.K. Sen, J.K. Bhar, J. Indian Chem. Soc., 52 (1975) 666. [11] M. Tanaka, H. Okawa, I. Hanaoka, S. Kida, Chem. Lett., (1974) 71. [12] P.K. Dutta, J. Inclus. Phenom. Mol. Recognition Chem., 21 (1995) 215. [13] I.F.J. Vankelecom, R.F. Patron, M.J.A. Casselaman, J.B. Uylterhoeven, P.A. Jacobs, J. Catal., 163 (1996) 457. [14] N. Herron, J. Coord. Chem., 19 (1988) 25. [15] D. Chatterjee, H.C. Bajaj, A. Das, K. Bhatt, J. Mol. Catal., 92 (1994) L235. [16] R. Raja, P. Ratnaswamy, J. Catal., 170 (1997) 244. [17] K.O. Xavier, J. Chacko, K.K.M. Yusuff, J. Mol. Catal. A: Chemical, 178 (2002) 275. [18] S.N. Poddar, Z. anorg. allg. Chem., 322 (1963) 326. [19] S.N. Poddar, K. Dey, J. Indian Chem. Soc., 47 (1970) 909. [20] S.N. Poddar, K. Dey, Z. anorg. allg. Chem., 327 (1964) 104. [21] U. Caselato, D. Fregona, S. Sitram, S. Tamburini, P.A Vigato, Inorg. Chim. Acta, 95 (1984) 309. [22] K. Dey, K.K. Chatterjee, S.K. Sen, J. Indian Chem. Soc., L (1973) 167. [23] K. Dey, J. Sci. Indus. Res., 33 (1974) 76. [24] L.G. Vanquickenborne, S.P. McGlynn, Theo. Chim. Acta, 9 (1968) 390. [25] H.J. Bielig, E. Bayer, Annalen, 584 (1953) 96. [26] B. Bleaney, K.D. Bowers, Proc. Roy. Soc., London, A214 (1952) 451. [27] M. Tanaka, H. Okawa, T. Tamura, S. Kida, Bull. Chem. Soc. Japan, 47 (1974) 1669. [28] J.P. Lebreton, FEBS Lett., 80 (1977) 351. [29] W.R. Cullen, Y. Sugi, Tet. Letts., (1978) 1635. [30] W.F. Anderson, M.C. Miller (Eds.), ‘Proceedings of symposium on development of iron chelators for clinical use’, U.S. Department of Health, Education and Welfare (1975). [31] M.J. Adam, L.D. Hall, Can. J. Chem., 60 (1982) 2229. [32] K. Dey, A. Ganguly, Unpublished work. [33] L.D. Hall, M. Yalpani, Carbohydr. Res., 83 (1980) C5. [34] J.K. Nag, D. Das, B.B. De, C. Sinha, J. Indian. Chem. Soc., 75 (1998) 496. [35] K. Dey, K. Chakraborty, R. Bhowmick, S.K. Nag, in ‘Advances in Metallo Organic Chemistry’, Ed. R. Bohra, Jaipur (1999) 307. [36] K. Dey, R. Bhowmick, S. Sarkar, Synth. React. Inorg. Met-Org. Chem., 32 (2002) 1393. [37] Y.M. Issa, H.M. Abdel-Fattah, M.M. Omar, A.A. Soliman, Indian J. Chem., 33A (1994) 959. Saikat Sarkar and Kamalendu Dey 212 [38] K. Dey, D. Bandyopadhyay, J. Indian Council Chem., 11 (1995) 75. [39] H.P.S. Chauhan, G. Srivastava, R.C. Mehrotra, Indian J. Chem., 23A (1984) 436. [40] K. Dey, R. Bhowmick, S.K. Nag, K. Chakraborty, S. Biswas, J. Indian Chem. Soc., 76 (1999) 427. [41] R. Bhowmick, ‘Metal complexes of ligands derived from 3-formylsalicylic acid’, Ph.D. thesis, University of Kalyani, India (2003). [42] K. Dey, S. Sarkar, S. Mukhopadhyay, S. Biswas, B.B. Bhaumik, J. Coord. Chem., 59 (2006) 565. [43] M.F. Iskander, L. Labid, M.M.Z. Nour-Ed-Din, M. Tawfik, Polyhedron, 8 (1990) 2755 and references cited there in. [44] B. Singha, B.P. Yadava, R.C. Agarwal, Indian J. Chem., 23A (1984) 441. [45] R.P. Bonamo, E. Rizzarelli, N.B. Pahor, G. Nardin, J. Chem. Soc. Dalton Trans., (1982) 681. [46] K. Dey, S. Sarkar, S. Mukhopadhyay, A.K. Mallick, S. Biswas, B. B. Bhaumik, J. Coord. Chem., 59 (2006) 1233. [47] A. Syamal, K.S. Kale, Indian J. Chem., 16A (1978) 46. [48] J.F. Weither, L.R. Melby, R.E. Benson, J. Am. Chem. Soc., 86 (1964) 4329. [49] B.N. Keshari, L.K. Mishra, Indian J. Chem., 20A (1981) 883. [50] A. Syamal, M.M. Singh, Indian J. Chem., 32A (1993) 42. [51] A. Syamal, D. Kumar, A.K. Singh, P.K. Gupta, Jaipal, L.K. Sharma, Indian J. Chem., 41A (2002) 1385. [52] T.M. Suzuki, T. Yokoyama, H. Matsunga, T. Kimura, Bull. Chem. Soc. Japan, 59 (1986) 865. [53] M.S. Hutchins, T.K. Chapman, Tet. Letts., 35 (1994) 4055. [54] R.A. Vaino, K.D. Janda, J. Comb. Chem., 2 (2000) 579. [55] A. Syamal, M.M. Singh, D. Kumar, React. Funct. Polymers, 39 (1999) 27. [56] D. Kumar, P.K. Gupta, A. Syamal, J. Chem. Sci., 117 (2005) 247. [57] D. Kumar, A. Syamal, Jaipal, L.K. Sharma, J. Chem. Sci., 121 (2009) 57. [58] C. Arunan, V.N.R. Pillai, Tetrahedron, 56 (2000) 3005. [59] D.C. Sherrington, Stud. Surf. Sci. Catal., B130 (2000) 1655. [60] N. Pesavento, R. Biesuz, F. Baffi, C. Gencco, Anal. Chim. Acta, 401 (1999) 265. [61] M.R. Maurya, U. Kumar, P. Manikandan, Dalton Trans., (2006) 3561. [62] M.R. Maurya, M. Kumar, A. Kumar, J.C. Pessoa, Dalton Trans., (2008) 4220. [63] M.R. Maurya, S. Sikarwar, M. Kumar, Cat. Commun., 8 (2007) 2017. [64] M.R. Maurya, U. Kumar, P. Manikandan, Eur. J. Inorg. Chem., (2007) 2303. [65] M.R. Maurya, A. Arya, A. Kumar, M.L. Kuznetsov, F. Avecilla, J.C. Pessoa, Inorg. Chem., 49 (2010) 6586. [66] M.E. Mahmoud, E.M. Soliman, Talanta, 44 (1997) 15. [67] M.E. Mahmoud, E.M. Soliman, M. Ezzat, A. El-Dissouky, Anal. Sci., 13 (1997) 765. [68] R.L. De, I. Banerjee, S. Guha, A.K. Mukherjee, Indian J. Chem., 41A (2002) 1380. [69] R.K. Verma, B.K. Mishra, K.C. Satpathy, A. Mahapatra, Asian J. Chem., 9 (1997) 365. [70] M. Coppola, S. Catinella. P. Traldi, P. Guerriero, S. Tamburini, P.A. Vigato, Org. Mass Spectr., 29 (1994) 566. [71] M. Tanaka, H. Okawa, Ken. Hokoku-Kagawa Dai. Kyoik., Dai-2-bu, 31 (1981) 33. [72] A. Erxleben, D. Schumacher, Eur. J. Inorg. Chem., (2001) 3039. [73] J. Hermann, D. Schumacher, A. Erxleben, Eur. J. Inorg. Chem., (2002) 2276. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 213 [74] O. Kahn, Struct. Bonding (Berlin), 68 (1987) 89. [75] L.K. Thompson, S.K. Mandal, S.S. Tandson, J.N. Bridson, M.R. Park, Inorg. Chem., 35 (1996) 3117. [76] M. Andruh, I. Ramade, E. Codjovi, O. Guillou, O. Kahn, J.C. Trombe, J. Am. Chem. Soc., 115 (1993) 1822. [77] F. Tuna, L. Patron, Y. Journaux, M. Andruh, W. Plass, J.C. Trombe, J. Chem. Soc. Dalton Trans., (1999) 539. [78] F. Tuna, G. Grasa, L. Patron, M. Andruh, Rev. Roum. Chim., 42 (1997) 793. [79] F. Tuna, L. Patron, M. Andruh, Inorg. Chem. Commun., 6 (2003) 30. [80] F. Tuna, G.I. Pascu, J-P. Sutter, M. Andruh, S. Golhen, J. Guillevic, H. Pritzkow, Inorg. Chim. Acta, 342 (2003) 131. [81] A. Erxleben, Inorg. Chem., 40 (2001) 208. [82] S. Yamanaka, H. Okawa, K. Motoda, M. Yonimura, D.E. Fenton, M. Ebadi, A.B.P. Lever, Inorg. Chem., 38 (1999) 1825. [83] P. Zanello, S. Tamburini, P.A. Vigato, G.A. Mazzochim, Coord. Chem. Rev., 77 (1987) 165 and references cited there in. [84] T. Shiga, H. Oshio, Polyhedron, 26 (2007) 1881. [85] R-J. Tao, F-A. Li, Y-X. Cheng, S-Q. Zang, Q-L. Wang, J-Y. Niu, D-Z. Liao, Inorg. Chim. Acta, 359 (2006) 2053. [86] A. Lalehzari, J. Desper, C.J. Levy, Inorg. Chem., 47 (2008) 1120. [87] P. Cucos, M. Pascu, R. Sessoli, N. Avarvari, F. Pointillart, M. Andruh, Inorg. Chem., 45 (2006) 7035. [88] A. Chakravorty, Coord. Chem. Rev., 13 (1974) 1. [89] Luneau, H. Oshio, H. Okawa, S. Kida, Chem. Lett., (1989) 443. [90] H. Okawa, M. Koikawa, S. Kida, D. Luneau, H. Oshio, J. Chem. Soc. Dalton Trans., (1990) 469. [91] Luneau, H. Oshio, H. Okawa, M. Koikawa, S. Kida, Bull. Chem. Soc. Japan, 63 (1990) 2212. [92] Luneau, H. Oshio, H. Okawa, S. Kida, J. Chem. Soc. Dalton Trans., (1990) 2282. [93] C.B. Singh, B. Sahoo, J. Inorg. Nucl. Chem., 36 (1974) 1259. [94] Z.J. Zhong, H. Okawa, N. Matsumoto, H. Sakiyama, S. Kida, J. Chem. Soc. Dalton Trans., (1991) 497. [95] R. Ruiz, M. Julve, J. faus, F. Lloret, M.C. Munoz, Y. Journaux, C. Bois, Inorg. Chem., 36 (1997) 3434. [96] Colacio, J.M. Dominguez-Versa, A. Escuer, R. Kivekas, A. Romerosa, Inorg. Chem., 33 (1994) 3914. [97] C. Krebs, M. Winter, T. Weyhermuller, E. Bill, K. Wieghardt, P. Chaudhuri, J. Chem. Soc. Chem. Commun., (1995) 1913. [98] C.N. Verani, E. Rentschler, T. Weyhermuller, E. Bill, P. Chaudhuri, J. Chem. Soc. Dalton Trans., (2000) 251. [99] N. Fukita, M. Ohba, H. Okawa, J. Chem. Soc. Dalton Trans., (2000) 64. [100] K. Ikeda, M. Ohba, H. Okawa, J. Chem. Soc. Dalton Trans., (2001) 3119. [101] K. Dey, R.K. Maiti, J.K. Bhar, Trans. Met. Chem., 6 (1981) 346. [102] K. Dey, J. Inorg. Nucl. Chem., 32 (1970) 3125. [103] A. Zarembowitch, O. Kahn, Inorg. Chem., 23 (1984) 589. [104] K. Dey, Indian J. Chem., 9 (1971) 600. Saikat Sarkar and Kamalendu Dey 214 [105] K. Dey, R.L. De, J. Indian Chem. Soc., 51 (1974) 374. [106] K. Dey, R.L. De, Z. anorg. allg. Chem., 402 (1973) 120. [107] K. Dey, K.K. Chatterjee, Z. anorg. allg. Chem., 383 (1971) 199. [108] K. Dey, Z. anorg. allg. Chem., 376 (1970) 209. [109] K. Dey, J. Indian Chem. Soc., 48 (1971) 641. [110] S.N. Poddar, N.R. Sengupta, K. Dey, Science and Culture, (1963) 257. [111] S.N. Poddar, N.R. Sengupta, K. Dey, Indian J. Chem., 2 (1964) 12. [112] K. Dey, R.L. De, K.C. Ray, Indian J. Chem., 10 (1972) 864. [113] M. Sakamoto, M. Hashimura, Y. Nakayama, Bull. Chem. Soc. Japan, 65 (1992) 1162. [114] K. Dey, Indian J. Chem., 9 (1971) 887. [115] K. Dey, A. Gangopadhyay, A.K. Biswas, J. Indian Chem. Soc., 66 (1989) 512. [116] K. Dey, R.L. De, J. Inorg. Nucl. Chem., 37 (1975) 843. [117] S.N. Poddar, K. Dey, J. Indian Chem. Soc., 43 (1966) 359. [118] S. Fritzsche, P. Lonnecke, T. Hocher, E. He-Hawkins, Z. anorg. Allg, Chem., 632 (2006) 2256. [119] B. N. Figgis, J. Lewis, ‘Modern Coordination Chemistry’, Interscience Publisher Inc., New York (1960). [120] A. Vandenbergen, K.S. Murray, M.J. O’Connor, B.O. West, Aust. J. Chem., 22 (1969) 39. [121] R. Dingle, Acta. Chem. Scand., 20 (1966) 33. [122] R.W. Kolaczkowski, R.A. Plane, Inorg. Chem., 3 (1964) 322. [123] M.J. O’Connor, B.O. West, Aust. J. Chem., 22 (1969) 369. [124] P. Coggon, A.T. McPhail, F.E. Mabbs, A. Richards, A.S. Thornley, J. Chem. Soc. A, (1970) 3296. [125] C.J. Ballhausen, W. Mafitt, J. Inorg. Nucl. Chem., 3 (1956) 178. [126] R.A.D. Wentworth, T.S. Piper, Inorg. Chem., 4 (1965) 202,709. [127] K.I. Legg, D.W. Cooke, Inorg. Chem., 4 (1965) 1576. [128] K.I. Legg, D.W. Cooke, Inorg. Chem., 5 (1966) 594. [129] K. Kuroda, P.S. Gentile, J. Inorg. Nucl. Chem., 27 (1965) 155. [130] J.H. Dunlop, R.D. Gillard, Mol. Phys., 7 (1963) 493. [131] M. Gerloch, J. Lewis, F.E. Mabbs, A. Richards, J. Chem. Soc. (London) Sec. A, (1968) 112. [132] J.S. Griffith, Mol. Phys., 8 (1964) 213. [133] J. Lewis, F.E. Mabbs, A. Richards, Nature (London), 207 (1965) 855. [134] M. Gerloch, F.E. Mabbs, A. Richards, Nature (London), 212 (1966) 809. [135] J. Lewis, F.E. Mabbs, H. Weigold, J. Chem. Soc. A, (1968) 1699. [136] R.W. Asmussen, H. Soling, Acta. Chem. Scand., 11 (1957) 1331. [137] J. Lewis, R.A. Walton, J. Chem. Soc. A, (1966) 1559. [138] R. Belford, T. Piper, Mol. Phys., 5 (1962) 251. [139] R.S. Downing, F.L. Urbach, J. Am. Chem. Soc., 91 (1969) 5977. [140] L. Sacconi, M. Ciampolini, J. Chem. Soc., (1964) 276. [141] L. Sacconi, M. Ciampolini, F. Maggio, F.P. Cavasino, J. Inorg. Nucl. Chem., 19 (1961) 73. [142] F.A. Cotton, G. Wilkinson, ‘Advanced Inorganic Chemistry’, Interscience Publisher Inc., New York (1966). [143] J. Ferguson, J. Chem. Phys., 34 (1961) 1612. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 215 [144] T. Tanaka, J. Am. Chem. Soc., 80 (1958) 4108. [145] G. Basu, S. Basu, Z. Phys. Chem. (Leipzig), 213 (1960) 158. [146] S.M. Crawford, Spectrochim. Acta, 19 (1963) 255. [147] S.V. Sheat, T.N. Waters, J. Inorg. Nucl. Chem., 26 (1964) 1221. [148] T.N. Waters, D. Hall, J. Chem. Soc., (1959) 1200. [149] J.M. Waters, T.N. Waters, J. Chem. Soc., (1964) 2489. [150] T.S. Kanan, A. Chakroborty, Inorg. Chem., 9 (1970) 1153. [151] R.H. Holm, J. Am. Chem. Soc., 82 (1960) 5632. [152] S. Yamada, Coord. Chem. Rev., 1 (1966) 415. [153] W. Manch, W.C. Fernelius, J. Chem. Edu., 38 (1961) 192. [154] R.J.H. Clark, ‘The Chemistry of Titanium and Vanadium’, Elsevier Publishing Company, Amsterdam (1968) 201. [155] L.J. Boucher, T.F. Yen, Inorg. Chem., 8 (1969) 689. [156] H.P. Jensen, Acta. Chem. Scand. A, 34 (1980) 469. [157] L.J. Boucher, D.E. Bruins, T.F. Yen, D.L. Weaver, J. Chem. Soc. Chem. Commun., (1969) 363. [158] D.E. Bruins, D.L. Weaver, Inorg. Chem., 9 (1970) 130. [159] M. Mathew, A.J. Carty, G.J. Palenik, J. Am. Chem. Soc., 92 (1970) 3197. [160] F.E. Dickson, L. Petrakis, J. Phys. Chem., 74 (1970) 2850. [161] O. Kahn, R. Claude, H. Coudanne, Nouv. J. Chim., 4 (1980) 167. [162] J. Zarembowitch, O. Kahn, Inorg. Chem., 23 (1984) 589. [163] J. Zarembowitch, R. Claude, O. Kahn, Inorg. Chem., 24 (1985) 1576. [164] R.C. Stoufer, D.W. Smith, E.A. Clevenger, T.E. Norris, Inorg. Chem., 5 (1966) 1167. [165] D. Willams, D.W. Smith, R.C. Stoufer, Inorg. Chem., 6 (1967) 590. [166] A. Earnshaw, P.C. Hewlett, E.A. King, L.F. Larkworthy, J. Chem. Soc. A, (1968) 241. [167] P.S.K. Chia, S.E. Livingstone, Aust. J. Chem., 22 (1969) 1825. [168] C.M. Harris, T.N. Lockyer, R.L. Martin, H.R.H. Patil, E. Sinn, I.M. Stewart, Aust. J. Chem., 22 (1969) 2105. [169] L.G. Marzilli, P.A. Marzilli, Inorg. Chem., 11 (1972) 457. [170] R. Morassi, F. Mani, L. Sacconi, Coord. Chem. Rev., 11 (1973) 343. [171] M.G. Simmons, L.J. Wilson, Inorg. Chem., 16 (1977) 126. [172] S. Kremer, W. Henke, D. Reinen, Inorg. Chem., 21 (1982) 3013. [173] B.J. Kennedy, G.D. Fallon, B.M.K.C. Gatehouse, K.S. Murray, Inorg. Chem., 23 (1984) 580. [174] P. Thuery, J. Zarembowitch, Inorg. Chem., 25 (1986) 2001. [175] M. Calligaris, G. Nardin, L. Randaccio, J. Chem. Soc. Dalton Trans., (1974) 1903. [176] M.A. Hitchman, Inorg. Chim. Acta, 26 (1977) 237. [177] M. Calligaris, D. Mminichelli, G. Nardin, L. randaccio, J. Chem. Soc. A, (1970) 2411. [178] R. Delasi, S.L. Holt, B. Port, Inorg. Chem., 10 (1971) 1498. [179] D.K. Geiger, Y.J. Lee, W.R. Scheidt, J. Am. Chem. Soc., 106 (1984) 6339. [180] W.R. Scheidt, Y.J. Lee, D.K. Geiger, K. Taylor, K. Hatano, J. Am. Chem. Soc., 104 (1982) 3367. [181] F. Tuna, L. Patron, E. Riviere, M-L. Boillot, Polyhedron, 19 (2000) 1643. [182] C. Roux, J. Zarembowitch, B. Gallois, T. Granier. R. Claude, Inorg. Chem., 33 (1994) 2273. Saikat Sarkar and Kamalendu Dey 216 [183] M-L. Boillot, C. Roux, J.P. Audiere, A. Dausse, J. Zarembowitch, Inorg. Chem., 35 (1996) 3975. [184] T.H. Wirth, N. Davidson, J. Am. Chem. Soc., 86 (1964) 4314. [185] M. Ali, D.V. Ramana, J. Indian Chem. Soc., 43 (1966) 583. [186] Z. Zude, S. Yan, Z. Tao, S. Qingde, J. Mol. Struct., 440 (1998) 9. [187] A. Bigatto, G. Costa, G. Mestroni, Inorg. Chim. Acta Rev., 4 (1970) 41. [188] S.N. Poddar, D.K. Biswas, J. Inorg. Nucl. Chem., 31 (1969) 565. [189] L.J. Boucher, Inorg. Chim. Acta, 6 (1972) 29. [190] A.B.P. Lever, ‘Inorganic Electronic Spectroscopy’, American Elsevier, New York (1968) 306. [191] L.J. Boucher, D.R. Herington, J. Inorg. Nucl. Chem., 33 (1971) 4349. [192] J. Lewis, R.F. Long, C. Oldham, J. Chem. Soc. (London) Sec. A, (1965) 6740. [193] R.J. York, W.D. Bonds (Jr), B.P. Cotsoradis, R.D. Archer, Inorg. Chem., 8 (1969) 789. [194] K. Ueno, A.E. Martell, J. Phys. Chem., 59 (1955) 998. [195] S.J. Gruber, C.M. Harris, E. Sinn, J. Inorg. Nucl. Chem., 30 (1968) 1805. [196] J.E. Kovacic, Spectrochim. Acta, 23A (1967) 183. [197] P.C. Hewlett, L.F. Larkworthy, J. Chem. Soc. (London), (1965) 882. [198] K. Nakamoto, ‘Infrared Spectra of Inorganic and Coordination Compound’, John Willey and Sons Inc., New York (1963). [199] B.J. Hathaway, A.E. Underhill, J. Chem. Soc. (London), (1961) 3091. [200] S. Buffagni, L.M. Vallarino, J.V. Quagliano, Inorg. Chem., 3 (1964) 671. [201] R.D. Archer, B.P. Cotsoradis, Inorg. Chem., 4 (1965) 1584. [202] E. Cara, A. Cristini, A. Diaz, G. Ponticelli, J. Chem. Soc. Dalton Trans., (1972) 527. [203] G.W. Everett (Jr), R.H. Holm, J. Am. Chem. Soc., 88 (1966) 2442. [204] H. Nishikawa, S. Yamada, Bull. Chem. Soc. Japan, 37 (1964) 8. [205] C.J. Hipp, W.A. Baker (Jr), J. Am. Chem. Soc., 92 (1970) 792. [206] M. Hariharan, F.L. Urbach, Inorg. Chem., 8 (1969) 556. [207] F.N. Moore, R.E. Rice, Inorg. Chem., 7 (1968) 2510. [208] P.C.H. Mitchel, Quart. Rev., 20 (1966) 103. [209] J.R. Dilworth, C.A. McAuliffe, B.J. Sayle, J. Chem. Soc. Dalton Trans., (1977) 849. [210] M. Calligaris, G. Manzini, G. Nardin, L. Randaccio, J. Chem. Soc. Dalton Trans., (1972) 543. [211] R.J. Cozens, K.S. Murray, Aust. J. Chem., 25 (1972) 911. [212] C. Florini, M. Puppis, F. Calderazzo, J. Org. Met. Chem., 12 (1968) 209. [213] H.A.O. Hill, K.G. Morllee, G. Pellizer, G. Costa, J. Org. Met. Chem., 12 (1968) 167. [214] S. Yamada, K. Yamanouchi, Inorg. Chim. Acta, 9 (1974) 83,161. [215] K. Dey, A. Gangopadhyay, A.K. Biswas, J. Bangladesh Acad. Sci., 11 (1987) 55. [216] K. Dey, A. Gangopadhyay, A.K. Biswas, J. Indian Chem. Soc., 66 (1989) 512. [217] A. Hebeish, J. Appl. Polym. Sci., 20 (1976) 2631. [218] M.F. Hawthorne, R.J. Wiersema, J. Med. Chem., 15 (1972) 449. [219] K. Dey, R.K. Maiti, J.K. Bhar, R.D. Banerjee, G.M. Sarkar, A. Malakar, S. Dutta, P. Banerjee, Agents and Actions, 11 (1981) 762. [220] K. Dey, A. Gangopadhyay, A.K. Biswas, C. Bhattacharyya, S. Sarkar, J. Bangladesh Acad. Sci., 12 (1988) 45. [221] K. Dey, S.B. Ray, P.K. Bhattacharyya, A. Gangopadhyay, A.K. Biswas, R.D. Verma, J. Indian Chem. Soc., 62 (1985) 809. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 217 [222] K. Dey, A. Gangopadhyay, A.K. Biswas, Unpublished Work. [223] A.K. Biswas, ‘Compounds of Boron. Synthesis, characterization and biological actvity’, Ph.D. thesis, University of Kalyani, India (1983). [224] K. Dey, A.K. Biswas, A.K. Sinha Roy, Indian J. Chem., 20A (1981) 848. [225] K. Nakamoto, P.J. McCarthy, ‘Spectroscopy and Structure of Metal Chelate Compounds’, Wiley, New York (1968). [226] R.M. Silverstein, C.C. Bassler, T.C. Morril, ‘Spectrometric Identification of Organic Compounds’, 3rd Edn., Wiley, New York (1974). [227] W. Fedler, F. Umland, E. Hohaus, Z. anorg. allg. Chem., 471 (1980) 77. [228] F.K. Butcher, W. Gerrad, E.F. Mooney, H.A. Wielis, Spectrochim. Acta, 20 (1964) 79. [229] A.T. Balaban, C.W. Rentea, M. MoCaunparaschiv, E. Romas, Rev. Roum. Chim., 10 (1965) 849. [230] L.J. Bellamy, W. Gerrard, M.F. Lappert, R.L. William, J. Chem. Soc., (1953) 2412. [231] H. Junge, H. Musso, Spectrochim. Acta Part-A, 24 (1965) 1219. [232] K. Dey, K.K. Nandi, Indian J. Chem., 35B (1996) 318. [233] K. Dey, A.K. Biswas, D. Koner, S.B. Roy, J. Chem. Soc. Dalton Trans., (1982) 911. [234] K. Dey, S.B. Roy, D. Koner, Proc. Indian Acad. Sci. (Chem. Sci.), 92 (1983) 257. [235] J.R. Dilworth, C.A. McAuliffe, B.J. Sayle, J. Chem. Soc. Dalton Trans., (1977) 849. [236] P.G. Lenhert, D.C. Hodgkin, Nature, 192 (1961) 937. [237] P.G. Lenhert, Proc. Royal Soc. (A), 303 (1968) 45. [238] J.A. Hill, J.M. Pratt, R.J.P. Williams, J. Chem. Soc., (1964) 5149. [239] R. Bonnett, Chem. Rev., 63 (1963) 573. [240] J. Halpern, J.P. Maher, J. Am. Chem. Soc., 87 (1965) 5361. [241] G.N. Schranzer, Acc. Chem. Res., 1 (1968) 97. [242] G. Costa, G. Mestroni, G. Tauzher, J. Chem. Soc. Dalton Trans., (1972) 450. [243] D. Dolphin, A.W. Hohnson, R. Rodrigo, J. Chem. Soc., (1964) 3184. [244] J.M. Pratt, J. Chem. Soc., (1964) 5154. [245] G. Costa, G. Mestroni, L. Stefaini, J. Org. Met. Chem., 7 (1967) 3184. [246] G. Costa, G. Mestroni, G. Tauzher, L. Stefaini, J. Org. Met. Chem., 6 (1966) 181. [247] G. DeAlti, U. Galasso, A. Bigatto, Inorg. Chim. Acta, 6 (1972) 129, 153 [248] P. Zanello, S. Tamburini, P.A. Vigato, G.A. Mazzocchin, Trans. Met. Chem., 9 (1984) 176. [249] P. Zanello, P.A. Vigato, U. Casellato, S. Tamburini, G.A. Mazzocchin, Trans. Met. Chem., 8 (1983) 294. [250] P. Zanello, P.A. Vigato, G.A. Mazzocchin, Trans. Met. Chem., 7 (1982) 291. [251] G. Fachinetti, C. Floriani, P.F. Zanazzi, J. Am. Chem. Soc., 100 (1978) 7405. [252] D.E. Fenton, R.L. Lintvedt, J. Am. Chem. Soc., 100 (1978) 6367 and references therein. [253] R.R. Gagne, C.L. Spiro, T.J. Smith, C.A. Hamann, W.R. Thies, A.K. Shiemke, J. Am. Chem. Soc., 103 (1981) 4073. [254] G.L. Eichorn, ‘Inorganic Biochemistry’, 1 & 2, Elsevier, New York (1973). [255] J.S. Richardson, K.A. Thomas, B.H. Rubin, D.C. Richardson, Proc. Natl. Acad. Sci. (USA), 72 (1975) 1349. [256] G. Palmer, G.T. Badcock, L.E. Vickery, Proc. Natl. Acad. Sci. (USA), 73 (1976) 2206. [257] S. Gambarotta, F. Arena, C. Floriani, P.F. Zanazzi, J. Am. Chem. Soc., 104 (1982) 5082. [258] F. Arena, C. Floriani, A. Chiesi-Villa, C. Guastini, Inorg. Chem., 25 (1986) 4589. Saikat Sarkar and Kamalendu Dey 218 [259] P. Zanello, S. Tamburini, P.A. Vigato, G.A. Mazzocchin, Coord. Chem. Rev., 77 (1987) 165. [260] P. Guerriero, S. Tamburini, P.A. Vigato, Coord. Chem. Rev., 139 (1995) 17. [261] V. Alexander, Chem. Rev., 95 (1995) 273. [262] B-Y. Jiang, J. Du, C-W. Hu, X-C. Zeng, Trans. Met. Chem., 29 (2004) 361. [263] Tanaka, M. Kitaoka, H. Okawa, S. Kida, Bull. Chem. Soc. Japan, 49 (1976) 2469. [264] H. Okawa, Y. Nishida, M. Tanaka, S. Kida, Bull. Chem. Soc. Japan, 50 (1977) 127. [265] N. Torihara, H. Okawa, S. Kida, Inorg. Chim. Acta, 26 (1976) 97. [266] N. Torihara, H. Okawa, S. Kida, Chem. Lett., 185 (1978) 1269. [267] M. Mikuriya, H. Okawa, S. Kida, I. Ueda, Bull. Chem. Soc. Japan, 51 (1978) 2920. [268] N. Torihara, H. Okawa, S. Kida, Chem. Lett., (1979) 683. [269] H. Okawa, W. Kanda, S. Kida, Chem. Lett., (1980) 1281. [270] Morgenstern-Badarau, M. Rerat, O. Kahn, J. Jaud, J. Galy, Inorg. Chem., 21 (1982) 3050. [271] S. Desjardins, I. Morgenstern-Badarau, O. Kahn, Inorg. Chem., 23 (1984) 3833. [272] Y. Journaux, O. Kahn, J. Zarembowitch, J. Galy, J. Jaud, J. Am. Chem. Soc., 105 (1983) 7585. [273] M. Sakamoto, M. Takagi, T. Ishimori, H. Okawa, Bull. Chem. Soc. Japan, 61 (1988) 1613. [274] J.P. Veale, J.A. Cunningham, D.J. Phillips, Inorg. Chim. Acta, 33 (1979) 113. [275] Y. Aratake, H. Okawa, E. Asato, H. Sakiyama, M. Kodera, S. Kida, M. Sakamato, J Chem. Soc. Dalton Trans., (1990) 2941. [276] H. Nishikawa, S. Yamada, Bull. Chem. Soc. Japan, 37 (1964) 8. [277] S. Yamada, Coord. Chem. Rev., 1 (1966) 415. [278] Y. Nishida, S. Kida, Chem. Lett., (1973) 57. [279] Y. Nishida, S. Kida, Coord. Chem. Rev., 27 (1979) 275. [280] Y. Nishida, S. Kida, Bull. Chem. Soc. Japan, 45 (1972) 461. [281] Y. Nishida, S. Kida, Bull. Chem. Soc. Japan, 51 (1978) 143. [282] G.H. Dieke, ‘Spectra and Energy Levels of Rare Earth Ions in Crystals’, Interscience, New York (1968). [283] E. Cesarotti, M. Gullotti, A. Pasini, R. Ugo, J. Chem. Soc. Dalton Trans., (1977) 757. [284] K. Nakamoto, H. Oshio, H. Okawa, W. Kanda, H. Horicuchi, S. Kida, Inorg. Chim. Acta, 108 (1985) 231. [285] M.A. Hitchman, Inorg. Chem., 16 (1977) 1985. [286] H. Okawa, M. Tanaka, S. Kida, Chem. Lett., (1974) 987. [287] W. Kanda, M. Nakamura, H. Okawa, S. Kida, Bull. Chem. Soc. Japan, 55 (1982) 471. [288] H. Okawa, S. Kida, Bull. Chem. Soc. Japan, 45 (1972) 1759. [289] F.A. Miller, C.H. Wilkins, Anal. Chem., 24 (1952) 1253. [290] K.K. Abid, D.E. Fenton, Inorg. Chim. Acta, 109 (1985) L-5. [291] R.B. King, P.R. Heckley, J. Am. Chem. Soc., 96 (1974) 3118. [292] A.B.P. Lever, E. Mantovani, B.S. Ramaswamy, Can. J. Chem., 49 (1971) 1957. [293] M. Sakamoto, T. Ishimori, H. Okawa, Bull. Chem. Soc. Japan, 61 (1988) 3319. [294] M. Sakamoto, M. Ohsaki, K. Yamamoto, Y. Nakayama, A. Matsumoto, H. Okawa, Bull. Chem. Soc. Japan, 65 (1992) 2514. [295] W.J. Stratton, D.H. Busch, J. Am. Chem. Soc., 82 (1960) 4883. [296] K. Shindo, H. Okawa, Y. Aratake, S. Kida, Inorg. Chim. Acta, 180 (1991) 47. Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 219 [297] J.K. Nag, D. Das, S. Pal, C. Sinha, Proc. Indian Acad. Sci. (Chem. Sci.), 113 (2001) 11. [298] A. Syamal, D. Kumar, A. Ahmad, Indian J. Chem., 21A (1982) 634. [299] J.K. Nag, S. Pal, C. Sinha, Trans. Met. Chem., 26 (2001) 237. [300] K. Dey, S.B. Ray, D. Bandyopadhyay, Proc. Nat. Indian Acad. Sci., LIX (1989) 367. [301] Kahn, J. Galy, Y. Journaux, J. Jaud, I. Morgenstern-Badarau, J. Am. Chem. Soc., 104 (1982) 2165. [302] U. Casellato, D. Fregona, S. Sitran, S. Tamburini, P.A. Vigato, Inorg. Chim. Acta, 110 (1985) 161. [303] J. Choisnet, N. Abadzhieva, P. Stefanov, D. Klissurski, J.M. Bassat, V. Rives, L. Minchev, J. Chem. Soc. Faraday Trans., 90 (1994) 1987. [304] L.G. Tejuca, J.L.G. Fierro, J.M.D. Tascon, in ‘Advances in Catalysis’, Ed. D.D. Eley, H. Pines, P.B. Weisz, Academic Press, 36 (1989) 237. [305] T. Seiyama, Catal. Rev. Sci. Eng., 34 (1992) 281. [306] B. Viswanathan, in ‘Properties and Applications of Perovskite-Type Oxides’, Ed. L.G. Tejuca, J.L.G. Fierro, Marcel Dekker, New York (1992) 271. [307] R.J.H. Voorhoeve, in ‘Advanced Materials in Catalysis’, Ed. J.J. Burton, R.L. Garten, Academic Press, New York (1977) 129. [308] A. Wold, B. Post, E. Banks, J. Am. Chem. Soc., 79 (1957) 4911. [309] S.P. Skaribas, P.J. Pomonis, A.T. Skouvos, J. Mater. Chem., 1 (1991) 781. [310] S. Moreau, J. Choisnet, F. Beguin, J. Phys. Chem. Solids, 57 (1996) 1049. [311] S. Moreau, V. Balek, F. Beguin, Mater. Res. Bull., 34 (1999) 503. [312] A.K. Ladavos, F. Kooli, S. Moreno, S.P. Skaribas, P.J. Pomonis, W. Jones, G. Poncelet, Appl. Clay Sci., 13 (1998) 49. [313] U. Casellato, D. Fregona, S. Sitran, S. Tamburini, P.A. Vigato, P. Zanello, Inorg. Chim. Acta, 95 (1984) 279. [314] K. Dey, A.K. Sinha Roy, A.K. Mallick, K.K. Nandi, Synth. React. Inorg. Met-Org. Chem., 22 (1992) 145. [315] U. Casellato, P.A. Vigato, M. Vidali, Coord. Chem. Rev., 23 (1977) 31. [316] K. Dey, R.K. Maiti, S.K. Sen, Inorg. Chim. Acta, 20 (1976) 197. [317] K. Dey, R. Bhowmick, S. Biswas, D. Koner, S. Sarkar, Synth. React. Inorg. Met-Org. Nano Met. Chem., 35 (2005) 285. [318] K. Dey, S. Sarkar, R. Bhowmick, S. Biswas, D. Koner, Indian J. Chem., 44A (2005) 1995. [319] P.C.H. Mitchell, Coord. Chem. Rev., 1 (1966) 315. [320] S. Sarkar, S. Biswas, M-S. Liao, T. Kar, Y. Aydogdu, F. Dagdelen, G. Mostafa, A.P. Chattopadhyay, G.P.A. Yap, R-H. Xie, A.T. Khan, K. Dey, Polyhedron, 27 (2008) 3359. [321] S. Sarkar, K. Dey, Spectrochim. Acta A, 77 (2010) 740. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 5 STRUCTURAL AND MAGNETIC CHARACTERIZATION OF CU-PICOLINATE AND CU-QUINALDINATE MOLECULAR SYSTEMS Bogumiła Żurowska * Faculty of Chemistry, University of Wroclaw, Wroclaw, Poland ABSTRACT Review article concerns information on a synthesis, structural and magnetic characterization of the copper(II) compounds based on two classes of carboxylate ligands containing heterocyclic nitrogen atom of pyridine and quinoline, e.g. pyridine-2- carboxylate (2-picolinate, 2-pic) and quinoline-2-carboxylate (2-quinaldinate, 2-qic), respectively. Such compounds are products of a direct reaction of picolinate or quinaldynate acids with copper(II) salts and hydrolytic or non hydrolytic decomposition of the some ligands. Picolinate ion forms polymeric compounds of the general formula {[Cu(2-pic) 2 ]·2H 2 O} n , [Cu(2-pic) 2 Br 2 ][(2-picH) 2 ], {[Cu 2 (2-pic) 3 (H 2 O)]X} n , where X = ClO 4 , BF 4 or NO 3 . The compound of the formula [Cu(2-pic) 2 ] exists in three polymorphic forms: monomeric with Cu(N 2 O 2 ) chromophore and two polymeric (1D) of the same Cu(N 2 O 4 ) chromophore. With halide ions isostructural polymeric (2D) compounds of the formula [Cu(2-pic)X], X= Cl or Br are formed of Cu(N 2 O 2 X chromophore. However, quinaldynate ion forms compounds of the stoichiometries: two isomeric forms of [Cu(2-qic) 2 ·H 2 O], which involve the same CuN 2 O 3 chromophore (distortion isomers), and [Cu(2-qic)X], X = Cl or Br. The chloride and bromide polymeric (2D) [Cu(2-qic)X] compounds, which crystal structure consists of two different chromophore [Cu(N 2 O 2 X] and Cu(O 2 X 2 ) are isostructural. Crystal structure of these copper-picolinate and copper-quinaldinate systems, indicate that carboxylate group in both ligands offers a variety of coordination modes leading to the formation of mononuclear and polynuclear compounds. The monomeric form of [Cu(2-pic) 2 ] is an example of a square-planar copper(II) compound in which structure is achieved by important π-π stacking intermolecular interaction, which leads to 1D network. Polymeric Cu-picolinate and Cu-quinaldynate systems, based on syn-anti or out-of-plane carboxylates (COO) and di- or monohalogenes bridges (Cl, Br) are interesting material to * E-mail:
[email protected] Bogumiła Żurowska 222 magnetic investigations and magneto-structural correlations, because included magnetically couplet copper(II) centers. This work presented also the role of non- covalent interactions (π-π stacking, hydrogen bonds), stabilizing structures, in transmission of the magnetic interactions. The magnitude of the exchange interactions between copper(II) centers are discussed on the basis of the molecular and crystal structures, in terms of bond properties and well-known theories and thesis of the exchange being base explanation of the magnetic properties. INTRODUCTION The structure, bond properties, and magnetic behavior of copper(II) compounds are continuous interest in inorganic and bioinorganic chemistry [1-5]. The copper ions as centers of the active sites of various metaloproteins, play an essential role in biological processes such as electron transfer, oxidation catalysis and dioxygen transport [6-8]. Generally, the research of the relationship between structure and magnetic properties are important for the understand of the fundamental factors responsible for magnetic properties [9-13] and, furthermore, allows for modeling and understanding of the mechanisms of many bioinorganic processes. The copper(II) complexes are the best systems to investigation the magnetic interaction between metal centers, because of the d 9 (one unpaired electron) electronic structure. The copper(II) complexes characterize a structural diversity, largely related to a Cu(II) d 9 system. It enables the creation the compounds with different coordination number i.e. 4, 5 and 6, and stereochemistry [14-17]; (distorted) octahedral, distorted trigonal bipyramidal, (distorted) square pyramidal, (distorted) square planar, (distorted) tetrahedral complexes have been observed [for example 18-26]. However, because of the influence of the Jahn-Teller effect square-planar-based geometries are usually preferred [27]. Steric constraints are known to generate tetrahedral geometries. Copper(II) with regard on “plasticity effect” and results from the Jahn-Teller distortion of coordination sphere, yields a polymorphic and isomers forms [16, 26, 28]. Generally, the symmetry of the coordination polyhedron around Cu(II) appears to be determined by subtle factors. The shape of the coordination polyhedron is determined to a much greater extent by ligand constraints, steric hindrance, or the donor properties of the ligand. Copper(II) complexes are well-known from the ability of the creation of interesting structurally and magnetically di- and polynuclear species with poli- (for example e.g. COO - , CO 3 2- C 2 O 4 2- and NCS - ) [for example 29-35] and monoatomic bridges (for example e.g. μ- OH, OCH 3 and Cl) [for example 36-39]. These compounds provide a substantial knowledge to several scientific areas, including bioinorganic chemistry, solid-state physics, molecular magnetism and material science. Particularly interesting is the phenomenon of interaction between metal centers, which is important for physics of magnetic materials [40, 41]. On the other hand, the study of the molecular magnetism in correlation with the structure of the mono- and polynuclear complexes allow to know of the role of the mono- and polymetallic active sites in biological systems [42, 43]. Many polynuclear complexes relevance as models for active sites of biomolecules. Among copper (II) complexes synthesis, structural and magnetic investigations of copper(II) carboxylates have been the object of special interest [44-48]. The chemistry of Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 223 these compounds, particularly those including N-heterocyclic donor atom has been in recent years the subject of many studies [44,45]. The reason of this interest are their numerous applications in diverse areas such as pharmaceuticals, fungicides, catalysts, gas occlusion compounds and solvent extraction processes. Moreover, the attention of, bioinorganic chemists has been directed towards the synthesis and characterization of copper(II) carboxylates with N-donor ligands to model the active sites in metalloenzymes [49]. The carboxylate groups are the versatile ligands, able to generate diverse compounds, mono-, di- and polynuclear] with interesting magnetic properties. The study of the magnetic interactions in these compounds permit, on the one hand, the creation of the new magnetic materials and building of the model systems, on the other hand. These models serve the explanation of the role of the mono- and polymetallic active sites in protein, because some carboxylate group play essential role as the ligands in many metalloenzymes. It is worth to mention that the study of the magnetic interactions between the copper centers occurring in the crystal network through non-covalent bonds (π-π, hydrogen bonds) permit the knowledge of the mechanism of this interactions in the biological molecules. In addition, polynuclear metal carboxylates are good candidates for the investigation of exchange-coupling interaction between adjacent metal ions. The structurally and magnetically interesting group of the d 9 carboxylate systems with low molecular weight are the copper(II) complexes, derivatives of pyridine and quinoline, e.g. pyridine-2-carboxylate (2-picolinate, 2-pic) and quinoline-2-carboxylate (2-quinaldinate, 2- qic), respectively. Among these species, polymeric compounds have in their structure rare conformations of the carboxylate group (syn-anti and out-of-plane). It is worth to mention, that the including in the copper picolinate and quinaldynate systems, the halogene bridges is unusual and leads to structurally and magnetically interesting polymeric complexes. This review article presents and summarize, known in literature until now, the results of the synthetic study, structural and magnetic analysis of the mono- and polinuclear copper(II)- picolinate and the copper-quinaldynate systems. Magneto-structural correlations, based on known theories and thesis, explain character of the magnetic interactions occurring through the carboxylate and halogene bridges, as well as through weak non-covalent bonds (π-π stacking, hydrogen bonds) in presented systems. 1. THE PICOLINATE AND QUINALDINATE COMPLEXES 1.1. Coordination Properties of the Picolinate and Quinaldinate Acids Among the carboxylate compounds, containing heterocyclic donor atom, the interesting group are (stanowią), 2-picolinate (pyridine-2-carboxylate, 2-Hpic)) and 2-quinaldinate (quinoline-2-carboxylate, 2-Hqic) acids (Figure 1), which contain both O- and N- donor atoms. These acids coordinated usually in deprotonated form. Bogumiła Żurowska 224 N COOH N COOH Hqic Hpic 2- 2- Figure 1. Scheme of the structure of picolinate (2-Hpic) and quinaldinate (2-Hqic) acids. The broad spectrum of the physiological effects of 2-picolinic acid and its derivatives on the activity functions of both animal and plant organisms has been attributed to their ability to form complexes with transition metals. The picolinate acid is known to form complexes of the type M(2-pic) 2 ·(H 2 O) n with n = 0, 2 or 4 and M = Mn, Fe, Co, Ni, Cu, Zn, Cd, Mg and Hg [50-60]. The X-ray crystal analysis of these compounds shows that the ligand acts predominantly as N,O-chelating agent with water molecule occupying the crystal lattice (Figure 3). Also a number of Mn-2-picolinate complexes with high nuclearity have been reported [61]. Figure 2. Crystal structure of the Cu(2-pic) 2 ⋅2H 2 O (1) [52]. N O O M C N O O M C M M N O O M C N O O M C M M N O O M C M Figure 3. Scheme of the coordination mode of the picolinate anion. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 225 The multidentate picolinate ion is versatile ligand, coordinating in variety modes, namely acts as N,O-, O,O-chelate, or O,O-bridge. (Fig 3). Despite its coordination modes, a chelating five-membered ring is invariably formed. The O,O-chelate carboxylate group forms symmetric and asymmetric chelate, and finally monodentate complexes (Figure 4). N C O O M O O C N M N C O M O Figure 4. Coordination modes of the carboxylate. The 2-quinaldynic acid (2-Hqic) shows also a strong N,O-chelating properties [62-71]. The 2-picolinate and 2-quinaldinate acids indicate the ability of the existing not only in deprotonated form but also as zwitterion (Figure 5) [72, 73]. In this case the negative charge is spread over the O-C-O group while the positive charge, formally located on the nitrogen atom, is delocalized over the pyridine ring. The ligands acting as zwitterions coordinate to one carboxylic oxygen, however, nitrogen atom interacts with oxygen atom through hydrogen N-H…O bonds [73]. N H C O O N H C O O 2-Hqic Hpic 2- Figure 5. The 2-picolinate and 2-quinaldinate acids as zwitterions. The neutral acid molecule is demonstrated in the structure [Cu(2-pic) 2 Br 2 ][(2-pic) 2 -H] in which nitrogen atom from [(2-pic-H) 2 ] 2+ cation interacts with [Cu(2-pic) 2 Br 2 ] 2- through intermolecular N-H…Br hydrogen bond (Figure 6) [74]. The X-ray analysis of the Cu-picolinate and Cu-quinaldinate systems indicate not only a strong N,O-chelating ability these ligands but also ability the carboxylate -O-C-O- group to bridge between metal centers [75-81]. The inclusion in the structure containing the bridging carboxylate groups also the bridging halogene ions (Cl, Br) leads to structurally and magnetically interesting polymeric complexes (Part 3) [75, 76, 79]. Bogumiła Żurowska 226 Figure 6. The molecular structure of [Cu(2-pic) 2 Br 2 ][(2-picH) 2 ] (3) [74]. 1.2. Synthesis of Copper (II) Picolinate and Quinaldinate Complexes The literature survey indicate that the picolinate and quinaldinate complexes of the Cu(II) are formed not only in the direct reaction of the copper(II) salts with appropriate carboxylate acid [50, 53, 69, 74, 77] but also are the product of the hydrolytic and non hydrolytic processes of the degradation of the some ligands [52, 82-84]. In Table 1 known in the literature 2-picolinate and 2-quinaldinate complexes of Cu(II) are presented. The complex of the stoichiometry {[Cu(2-pic) 2 ]·2H 2 O} n is the product of the direct reaction [50, 53] of the Cu(II) salt with 2-picolinic acid (1) or hydrolytic degradation pyridyne-2-carbonitrile (2) [52]. The picolinate 3, 5, 10 and 11, and quinaldinate 12, 14 and 15 complexes are the products of the direct reaction of copper(II) salts with picolinic (2-Hpic) or quinaldinic (2-qic) acids, respectively. However, the picolinate (4, 6) and quinaldinate (13) complexes are the product of the oxidative P-dephosphorylation reaction of R-CH 2 P(O)(OEt) 2 phosphonate ligand leading to transformation of this ligand to R-COOH, according to scheme [83]: R-CH 2 -P(O)(OEt) 2 → R-COOH + OHP(OEt) 2 , where R = C 5 H 4 N or R = C 9 H 6 N. Final products of this process are copper(II) complexes with 2-pic or 2-qic ligands. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 227 These complexes cannot be obtained directly in the reaction of the copper(II) salts with picolinic and quinolinic acid. These complexes are formed only in the oxidative degradation of the phosphonate ligands. However, the complexes 10, 12 and 14 are formed in both above reactions. The complexes 7, 8 and 9 of formula {[Cu 2 (2-pic) 3 (H 2 O)]X} n , where X = ClO 4 , BF 4 or NO 3 , were prepared by taking advantage of the carboxylate bridge of the “metalloligand” [Cu(2-pic) 2 ]. Table 1. Cu(II) complexes with pyridyne-2-carboxylate and quinoline-2-carboxylate Compound a Structure Chromophore Ref. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 {[Cu(2-pic) 2 ]·2H 2 O} n {[Cu(2-pic) 2 ]·2H 2 O} n [Cu(2-pic) 2 Br 2 ][(2-pic-H) 2 ] [Cu(2-pic) 2 ] [Cu(2-pic) 2 ] n [Cu(2-pic) 2 ] n {[Cu 2 (2-pic) 3 (H 2 O)]ClO 4 } n {[Cu 2 (2-pic) 3 (H 2 O)]BF 4 } n {[Cu 2 (2-pic) 3 (H 2 O)]NO 3 } n [Cu(2-pic)Cl] n [Cu(2-pic)Br] n [Cu(2-qic) 2 ·H 2 O] [Cu(2-qic) 2 ·H 2 O] [Cu(2-qic)Cl] n [Cu(2-qic)Br] n polimer (1D) polimer (1D) monomer monomer polimer (1D) polimer (1D) polimer (2D) polimer (2D) polimer (1D) polimer (2D) polimer (1D) monomer monomer polimer (2D) polimer (1D) Cu(N 2 O 4 ) Cu(N 2 O 4 ) Cu(N 2 O 2 Br 2 ) Cu(N 2 O 2 ) Cu(N 2 O 2 O 2 ) Cu(N 2 O 2 O 2 ) CuO 4 , CuN 2 O 3 CuN 2 O 4 CuO 4 , CuN 2 O 3 CuN 2 O 4 CuNO 4 , CuN 2 O 4 Cu(N 2 O 2 Cl) Cu(N 2 O 2 Br) Cu(N 2 O 3 ) Cu(N 2 O 3 ) Cu(N 2 O 2 Cl) Cu(O 2 Cl 2 ) Cu(N 2 O 2 Br) Cu(O 2 Br 2 ) [50, 52] [53] [74] [83] [77] [78, 83] [80] [80] [80] [75, 81, 83] [79] [69] [83] [76, 83] [79] 1.3. Polymorphic and Isomeric Forms The polymeric complexes 1 and 2 of formula {[Cu(2-pic) 2 ]·2H 2 O} n (Figure 2 and 7) are polymorphic forms, in which the copper(II) ions are a doubly out-of-plane carboxylate bridged along the a axis. The adjacent polymeric chains are joined by the lattice water chains leading to a 2D sheet. The crystallographic parameters for both polymorphic forms are presented in Table 2. Bogumiła Żurowska 228 Figure 7. Crystal structure of the [Cu(2-pic) 2 ⋅2H 2 O] n (2) [53]. Table 2. Crystallographic parameters for polymorphic forms of the {[Cu(2- pic) 2 ]∙2H 2 O} n [52, 53] Compounds {[Cu(2-pic) 2 ]·2H 2 O} n (1) {[Cu(2-pic) 2 ]·2H 2 O} n (2) Crystal system triclinic triclinic Space group P1̅ P1̅ a(Å) 5.090(2) 5.172(1) b(Å) 7.480(4) 7.654(2) c(Å) 9.067(6) 9.175(2) α( o ) 75.89(5) 74.92(3) β( o ) 84.94(5) 84.22(3) γ( o ) 71.96(4) 71.69(3) Z 1 1 The complexes 4, 5, and 6 are polymorphic forms of the [Cu(2-pic) 2 ]. The crystallographic parameters are presented in Table 3. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 229 Table 3. Crystallographic parameters for polymorphic forms of the Cu(2-pic) 2 [77, 78, 83] Compounds Cu(2-pic) 2 (4) [Cu(2-pic) 2 ] n (5) [Cu(2-pic) 2 ] n (6) Space group P2 1 /c P2 1 /c P1̅ Crystal system monoclinic monoclinic triclinic a(Å) 3.6975(7) 5.163(1) 5.178(3) b(Å) 11.9890(19) 24.658(1) 7.614(6) c(Å) 11.8886(19) 8.452(1) 8.109(6) α( o ) 90 90 67.06 β( o ) 91.108(14) 92.22(1) 73.81(6) γ( o ) 90 90 71.74(6) Z 2 4 1 The structure of 4, 5 and 6 is shown in Figure 8 and 9. Cu1 C1 C2 C3 C4 C5 C6 O1 O2 N1 (A) (B) Figure. 8. (a) The molecular structure of the [Cu(2-pic) 2 ] (4); (b) π-π stacking interactions in the crystal lattice of the compound 4 [83]. The [Cu(2-pic) 2 ] (4) compound is monomeric. The crystal packing is mainly due to short stacking (3.27 Å) between pyridine rings belonging to different molecules giving rise to a mono-dimensional polymeric network arrangement, resulting the Cu-Cu contacts of 3.8975(7) Å. The structures of 5 and 6 are the one-dimensional polymeric chains. Each Cu(II) ion is connected to the two adjacent metal ions by two out-of-plane carboxylate bridges, creating a polymeric chain along the a axis in which the Cu…Cu distance within the chain is 3.6975(7) and 5.163(1)Å for 5 and 6 respectively. The Cu(2-pic) 2 molecule as a whole, are nearly planar and forms obliquely stacked planes. The essential difference between structures 5 and 6 results from the Cu-O apical distances, which are 2.745(8) - 2.770(8), 2,737(4) Å, respectively. These differences in distances are responsible for observed magnetic properties (see Part 5.1.1 ) Bogumiła Żurowska 230 (A) (B) Figure 9. The molecular structure of the [Cu(2-pic) 2 ] n 5 (a) and 6 (b) [77, 78]. These compounds are the coordination isomers, with the different coordination number, which are 4 for 4, and 4+2 for 5 and 6, and these last are also called polymeric isomers [16]. Figure 10. The molecular structure of Cu(2-qic) 2 ·H 2 O (12) [69]. The monomeric compounds with quinaldinate ion 12 and 13 of formula [Cu(2-qic) 2 ·H 2 O] are isomeric forms, in which 5-coordinated copper centers (CuN 2 O 3 ) differ from each other the geometry of the coordination sphere (geometrical distortion). This is the result of the “plasticity” coordination sphere of the copper(II) and their ability to receive differ stereochemistry. 2. INTRODUCTION TO THE MAGNETISM OF THE MAGNETIC EXCHANGE COUPLED SYSTEMS In transition metal complexes containing more than one metal atom with unpaired electrons, the observed magnetic behavior often differs from the predicted sum of the Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 231 properties of the component units. This phenomenon is due to a coupling of the electron spins and is termed intramolecular anti- or ferromagnetism, depending upon whether antiparallel or parallel spin coupling, respectively, is found in the ground state. In numerous transition metal complexes magnetic interactions between metal centers is transmitted through mono-(e.g. Cl, Br, μ-OH, OCH 3 ) or multiatomic bridges (e.g. OCO, N 3 XCN, X=O, S, Se). In these compounds metal-metal distance is 3-5 Å. For monoatomic bridges this distance is about 3 Å, and for polyatomic bridges is about 5 Å [85]. Therefore magnetic interactions do not result from direct metal-metal interaction, but occur through bridging ligand. These intramolecular interactions, because of the large distances, are often termed as superexchange. In experimental studies, the energy of the magnetic interaction of magnetic centers through the bridge for copper(II) dimers between the local spins S i and S j for atoms i and j is given by Heisenberg Hamiltonian [69, 88]: H = -2JS i ·S j , where J is exchange parameter, called also isotropic interaction parameter. Positive values of J indicate a triplet ground state (ferromagnetic coupling), while for negative values, the singled state is lower in energy (antiferromagnetic coupling). Generalizing, this expression for many interacting of the magnetic centers within a molecule is received: H = -2Σ J ij S i ·S j . Much experimental and theoretical works in recent decades have been done on the mechanism of this exchange coupling. Mechanism of magnetic coupling have been described by Goodenougha [87] in terms of the overlap of the d orbitals on one metal ions with the s and p orbitals on a bridging anion and with the d orbitals on the other metal. According to the conception of Kahn [9] and Alvarez [88], on strength of the observed antiferromagnetic coupling decides the magnitude of the overlap of the magnetic orbitals (build up from the d orbitals of the metal and p orbitals of the ligand atom on the appropriate symmetry). Maximal overlap leads to strong antiferromagnetic coupling. When the overlap between magnetic orbitals is zero, the antiferromagnetic contribution is also zero and the coupling is purely ferromagnetic. The overlap criterion of the orbitals is confirmed by Hay theory [89], which on the basis of the calculations for Cu(II) dimers, based on theory of molecular orbitals, state, that the increase of the electron density on the orbital bridging ligand leads to increase of the antiferromagnetic coupling (increase of the value |J|). However, decrease of the electron density leads to decrease antiferromagnetic coupling`(decrease of the value |J|). This conclusion confirms Hodgson, Hatfield and other [90]. According to Kahn theory, the exchange coupling is the sum of the ferromagnetic (F) and antiferromagnetic (AF) contributions i.e. J = J F + J AF . In this model the value of J AF is proportional to the square of the integral overlap (S 2 ) [91, 92]. Therefore, the magnitude of antiferromagnetic interaction is governed primarily by the overlap of two magnetic orbitals centered on the nearest neighbor copper(II) ions. The magnitude of the antiferromagnetic interaction is more sensitive on change of the structural parameters, deciding on degree of the overlap of the magnetic. orbitals. At very unfavorable structural conditions of the overlap, the coupling will be ferromagnetic (J AF ≅ 0). Summing up, mechanism superexchange interactions between metal centers through bridging ligands for coupled systems is based on concept overlap of the two magnetic orbitals and delocalization of the electron density unpaired electron in direction of the orbital of the bridging ligands. This factors decides on the sign and magnitude of interactions expressed by J parameter. In other words, the magnitude of the ground spin with regard to the excited spin Bogumiła Żurowska 232 is explained in a topologic way from the map of the overlap density. The symmetry of the metal orbitals, that contains the unpaired electron density, and the symmetry of the bridging atom about this overlap decides. 3. MAGNETO-STRUCTURAL CORRELATIONS Magneto-structural correlation based on investigation of the influence a topological way (geometry of the bridge, stereochemistry of the central ion) occurring between metallic centers through the bridged ligand, permits to determine magnetic orbitals of the central ions and the ligands involved in magnetic interaction. Knowledge of the geometry of the superexchange permits the explanation of the sign and magnitude of the magnetic exchange parameter, J. Due to known of the plasticity of the coordination sphere, the Cu(II) adopts in the complexes different stereochemistry with coordination number: 4, 4+1 or 4+2 with four atoms in plane and eventually with one or two in axial position, leading to square-planar or tetragonal pyramid (SP) structure or tetragonal distortion octahedron, respectively. In these three cases, unpaired electron is on a d(x 2 -y 2 ) orbital however, for 4+1 trigonal bipyramid (TBP), on dz 2 orbital. For geometry between SP and TBP, unpaired electron is on a d(x 2 -y 2 ) orbital with some admixture of a dz 2 . Stereochemistry of the copper(II) ions as well as geometry of the bridge have essential meaning for explanation of the magnetic properties for coupled systems. 4. ROLE OF THE CARBOXYLATE AND HALOGENE BRIDGES IN TRANSMISSION OF MAGNETIC EXCHANGE 4.1. The Conformation of the Carboxylate Bridges Copper(II) carboxylates are structurally a very diverse group of coordination compounds due to the various coordination behavior displaying distinct bonding modes towards metal centers such as monodentate and chelate, as well as bridging ligands (Figure 3). Different coordination behavior of the carboxylato group lead to the formation of the mono- di- and polynuclear structures. Carboxylate can assume many types of bridging conformations, the most important being monoatomic and triatomic syn-syn, syn-anti and anti-anti (Figure 11). Different conformations are responsible for observed magnetic properties which are from strongly coupled to moderate or weak antiferromagnetic and even ferromagnetic ones. Copper(II) compounds in which carboxylate group adopts syn-syn conformation, exhibit strong antiferromagnetic coupling (singlet-triplet distance is about 300 cm -1 ) [29]. The classical example is dimeric copper(II) acetate [Cu(CH 3 COO)·H 2 O] 2 [93], for which singlet- triplet distance is -284 cm -1 . Weak antyferro- or ferromagnetic interactions are observed for complexes, in which carboxylate group adopts syn-anti conformation [see e.g. 75, 76, 79, 85, 94-97]. For anti-anti conformation weak or moderately antiferromagnetic coupling is observed [98-100]. For the coupling through monoatomic bridge interactions are very weak antiferromagnetic [101, 102]. It is worth to mention, that in spite of large Cu-Cu distances in Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 233 the complexes with syn-anti conformation, anti-anti is more favorable for transmission of the coupling. This shows that the 2p orbitals of the oxygens are favorable oriented to give more effective overlap with magnetic copper orbitals. It is interesting, that the complexes with bridging carboxylate group in syn-anti and anti-anti conformation are ever rare, because anti electron pair on the oxygen atom indicates a lower basicity than the syn ones [103, 104]. Therefore, the largest group are these, which adopt syn-syn conformation. Figure 11. Conformations of the carboxylate group. 4.2. The Carboxylate Bridges Syn-Anti Type Generally, the weak ferro- and antyferromagnetic interactions observed in copper(II) complexes, which copper centers are connected carboxylate bridges in syn-anti conformation, is result this conformation leading to poor overlap of the magnetic orbitals. The structural features of the bridge, geometry of the coordination sphere and manner of the coordination, which may be (Fig 12): equatorial-equatorial (Type I), axial-equatorial (Type II) and axial- axial (Type III) type, are additional factors responsible for the kind and magnitude of the magnetic interactions. C R Cu Cu O O R C Cu Cu O O R C Cu Cu O O Typ I Typ II Typ III Figure 12. Relative orientation of d(x 2 -y 2 ) magnetic orbitals of copper(II) and 2p orbitals of oxygen for carboxylate bridge in syn-anti conformation. C R Cu Cu O O R C C R O C R O O Cu Cu C R C R C R O O Cu Cu Cu O C R O Cu _ syn syn syn anti _ anti anti _ monoatomowe wiazanie Bogumiła Żurowska 234 Generally, as it has been stated by several authors and also substantiated by DFT calculation [32] syn-anti Cu-O-C-O-Cu carboxylate bridge leads to weak magnetic interactions because 2p orbitals of oxygen atoms belonging to the magnetic orbitals centered on Cu(II) ions are unfavorably oriented to give a significant overlap. Figure 12 presents mutually orientation of the magnetic orbitals of Cu(II) and 2p orbitals of oxygen resulting into weak antyferromagnetic (I), weak ferromagnetic (II) and near zero interactions. Very important factor which has an influence on magnitude of superexchange coupling is non-planarity of the Cu-O-C-O-Cu bridge (an out-of-phase exchange pathway), measured by the dihedral angle. For high dihedral angles the overlap of the magnetic orbitals is reduced, which implies a reduction of the antiferromagnetic contribution and, consequently, ferromagnetism is dominant. The strongest ferromagnetic coupling is expected for a dihedral angle of 90 o [80]. 4.3. The Carboxylate Bridge Out-of-Plane Type The interesting group of the copper(II) carboxylate are rare complexes in which carboxylate group bridges in out-of-plane type (Figure 13) leading to very weak antiferromagnetic interactions. [77, 78, 105]. C R O O Cu Cu Cu Cu C R O O (A) (B) Figure 13. (a) Single carboxylate bridge of out-of-plane type; (b) Relative orientation of the d(x 2 -y 2 ) magnetic orbitals of Cu(II) and 2p orbitals of oxygen atoms of carboxylate group. In this type of complexes, the magnetic orbitals of the Cu(II) interact through orthogonal 2p orbitals of the oxygen atom. Generally, magnetic coupling for all known out-of-plane polynuclear compounds is relatively weak, because of the near-orthogonality of magnetic orbitals, as it has been shown for carboxylato [77, 78], chlorido- [37, 106], carbonato- [107] or oximato- [108] bridged compounds. In this case of the magnetic interactions in apical- equatorial bond modes, the orthogonality of magnetic orbitals leads to a coupling which must be very weakly antiferromagnetic or weak ferromagnetic and even near zero. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 235 4.4. Halogene Bridges (Cl, Br) The halogene bridges, beside the carboxylate bridges, play essential role in transmission of the magnetic interactions. These bridges included in the structure of the carboxylate derivatives of the pyridine and quinoline, build interesting polymeric structures (Part.5.2.1. ) [76, 79]. In the past two decades the copper(II) complexes containing single (μ-Cl) and double (μ- Cl) 2 bridges have been the object of numerous theoretical analysis [89] and magneto- structural correlations [37, 106, 109]. In the majority of known halogene-bridges di- and polinuclear Cu(II) complexes, the bridges are out-of-plane type (apical-equatorial bond mode) with bridging angle about 90 o . (Figure 14, Type I). This conformation leads to very weak ferro-and antyferromagnetic interactions, characterizing small value of the coupling parameter |J | [37, 106]. Cu Cu Cl Cu Cu Cl Cu Cu Cl Type I Type II Type III Cu Cu Cl Type IV Figure 14. Bridging type for Cu(μ-Cl)Cu system. Exceptional in respect of topology of chloro- bridge, reported so far, are three structurally and magnetically characterized copper(II) complexes with linear and near linear Cu-Cl-Cu bridge of apical-apical mode ( Figure 14, Type II) [110, 111], which leads to weak ferromagnetic interactions and these with equatorial-apical bridge (Figure 14, Type III) [76] for which moderately strong antiferromagnetic coupling is observed. The type IV (equatorial- equatorial bridge) is rare and rather characterize other bridging ligands [112]. Bogumiła Żurowska 236 5. STRUCTURE AND MAGNETIC PROPERTIES OF THE POLYMERIC CU- PICOLINATE AND CU-QUINALDINATE SYSTEMS Structures of the polymeric picolinate and quinaldinate complexes presented in the literature are based on, depending on the compounds (Table 1), carboxylate bridges out-of- plane (5 and 6) and syn-anti type (7, 8, 9, 10, 11, 14, and 15). Additionally, in the structure of 10, 11, 14 and 15 halogene bridges (Cl or Br) are included. 5.1. Picolinate Complexes 5.1.1. Structure and Magnetic Exchange through Out-of-Plane Carboxylate Bridges Molecular structure of 5 and 6 compounds of formula Cu(2-qic) 2 ·H 2 O as it is seen from Figure 9 and as mentioned in Part 1.3. is an infinite linear one-dimensional (1D) polymeric chains [Cu(2-pic) 2 ] n results from the fact that the copper(II) ions are sequentially doubly bridged by carboxylate groups [77, 78]. The structures are stabilized by weak C-H…O hydrogen bonds (Part 6). Coordination polyhedron around the copper can be described as a strongly distorted octahedron (4+2). Both compounds are parallel-planar type with out-of- plane carboxylate bridges (Figure 14, Type I). The magnetic behavior of these picolinate complexes can be explained as a results of the magnetic exchange within the chains through long Cu-O axial bond (2.737(4) Å and 2,745(8)-2.770(8) Å for 5 and 6, respectively). The small values of the exchange parameters J for 5 and 6 of -0.73 and -1.04 cm -1 , respectively, are in accordance with the expection for this out-of-plane type bridges with the orthogonality of the orbitals (Figure 15). Cu Cu Cl Cu(2) Cl Figure 15. Bridging type for Cu(μ-Cl)Cu system. On magnitude values of J obtained decides not only topology of the bridges, causing the weak delocalization of the spin density unpaired electron located on the dx 2 -y 2 orbital in direction an axial position of the bridging oxygen, but also significant axial bond Cu-O distance. Sequence of |J | (5) < |J | (6) is in accordance with difference of the Cu-O axial distance (d cu-o (5) > d cu-o (6)) observed. Both compounds are example of the influence the axial bond on the magnetic properties and indicates that the magnetic interactions may be transmitted, through long apical ligand distance. Weak interactions between copper(II) Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 237 centers through out-of-plane carboxylate bridge has been observed for other complexes (J from ∼0.5 to ∼-1 cm -1 ) with long axial distance (2.28-2.68 Å) [108]. Comparison between the J values for [Cu(2-pic) 2 ] n (5 and 6) and for out-of-plane single carboxylate bridged compounds [105], reveals that the monocarboxylato-bridged series exhibit weaker antiferromagnetic coupling. This is consistent with the simple orbital model proposed by Kahn et al. [116, 117], in which magnetic coupling is proportional to the square of the overlapping integral. So, for mono-out-of-plane bridged copper(II) compounds, the values of coupling constant are smaller due to a decreasing number of the bridging groups. 5.1.2. Structure and Magnetic Exchange through Syn-Anti Carboxylate and Halogene (Cl, Br) Bridges Molecular structure of the polynuclear complexes of formula: {[Cu 2 (2-pic) 3 (H 2 O)]ClO 4 } n (7) , {[Cu 2 (2-pic) 3 (H 2 O)]BF 4 } n (8), {[Cu 2 (2-pic) 3 (H 2 O)]NO 3 } n (9) contains syn-anti carboxylate bridges [80]. These complexes were synthesized by taking advantage of the carboxylate bridge of “metalloligand” [Cu(2-pic) 2 ] building block. Isomorphous 7 and 8 complexes are constructed by “fish backbone” chains through syn-anti (equatorial-equatorial) carboxylate bridges, which are linked to one another by syn-anti (equatorial-axial) carboxylate-bridges, giving rise to a rectangular grid-like two-dimensional net [80] (Figure 16, 17). Figure 16. Metallocycle formed in the complex 7 and 8 [80]. Bogumiła Żurowska 238 Figure 17. Two-dimensional layer in the complex 7 [80]. The magnitude of the magnetic coupling in 7 and 8 through carboxylate bridges defines the exchange parameters J (chain) and J′ (side), respectively, according to scheme (Figure 18): Figure 18. Magnetic exchange scheme in the complexes 7 and 8 [80]. The values of the superexchange parameters, assuming J = J′ = J′′, are J = 1.74 cm -1 , J′ = 0.19 cm -1 for 7, and J = 0.99 cm -1 , J′ = 0.25 cm -1 for 8. The difference between two values J and J′ for 7 and 8 is a result of the difference of the dihedral angles in the Cu-O-C-O-Cu carboxylate bridge. Because, in the backbone of the chain (J) the dihedral angle (48.5 o ), which is measure of non-planarity bridge, is greater from this (31.6 o ) in the side chain (J'), the stronger ferromagnetic coupling (J > J′) in 7 is observed. The same arguments explain the stronger exchange coupling (J > J′) observed in 8, where the dihedral angle is 48.0 o and 31.8 o , respectively. The structure of 9 is one-dimensional polymeric chain formed by alternating syn-anti carboxylate-bridges (Figure 19). Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 239 Figure 19. Alternating chain in 9 [80]. The geometry of the Cu(1) is intermediate between square pyramid and trigonal bipyramid (Adison parameter [115] τ is 0.47). In contrast, the arrangement about Cu(2) is an elongated octahedral. Therefore, it was assumed, that both copper(II) atoms are connected through equatorial-equatorial syn-anti carboxylate bridges [80]. The magnitude of the magnetic coupling in 9 through carboxylate bridges defines the exchange parameters J and J′, according to scheme (Figure 20): Figure 20. Magnetic exchange scheme in complex 9 [80]. The obtained the value of the parameter J and J′ is 1,19 cm -1 . This value is very close to that observed for compounds 7 and 8, where very similar syn-anti carboxylate bridges are present [80]. The structure of the polymeric complex [Cu(2-pic)Cl] n (10) is presented in Figure 21 [75]. The element of the structure is the Cu 4 cluster. Namely, each carboxylate group links in syn-anti conformation two copper centers, forming a 16-membered ring (-Cu-O-C-O-) 4 . Each copper(II) ion of an individual tetrameric units is connected to others through a dichlorobridge (μ-Cl 2 ) resulting in the layer (2D) structure. The copper is five- coordinate with CuNO 2 Cl 2 chromophore (4+1). Consideration of the O(1a) atom, included in semicoordination leads to 4+1+1 * type coordination. Local CuNO 2 Cl 2 geometry involves a very distorted five-coordinate stereochemistry, intermediate between two idealized geometries: square-pyramidal and trigonal-bipyramidal, as indicates structural index τ = 0.39 [115]. Bogumiła Żurowska 240 C1 C2 C3 C4 C5 C6 N1 Cl1 Cu1 O1 O2 O1a Cl1a O2a (A) (B) Figure 21. The fragment of Cu(2-pic)Cl structure (10); (b) The view of the layer structure (2D) of [Cu(2-pic)Cl] n [75]. The [Cu(2-pic)Br] n complex (Figure 22) is izostructural with [Cu(2-pic)Cl] n . Hydrogen contacts of C-H-X (X = Br or Cl, respectively)) type stabilize the structure of 10 and 11. (A) (B) Figure 22. The fragment of [Cu(2-pic)Br] n structure (11); (b) The view of the layer structure (2D) of [Cu(2-pic)Br] n [79]. The bridges Cu-O-C-O-Cu in 10 and 11 indicate the same structural features. The τ parameter is 0.39, indicating the same stereochemistry. However, reliably some structural differences in halogene bridges, essential with magnetic point of view, are observed. Namely, The Cu-Cu distances in dimeric units are 4.446(2) and 3.676(2) Å for 10 and 11, respectively. The bridging distances Cu-Br (2.390(1) and 2.849(1) Å) are longer than these Cu-Cl (2.242(4) and 2.756(4) Å). Bridging angle Cu-X-Cu are 90.79(2) o and 87.9(1) o for X=Cl and Br, respectively. The magnitude of the magnetic coupling through dihalogene and Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 241 carboxylate bridges defines the exchange parameters J and J′ , respectively, according to scheme presented in Figure 23. Figure 23. Scheme of magnetic exchange in complexes 10 and 11. They are J = 15 and 8.31 cm -1 for 10 and 11, respectively, and J′ = 0.38 and 0.34 cm -1 for 10 and 11, respectively. The results obtained indicates that the magnetic interactions inside of the layer is ferromagnetic, and ferromagnetic interaction through chloride-bridge is larger than through bromido-bridge, according to sequence: J(Cl) > J(Br). Weak ferromagnetic interactions through the carboxylate bridge observed for 10 and 11 complexes is results of the syn-anti conformation and low site symmetry of the chromophore group (C 2v ), which causing a weak delocalization of the spin density towards the 2p oxygen orbital of the COO bridge. Additionally, non-planarity of the Cu-O-C-O-Cu bridge leads to stronger ferromagnetic coupling. 5.2. Quinaldinate Complexes 5.2.1. Magnetic Exchange through Syn-Anti Carboxylate and Halogene (Cl, Br) Bridges The crystal structure of the [Cu(2-qic)Cl] n (14) consist of copper(II) ions sequentially bridged through carboxylate groups in the syn-anti conformation forming an infinite one- dimensional zigzak chain with two alternating non-equivalent copper(II) chromophores: CuO 2 Cl 2 on square-planar geometry and CuN 2 O 2 Cl on geometry involves a very distorted five-coordinate stereochemistry, intermediate between two idealized geometries: square- pyramidal and trigonal-bipyramidal, as indicates structural index τ = 0.64 [115]. The neighbouring chains are linked by linear mono-chloride atoms (bridging angle Cu-Cl-Cu is 180 o ) link adjacent chains, forming a ribbon type structure (1D). (A) Figure 24. Continued. Bogumiła Żurowska 242 (B) Figure 24. (a) The fragment of [Cu(2-qic)Cl] n structure (14); (b) View of ribbon type structure (1D) of [Cu(2-qic)Cl] n [76]. The planes of the quinoline rings are stacked, and additionally, the contacts C-H…Cl stabilize the crystal structure (Figure 25). Figure 25. Arrangement of the [Cu(2-qic)Br] n (14) ribbons of the compound 14 in the crystal lattice . Hydrogen contacts of C-H··O and C-H···Br type are shown with dashed lines [79]. The [Cu(2-pic)Br] n (15) is izostructural with [Cu(2-pic)Cl] n (14). Similarly as in the case picolinate complexes (10 and 11) the some structural differences in halogene bridges are observed. The distances Cu-Cu in bridged unit Cu(μ-X)Cu is 4.860(3) Å (X=Cl) and 5.149(2) Å (X=Br). The bridging distances Cu-X are 2.376(2) and 2.515(4) Å (X=Cl), and 2.490(2) and 2.659(2) (X=Br). The crystal structure of Cu(2-qic)Cl suggests that two kinds of coupling parameters must be considered to interpret the magnetic properties, according to the scheme presented in Fig 26. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 243 J 2 J 2 J 2 J 2 J 2 J 1 J 1 J 2 Cu Cu Cu Cu Figure 26. Scheme of the magnetic exchange in complexes 14 and 15. where J 1 and J 2 are the constants for exchange coupling via the mono-μ-chlorobridge (or bromide bridge) in the dimeric unit and the carboxylate bridge in the chain, respectively. The values parameters coupling are for Cu(2-qic)Cl) (14): J 1 = -57 cm -1 , J 2 = 0.37 cm -1 , and for Cu(2-qic)Br) (15): J 1 = -102,5 cm -1 , J 2 = 0.37 cm -1 . 5.3. Magneto-Structural Correlation for Halogene Bridges As it is seen from the Table 2, the coupling between metallic centers in the complexes 14 and 15 in the chain (carboxylate bridge) is ferromagnetic, however, between the chains (halogene bridge) is moderately antiferromagnetic and |J| (Cl) > |J| (Br) sequence is observed. One of the major problem that remains open in magnetochemistry research is to discover the factors which determine whether the magnetic interactions in singly and doubly chlorobridged copper systems will be antiferromagnetic or ferromagnetic. For such systems some theoretical analyses [91] have been presented. 5.3.1. Monohalogene Bridges From the Table 3 it is seen, that antiferromagnetic coupling between copper(II) centers through mono-chloride and bromide bridges is dominating in Cu(2-pic)Cl (10) and Cu(2- pic)Br (11). It is worth to emphasize that the antiferromagnetic coupling is the strongest one observed for halogeno-bridged systems up to now. The structures of the complexes with linear Cu-Cl-Cu bridges are known, but besides carboxylate compound 14 [78], only two with other ligands including linear 16 [11o] and near linear (177.35 o ) (17) [111] were characterized magnetically. For the complexes including linear Cu-Cl-Cu systems with bridging angle of 180 o moderately strong antiferromagnetic (14) and very weak interactions are observed. As results with Table 4, presented structural parameters for linear and nearly linear Cu(μ-Cl)Cu bridges in correlation with coupling parameters J, bridging angle Φ directly not determined magnitude of the coupling through chloride-bridge. Also such parameters as Cu-Cu and Cu- Cl distances and structural parameter τ, have not larger influence on value of J parameter. Table 4. Coupling parameters J and symmetry of the chromophore group for the chloride (10, 14) complexes and its bromide analogs (11, 15) Compound Type of bridge a) Coupling parameter J (cm -1 ) Chromophore Group Symmetry Reference (μ-X) 2 (μ-X) OCO J 1 (cm -1 ) J 2 (cm -1 ) Cu(2-pic)Cl (10) 15.0 0.38 Cu(N 2 O 2 Cl) C 4v ↔ D 3h (C 2v ) [75] Cu(2-pic)Br (11) 8.31 0.34 Cu(N 2 O 2 Br) C 4v ↔ D 3h (C 2v ) [79] Cu(2-qic)Cl (14) -57.0 0.37 Cu(N 2 O 2 Cl) Cu(O 2 Cl 2 ) C 4v ↔ D 3h (C 2v ) D 4h [76] Cu(2-qic)Br (15) -102.5 0.37 Cu(N 2 O 2 Br) Cu(O 2 Br 2 ) C 4v ↔ D 3h (C 2v ) D 4h [79] X= Cl lub Br; Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 245 Table 5. Structural and magnetic parameters for complexes with linear bridge Cu(μ-Cl)Cu Compound a Cu⋅⋅⋅Cu (Å) R (Å) Cu-Cl-Cu Φ ( o ) τ symmetry J (cm -1 ) Ref. Cu(2-qic)Cl (14) 4.86 2.51, 2.65 180 0.64 b (C 2v ) -57.0 [76] [Cu(tach) 2 Cl] 5+ (16) 5.3 2.34, 2.65 180 0.07 (D 4h ) -0.86 [110] Cu 2 (μ-Cl)(L) 2 (ClO 4 ) 3 (17) 2.75, 2.71 177.35 0.06 (D 4h ) 0.03 (D 4h ) -1.30 [111] a) R- Cu-Cl distance, τ- Adison parameter [119] b) concern of Cu(2) c) Φ -bridging angle Chloride bridges in 16 and 17 compounds belong to II type (axial-axial), however, the compound 14 to type III (axial-equatorial) (Figure 14). Fig 27 shows the scheme of the bridges and mutual orientation of the copper(II) magnetic orbitals and 2p ligand orbitals for above complexes. O O Cl Cu(1) Cl Cu(2) O N O N Cu(2) O O O O Cl Cu(1) N N Cl Cl Cl N N N N N N Cu N N Cu N N Cl N N N N N N Cu Cu Cu(2-qic)Cl (14) [Cu(tach) 2 Cl] 5+ (16) Figure 27. Relative orientation of magnetic orbitals in Cu(2-qic)Cl (14) and [Cu(tach) 2 Cl] 5+ (16). According to Kahn’s theory [116, 117] the sign and magnitude of the magnetic exchange coupling are very sensitive to the orientation of the unpaired electrons on metal ions. Different geometries usually result in different energies (and orientation). Such a different orientation of the d orbitals in the cited compounds must be responsible for the magnetic behavior. The explanation of the magnetic properties of the 14 and 16 and 17 is based on determination of the superexchange geometry and topology of the spin density of the unpaired electron. From Adison structural parameters [115] it is evident, that the geometry of the copper(II) coordination sphere in 16 and 17 is near square pyramid (D 4h ), in which axial position occupy chloride atom. In this case weak delocalization of the spin density in Bogumiła Żurowska 246 direction of the axial position is expected. So, in spite of bridging angle of 180 o , in 16 and 17 compounds of an axial(apical)-axial(apical) type only weak antiferromagnetic coupling through chloro-bridge is observed. Stronger coupling observed in 14 is a result of significantly delocalization of the spin density of the copper magnetic orbital in direction of the equatorial position occupied by a chloride atom. Then, the Cu(1)-Cl(1) eq pathway in 14 is more effective in allowing for the spin delocalization than Cu-Cl ax , pathway in the mono- chloro-bridged dimers 16 and 17 of an axial(apical)-axial(apical) type, an increase of the exchange transmitted through the bridging chloride ion in 14 is expected. On the other hand, the distortion from a square-pyramidal towards a trigonal-bipyramidal copper coordination geometry (τ = 64) is expected to increase the spin density on the bridge. For this distortion, magnetic orbital of copper(II), on which is localized the spin density of the unpaired electron, is dx 2 -y 2 with admixture of the dz 2 . Then partial delocalization of the spin density on 2p orbital of the chloride atom in axial position occurs. This is consistent with relationship between Addison structural parameter τ and the magnitude of the constant coupling |J|, observed for other systems with chloride-bridged connecting five-coordinated copper centers [37, 106]. Generally, the Adison parameter τ plays an important role in determination of magnetic interaction. It has been pointed out that the greater is this parameter, the higher is the spin delocalization on the bridge, consequently, the stronger is the antiferromagnetic coupling and vice-versa. Namely, this confirms the Hay’s theory [89], which on the basis of calculations on a hypothetical mono-chloro-bridged copper(II) dimer predicts an increase of the antiferromagnetic coupling as such a distortion proceeds. However, the parameter τ has a minor influence on the relatively superexchange interaction in 14 compound. Mutual orientation of the equatorial plane of Cu(1) and Cu(2) (Fig 27) is mainly responsible for the observed strength of the magnetic interaction. In summary, for 14 compound better overlap of the copper magnetic orbitals with ligand orbitals leads to, the stronger antiferromagnetic coupling, compared with 16 and 17 compounds. So, the electronic and structural features of the linear Cu-Cl-Cu bridge in 14 are favorable for the propagation of strong interaction. These features also explain strong antiferromagnetic coupling observed in bromide analog Cu(2-qic)Br (15), J = -102.5 cm -1 . 5.3.2. Dihalogene Bridges Although there is not simple correlation in the case of chloride bridges, Hatfield [109] has obtained interesting magneto-structural correlations which show that the sign and the strength of coupling occurring through the bridging chloride ions in di- and polynuclear copper(II) complexes depend critically on the structural parameter Φ/R o , where Φ is the Cu- Cl-Cu bridging angle and R o the longer Cu-Cl distance (out-of-plane) within the bridge. For bromide bridges this correlation is not observed [79, 118, 119]. Alves et all. [120] presented correlation in a variety of chloro-bridged copper(II) dimers. The empirically established correlation between J and Φ/R o leads to conclusion that for the values lower than 32.6 o Å -1 , and higher than 35 o Å -1 the antiferromagnetic magnetic exchange is observed, whereas the ferromagnetic coupling appears when the value of this structural parameter is intermediate between these two values. Ferromagnetic coupling through dichloro-bridge in Cu(2-pic)Cl (14) is well correlated with the calculated structural parameter (J = 15 cm -1 , Φ/R o =33.2 o Å -1 ). However, in the case of dibromo-bridged copper(II) compound Cu(2-pic)Br (11) the exchange value J does not correlate with Φ/R o . Namely, for Φ/R o < 32.6, i.e. 31.9 o Å -1 Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 247 ferromagnetic exchange was found (J = 8.32 cm -1 ). Thus, values of the exchange coupling do not correlate with the bridging angle or bridging distance R o . It is in accordance with earlier observations [118, 119] which indicate that there is no simple magneto-structural correlation for bromo-bridged dimmers as it was found for dichloro-bridged copper(II) complexes. 5.3.3. Correlation between J(Br) and J(Cl) The larger antiferromagnetic interaction in [Cu(2-qic)Br] n (15) through the bromide bridge (J = -102.5 cm -1 ) than that observed in [Cu(2-qic)Cl] n (14) through the chloride bridge (J = -57 cm -1 ), in spite of a longer Cu…Cu distance (5.149(2) Å) in the bromide bridging unit than that of the chloride compound (4.860(3) Å), may be explained on the basis of the fact, that the magnetic orbital of bromide atom contacts easier with the copper atom than that of chloride (the orbitals 3p of the bromide atom, in contrary to 2p orbitals of chloride atom are energetically nearier of the 3d orbitals of copper atom). In other words, the contribution of the orbital overlap between Cu(II) and bridging chloride atom, suggesting that the spin density localized on the bridging Br atom is a larger than that on the bridging Cl atom. Relationship |J | (Br) > |J | (Cl) is consistent with the value of the exchange constant observed for other antiferromagnetic monohalide bridging compounds [118, 119]. The dihalido-bridges (μ-Cl) 2 transmit the ferromagnetic exchange with J = 8.31 and 15.0 cm -1 in [Cu(2-pic)Cl] n (10) and [Cu(2-pic)Br] n (11), respectively. Thus, in contrary to relation |J| (Br) > |J | (Cl) obtained for [Cu(2-qic)Br] n (15) and the chloride analog, the sequence |J | (Cl) > |J| (Br) is observed for 10 and 11. According to Kahn theory: J = J F + J AF [91-94]. Because the magnetic orbital of bromide atom contacts easier with copper atom than chloride, the antiferromagnetic contribution J AF in J should be larger in the case of bromide compounds. This model may explain the observed increase of |J| along the sequence Cl, Br of briding atoms in Cu(2-pic)X and, Br, Cl of bridging atoms in Cu(2-qic)X. Concluding, the superexchange pathway Cu-Br-Cu is more favorable for propagation of magnetic interactions than Cu-Cl-Cu, and generally relationship is observed [79, 125], for the antiferromagnetic coupling: 2J AF (Cl) ≅ J AF (Br), and for ferromagnetic interaction: J F (Cl) ≅ 2J F (Br). 6. MAGNETIC INTERACTIONS THROUGH NON-COVALENT INTERACTIONS (H-BOND AND π-π STACKING) Studies of very weak non-covalent intermolecular interactions, such as hydrogen bonds [126, 127], π-π stacking of aromatic rings [128-131] are of fundamental importance not only for further development of inorganic supramolecular chemistry and prediction of crystal structure, but these contacts also generate interesting supramolecular properties, such as electrical, optical and magnetic ones [132], and play a major role in the functioning of biological macromolecules [133, 134]. Tabl. 6 shown exchange coupling parameters zJ′ (z is the number of nearest neighbors) obtained for Cu(2-pic) 2 (4, 5, 6) and Cu(2-qic) 2 ·H 2 O (12, 13) complexes. Bogumiła Żurowska 248 Table 6. Parameters of the magnetic coupling in 4, 5, 6, 12 and 13 complexes Compound Type interactions zJ′ (cm -1 ) Oddziaływanie poprzez mostek out-of-plane -O-C-O- J (cm -1 ) Ref. Cu(2-pic) 2 (4) π-π stacking C-H⋅⋅⋅O -0.76 -0.47 [83, 135] [Cu(2-pic) 2 ] n (5) C-H⋅⋅⋅O -0.06 -0.73 [77] [Cu(2-pic) 2 ] n (6) C-H⋅⋅⋅O 0.34 -1.04 [78, 83] Cu(2-qic) 2 ·H 2 O (12) O-H⋅⋅⋅O -0.25 [83, 135] Cu(2-qic) 2 ·H 2 O (13) O-H⋅⋅⋅O -0.23 [135] 6.1. Mononuclear Systems The crystal structures of the [Cu(2-pic) 2 Br 2 ][(2-pic-H) 2 ] picolinate complex (3) (Fig 6) indicate that the molecules are isolated in the crystal lattice and for that reason the magnetic interactions between copper centers are not observed. As it was mentioned earlier (Figure 8) intermolecular short (3.27 Å) π-π stacking interactions in Cu(2-pic) 2 (4) lead to one-dimensional (1D) network arrangement (Fig 8), resulting a Cu-Cu contacts of 3.6975(7) Å. Further hydrogen bonds, additionally stabilizing structure, link Cu(2-pic) 2 molecule leading to three-dimensional network. Crystal packing of 4 is presented in Figure 28. Figure 28. The crystal structure of Cu(2-pca) 2 (4). Hydrogen bonds are shown with dashed line [83]. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 249 The obtained exchange coupling constants J = -0.76 cm -1 , responsible for the π-π stacking and zJ ’ = -0.47 cm -1 , responsible for the hydrogen bonds interactions, indicate stronger antiferromagnetic coupling through the π-π stacking. In 4 an interaction through an offset π-π stacking (1.73 Å) between the pyridine molecules occurs (Figure 29) with a perfectly planar copper complex, allowing for the optimal stacking interaction. The mutual positions of coplanar pyridine rings show a very small value of the interplane distance (3.27 Å) and often observed centroid-centroid distance of 3.70 Å. However, the angle between the centre-centre line and the normal to the plane, of about 30 o , is large. For centroid-centroid distances up to 3.8 Å, being approximately the maximum distance for which π-π interactions are accepted, this displacement angle, observed for pyridine molecule, lies around 20 o . This angle corresponds to a horizontal displacement of 1.30 Å. Magnetic interaction through π-π stacking can have very weak antiferromagnetic [135- 138] or weak ferromagnetic [139, 140] character. Influence of the structural factor, such as Cu-Cu (R) distance, centroid-centroid distance R, distance between planes R 2 , offset R 1 and displacement angle Θ, as also influence of electronic factors (participation of π and σ electrons of the aromatic rings and dπ copper(II) ions) on magnitude and sign of J has been for several complexes the subject of the discussion [135]. Analysis of the structure and magnetic interactions in these complexes suggests that the interplane and offset distances are substantial parameters which could influence on the strength of magnetic exchange coupling between copper(II) centers. So, both short interplane and relatively large offset distances could be responsible for a larger antiferromagnetic exchange through π-π stacking interaction observed in 4. ) θ R 1 R 2 R N N Cu Cu R Figure 29. Geometry of the pyridyl rings in Cu(2-pca) 2 (4); R = 3.70 Ǻ, R 1 = 1.73 Ǻ, R 2 = 3.27 Ǻ, θ = 30 o [134]. The crystal structure of the Cu(2-qic) 2 ·H 2 O (12) (Figure 30), which molecular structure is depicted on Figure 10, present the layer (2D), created by strong O-H···O hydrogen bonds (O···O The spectroscopic studies of the complexes 12 and isomer 13, for which lack of the X- ray data, indicate that the structure of 13 is also stabilized by strong O-H…O hydrogen bonds. Bogumiła Żurowska 250 Figure 30. The crystal structure of Cu(2-qic) 2 ·H 2 O (12). Hydrogen bonds are shown with dashed line [141]. The coupling parameters of zJ’ = -0.25 (12) and -0.23 cm -1 (13) indicate the weak antiferromagnetic coupling transmitted by H-bonds [141]. Polynuclear systems. The molecular structures of isomeric forms of [Cu(2-pic) 2 ] n 5 and 6 are one-dimensional chains (1D) formed by double out-of-plane carboxylate bridges (Figure 9). The weak C-H…O hydrogen bonds and contacts link the chains forming two-dimensional (2D) network (Figure 31, 32). (A) (B) Figure 31.The crystal structure of Cu(2-pic) 2 (5). (a) Corrugated layers formed by planar molecules of Cu(2-pic) 2 of adjacent chains; (b) The layer (2D). Hydrogen bonds of C-H⋅⋅⋅O type are shown with dashed lines [77]. Exchange coupling parameters indicate weak antiferromagnetic (zJ’= -0.06 cm -1 ) in 5 and weak ferromagnetic (zJ’= 0.34 cm -1 ) in 6 interactions through hydrogen bonds. These interactions are weaker than those transmitted through out-of-plane bridges (Table 5). The role that hydrogen bonds play in the transmission of magnetic interactions is still not completely understood. For many years, hydrogen bonds have been reported to propagate essentially antiferromagnetic interactions between metal centers in variety of transition metal complexes [142]. Even Cu dimer with O-H···O distance of 2.32 Å with high J value of -90 a b Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 251 cm -1 has been reported [143]. Recent theoretical studies have been able to rationalize the antiferromagnetic coupling between copper(II) complexes mediated by hydrogen bonds [143]. (A) (B) Figure 32. The crystal structure of Cu(2-pca) 2 (6);(a) Layers formed by planar molecules of Cu(2-pca) 2 of adjacent chains; (b) The layer (2D). Hydrogen bonds of C-H⋅⋅⋅O type are shown with dashed line [78]. In recent years, ferromagnetically coupled hydrogen bond systems are growing exponentially, either some supramolecular copper structures, or even some organic radicals interactions has been observed but the mechanism of these interactions is not completely understood [143-148]. Although the ligands (2-pic) are the same in 5 and 6 complexes and the Cu(II) ions are doubly bridged by carboxylate out-of-plane bridges, the packing of the two complexes is different (Figure 31, 32). In these compounds difference in H-bond networks are responsible for different magnetic properties (F and AF). Both compounds show C-H···O intermolecular hydrogen bonds with similar O···H distance in the range 2.43-2.49 and 2.40-2.49 Å in 5 and 6, respectively. However, the relative C…O donor…acceptor separations in C-H…O hydrogen bonds in 5 are shorter (3.161-3.278 Å) than those (3.287-3.419 Å) in compound 6. The shorter Cu-O distance in 5 (1.944(7 Å) than this in 6 (1.957(3) Å) is also observed. On the other hand, the relative bond angles C-H···O in 5 of 150 o and 166 o are more favourable for transmission of the magnetic interaction through the H-bonds than those in compound 6 (140 o , 137 o , 143 o ). The above structural factors could explain the differences in the sign of the superexchange coupling observed in compounds 5 and 6, because the stronger coupling correspond to the shorter hydrogen bonded donor…acceptor distance [W] and shorter distance between copper ions and oxygen atom included in H-bond. These conclusions confirm earlier investigations [143, 144]. The crystal structure of the [Cu(2-pic) 2 Cl] (9) and izostructural [Cu(2-pic)Br] (11) (Fig 25) indicates that the magnetic interactions may be transmitted through non-covalent interactions (H-bond network and π-π stacking). However, lack of model do not permit the calculation of J parameter, characterizing these interactions. Bogumiła Żurowska 252 REFERENCES [1] Murphy, B.P., & Hathaway, B.J. (1993). Copper. Coord. Chem. Rev. 124 (1,2), 63-106. [2] Hathaway, B.J., (1987). Copper. In G. Wilkinson, R. D. Gillard, & J. A. McCleverty, (Eds.). Comprehensive Coordination Chemistry, Vol. 5,( pp. 534-774). Oxford: Pergamon Press. [3] Nelson, J. (2010). Copper, Annu. Rep. Prog. Chem., Sect A: Inorg. Chem., 106, 235- 254. [4] Hathaway, B.J. (1984). A new look at the stereochemistry and electronic properties of complex of the copper(II) ion. Structure and Bondings, Vol. 57 (pp. 55-118) Berlin- Heidelberg: Springer-Verlag. [5] Carlin, R.L. & Block, R. (1978). Magnetochemistry of copper(II). J. Chem. Sci. 98 (1- 2), 79-97. [6] Solomon, E.I., Baldwin, M.J., & Lowry, M.D. (1992). Electronic structures of active sites in copper proteins: contribution to reactivity. Chem. Rev. 92 (21), 521-542 [7] Karlin K.D., & Tyeklar, Z. (1993). Bioinorganic Chemistry of Copper, London: Chapman & Hall. [8] Hughes, M.N.( 1981). The Inorganic Chemistry of Biological Processes, 2 nd ed., New York: Wiley [9] Kahn, O. (1993). Molecular magnetism, New York: Wiley-VCH. [10] Kahn, O. (1985). Dinuclear complexes with predictable magnetic properties. Angev. Chem., Int. Ed. Engl., 24 (10), 834-850. [11] Kahn, O. (1987). Magnetism of the heteropolymetallic systems. Structure Bonding, 68 89-167. Berlin: Springer. [12] Gatteschi, D., Kahn, O., & Willett, R. D. (1984) Magneto-Structural Correlations in Exchange Coupled Systems, Dordrecht: Reidel, [13] Coronado, E., Georges, R., & Tsukerblat, B.S. (1996). Exchange Interactions. In E. Coronado, P. Delhačs, D. Gatteschi, & J. S. Miller, (Eds.) Mechanism Molecular Magnetism: from Molecular Assemblies to the Devices; NATO ASI E 321, pp. 267- 279. Dordrecht: Kluwer. [14] Gažo, J., Bersuker, I.B., Garaj, J., Kabešová, M., Kohout, J., Langfelderová, H., Melník, M., Serátor, M., & Valach, F. (1976). Plasticity of the coordination sphere of copper(II) complexes, its manifestation and causes. Coord. Chem. Rev., 19 (3), 253- 297. [15] Murphy, B., & Hathaway, B. (2003). The stereochemistry of the copper(II) ion in the solid-state – some recent perspectives linking the Jahn-Teller effect, vibronic coupling, structure correlation analysis, structural pathways and comparative X-ray crystallography. Coord. Chem. Rev., 243 (1-2), 237-262. [16] Melník, M. (1982). Structural isomerism of copper(II) compounds. Coord. Chem. Rev., 47 (3), 239-261. [17] Melník, M., Kabešova, M., Koman, M., Macaškova, L. & Holloway, C.E. (2000). Copper(II) coordination compounds: Classification and analysis of crystallographic and structural data V. Polymeric compounds. J. Coord. Chem., 50 (3-4), 177-322. [18] Ivarsson, G. (1973). Metal complexes with mixed ligands. Acta Chem. Scand., 27 (9), 3523-3530. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 253 [19] Quiroz-Castro, M.E., v. Albada, G.A., Mutikainen, I., Turpeinen, U. & Reedijk, J. (2000). The crystal structure, spectroscopy and EPR of tetragonal bis(2- (aminomethyl)pyridine) Cu(II) compounds. Rare cases of the absence of Cu(II) plasticity. Inorg. Chim. Acta, 297 (1-2), 129-133. [20] McFadden, D.L. , McPhail, A.T.. Garner, C.D., & Mabbs, F.E. (1976). Crystal and molecular structure, electron spin resonance, and electronic spectrum of tetrakis(imidazole)dinitratocopper(II) J. Chem. Soc., Dalton Trans. (1), 47-52. [21] Burke, P.J., Henrick, K. D. & McMillin, R. (1982). Crystal and molecular structures of bis(4,4',6,6'-tetramethyl-2,2'-bipyridyl)copper(I) perchlorate, bis(4,4',6,6'-tetramethyl- 2,2'-bipyridyl)copper(II) diperchlorate, and bis(4,4',6,6'-tetramethyl-2,2'- bipyridyl)copper(II) diperchlorate dihydrate. A search for copper(II) and copper(I) complexes with a common ligand environment. Inorg. Chem., 21 (5), 1881-1886 [22] Nieminen, K. (1981). Crystallographic and magnetic study of "tetraisothiocyanato- cuprate(I)-bis( μ-(2-[(3-aminopropyl)amino]ethanolato)-N,N',μ-O)dicopper(II) polymer thiocyanate. Acta Scand., ser. A, 35 (10), 753-757. [23] Haanstra, W.G.,.van der Donk, W.A.J.W., Driessen, W.L., Reedijk, J., Wood, J.S., & Drew, M.G.B.. (1990). Unusual behaviour of the thioether function of the ligand 1,8- bis(3,5-dimethyl-1-pyrazolyl)-3,6-dithiaoctane (bddo) towards transition-metal salts. X- Ray structures of a green and a red modification of [Cu(bddo)Cl 2 ]. J. Chem. Soc., Dalton Trans. (10), 3123-3128. [24] Kelly, P.F. Slawin, A.M.Z., & Waring, K.W. (1997). Preparation and crystal structures of two forms of trans-[CuCl 2 {N(H)SPh 2 } 2 ]; an unusual example of square planar/pseudotetrahedral isomerism in a neutral copper(II) complex. J. Chem. Soc. Dalton Trans., (17), 2853-2854. [25] Broughton, V. Bernandirelli, G. & Williams, A.F. (1998). Tetrahedral coordination by a seven-membered chelate ring. Inorg. Chim. Acta, 275-276 (1-2), 279-288. [26] van Albada, G.A., Smeets, W.J.J., Spek, A.L. & Reedijk, J. (1999). Synthesis, characterization, spectroscopy, magnetism and X-ray structures of red and green Cu(II) chloride adducts with bis(2-benzimidazolyl)propane. Inorg. Chim. Acta, 288 (2), 220- 225. [27] Greenwood, N.N., Earnshaw, A. (1997). Chemistry of the Elements, second ed., Oxford: Butterworth-Heinemann. [28] Flizner, K. Stassen, A.F., Mills, A,M., Spek, A.L., Haasnoot, J.G., & Reedijk, J. (2003). The chelating ligand 1,3-bis(pyrazol-1-yl)propane (Bpp) Enforces a tetrahedral geometry in both Cu II and Cu I species. Eur. J. Inorg. Chem. (4), 671-677. [29] Doedens, R.J. (1976). Structure and metal-metal interactions in copper(II) carboxylate complexes. In S.J. Lippard (Ed.). Progress in Inorganic Chemistry, Interscience Publishers: John Wiley & Sons, 29, 209-229. [30] Ruiz-Perez, C, Sanchiz J, Molina M.H., Lloret F., & Julve M., Ferromagnetism in Malonato-Bridged Copper(II) Complexes. Synthesis, Crystal Structures, and Magnetic Properties of {[Cu(H 2 O) 3 ][Cu(mal) 2 (H 2 O)]} n and {[Cu(H 2 O) 4 ] 2 [Cu(mal) 2 (H 2 O)]} [Cu(mal) 2 (H 2 O) 2 ]{[Cu(H 2 O) 4 ][Cu(mal) 2 (H 2 O) 2 ]} (H 2 mal = malonic Acid) (2000). Inorg.Chem.,39, (7), 1363. [31] Ruiz-Perez, C, Hernandez-Molina M., Lorenzo-Luis P, Lloret F. & Julve, M. (2000). Magnetic coupling through the carbon skeleton of malonate in two polymorphs of Bogumiła Żurowska 254 {[Cu(bpy)(H 2 O)][Cu(bpy)(mal)(H 2 O)]}(ClO 4 ) 2 (H 2 mal = malonic acid; bpy = 2,2‘- bipyridine). Inorg. Chem. 39 (17), 3845-3852. [32] Rodríguez-Fortea, A., Alemany, P., Alvarez, & S. Ruiz, E. (2001). Exchange coupling in carboxylato-bridged dinuclear copper(II) compounds: A density functional study. Chem. Eur. J., 7 (3), 627-637. [33] Konar, S. Mukherjee, P.S. Drew, Ribas, M.G.B., & Chaudhuri, J. N.R. ( 2003). . Syntheses of two new 1D and 3D networks of Cu(II) and Co(II) using malonate and urotropine as bridging Ligands: Crystal structures and magnetic studies. Inorg. Chem. 42 (8), 2545-2552. [34] Żurowska, B. Mroziński, J. Julve M. , Lloret, F. Maslejova, A. & Sawka-Dobrowolska, W. (2002). Structural, spectral and magnetic properties of end-to-end di-μ-thiocyanato bridged polymeric complexes of Ni(II) and Co(II). X-ray crystal structure of di-μ- thiocyanato-bis- imidazole)nickel(II). Inorg. Chem. 41 (7) 1771-1777. [35] Youngame, S., Chaichit, N. Kongsaeree, P., van Albada, G.A., & Reedijk, J. (2001). Synthesis, structure, spectroscopy, and magnetism of two new dinuclear carbonato- bridged Cu(II) complexes. Inorg. Chim. Acta, 324 (1-2), 232-240. [36] E. Ruiz, Alemany, P., Alvarez, S., & Cano, J. (1997). Toward the prediction of magnetic coupling in molecular systems: Hydroxo- and alkoxo-bridged Cu(II) binuclear complexes. J. Am. Chem. Soc, 119 (6), 1297-1303. [37] Hernández-Molina, M., González-Platas, J., Ruiz-Pérez, C., Lloret, F., & Julve, M. (1999). Crystal structure and magnetic properties of the single-μ-chloro copper(II) chain [Cu(bipy)Cl 2 ] (bipy=2,2′-bipyridine). Inorg. Chim. Acta, 284 (2), 258-265. [38] Ruiz, E., Alemany P., Alvarez S.,& Cano., J. (1997). Structural modeling and magneto- structural correlations for hydroxo-bridged copper(II) binuclear complexes. Inorg. Chem., 36 (17), 3683-3688. [39] Rodríguez-Fortea, A., Ruiz, E., Alvares, S., & Alemany, P. (2005). Exchange coupling in di-μ-hydroxo dinuclear cu(II) compounds: a density functional study. Dalton Trans. (15), 2624-2629 [40] Turnbull, T. & Sugimoto, L.K. (1996). In M.M. Turnbull, T. Sugimoto, L.K. Thompson. (Eds). Molecule-based Magnetic Materials: Theory, Techniques, and Applications. (pp 1-352); ASC Symposium Series, Vol. 644; American Chemical Society: Washington, D.C. [41] Magnetism: Molecules to Materials; J.S. Miller, M. Drillon., (Eds).; Wiley-VCH: New York, 2000-2005; Vols. 1-5. [42] Law, N.A., Caudle, M. T. & Pecoraro, V. L. (1998). Manganese Redox Enzymes and Model Systems: Properties, Structures, and Reactivity. Adwances in Inorganic Chemistry, 46, 305-440. [43] Wieghardt, K., (1989). The active-sites in manganese-containing metalloproteins and inorganic model complexes. Angev. Chem. Int. Ed. Engl. 28, 1153-1172. [44] Melník, M. (1981). Mono-, bi-, tetra and polynuclear copper(II) halogeno-carboxylates. Coord. Chem. Rev., 36 (1), 1-44. [45] Kato, M., & Muto, Y. (1988). Factors affecting the magnetic properties of dimeric copper(II) complexes. Coord. Chem. Rev., 92, 45-83. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 255 [46] Sundberg, M.R., Uggla, R. & Melnik, M.( 1996). Comparison of the structural parameters in copper(II) acetate-type dimers containing distorted square pyramidal CuO 4 O and CuO 4 N chromophores. Polyhedron, 15 (7), 1157-1163. [47] Oldham, C. (1987). Carboxylates, Squarates and Related Species, In G. Wilkinson (Ed.). Comprehensive Coordination Chemistry., Oxfort: Pergamon Press. [48] Mehrotra, R.C., & Bohra, R. (1983). Metal Carboxylates, London: Academic Press. [49] Holz, C.R., Bradshaw, J.M. , & Bennet, B. (1998). Synthesis, Molecular Structure, and Reactivity of Dinuclear Copper(II) Complexes with Carboxylate-Rich Coordination Environments. Inorg. Chem., 37 (6), 1219-1225. [50] Faure, R., Loiseleu. H., & Thomas-David, G., (1972). New refining of crystalline- Structure of hydrated bis(pyridine-2-carboxylato)copper(II). Acta Crystallogr. B, 28 (9), 1890-1893. [51] Faure R., & Loiseleu.H. (1998 ). Structure of zinc 2-pyridylacetate dihydrate . Acta Crystallogr. B, 28 (25-26), 811-812. [52] Segl’a, P., Jamnický, M., Koman, M., Šima, J., & Głowiak, T. (1998). Metal(II)- promoted hydrolysis of pyridine-2-carbonitryle to pyridine-2-carboxylic acid. The structure of [Cu(pyridine-2-carboxylate) 2 ]·H 2 O. Polyhedron, 25 (26), 4525-4533. [53] Dutta, D., Jana, A. D., Ray, A., Marek, J., & Ali, M. (2008). Synthesis of a new polymorph in [Cu(pyridine-2-carboxylate) 2 ] system. Ind. J. Chem., 47 (11), 1656-1660. [54] Loiseleur, H., (1972). Structure du pyridyl-2-acétate de zinc, dehydrate. Acta Crystallogr., Sect. B, 28 (3), 811-815. [55] Deloume, J.P., & Loiseleur, H. (1974). Structure crystalline du pyridine-2 carboxylate de cadmium. Acta Crystallogr. B, 30 (3), 607- 609. [56] Deloume, J.P., Loiseleu, H., & Thomas, G., (1973). Structure du picolate de magnesium dehydrate. Acta Crystallogr. B, 29 (4), 668-673. [57] Deloume, J.P., & Loiseleu, H. (1974). Structure of zinc 2-pyridylacetate dehydrate Acta Crystallogr., B, 30 (3), 607-609. [58] Takenaka, A. Utsumi, H., Yamamoto, T, Furusaki, A., & Nitta, I. (1970). Crystal and molecular structure of trans-bis(picolinato)copper(II) dihydrate, Cu(pc) 2 . 2H 2 O. Nippon Kagaku Zasshi, 91(10), 928-929. [59] Takenaka A. Utsumi H, Ishihara N, Furusaki A, & Nitta I. (1970). Molecular and crystal structures of trans-diaquo-bis-(picolinato)nickel(II) dehydrate. Nippon Kagaku Zasshi, 91 (10), 921-922. [60] Lumme, P., Lundgrem, G., & Mark, W. (1969). The crystal structure of zinc picolinate tetrahydrate Zn(C 6 H 4 O 2 N) 2 (H 2 O) 4 . Acta. Chem. Scand., 23, 3011-3022. [61] Huang, D., Wang, W., Zhang, X., Chen, Ch., Chen, F., Liu, Q., Liao, D., Li, L., & Sun, L. (2004 ). Synthesis, Structural characterizations and magnetic properties of a series of mono- di- and polynuclear manganese pyridinecarboxylate compounds. Eur. J. Inorg. Chem. (7), 1454-1464. [62] Lamprecht, G.J., Leipoldt, & J.G., Roodt, A., (1991). Structure of carbonyl(2- quinolinecarboxylato)-kN,kO)-(triphenylphosphite-kP)rhodium(I). Acta Crystallogr., Sect C, 47, Part 10, 2209-2211. [63] Lamprecht, G.J., Beetge, J.H., Leipoldt, J.G., & De Waal, D.R. (1986). The structure of 2-carboxyquinolinato-bis(triphenylphosphite)-rhodium(I). Inorg. Chim. Acta, 113 (2), 157-160. Bogumiła Żurowska 256 [64] Graham, D.E., Lamprecht, G.J., Potegieter, I.M., Roodt, A., & Leipoldt, J.G. (1991). Observed trans influence of donor atoms in monocharged bidentate ligands – Crystal structure of the acetone solvate of 2-carboxyquinolinato-carbonyltriphenyl phosphinerhodium(I). Trans. Met. Chem., 16, (2), 193-195. [65] Li, W., Olmstead, M.M., Miggins, D., Fish, & R.H. (1996). Synthesis and structural studies of metal complexes of the biological ligand 2-quinaldic Acid: Utilization of the polymer pendant analog PS-2-QA for selective aluminum ion removal from aqueous solution. Inorg. Chem., 35, (1), 51-55. [66] Cano, M., Heras, J.V., Lobo, M.A., Pinilla, E., Gutierrez, E., & Monge, M.A. (1994). Mononuclear and binuclear quinaldinate complexes of rhodium with (P-P) donor ligands – crystal structure of [RH 2 (quin) 2 (CO) 2 (μ-DPPM)] - oxidative addition- reactions. Polyhedron, 13 (10), 1563-1573. [67] Haendler, H.M. (1996). A managanese quinaldinate complex: trans-[diaquabis(2- quinolinecarboxylato)managanese(II)]-water-ethanol (1/2/2). Acta Crystallogr., Sect. C, 52 (Part 4), 801-803. [68] Goher, M.A.S., & Mautner, F.A. (1993). Preparation, crystal-structure and spectroscopic study of azido(N,O-quinaldato)triaquamanganese(II) monohydrate and thiocyanato(N,O-quinaldato)-(O-quinaldic acid)diaquamanganese(II), [Mn(NC 9 H 6 COO)(N 3 )(H 2 O) 3 ].H 2 O and Mn(NC 9 H 6 COO)(NC 9 H 6 COOH)(NCS)(H 2 O) 2 ]. Polyhedron, 12 (15), 1863-1870. [69] Haendler, H.M. (1986). Copper quinaldinate monohydrate [aquabis(2- quinolinecarboxylato)copper(II); pentacoordinate copper. Acta Crystallogr, Sect. C, 42 (Part 2), 147-149. [70] Dobrzyńska, D., Duczmal, M., Jerzykiewicz, L.B., Warcholska, J., & Drabent, K. (2004). Synthesis, spectroscopy, and magnetic properties of Fe II and Co II quinoline-2- carboxylates-crystal structure of trans-bis(quinoline-2-carboxylato)bis(propanol)iron (II). Eur. J. Inorg. Chem., (1), 110-117. [71] Żurowska, A., & Brzuszkiewicz, A., (2008). Co(II) promoted transformation of diethyl(quinolin-2-ylmethyl)phosphonate to quinoline-2-carboxylate (2-qca): Synthetic, structural and magnetic studies of [Co(2-qca) 2 (EtOH) 2 ], Polyhedron, 27 (6),1623-1630. [72] Prasad, L., Gabe, E.J., & Smith, F.E. (1982). Chlorotriphenyl(pyridinium-2- carboxylato)tin(IV). Acta Cryst. B, 38, 1325-1327. [73] Gabe, E.J., Lee, F.L., Khoo, L.E., & Smith, F.E., (1985). Chlorotriphenyl(quinolinium- 2-carboxylato)tin(IV) monohydrate. Inorg. Chim. Acta, , 105, 103-106. [74] Żurowska, B., & Kochel, A. (2008 ). Synthesis, characterization and crystal structure of [Cu(2-pic) 2 Br 2 ][(2-pic-H) 2 ]. J. Mol. Struct., 877 (1-3), 100-104. [75] Żurowska, & B. Mroziński, J. (2003). Ferromagnetic exchange coupling in a two- dimensional copper(II) compound: Cu(pyridine-2-carboxylate)Cl. Inorg. Chim. Acta, 342, 23-28. [76] Żurowska, B., Mroziński, J. & Ciunik, Z. (2007). Structure and magnetic properties of a coper(II) compound with syn-anti carboxylato- and linear Cu-Cl-Cu chloro-bridges. Polyhedron, 26 (13), 3085-3091. [77] Żurowska, B., Mroziński, J. & Ciunik, Z. (2007). One-dimensional copper(II) compound with a double out-of-plane carboxylato-bridge-Another polymorphic form of Cu(pyridine-2-carboxylate) 2 . Polyhedron, 26 (6), 1251-1258. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 257 [78] Żurowska, B., Mroziński, J., & Ślepokura, K. (2007). Structure and magnetic properties of a double out-of-plane carboxylato-bridged Cu(II) compound with pyridine-2-carboxylate. Polyhedron, 26 (13) 3379-3387. [79] Żurowska, B., & Ślepokura, K. (2008). Structure and magnetic properties of polynuclear copper(II) compounds with syn-anti carboxylato and bromo-bridges. Inorg. Chim. Acta, 361 (5), 1213-1221. [80] Biswas, C., Mukherjee, P., Drew, M.G.B., Gómez-Garcia, C.J., Clemente-Juan, J.M., & Ghosh, A. (2007). Anion-directed synthesis of metal-organic frameworks based on 2- picolinate Cu(II) complexes: a ferromagnetic alternating chain and two unprecedented ferromagnetic fish backbone chains. Inorg. Chem., 46 (25), 10771-10780. [81] Goher, M.A.S., Hafez, A.K., Abu-Youssef, M.A.M., Popitsch, A., Fritzer, H.P. & Mautner, F.A. (1994). Synthesis and spectral and structural characterization of a bridging chloropicolinatocopper(II) complex, Cu(C 5 H 4 NCOO)Cl Monatsh. Chem., 125 (8-9), 833-840. [82] Belokon, Y.N., Tararov, V.I., Savel’eva, T.F., Vitt, S.V., Paskonova, E.A. Dotdayev, S. Ch., Borisov, Y.A., Struchkov, Y.T., Batasanov, A.S., & Belikov, V.M. (1988). Copper(II) ion promoted direct hydrolysis of 2-cyanopyridine to picolinic acid. Intramolecular catalysis by the coordinated N-β-hydroxyethyl group. Inorg. Chem., 27 (22), 4046-4052. [83] Żurowska , B., Ochocki, J., Mroziński, J., Ciunik, Z., & Reedijk, J. (2004). Synthesis, spectroscopic and magnetostructural evidence for the formation of Cu(II) complexes of pyridyl-2-carboxylate (2-pca) and quinolyl-2-carboxylate (2-qca) as a result of a novel oxidative P-dealcylation reaction of diethyl 2-pyridylmethylphosphonate (2-pmpe) and diethyl 2-quinolilmethylphosphonate (2-qmpe) ligands. Inorg. Chim. Acta., 357 (3), 755-763. [84] Barandika, M.G., Serna, Z.E., Urtiaga, M.K., de Larramendi, J.I.R., Arriortua, M.I. & Cortes, R. (1999). Crystal structure and magnetic properties of two metal-picolinate systems obtained from degradation of bis(2-pyridylketone) through reaction with Mn(II) and Cu(II). Polyhedron 18 (8-9), 1311-1316. [85] Colacio, E., Costes, J.P., Kivekäs, R., Laurent, J.P., Ruiz, J., & Sundberg, M. (1991). A new hydrogen-bonded dinuclear complex involving copper(II) ions in a pseudotetrahedral N 3 O environment: molecular and crystal structure and magnetic and spectroscopic properties. Inorg. Chem., 30 (7), 1475-1479. [86] Carlin, R.L., van Duyneveldt, A.I. (1977). Magnetic properties of transition metal compounds, New York: Springer-Verlag, [87] J.B. Goodenough, (1963). Magnetism and the Chemical Bond, New York: Interscience, 165-184. [88] Ruiz, E., Alemany, P., Alvarez, S., & Cano, J. (1997). Structural modeling and magneto-structural correlations for hydroxo-bridged copper(II) binuclear complexes, J. Am. Chem. Soc., 119 (6), 1297-1303. [89] Hay, P.J., Thibeault, J.C., & Hoffman, R. (1975). Orbital interactions in metal dimer complexes. J. Am. Chem. Soc., 97 (17), 4884. [90] Jeter, D.Y., Lewis, D.L., Hempel, J.C., Hodgson, D.J., & Hatfield, W.E. (1972). Magnetic properties of the complex di-µ-hydroxo-bis[2-(2-ethylamino- ethyl)pyridine]dicopper(II) perchlorate. Inorg. Chem., 11, (8), 1958-1960. Bogumiła Żurowska 258 [91] Kahn,O. (1982). Molecular Engineering of coupled polynuclear systems: orbital mechanism of the interaction between metallic centers. Inorg. Chim. Acta, 62 (1) 3-14. [92] Girerd, J.J., Charlot, M. F., & Kahn, O. (1977). Orbital interaction in one-dimensional magnetic compounds. Mol. Phys. 34 (4), 1063-1076. [93] Figgis, B.N., & Martin, R.L., (1956). Magnetic studies with copper(II) salts .1. Anomalous paramagnetism and σ-bonding in anhydrous and hydrated copper(II) acetates. J. Chem. Soc., 3837-3846. [94] Colacio, E., Dominguez-Vera, J.M., Costes, J.P., Kivekäs, R., Laurent, J.P., Ruiz, J., & Sundberg, M. (1992). Structural and magnetic studies of a syn-anti carboxylate- bridged helix-like chain copper(II) complex. Inorg. Chem., 31 (5), 774-778. [95] Colacio, E., Dominguez-Vera, J.M., Kivekäs, R. & Ruiz, J. (1994). Preparation, crystal structures and magnetic properties of a syn-anti carboxylate-bridged dinuclear copper(II) complex and its precursor, a hydrogen-bonded polynuclear copper(II) complex. Inorg. Chim. Acta, 218 (1-2), 109-116. [96] Colacio, E., Costes, J.P., Kivekäs, R., Laurent, J.P. & Ruiz, J. (1990). A quasi- tetrahedral tetracopper cluster with syn-anti bridging carboxylate groups: crystal and molecular structure and magnetic properties. Inorg. Chem., 29 (21), 4240-4246. [97] Colacio, E., Dominguez-Vera, J.M., Kivekäs, R., Moreno, J.M., Romerosa, A., & Ruiz, J. (1993). Structure and magnetic properties of a syn-anti carboxylate bridged linear trinuclear copper(II) complex with ferromagnetic exchange. Inorg. Chim. Acta, 212 (1- 2), 115-121. [98] Inoue, M., & Kubo, M., (1970). Superexchange interaction in anhydrous copper(II) formate. Inorg. Chem., 9 (10), 2310-2314. [99] Youngme, S., Pakawatchai, C., Somjitsripunya, W., Chinnakali, K., & Fun, H.-K. (2000). Preparation, crystal structure, spectroscopic and magnetic characterisation of acetatobis(di-2-pyridylamine)copper(II) tetrafluoroborate and μ-carbonato-tetrakis(di-2- pyridylamine) dicopper(II) bistetrafluoroborate tetrahydrate. Inorg. Chim. Acta, 303 (2), 181-189. [100] Colacio, E., Domínguez-Vera, J.M., Ghazi, M., Kivekäs, R., Klinga, M., & Moreno, J.M. (1999). Singly anti-anti Carboxylate-Bridged Zig-Zag Chain Complexes from a Carboxylate-Containing Tridentate Schiff Base Ligand and M(hfac) 2 [M = Mn II , Ni II , and Cu II ]: Synthesis, Crystal Structure, and Magnetic Properties. Eur. J. Inorg. Chem., (3), 441-445. [101] Costes, J.P., Dahan, F., & Laurent, J.P. (1985). A further example of a dinuclear copper(II) complex involving monoatomic acetate bridges. Synthesis, crystal structure, and spectroscopic and magnetic properties of bis(μ.-acetato)bis(7-amino-4-methyl-5- aza-3-hepten-2-onato(1-))dicopper(II). Inorg. Chem., 24 (7), 1018-1022. [102] Chiari, B., Helms, J.H., Piovesana, O., Tarantelli , T.& Zanazzi, P.F. (1986). Exchange interaction in multinuclear transition-metal complexes. 8. Structural and magnetic studies on bis(acetato)bis(N-methyl-N'-(5-methoxysalicylidene)-1,3-propanediaminato) dicopper dihydrate, a novel "structural" ladderlike compound with "magnetic" alternating-chain behavior. Inorg. Chem., 25 (6), 870-874. [103] Gandour, R.D. (1981). On the importance of orientation in general base catalysis by carboxylate. Bioorg. Chem., 10 (2), 169-176. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 259 [104] Wiberg, K.B., & Laidig, K.E.( 1987). Barriers to rotation adjacent to double bonds. 3. The C-O barrier in formic acid, methyl formate, acetic acid, and methyl acetate. The origin of ester and amide “resonance”. J. Am. Chem. Soc., 109, 5935-5943. [105] Levstein, P.R., & Calvo, R. (1990). Superexchange coupling mediated by carboxylate and hydrogen bridges in copper amino acid complexes. Inorg. Chem. Soc., 29, 1581- 1583. [106] Grove, M., Sletten, J., Julve, M., & Lloret, F. (2001) Solid-State polymerization causing transition to a ferromagnetic state. Crystal structures and magnetic properties of [Cu 2 (dpp)(H 2 O)(dmso)Cl 4 ]·dmso and [Cu 2 (dpp)Cl 4 ] n (dpp = 2,3-bis(2-pyridyl)pyrazine. J. Chem. Soc. Dalton Trans., (17) 2487-2493. [107] Youngme, S., Chaichit, N., Kongsaeree, P., van Albada, G.A. & Reedijk, J. (2001). Synthesis, structure, spectroscopy, and magnetism of two new dinuclear carbonato- bridged Cu(II) complexes. Inorg. Chim. Acta, 324, (1-2), 232-240. [108] Cervera, B., Ruiz, R. Lloret, F., Julve, M., Cano, J., Faus, J., Bois, C. & Mroziński, J. (1997 ). Tuning the nature of the exchange interaction in out-of-plane oximato-bridged dinuclear copper(II) complexes. J. Chem. Soc. Dalton Trans., (3), 395-401. [109] W.E. Hatfield, (1985). Magneto-Structural Correlation’s in Exchange Coupled Systems, In R.D. Willett, D. Gatteschi, O. Kahn ((Eds). Dordrecht: D. Reidel. [110] Seeber, G., Kariuki, B.M., Cronin, L., & Kögerler, P. (2005). Synthesis, structure and magnetism of a linear Cu–Cl–Cu entity found in [(Cu(tachH)(tach)) 2 (μ-Cl)] 5+ Polyhedron, 24, 1651-1655. [111] Du, M., Guo, Y.M., Bu, X.H., Ribas, J., & Monfort, M. (2002). Structural and first magnetic characterization of unique mono-μ-chloro bridged dinuclear Cu II complexes with heterocycle-functionalized diazamesocyclic ligands. New J. Chem., 26, 939-945. [112] Chou, J.L., Chyn, J.P., Urbach, F.L., & Gervasio, D.F. (2000). Dinuclear copper(II) complexes incorporating a novel pyrazolo-based ligand with S- and N-rich coordination spheres. Polyhedron, 19 (20-21), 2215-2223. [113] Kahn, O., & Charlot, M.F. (1980). Overlap density in binuclear complexes - A topological approach of the exchange interaction. Nouv. J. Chim. 4, 567-576. [114] Kahn, O., & Briat, B., (1976). Exchange interaction in polynuclear complexes. J. Chem. Soc., Faraday Trans., 2, 268-285. [115] Addison, A.W., Rao, T.N., Reedijk, J., van Rijn, J., & Verschoor, G.C. (1984). Synthesis, structure, and spectroscopic properties of copper(II) compounds containing nitrogen–sulphur donor ligands; the crystal and molecular structure of aqua[1,7-bis(N- methylbenzimidazol-2′-yl)-2,6-dithiaheptane]copper(II) perchlorate. J. Chem. Soc. Dalton Trans., (7), 1349-1349. [116] Kahn, O., Claude, R.,& Coudanne, H. (1978 ). Ferromagnetic coupling and electron- transfer in CoCu(ben).3H 2 O [H 4 ben = NN'-bis(2-hydroxy-3-carboxybenzylidene)-1,2- diaminoethane]. J. Chem. Soc., Chem. Commun., (23), 1012-1013. [117] Kahn, O., Tola, P., Galy, J., & Coudanne, H. (1978). Interaction between orthogonal magnetic orbitals in a copper(II)-oxovanadium(II) heterobinuclear complex. J. Am. Chem. Soc., 100, 3931-3933. [118] Lee, Y-M., Lee, H.-W., & Kim, Y-I. (2005). Structural and magnetic characterization of copper(II) halide complex with 2-(dimethylaminomethyl)-3-hydroxypyridine Polyhedron, 24 (2), 377-382. Bogumiła Żurowska 260 [119] Towle, D.K., Hoffmann, S.K., Hatfield, W.E., Singh, P., Chaudhuri, P., & K. Wieghard, (1985). Ferromagnetic intramolecular interactions in a bis(μ-bromo)-bridged copper(II) dimeric compound: crystal structure and molecular structure determination, electron paramagnetic resonance studies, and magnetic susceptibility measurements on bis(μ-bromo)bis(diethylenetriamine)copper(II)] perchlorate. Inorg. Chem., 24 (25), 4393-4397. [120] Alves, W.A., de Almeida Santos, R.H., Paduan-Filho, A., Becerra, C.C. Borin, A., & da Costa Ferreira, A.M. (2004). Molecular structure and intra- and intermolecular magnetic interactions in chloro-bridged copper(II) dimers. Inorg. Chim. Acta, 357 (8), 2269-2278. [121] Folgado, J.V., Coronado, E., Beltran-Porter, D., Burriel, R., Fuertes, A., & Miravitlles, C. (1988 ). Crystal structures and magnetic properties of the mono-µ-halogeno-bridged copper(II) chains Cu(pcpci)X [pcpci =N-(2′-pyridylcarbonyl)pyridine-2-carboximidate, X = Cl or Br]. J. Chem. Soc. Dalton Trans., (12), 3041-3045. [122] van Ooijen, J.A.C., & Redijk, J.( 1978 ). Magnetic exchange in some polynuclear bis(azole)dihalogenocopper(II) complexes. J. Chem. Soc. Dalton Trans., (9), 1170. [123] van Ooijen, J.A.C., & Reedijk, J. (1977). Linear-chain anti-ferromagnetism and spectroscopy of compounds CuX 2 L 2 , with X = Cl, Br and L = substituted pyridine. Inorg. Chim. Acta, 25, 131-140. [124] Estes, W.E., Gavel, D.P., & Hatfield, W.E., ( 1978). Magnetic and structural characterization of dibromo- and dichlorobis(thiazole)copper(II). Inorg. Chem., 17 (6), 1415-1421. [125] Jeter, D.Y., & Hatfield, W.E. (1972). Out-of-plane chain interactions in dichlorobis(pyridine)copper(II) and dibromobis (pyridine)-copper(II). J. Inorg. Nucl. Chem., 34, 3055-3060. [126] Jeffrey, G.A., & Saenger, W. (1991). Hydrogen Bonding in Biological Structures; Springer: Berlin. [127] Jeffrey, G.A., (1997) An Introductioon to Hydrogen Bonding; Oxford: New York. [128] Fisher, B.E., & Sigel, H. (1980). Ternary complexes in solution. 35. Intramolecular hydrophobic ligand-ligand interactions in mixed ligand complexes containing an aliphtic amino acid. J. Am Chem. Soc., 102, 2998-3008. [129] Sugimori, T., Shibakawa, Masuda, K. H., Odani, A., & Yamauchi, O. (1993). Ternary metal(II) complexes with tyrosine-containing dipeptides. Structures of copper(II) and palladium(II) complexes involving L-tyrosylglycine and stabilization of copper(II) complexes due to intramolecular aromatic ring stacking. Inorg. Chem., 32 (22), 4951- 4959. [130] Costa-Filho, A.J., Munte, C. E., Barberato, C., Castellano, E.E., Mattioli, M.P.D. Calvo, R., & Nascimento, O.R. (1999). Crystal Structures and Magnetic Properties of CuX 2 (pdmp) 2 Complexes (X = Br, Cl). Inorg. Chem., 38 (20), 4413-4421. [131] Janiak, Ch. (2000 ). A critical account on π–π stacking in metal complexes with aromatic nitrogen-containing ligands. J. Chem. Soc. Dalton Trans., (21), 3885-3896. [132] Roesky, H.W., & Andruh, M. (2003). The interplay of coordinative, hydrogen bonding and π-π stacking interactions in sustaining supramolecular solid-state architectures. A study case of bis(4-pyridyl)- and bis(4-pyridyl-N-oxide) tectons. Coord. Chem. Rev., 236 (1-2), 91-119. Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 261 [133] Brill, A.S. (1977). Transition Metals in Biochemistry, Berlin: Springer Verlag. [134] S.J. Lippard, & J.M. Berg. (1994) Principles of Bioinorganic Chemistry, California, University Science Books; Mill Valley. [135] Żurowska, B., & Mroziński, J. (2007). Magnetic interaction in Cu(pyridine-2- carboxylate) 2 . Pol. J. Chem., 81, 403-410. [136] Madalan, J., Kravtsov, V., Pajic, Ch., Zadro, D., Simonov, K., Stanica, Y. A., Ouahab, N. Lipkowski, L., & Andruch, M. (2004). Chemistry at the apical position of square- pyramidal copper(II) complexes: synthesis, crystal structures, and magnetic properties of mononuclear Cu(II), and heteronuclear Cu(II)–Hg(II) and Cu(II)–Co(II) complexes containing [Cu(AA)(BB)] + moieties (AA=acetylacetonate, salicylaldehydate; BB=1,10- phenanthroline, Me 2 bipy=4,4 ′ -dimethyl-2,2 ′ -bipyridine). Inorg. Chim. Acta, 357 (14), 4151-4164. [137] Policar, C., Lambert, F., Cesario, M., & Morgenstern-Badarau, I. (1999). An Inorganic Helix [Mn(IPG)(MeOH)] n [PF6] n : Structural and Magnetic Properties of a syn-anti Carboxylate-Bridged Manganese(II) Chain Involving a Tetradentate Ligand. Eur. J. Inorg. Chem. (12), 2201-2207. [138] Stachová, P., Korabik, M., Koman, M., Melnik, Mroziński, M.J. Głowiak, T.,Mazur, M.,& Valigura, D. (2006). Synthesis, spectral and magnetical characterization of monomeric [Cu(2-NO 2 bz) 2 (3-pyme) 2 (H 2 O) 2 ] and polymeric [Cu{3,5-(NO 2 ) 2 bz} 2 (3- pyme) 2 ] n . Inorg. Chim. Acta., 359 (4), 1275-1281. [139] Yamauchi, O., Odani, A., & Masuda, H. (1992). Weak interactions in metal complexes of amino acids with a phosphorylated side chain. Conversion of aromatic ring stacking to electrostatic bonding by tyrosine phosphorylation. Inorg. Chim. Acta, 200-198, 749- 761. [140] Brondino, C.D., Calvo, R., Atria, A.M,. Spodine, E., & Peña, O.( 1995). Polynuclear complexes with hydrogen-bonded bridges. 4. Structure and magnetic properties of dinuclear copper(II) complexes of amino alcohols. Inorg. Chim. Acta, 228 (2), 261-266. [141] Żurowska, B., & Mroziński, J., (2005). Isomeric forms of Cu(quinoline-2- carboxylate) 2 ·H 2 O. Spectroscopic and magnetic properties. Mater. Sci-Poland., 23 (3), 737-744. [142] Xie, Y. Liu, Q., Jiang, H., Du, C., Xu, X., Yu, M., & Zhu, Y. ( 2002). An unusual alternating ferro- and antiferromagnetic 1D hydrogen-bonded μ 2 -1,3-azide-bridged copper(II) complex: a dominant ferromagnetic coupling New. J. Chem., 26 (1), 176- 179. [143] Desplanches, C., Ruiz, E., Rodríguez-Fortea, A., Alvarez, S. (2002). Exchange coupling of transition-metal ions through hydrogen bonding: A theoretical investigation. J. Am. Chem. Soc., 124 (18), 5197-5205. [144] Desplanches, C., Ruiz, E., & Alvarez, S., (2002). Early-late transition metal ferromagnetic coupling mediated by hydrogen bonding. Chem. Commun., (22), 2614- 2615. [145] Bertrand, J.A., Fujita, E., & VanDerveer, D.G. (1980). Polynuclear complexes with hydrogen-bonded bridges. 4. Structure and magnetic properties of dinuclear copper(II) complexes of amino alcohols., Inorg. Chem., 19, (7), 2022-2028. [146] Tercero, J., Diaz, C., Ribaz, J., Machia, J., & Maestro, M.A. (2002). New oxamato- bridged Trinuclear Cu II −Cu II −Cu II complexes with hydrogen-bond supramolecular Bogumiła Żurowska 262 structures: Synthesis and magneto−structural studies. Inorg. Chem., 41, (21), 5373- 5381. [147] Maspoch, D., Catalá, L., Gerbier, P., Ruiz-Molina, D., Vidal-Gancedo, J., Wurst, K., Rovira, C., & Veciana, J. (2002). Radical para-benzoic acid derivatives: transmission of ferromagnetic interactions through hydrogen bonds at long distances. Chem. Eur. J., 8 (16), 3635-3645. [148] Paine, T.K., Weyhermuller, T., Wieghardt, K., & Chaudhuri, P., (2002). The methanol−methanolate CH 3 OH···OCH 3 - Bridging ligand: Tuning of exchange coupling by hydrogen bonds in dimethoxo-bridged dichromium(III) complexes. Inorg. Chem., 41 (25), 6538-6540. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 6 REVIEW: TRANSITION METALS IN MEDICINE Hanan F. Abdel-Halim Pharmaceutical Chemistry Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt INTRODUCTION Opportunities exist to exploit inorganic chemistry in the discovery and development of pharmaceuticals. Preparation of model compounds, synthesis of potential medicinal agents and imaging agents are the new area of pharmaceutical researches[1]. This involves the synthesis of metal complexes, usually of relatively small molecule ligands, which in some way mimic the naturally occurring metallomolecules, or which have desirable properties such as solubility, stability in vivo, selective absorption into certain tissues, are the main core of studying metals in medicine. Fear of metal toxicity is a limiting factor, but may be, in part, a matter of perception. Not all metals are bad and not all metals are "heavy metals", yet, even essential metals are toxic at certain levels and in some chemical forms [2,3]. The key is to understand and to control the interaction of the metal with the living system. Metal metabolism is emerging as an exciting area of cell biology and a potential site for therapeutic interventions where normal metal metabolism appears to maintain free metal ion concentrations at a very low level and to deliver metals very selectively to their sites of action, while maintaining tight control over their reactivity [3]. The unique properties of metal complexes may offer advantages in the discovery and development of new drugs. These unique properties include redox activity, Lewis acidity, electrophilicity, access to cationic/anionic/radical species, flexible bond orders, unique geometries, easily accessed structure/activity variations, and magnetic, spectroscopic, and radioactive signatures. The fundamental properties of metals and of metal-ligand chelation chemistry remain an important area for research. Examples include regulation of spin relaxation processes, complex stability, ligand exchange kinetics, and other physico- chemical properties (electrochemical potentials, fluorescence quantum yields, ligand pKa values, etc.).[3] Metals can be useful probes of cellular function. Understanding these interactions is Hanan F. Abdel-Halim 264 paving the way toward rational design of metallopharmaceticals and implementation of new co-therapies. Metal complexes can be potent and highly selective ligands of cell surface receptors. As metal complexation is the basis for chelation therapy and to rectify abnormal metal accumulations or toxic metal exposures (e.g., iron overload; lead, cadmium, and mercury poisoning),improving chelator designs are needed to enhance selectivity, affinity, stability, renal clearance, and oral activity, while maintaining low toxicity and low cost. Ligand must be designed to optimize desired metal complex properties (e.g: thermodynamic and kinetic stability, hydrolytic stability, catalytic activity, molecular weight, charge, lipophilicity, water solubility, targeting functionalization, and ligand metabolism).In addition, the essential transition metal ions are accumulated by cells, to be used as required cofactors, and to catalyze cytotoxic reactions in which several families of proteins are emerging to control the activity of intracellular metal ions and to help confine them to vital roles. These include integral transmembrane transporters, metalloregulatory sensors, and metallochaperone proteins [soluble metal receptor proteins] that protect and guide metal ions to targets [3]. In this review we try to present the importance of some examples of transition metals in the treatment of certain diseases and their role in avoid these diseases. METTALOENZYMES Metals play roles in approximately one-third of the known enzymes. Metals may be a co- factor or they may be incorporated into the molecule, and these are known as metalloenzymes. Amino Acids in peptide linkage posses groups that can form coordinate- covalent bonds with the metal atom , the free amino and carboxyl group bind to the metal affecting the enzymes structure resulting in its active conformation [4]. The metalloproteins are part of enzymatic systems, have structural functions, and use the protein to be transported to their target site in the organism. In enzymes, the metals participate in catalytic processes as: • constituents of enzyme active sites. • stabilizers of enzyme tertiary or quaternary structure. • contributors in forming weak bonding complexes with the substrate that can carrying out the orientation of the substrate for reactions. • Stabilizers for charged transition states. As constituents of active sites, metal cations with unpaired electrons mediate oxidation– reduction (redox) processes by reversible changes in their oxidation state, transferring or receiving electrons to or from the substrate and co-factor. For example, human superoxide dismutases reduce one superoxide anion to hydrogen peroxide, and oxidize a second superoxide anion to generate molecular oxygen by means of either Cu or Mn present in the active site of the cytosolic or mitochondrial enzyme, respectively. The presence of metals bound to lipids, nucleic acids, and carbohydrates is well documented, but the biochemical functions of the metals present in these molecules is unclear. ac w st di ov th co im an pr co co th be de un m m sy be st ch sy cl m m pr Fi th su w w Because m ccepting an el with anionic a tructure and fu isrupt this ele verall effectiv Nucleases hat contain a omplexes, wh mportant signi nd in the deve ropose a simp ontain, recent ontaining two hese complex enzimidazolyl erivatives, and nderstand the multinuclear metallonuclease ynthetic multi etween metal tudies and com hemistry that p ynthetic metal leavage (Fig metallonuclease multinuclear m rinciples of co igure 1. DNA h Transition hey mimic the ubstrate. Meta with more than whatever molec R metals resembl lectron pair to and neutral li unction but m ectron flow th veness of the m which are me variety of d ich can media ificance in elu elopment of t ple mechanism progress has e or more Fe (I xes include l- and pyridyl d their conjug e differences metallonuclea es; the rela inuclear meta sites and lig mparison must provides insig llonucleases m gure 1).In a es and the cha metallonuclease oordination an hydrolytic cleav state is a key e structure of al's larger size n one ligand. M cule the metal Review: Transi le protons (H + o form a chem igands. This makes the enzy hat the metal w metalloenzyme etalloenzymes different meta ate phosphodie ucidation of t the biomacrom m for these en extended to th III), Zn (II), C natural and l-based organi gates to polyp in structure ases; the ationship betw llonucleases; gands in the c t be illustrated ght into how ch may lead to the addition, the allenges that sh es with DNA nd enzymatic c vage catalyzed b y role in the f the substrat e relative to p Metals typica l interacts with ition Metals in + ) in that they mical bond, th characteristic yme it is part would normal e. s that have a w al ions, there ester bond cle the catalytic m molecule - tar nzymes due to he design of sy u (II), Co (II/I d non-natural ic molecules, peptides or o and compos design stra ween the stru and the coo courses of ph d. Indeed, ther hanges in met e same overall e solvation hould be faced A sequence or chemistry [5,6 by synthetic mu competitive i tes transition protons is com lly react with h. If a metal is n Medicine y are electroph hey may act a c of metals i of pH depend lly help facili wide variety o fore, design eavage via hyd mechanisms f rgeted drugs. o the variation ynthetic multin III), or Ln (III l organic m azamacrocyc ligonucleotide ition between ategies of uctures and n operativities b hospodiester l re are features tal ions and lig l outcome of p effect of d toward the d structure sele ]. ultinuclear meta nhibition of m state in the r mpensated for two, four, or s bound with tw hiles that are as general aci is helpful in dent. Changes tate and thus of active site and synthesis drolytic pathw for the natural Despite the d n of metal ion nuclear metall I/IV) ions. The molecules, i.e lic and amino es. Owing to n natural and synthetic m nucleolytic ac between metal inkage hydro s that converg gands of both n phosphodieste synthetic m development o ectivity by ap llonucleases. metalloenzym reaction of en by their abili r six ligands. A wo ligands it w 265 capable of ids to react enzymatic s in pH can inhibit the motifs and s of metal ways, are of l nucleases difficulty to ns that they lonucleases e ligands in e., mainly ocarboxylic be able to d synthetic multinuclear ctivities of l sites, and lysis, deep e about the natural and r backbone multinuclear of synthetic pplying the mes because nzyme and ity to react A ligand is will form a 26 lin of m po T pr im to re (s pH di ox sy re tr ac re an m of di tr ne re se pr is ni w to m 66 near complex f a square that metal sits in th ossess groups he free amino rotein to a sp mportant in th ogether and he As transiti eactions of act superoxide, H and chelatio ioxygen and xidative dama ystems the co eactions appea ransport prote ctive metals [ eaction of any ntioxidant is a Chromium metabolism, bu f risk factors a Insufficien iabetes and riglycerides, to Severe sig europathy that Chromium eceptor numbe ensitivity [10- revent weight s better absorb icotinic acid). well. Chromiu olerance factor mechanism of a . So that, if th t is planer or i he center of a s with the abil o and carboxy pecific, active hat metals pla elp establish an on metal cata tivated oxygen ; on govern the “oxy-radicals age to phosph oncentrations ars to be relat eins (ferritin, [7].Antioxidan y substance w any substance is not only a ut also, its diet associated with t dietary intak cardiovascula otal cholestero gns of diabet t were refracto improves in er, and phosp -12]. Research gain associat bed than othe Other forms um is an esse r." Despite th action is not k Hanan e metal reacts t will form a t an octahedron lity to bind to l groups in a p e conformation ay a role in b n active confo alysis is recog n species (par hydrogen per e reactivity of ” and therefo holipids, DNA of redox-act tively low. Ho transferrin, c nt has been d with dioxygen that hinders a CH an essential el tary intake is h diabetes and ke of chromiu ar diseases ol, reduced HD tes including ory to insulin w nsulin functio phorylation of h has shown ted with the u er forms, in w of chromium, ential nutrient his, chromium known [13-16] F. Abdel-Hal s with four liga tetrahedral stru n. Amino acid o the metal re protein can bi n. The fact th bringing remo ormation of the gnized as bein rtially-reduced roxide H 2 O 2 ; the transition ore influence A, and other b ive transition owever, under ceruloplasmin, described as a n. The more free radical re HROMIUM lement requir often sub opt d cardiovascul um leads to inc including ele DL-cholesterol weight loss, were treated b n by increas f the insulin that chromiu use of the diab which, chromi , such as chro t forming the m remains the . im ands the meta ucture, and wh ds in their pep esulting in coo ind to the met hat metals bin ote parts of th e enzyme. ng integral to d forms of dio hydroxyl radi n metals as we the apparent iomolecules i n metals capa r certain cond , etc.) may f any substance mechanistic d eaction ed for normal timal in the pr lar diseases. creases in risk evated circul l, and impaire glucose into by supplement ing insulin b receptor lead um(III) picolin betic drug as c ium is bound omium glycina e active com only essential l will be set in hen six ligand ptide linkage ordinate-coval tal and this ma nd to several he amino acid o the generatio oxygen or “ox ical OH) ,facto e mentioned b t mechanisms is initiated. In able of cataly ditions metal s furnish additio that interfere definition stat l carbohydrate revention and k factors assoc lating insulin d immune fun olerance and tal chromium binding to ce ing to increas nate (Figure 2 chromium pol to vitamin B ate chelate, m mponent of th l transition m n the center ds react, the in proteins lent bonds. ay bind the ligands is d sequence on and the xy-radicals” ors such as before, with by which n biological yzing these storage and onal redox es with the tes that an e and lipid alleviation ciated with n, glucose, nction. peripheral [8, 9]. lls, insulin sed insulin 2) helps to ynicotinate B3, known( ay work as e "glucose metal whose Fi so to ar th an at de ef or tr ef pr ph an ca ne di th co ty fu nu m igure 2. Chromi While the t olubility , Cr ( oxic systemica re uncertain, th hrough cell m nd the difficu ttributable to etoxification p ffect. While re r near the cell If Cr (VI) ransported int fficiently by a roteins and DN hosphate back nd larger pept an be dissocia Copper is eeded to abso ismutase (SOD he body runs ollagen (the yrosinase, whi unction. Copper com umber of body maintain and re R ium (III) picolin toxicity of chr (VI) compoun ally than Cr ( his variation i embranes and ulty of absorb the Cr(VI) f process when eduction of Cr nucleus of tar is reduced to to cells and an anion transp NA, this creat kbone of DNA tides and prote ated with chela an essential t orb and utiliz D) [22]. Copp on. Synthesis "glue" that ich plays a rol mbines with c y functions, o epair connecti Review: Transi nate. romium comp nds, which are III) compoun in toxicity may d its subseque bing Cr(III) b form as the r it occurs at a r(VI) may ser rget organs[17 o Cr (III) ext so toxicity is port system it tes adducts inv A, N-7 of guan ein molecules ators, such as E C trace element ze iron. It is per is needed s of some ho holds connec le in the produ certain protein thers help to f ive tissues [23 ition Metals in pounds are var powerful oxid ds. Although y be related to ent intracellula y any route. reduction of C distance from rve to activate 7-20] . tracellularly, t s not observe is reduced ins volving the six nine, and amin . These ternar EDTA. COPPER t present in th s also part of to make aden ormones requi ctive tissue t uction of skin ns to produce e form cross-lin 3]. References n Medicine ried due to the dizing agents mechanisms o the ease with ar reduction to The toxicity Cr (VI) is co m the target sit chromium to this form of t ed[21]. As C side the cells t x coordination no acids, such ry DNA comp he diet and in f the antioxid nosine triphosp ires copper, a together). In pigment (mel enzymes that nks in collagen s and further r e oxidation st appear to be m of biological h which Cr (V o reactive inte of chromium onsidered to te for toxic or xicity if it tak the metal is n Cr(VI) enters to Cr(III) whi n sites of Cr(II as cysteine, g plexes are very n the human dantenzyme, phate (ATP), as does the sy addition, th anin), require act as catalyst n and elastin a reading may b 267 ate and the much more interaction VI) can pass ermediates, m is mainly serve as a r genotoxic kes place in not readily cells very ch binds to II) with the glutathione, y stable but body. It is superoxide the energy ynthesis of e enzyme, s copper to ts to help a and thereby be available 26 fo es fa go a su co m of co an fo po al co dr co Fu ib pr Fi th co pr an 68 or this article. specially impo actor leading t It appears oes beyond a wide range o usceptibility o opper plays a mediated dama Copper has f chest wound opper helps pr nti-ulcer and or treating co ossess anti-in lways have s ompounds, it h rugs are their It has been opper tryptop urther, it has buprofen and romote norma igure 3. Copper Copper has hat are not the opper [25]. T rocesses invol nd diabetes ar To view refer ortant for the h to an increased clear that the decrease in th of disturbance of lipoproteins a vital role in age and disease s also been us ds and the pu revent inflamm anti-inflamma onvulsions and nflammatory a significantly has been hypo copper chelate n demonstrated phanate (Figur been shown enefenamic a al wound heali r aspirinate. s a role in the mselves anti-c The hypothes lving copper-d re diseases of Hanan rences and fur heart and arter d risk of devel decrease in a he activity of c s in other ant s and heart tis the protectio e. sed as a medic urifying of dri mation in arth atory medicine d epilepsy. W activity, and stronger acti othesized that es[24]. d that copper c re 4), marked n that, wherea acid suppress ing while at th prevention of convulsants ex sis that coppe dependent enz f specific tissu F. Abdel-Hal rther reading y ries. Research loping coronar antioxidant pr copper-depend tioxidant enzy sue to peroxid on of the card cine for thous inking water. hritis and simil es containing With the know the finding t vity and hav the active for complexes su dly increase as non-steroid wound healin he same time r f seizures. It w xhibit anticon er complexes zymes and tha ues in disrepa im you must purc suggests that ry heart diseas rotection caus dent antioxida yme systems. dation, provid diovascular sy sands of years Recently, res lar diseases. R copper, and wledge that m that these co ve lower tox rm of many po ch as copper a healing rate dal anti-inflam ng, copper co retaining anti-i was discovered vulsant activit s facilitate or at arthritis, ulc ir. The coroll chase this arti copper deficie se. ed by copper ant enzymes b as well as inc ding strong ev ystem from fr s including the search has ind Research is go its use in rad many copper opper complex xicity than th opular anti-inf aspirinate (Fig of ulcers an mmatory drug omplexes of t inflammatory d that organic c ty when comp r promote tis cers, seizures, ary to this hy cle. This is ency is one deficiency by inducing creases the idence that ree -radical e treatment dicated that ing on into diology and complexes xes almost heir parent flammatory gure 3) and nd wounds. gs, such as these drugs activity. compounds plexed with ssue repair , neoplasia, ypothesis is th dy Fi su or in re ra im th su th th ca th tr ra be m in m ti of as ar en tr th re nu ca de fu bl hat the loss o ysfunction tha igure 4. Copper Treating fo ucceeded. Rec rganic comple ncreased survi evert to norma Copper me adiation reco mmunocompet his activity ap uperoxide, or he capability o hese with non- apability. Sinc here would be reating patient adiation, and a Copper ha etween zinc a major contribut nvestigators h minimization o ssues followin f copper comp s a means o rteriosclerosis Ceruloplas nzyme that o ransport in the hroughout the esult. Due to umerous symp ause of myelo evelopment). unctions, dimi lood vessels, i R r reduction o at may be reve r tryptophanate. or facial epith cently research exes of copp ival rate. Thes al cells. etallo-organic overy activit tence and reco ppears to be ti "free," radical of breaking th -toxic doses o ce these comp merit in usin s undergoing astronauts und as also a dire and copper - w ting factor to t has shown th of damage to ng myocardial plexes. These f preventing ), coronary he min is the m xidizes Fe 2+ e plasma in as body ,theref its broad ran ptoms. The m odysplasia (w Other sympto inished pigme irregular heart Review: Transi of copper-depe ersed with cop . helioma with a h on the treatm er markedly se copper com complexes h ties. They overy from ra ied to the abi ls liberated by he bonds of n of pharmaceuti lexes may als ng copper com ionizing radia dertaking space ct effect on t with more emp the etiology o hat copper co the aorta and l infarction. T and other stu and controll eart disease, ao ajor copper-c (ferrous iron) ssociation wit fore, if copper nge of activit most common when a blood oms include ent in skin and t beat , increa ition Metals in endent enzym pper complex t a mixture of c ment of solid tu decreased tum mplexes did no have been sho are capable adiation induc ility of certain y ionizing rad atural copper ical copper co o have anticar mplexes in the ation therapy f e travel. the control o phasis on cop of coronary he omplexes also heart muscle This action is b udies suggest t ing such dis ortic aneurysm arrying protei ) into Fe 3+ (f th transferrin, r levels are t ties in the bo symptom of profile has in weakness and d hair, osteop ased levels of n Medicine me-mediated p therapy [26]. copper chlorid umors with no mor growth a ot kill cancer own to have r of causing ed tissue chan n copper com iation. In addi enzymes in t omplexes resto rcinogenic act treatment of for their cance f cholesterol, pper deficiency art disease. Su o can have e as oxygenate based on the a the use of cop eases as athe ms and myocar in in the bloo ferric iron), th which carrie too low, iron ody, copper d copper deficie ndicators of p d fatigue, po orosis, proble LDL choleste processes lead de and lecithin on-toxic doses and metastasi cells but caus radiation prot g rapid rec nges. The mec mplexes to dea ition, since ra the body, supp ores the lost ti tivity, it is sug cancer and in er, accidental e a metabolic y than zinc ex ubsequent wo a valuable r ed blood repe anti-inflamma pper dietary su erosclerosis ( rdial infarction od. Ceruloplas herefore assis es iron in the deficiency an deficiency can ency is anemi possible future or immune a ems with joint erol and decre 269 ds to tissue n has been s of various s and thus sed them to tection and covery of chanism of activate the adiation has plementing issue-repair ggested that n particular, exposure to imbalance xcess - is a rk by other role in the erfuses into atory action upplements (a form of n [27]. smin as an sting in its ferric state nemia may n result in ia and as a e leukemia and thyroid ts, ruptured ased levels Hanan F. Abdel-Halim 270 of HDL cholesterol, resulting in an increase in cardiovascular disease risk [28,29]. It has also been demonstrated that copper deficiency significantly increases the susceptibility of lipoproteins and cardiovascular tissues to lipid peroxidation, thus increasing the risk of cardiovascular disease [30-34]. and breathing problems. Copper is also involved in normalized function of many enzymes, such as cytochrome c oxidase, which is complex IV in mitochondrial electron transport chain, ceruloplasmin, Cu/Zn superoxide dismutase, and in amine oxidases[35,36]. These enzymes catalyze reactions for oxidative phosphorylation, iron transportation, antioxidant and free radical scavenging and neutralization, and neurotransmitter synthesis, respectively [37]. It has long been suspected that free radicals may play a role in iron- and copper-induced cell toxicity because of the powerful prooxidant action of iron and copper salts in vitro. In the presence of available cellular reductants, iron or copper in low molecular weight forms may play a catalytic role in the initiation of free radical reactions. The resulting oxyradicals have the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates, resulting in wide-ranging impairment in cellular function and integrity. However, cells are endowed with antioxidants, scavenging enzymes, repair processes that act to counteract the effects of free radical production. Thus, the net effect of metal-induced free radicals on cellular function will depend on the balance between radical production and the cytoprotective systems As a result, there may be a rate of free radical production that must be exceeded before cellular injury occurs. Despite the importance role of Cu (II) complexes as we mentiond above, we must clarify that copper (II)ion has a critical role in chronic neurologic diseases. The amyloid precursor protein (APP) of Alzheimer's disease or a synthetic peptide representing its copper-binding site reduced bound copper (II) to copper (I). This copper ion-mediated redox reaction led to disulfide bond formation in APP, which indicated that free sulfhydryl groups of APP were involved. Neither superoxide nor hydrogen peroxide had an effect on the kinetics of copper (II) reduction. The reduction of copper (II) to copper (I) by APP involves an electron-transfer reaction and could enhance the production of hydroxyl radicals, which could then attack nearby sites. Thus, copper-mediated toxicity may contribute to neurodegeneration in Alzheimer's disease [38]. Zinc and vitamin C supplements are strong antagonists of copper status and absorption. In the case of zinc, numerous studies have shown that relatively small increases in dietary zinc significantly lower copper absorption [39, 40]. This antagonism has been utilized as a treatment of Wilson's disease. Copper complexes like copper salicylate have been extensively studied for their anti- inflammatory and antioxidant activity, as well as their ability to mimic the superoxide-radical scavenging activity of superoxide dismutase. Numerous researchers have examined the paradoxical role of copper in the process of inflammation, and they have determined that the increase in serum copper is a physiological response to inflammation, rather than a promoter of it [41]. In fact, the main copper containing enzyme, ceruloplasmin, is significantly elevated in inflammatory conditions and has anti -inflammatory activity [42] .Additionally, it has been shown that copper deficiency increases the severity of experimentally-induced inflammation,[43] and that dietary copper must be increased to maintain adequate copper status [44] . The therapeutic potency and safety of the copper complexes of aspirin (acetyl-salicylic acid) and salicylic acid is much better than for aspirin itself or for other copper compounds Review: Transition Metals in Medicine 271 such as copper acetate. These complexes are 5 to 8 times more effective than aspirin but less toxic. The therapeutic index (the margin between effectiveness and toxic effects) has been stated as being significantly greater than for other anti-inflammatory drugs. While aspirin and other anti-inflammatory drugs cause or aggravate ulcers and gastro- intestinal bleeding and distress, the copper complexes have a better ulcer-healing effect than commonly used anti-inflammatory ulcer drugs. Harmful effects of aspirin, salicylic acid and similar drugs apparently arise because they bind copper in the stomach and intestines wall and cause a localised copper deficiency in these tissues. This then causes connective tissue disintegration with bleeding and ulcers. Copper salicylate supplies the necessary copper in a useable form to heal these lesions. Then we can say that patients who are allergic to salicylates are mainly reacting because of copper deficiency. In addition copper salicylate has also good anti-cancer and anti-convulsive properties suitable for treatment of epilepsy and possibly Parkinson's disease. After the liver the brain is the second-highest copper-containing organ. There are at least 6 important copper-dependent enzymes in the brain. Experimental evidence showed that copper complexes can cause established tumor cells to re-differentiate into normal cells and it has been suggested that the future use of copper complexes to treat neoplastic diseases has some exciting possibilities [45]. Wearing copper bracelets is a time-tested anti-inflammatory, in contrast, copper salicylates were found to be the best copper complex for the treatment of arthritic pain [46, 47]. Prion diseases such as Creutzfeldt-Jakob or "mad cow" disease, and also Alzheimer’s and Parkinson’s disease are related to the accumulation of wrongly folded and entangled prion proteins. It has now been shown that this may be due to a copper deficiency in the brain, and that copper stabilises prions and helps them to fold correctly [48]. In addition to copper salicylate complexes also a salicylate complex with zinc and boron is a good healing remedy. This has been called the Schweitzer Formula, and is formed from zinc (oxide or carbonate), boron (boric acid) and salicylic acid. It has been used as an antibiotic, disinfectant, fungicide, and anti-inflammatory agent. The Schweitzer Formula was developed 1915, in addition to any kind of infection or inflammation, it has been used in cancer treatment, to improve the immune response and blood oxygenation. Applied externally it is claimed to heal injuries and skin diseases, including acne, scarring varicose veins and varicose ulcers. The decrease in antioxidant protection caused by copper deficiency goes beyond a decrease in the activity of copper-dependent antioxidant enzymes by inducing a wide range of disturbances in other antioxidant enzyme systems. Copper plays a vital role in the protection of the cardiovascular system from free -radical mediated damage and disease.[49] Thus, it appears clear that adequate copper is vital for optimal functioning of many antioxidant enzymes, both copper dependent and otherwise, in varied organs and tissues. Lysyl Oxidase, which is involved in the synthesis of the collagen that constitutes much of bone and connective tissue, is a copper dependent enzyme. Insufficient copper intake has also been shown to lower bone calcium levels during long-term deficiency [50]. With the essential role that copper plays in maintaining bone health, it is surprising how little attention has been given to copper's role in bone diseases, estrogens, which have a beneficial effect on preventing post-menopausal bone loss, have been shown to raise the level of ceruloplasmin (the main copper transport protein) two to three fold, providing a possible Hanan F. Abdel-Halim 272 explanation for how estrogen positively influences bone health, as well as cardiovascular health [51]. Copper plays another role in the development of cancer in which is somewhat similar to its role in cardiovascular disease. Numerous copper complexes that demonstrate SOD- mimetic properties, including copper salicylate, have been shown to possess anticancer, anticarcinogenic, and antimutagenic effects both in vitro and in vivo [52]. With cancer copper serum levels behave similar to those described for atherosclerosis. Various studies show a beneficial effect of copper on cancer. However, if growing tumours are present, then copper is needed to form new blood vessels. Therefore one form of cancer therapy creates artificial copper deficiency by removing copper with a molybdenum compound, and high amounts of zinc may be used to prevent the absorption of copper. It has now been shown that in the long-term this so-called anti-angiogenesis therapy does more harm than good by stressing tumours and inducing them to spread [53]. The main metabolic defect of cancer cells, according to researchers, is a deficiency of the enzyme cytochrome oxidase. This causes a blockage in the cellular respiration or oxidative energy production of the affected cells. Cytochrome oxidase is a copper dependent enzyme and additional copper might be beneficial. In the final stages of this oxidative energy production cytochrome oxidase transfers electrons to copper (II) and iron (III) to form copper (I) and iron (II). In the last step these electrons are then transferred to oxygen, which now can attract hydrogen ions to form water. In cancer cells this electron transfer is blocked and energy is inefficiently produced by converting glucose into lactic acid. Due to copper deficiency this electron transfer is defective in Menkes disease, a genetic disorder of early childhood. This is sometimes called Menkes kinky hair disease because such babies have very fragile hair; they also have abnormal brain development and a low body temperature. They are very floppy, lack energy and usually will not survive beyond 3 years of age. ZINC Zinc (Zn) is a trace element essential for cell proliferation and differentiation. It is a structural constituent of enzymes and proteins, including metabolic enzymes, transcription factors, and cellular signaling proteins. There is increasing evidence for a direct signaling function of Zn at all levels of cellular signal transduction [54]. Zinc is an important element in preventing free radical formation, in protecting biological structures from damage and in correcting the immune functions. Zinc deficiency produces growth retardation, anorexia, delayed sexual maturation and iron-deficiency anemia [55]. Zinc is often used for the prevention or treatment of common colds and sinusitis (inflammation of sinuses due to an infection), ulcers, sickle cell disease, celiac disease, memory impairment and acne [56,57 ]. Zinc is found in many common vitamin supplements and is also found in denture creams [56, 58]. There is also increasing evidence that zinc plays an important role in protein biosynthesis and utilization. The addition of small amounts of zinc to a diet containing suboptimal amounts of a vegetable protein causes a pronounced increase in protein utilization and growth. This defect may result from a failure in adequate RNA synthesis. Zinc apparently Review: Transition Metals in Medicine 273 inhibits the enzyme ribonuclease. Thus, in zinc deficiency, excessive destruction of RNA could occur. Zinc-binding proteins, such as metallothioneins (MTs), belong to the family of intra-cellular metal binding proteins that are present in virtually all living organisms and they play a key role in the Zn effect upon the immune system. Metallothioneins are protective against stress and increase in ageing [59]. Zinc plays major biological roles in the organism such as its role as catalyst, and as structural and regulatory ion [60]. The dysregulation of apoptosis is central to pathogenic mechanisms in many diseases such as neurodegenerative disorders, acquired immune deficiency syndrome, autoimmune disease and cancers [61, 62]. Increased apoptosis in vivo may occur as direct or indirect consequence of a decrease in intracellular Zn concentrations. Therefore, cellular Zn is described as an inhibitor of apoptosis, while its depletion induces death in many cell lines [63]. In ageing MTs preferentially bind Zn rather than copper and they are unable to release Zn. Indeed, during ageing the stress like-condition is persistent provoking sequester of intracellular Zn with subsequent low Zn ion bioavailability for immune efficiency and for the activity of Zn- dependent enzymes and proteins [60, 64]. Low Zn ion bioavailability and high MTs levels are present in aging and stress . A low Zn ion bioavailability may also trigger impaired cognitive functions, via altered thyroid hormones turnover [60]. Unlike other first-row transition metals (e.g., Sc 2+ , Ti 2+ , V 2+ , Cr 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ and Cu 2+ ), the zinc ion (Zn 2+ ) contains a filled d orbital (d 10 ) and therefore does not participate in redox reactions but rather functions as a Lewis acid to accept a pair of electrons [65]. This lack of redox activity makes Zn 2+ a stable ion in a biological medium whose potential is in constant flux. Therefore, the zinc ion is an ideal metal cofactor for reactions that require a redox-stable ion to function as a Lewis acid–type catalyst [66] such as proteolysis and the hydration of carbon dioxide. Furthermore, due to the filled d-shell orbitals, Zn 2+ has ligand-field stabilization energy of zero [67]. In all liganding geometries, and hence no geometry is inherently more stable than another. This lack of an energetic barrier to a multiplicity of equally accessible coordination geometries can be used by zinc metalloenzymes to alter the reactivity of the metal ion and may be an important factor in the ability of Zn 2+ to catalyze chemical transformations accompanied by changes in the metal coordination geometry. Nevertheless, in all zinc metalloenzymes studied to date, the binding geometry observed most often is a slightly distorted tetrahedral (Scheme 1) with the metal ion coordinating three or four protein side chains. However, five-coordinate distorted trigonal bipyramidal geometry has been observed in the metal sites of Zn-substituted astacin [68]. A final important property of Zn 2+ that makes it well suited as a catalytic cofactor is that ligand exchange is rapid [69], allowing for the rapid product dissociation required for efficient turnover. Zinc is classified as a "borderline" metal, meaning that Zn 2+ does not consistently act either "hard" (not very polarizable) or "soft" (highly polarizable) and does not have a strong preference for coordinating with oxygen, nitrogen or sulfur atoms [70]. In protein zinc- binding sites, the zinc ion is coordinated by different combinations of protein side chains, including the nitrogen of histidine, the oxygen of aspartate or glutamate and the sulfur of cysteine. 27 In In w si en le nu as in ph th or of Sc us be be in co 74 In zinc pro n a catalytic zi n a cocatalytic where one play ite [71]. Finally, in nzyme in a ma ead to a loss o umber of zinc s described lat As unders ncreases, the henotypes can A unique f hat is, the zinc r four protein f [74-77]: • an acti • polariz • stabiliz cheme.1. Zinc m In structur sually in a tetr Cysteine is eing present in In contrast etween the pro n a rigid sec omplexes ens oteins, the maj inc site, the zi c zinc site, th ys a catalytic r structural zin anner analogo of enzymatic a c proteins has ter [72,73] . standing of th connection b n be establishe feature for a c c-binding poly ligands act as vated water m zation of the ca zation of the n mettaloenzymes ral zinc sites, rahedral geom s by far the lig n many cases t to catalytic z otein zinc liga condary struc sure both loca Hanan jor role of the inc ion directly here are sever role and the o nc sites, the zin ous to disulfide activity. A sy established di he biochemica between the d ed. atalytic zinc s yhedron conta powerful elec molecule for nu arbonyl of the negative charg s. the metal io metry, so that s gand observed and aspartate zinc sites, thes ands, and the l cture. The hig al and overal F. Abdel-Hal e zinc ion can y participates ral metal ions ther metal ion nc ion mainly e bonds. In all stematic analy istinct feature al role of zinc detailed bioch site is the exis ains at least on ctrophilic cata ucleophilic att e scissile bond ge in the transi n is coordina olvent is exclu d most freque being present se sites conta ligands can be gh stability c ll structural s im be catalytic, in the bond-m s bound in pr ns enhance the y stabilizes the l cases, remov ysis of the str s of catalytic c in these bio hemical funct stence of an op ne water mole alyst by provid tack. d . tion state. ated by four a uded as an inn ently in these in one case [7 in no regular e located on a constants of stability simil cocatalytic or making or -bre roximity to on e catalytic acti e tertiary struc val of the boun ructure and fu and structural ological macro tions and ph pen coordinat ecule in additi ding all or a co amino acid si ner sphere liga sites, with his 75, 79]. pattern of spa flexible loop these tetrade lar to that pr r structural. eaking step. ne another, ivity of the cture of the nd zinc can nction of a l zinc sites, omolecules hysiological ion sphere; ion to three ombination ide chains, and [78]. stidine also acer length rather than entate zinc rovided by di of lo us ac ne be co en re fo am ch be ag su tr fo an Z ab us m zi of isulfides [78]. f functions. Zinc defici oss or defects sed as a treatm crodermatitis ervosa and bu ecause a wid oordinate dire nzyme. Zinc has b edox-active tr ormation of · O mounts of iro hemistry accor Reaction 2 een suggested gents (AH 2 ), uperoxide via The proces ransition metal orm · OH . Zinc can a nhydrase. Her n-OH group. bility to act as sed by many e Recent clin malnutrition an inc content in f zinc deficie R This enables p iency can caus leading to re ment of many enteropathica ulimia nervos de range of ctly to the me been shown in ransition meta OH from H 2 O n or copper to rding to the fo is commonly d that trace a such as asco the metal-cata ss of protein l to an enzyme also perform a re the metal bi The zinc me s an electrophi enzymes [81]. nical and expe nd diarrheal di virtually all t ency. Compe Review: Transi proteins conta se retardation, eproductive fa y illnesses and a (inflammatio a [80].Catalyt functional g etal, displacing n numerous sy als iron and O 2 and superox o catalyze for ollowing reacti y known as the amounts of so orbate, can c alyzed Haber- oxidation is i e to form a co a different rol inds H 2 O and etal serves as ile or as the so erimental findi isease. Becaus types of foods nsatory mech ition Metals in aining structur , cessation of ailure. Zinc su d disorders, in on of the ski tic zinc sites groups (i.e., s g the zinc-wat ystems to anta copper with xide. There is rmation of · OH ions [81]. e Haber-Weiss oluble iron or catalyze the Weiss reaction initiated by th oordination com le in enzymes makes it acid a nucleophile ource of a nuc ings have rein se there is a st s, insufficient hanisms opera n Medicine ral zinc atoms growth, impa upplementatio ncluding dwarf in and the sm provide conv sulfonamides ter in the activ agonize the ca respect to th s a well know H from H 2 O 2 s reaction and r copper in th formation of n (Fenton reac he binding of mplex that can s like the role dic enough to l e to the subst cleophilic gro forced the link trong associat protein intake ating in mon to perform a w ired wound he on has success fism, sexual i mall intestine) venient targets or hydroxam ve site and inh atalytic prope heir abilities t wn requiremen and O 2 - throu d is relatively s he presence o f hydroxyl rad ction (reaction f a reduced re n then react w it performs i lose a proton trate. Since zi up it is incorp k among zinc tion between p e may often be nogastric spec 275 wide range ealing, hair sfully been mmaturity, ), anorexia s for drugs mates) can hibiting the rties of the to promote nt for trace ugh Fenton (1) (2) (3) (4) (5) (6) slow. It has of reducing dical from n 6). edox-active ith H 2 O 2 to in carbonic and form a inc has the porated and deficiency, protein and e the cause cies during Hanan F. Abdel-Halim 276 malnutrition are less effective for the absorption of transition divalent elements such as zinc, which remain bound to ligands of dietary or endogenous origin. Both protein and zinc deficiencies are strong negative determinants for normal cellular immunity. Zinc deficiency may impair the absorption of water and electrolytes, delaying the termination of normally self-limiting gastrointestinal disease episodes. As zinc has an antioxidant and anti-inflammatory action in the uterus. Improvement in micro-vessel circulation by zinc may help prevent cramping and pain. Since strong uterine contractions temporarily reduce or stop the blood supply to the uterus, thus depriving the uterus of oxygen resulting in contractions and pain, perhaps improvement in micro-vessel circulation by zinc treatment is sufficient to prevent cramping and pain. Ischemia is partly caused by reperfusion, which results in the release of much active oxygen species which can cause tissue damage and pain. Thus, much of the discomfort of dysmenorrhea is likely to be due to these free oxygen radicals. The enzyme which inactivates these oxygen species is dismutase. Copper–zinc dismutase is present in the uterus [82] and zinc treatment allows for more adequate levels of this enzyme – which in turn could relieve cramping and pain. Zinc is an effective anti-inflammatory and antioxidant agent, and it can readily down regulate inflammatory cytokines [83]. Zinc protects plasma cell membranes preventing damage to cells by a wide variety of cytotoxic agents in a dose dependent manner extending far above physiologic concentrations. GOLD For decades, gold salts have been utilized for the treatment of inflammatory rheumatoid arthritis [84].Although their exact mechanism of action is not clearly understood, gold salts decrease the inflammation of the joint lining, thereby preventing destruction of bone and cartilage. It is quite likely that the mechanism by which gold anti-rheumatic drugs modulate the immune response is multifactorial. Their therapeutic activity may be derived from an ability of gold to undergo facile ligand exchange with biological thiolates, particularly those with low pKa values, resulting in the inhibition of activity of several different enzymes. Gold (I) can chelate thiol peptides with two or more cysteine residues thus affecting antigen presentation [85].While some gold compounds can affect the cellular redox balance. Additionally, it has also been proposed that gold’s anti-arthritic activity may be due to its ability to release peptides from major histocompatibility complex-class II (MHC-II) proteins [86]. Among the non-platinum antitumor drugs, gold complexes have recently gained considerable attention due to their strong antiproliferative potency. In many cases the cell growth inhibiting effects could be related to anti-mitochondrial effects making gold species interesting drug candidates with a mode of action different from that of the platinum agents. The spectrum of gold complexes described as antiproliferative compounds comprises a broad variety of different species including many phosphine complexes as well as gold in different oxidation states[87]. Auranofin - Au - oral rheumatoid arthritis drug (Figure 5) , has a triethylphosphinegold unit, is just as effective, as Disodium aurothiomalate AuSCH(CO 2 Na)CH 2 CO 2 Na (Figure 6) is a coordination complex used to treat rheumatoid arthritis.The injectable thiolate complexes ar st au th he af T T pr Fi Fi A is en G re polymers c tructures Au-S urothiomalate hiolate drugs exameric 1 : ffinity for thio herefore Au(1 hiolate exchan robably not th igure 5. Aurano ig 6. Disodium Albumin c Au(1) in the cy s mobile withi nzyme glutath GSH-Px-Se-Au R containing lin S-Au-S- with usually conta have been cr 1 Au(1) thiola olate S compar 1) binds to D nge reactions he pharmacolo ofin. aurothiomalate can transfer A ytoplasm. Glut n the cell due hione peroxida u-SG [93]. Review: Transi near Au (1) h succinoyl gr ains a slight e rystallized, bu ate complex h red to thioethe NA very wea on Au(1) are gically-active e. Au(1) into cell tathione is kno e to dynamic e ase by bindin ition Metals in and bridging roups attached excess of thiol ut the X-ray has been repo er S, and a mu akly and is no facile [90] an species. ls,specific me own to bind to exchange react ng to the activ n Medicine thiolate sulf d to the sulfur late over gold crystal struct orted [89]. Go uch lower affin ot usually car d therefore th etal transport o intracellular tions. This co ve site selenoc furs, in chain r atoms.[88]. F d. None of the ture of a rela ld(1) has a m nity for N and cinogenic or e administered proteins, [91] Au(1) [92] an mplex can inh cysteine residu 277 n or cyclic Formulated e injectable ated cyclic much higher d 0 ligands. mutagenic. d drugs are ], transport nd the gold hibit the Se ue forming Hanan F. Abdel-Halim 278 Under the oxidative conditions that exist in inflamed joints, oxidation of Au(1) to Au(III) is likely formed. The formation of Au(III) may be responsible for some of the side-effects of gold therapy [94]. Gold(III) has a remarkable ability to deprotonate peptide amide bonds even at highly acidic pH values. The tripeptide Gly-Gly-His, for example, readily forms a square- planar complex with Au(III) at (pH 2) via binding to the terminal amino group, two deprotonated amide nitrogens and imidazole N of His. [95]. Ultimately much gold is deposited in lysosomes of cells but the chemical form of it is not known. It is not metallic Au, but probably a protein complex. Here gold may inhibit lysosomal enzymes which are responsible for destruction of joint tissue [96]. As Gold(III) is isoelectronic and isostructural with Platinum (II), it was suggested that gold compounds may also be useful as anticancer. Although the screening of Auranofin and Auranofin analogues yielded a limited spectrum of activity [97,98] organogold(III) DAMP(DAMP = o-C 6 H 4 CH 2 NME2) complexes[99,100] and triphenylphosphine-gold (I) complexes have shown significant activity . The work conducted on the latter compounds led to the development of bis(diphos)gold(I) complexes [101,102]. Mononuclear gold(III) complexes, organogold(III) compounds and dinuclear oxobridged gold(III) complexes were evaluated in several human tumor cell-lines [103]. and novel targets proposed include the mitochondrial membrane, cysteine proteases (notably caspases and cathepsins) and thioredoxin reductase [104,106]. In 2011 researchers synthesis and study new gold(III) complexes 5-aryl-3-(pyridin-2-yl)- 4,5-dihydropyrazole-1- carbothioamide . The cytotoxicity was tested by MTT assay. The results indicate that some complexes have higher cytotoxicity than cisplatin against HeLa cell line. The study suggests that the substituent groups on benzene have important effect on cytotoxicity [107]. VANADIUM Vanadium is a curious trace element which seems to be required by the body in relatively tiny amounts. There is nevertheless increasing excitement about its potential therapeutic value. Low blood levels of vanadium have been associated with increases in cholesterol and blood sugar, and it is also believed by some researchers that the mineral may play a role in maintaining the vital balance between sodium and potassium in cells. These characteristics of vanadium have led to speculation that it may act as a protector against heart disease, cancer and especially diabetes. Some nutritional therapists have rushed to embrace vanadium's potential, insisting that high dose vanadium supplements can reduce levels of fasting blood sugar and reducing cellular inflammation [108,109 ], as well as those of low density lipids (LDLs), the so-called "bad cholesterol" which is strongly associated with atherosclerosis (hardening of the arteries) [110]. The initial use of vanadium to treat diabetes was in 1899 [111]. The ability of sodium vanadate (NaVO3) to lower blood glucose levels has been tested. The result was very promising in lowering sugar levels, with no side effects [112]. Vanadyl sulfate (VOSO4) soon replaced sodium vanadate in animal testing due to the decreased toxicity of vanadyl compared to vanadate . Also, much of the vanadate ad fo th 7) T T Fi in m am in m va an ca pr co ho co tr (v so oc an de ar th vi sp to in va pr dministered is ocus off of van he major treatm ) was the first here is also a here are differ igure 7. Bis(ma Vanadium ncrease cell vo mimic the horm mino acids an ncreasing cell muscles look b anadium may nd fight age-r apacity and ab Vanadium roperties in e omplex exert owever exerts ombination w reatment of hu Most of th vanadate) prob olution. In van ccur simultane nd decameric epending on v re not taken in hat, particularl ivo [119]. In pectroscopy st o the iceberg nteresting one anadium spec romoted effec R s found in the nadium comp ment for the d t vanadium co an increase in rences in distr altolato)oxovana became popu olume and thu mone insulin nd blood suga volume, vana bigger and ful also be impor related loss o bility to enhan salts and com experimental ed antitumor s much more with its low to uman malignan e biological im bably due to nadium (+5) eously in equi (V10) and, vanadium conc n consideratio ly V10, they m vitro effects tudies. Allego phenomena: e, but clearly cies and the in ts. Review: Transi e vanadyl form lexes for treat disease [111,1 omplex prepare uptake and t ribution of ion adium (BMOV) ular with bod us was hoped in the body, v ar, into our mu adium has bee ller but even rtant for bone of bone. This ce calcium me mplexes have carcinogenes effects in tu e potent . Th oxicity provid nt diseases [11 mportance of similarities b solutions diff ilibrium such in same case centration, pH on in the majo may also influ can be conv orically, vanad there is alway y it is the es nteractions wi ition Metals in m [111]. The tment of diabe 113]. Bis(malt ed that has inc tolerability ass nic verses com ). dybuilders las to also boost vanadium is b uscle cells, w en suggested b result in mus formation, wh effect seems etabolism [115 been widely i is. Vanadyl umor bearing hese beneficia de evidence su 18]. vanadium is a etween the ph ferent oligome as monomeri s, with differ H and ionic stre ority of the bi uence enzyme veniently ana date studies in ys an invisibl ssential part n ith the system n Medicine discovery of etes, as hormo tolato)oxi-van creased effect sociated with mplex forms of st decade bec muscle mass believed to he which leads to by some expe scle growth. S hich could hel to be due to 5-117]. investigated fo sulfate, cyste g rats. The V al effects of uggest its pos associated wit hosphate and eric (n=1 to 1 c (V1), dimer rent states of ength. Many o ological studi e activity not alysed combin n biological sy le part that p needed to pr m before attem insulin in 192 one supplemen nadium (BMO tiveness again the complex f vanadyl. cause of its p .Due to its p elp shuttle nut greater cell v rts to not only Some evidenc lp maintain bo o an enzyme-s for their antica eine and V(II V(III)-cysteine the above co ssible applica th the +5 oxid vanadate che 0) vanadate s ric (V2), tetram protonation a of these vanad ies, although i only in vitro ning kinetic w ystems can be robably is no ecisely chara mpting to unde 279 22 took the nts became OV) (Figure st diabetes. [113,114]. potential to potential to trients, like volume. By y make the ce suggests one density stimulating arcinogenic II)-cysteine e complex, omplex, in ation in the dation state emistries in species can meric (V4) and forms, date species it is known but also in with NMR e compared ot the most acterize the erstand the Hanan F. Abdel-Halim 280 Among vanadate oligomers, decameric vanadate (V10), which may occur upon medium acidification, is considered as the vanadate oligomer with more biochemical relevance. Although unstable at physiologic pH, the slow rate of decameric vanadate decomposition allows studying its effects in biochemical systems [119,120]. In fact, it was suggested that even at physiological pH values an eventual local acidification of a vanadate solution will induce the formation of (V10) species. Once formed, decameric vanadate disintegration is in general slow enough to allow the study of its effects even in the micromolar range. Besides, it may become inaccessible to decomposition due to their stabilization upon binding to target proteins such as sarcoplasmic reticulum Ca 2+ -ATPase or actin [121]. Additionally, recently described in vivo toxicological studies demonstrated that decameric vanadate species are responsible for a strong increase in lipid peroxidation and oxidative stress markers, thus contributing to oxidative stress responses upon vanadate intoxication and pointing out to the importance of vanadate speciation on the evaluation of vanadium toxicity . The degree of toxicity depends on the mode of administration such as intraperitoneal or intravenous, and of course to the vanadate species such as decavanadate [122,123]. Other studies included the use of decavanadate as a probe in comprehension of muscle contraction and calcium homeostasis [119]. Actually, we are investigating the mechanisms of cell death induced by vanadate [122] and the effects of insulin-mimetic vanadium compounds in the activity of sarcoplasmic reticulum calcium pump . We believe that these recent advances in vanadium toxicology and pharmacology allow a better understanding of the role of the versatile vanadium in biological systems [124]. Vanadium is widely known for its toxic effects; however it is vestigial in muscles and other tissues and is considered an essential oligoelement for humans. Its biological role is far from a clear identification. Vanadium is present in petroleum, coal and gasoline, used as alloys and catalysts for industry and is well known for its environmental and biological impact (Nriagu, 1998). In spite of the emerging interest in the pharmacological effects of some vanadium compounds, for instance as an insulin-mimetic in the treatment of diabetes, the toxicology of vanadium constitutes an area of increasing interest (Aureliano, 2007). Recently, it was reviewed some medicinal applications of vanadium focusing structure- activity relationship of antidiabetic vanadium complexes, vanadium compounds as anti- tumour drugs and anti-parasitic agents, and osteogenic action of vanadium complexes in order to make vanadium compounds available and safe for clinical use. Milestones in the history of Vanadium Biochemistry are also the review chapters about the redox profile of vanadium, the biological role of vanadium in bromoperoxidases and the oxovanadates interactions with lipidic structures (Aureliano, 2007). Most of the biological importance of vanadium is associated with the +5 oxidation state (vanadate) probably due to similarities between the phosphate and vanadate chemistries in solution. In vanadium (+5) solutions different oligomeric (n=1 to 10) vanadate species can occur simultaneously in equilibrium such as monomeric (V1), dimeric (V2), tetrameric (V4) and decameric (V10) and, in same cases, with different states of protonation and forms, depending on vanadium concentration, pH and ionic strength. Many of these vanadate species are not taken in consideration in the majority of the biological studies, although it is known that, particularly V10, they may also influence enzyme activity not only but also (Aureliano, 2007). effects can be conveniently analysed combining kinetic with NMR spectroscopy studies. Allegorically, vanadate studies in biological systems can be compared to the iceberg phenomena: there is always an invisible part that probably is not the most interesting one, but Review: Transition Metals in Medicine 281 clearly it is the essential part needed to precisely characterize the vanadium species and the interactions with the system before attempting to understand the promoted effects. Among vanadate oligomers, decameric vanadate (V10), which may occur upon medium acidification, is considered as the vanadate oligomer with more biochemical relevance. Although unstable at physiologic pH, the slow rate of decameric vanadate decomposition allows studying its effects in biochemical systems (Aureliano and Gândara, 2005, Aureliano 2007). In fact, it was suggested that even at physiological pH values an eventual local acidification of a vanadate solution will induce the formation of V10 species. Once formed, decameric vanadate disintegration is in general slow enough to allow the study of its effects even in the micromolar range. Besides, it may become inaccessible to decomposition due to their stabilization upon binding to target proteins such as sarcoplasmic reticulum Ca 2+ - ATPase or actin (Ramos et al, 2006). Additionally, recently described toxicological studies demonstrated that decameric vanadate species are responsible for a strong increase in lipid peroxidation and oxidative stress markers, thus contributing to oxidative stress responses upon vanadate intoxication and pointing out to the importance of vanadate speciation on the evaluation of vanadium toxicity (Soares et al, 2007a). The degree of toxicity depends on the mode of administration such as intraperitoneal or intravenous, and of course to the vanadate species such as decavanadate. One of the most important recent results was the observation that decameric vanadate also affects mitochondrial oxygen consumption at the nM range of concentration (Soares et al, 2007b). In another line of research, the effects of vanadate on the mineralization of a fish bone-derived cell line were studied and compared to that of insulin, being suggested that it stimulates growth and prevents mineralization through multiple processes involving regulation that may or may not depend upon the activation of insulin stimulated pathways (Tiago et al, 2008). Other studies included the use of decavanadate as a probe in comprehension of muscle contraction (Tiago et al, 2004, 2007) and calcium homeostasis (Aureliano et al, 2007). Actually, we are investigating the mechanisms of cell death induced by vanadate (Soares et al, 2008) and the effects of insulin-mimetic vanadium compounds in the activity of sarcoplasmic reticulum calcium pump (Aureliano et al, 2008). We believe that these recent advances in vanadium toxicology and pharmacology allow a better understanding of the role of the versatile vanadium in biological systems (Kustin et al, 2007). IRON Hemoglobin, which is the principal oxygen carrier in humans has four sub-units in which the iron(II) ion is coordinated by the planar, macrocyclic ligand protoporphyrin IX and the imidazole nitrogen atom of a histidine residue[125]. Each ferrous iron within hemoglobin provides one binding site for O 2 (Figure 8) . Thus a single hemoglobin molecule has the capacity to combine with four molecules of oxygen. Hemoglobin binds oxygen in a cooperative fashion; occupation of one binding site enhances the affinity of another binding site for oxygen in the molecule[126,127]. 28 Fi ha as fo pr co m so ce fa sp to in of Fi ac 82 igure 8. Structu The sixth c as only one su s, without it, th or the formatio ressure of ox ooperativity myoglobin[128 olubility and p enter and the acilitates the p In both hem pecies contain o the fact that n the plane of t iron atom l f higher crysta igure 9. Rubred Rubredoxin ctive site cont ure of Heme b, i coordination si uch unit. The he iron(II) wo on of HbO 2 is xygen in the l effect which 8].A combina prevents aggre presence of peroxidation re moglobin and ns iron(III). It the iron(II) is the porphyrin lies above the al field splittin doxin. n is an electro tains an iron Hanan in the protein. ite contains a active site is l ould be irrever such that oxy lungs or in m h allows for ation of a hy egation of hem a relatively p eaction. myoglobin it is now known in the low-sp ring, but in th plane of the r ng and smaller on-carrier foun ion which is F. Abdel-Hal water molecu located in an h rsibly oxidised ygen is taken u muscle. In he r easy oxyg ydrophobic b min, tentative d polar site clos is sometimes n that the diam pin state. In ox he paramagnet ring. The chan r ionic radius o nd in sulfur-m coordinated b im ule or a dioxyg hydrophobic p d to iron(III). T up or released emoglobin the gen transfer binding pocke donation of an se to the iron incorrectly st magnetic natur xyhemoglobin tic deoxyhemo nge in spin sta of Fe 2+ in the o metabolizing b by the sulphur gen molecule. pocket. This is The equilibriu depending on e four sub-un from hemo et, which inc n axial ligand t n-oxo center p tated that the o re of these spe n the iron atom oglobin , ate is a coopera oxy- moiety [ acteria and ar r atoms of fou myoglobin s important um constant n the partial its show a oglobin to creases the to the Fe3+ presumably oxygenated ecies is due m is located ative effect 128]. rchaea. The ur cysteine Review: Transition Metals in Medicine 283 residues forming an almost regular tetrahedron. Rubredoxins perform one-electron transfer processes. The oxidation state of the iron atom changes between the +2 and +3 states. In both oxidation states the metal is high spin, which helps to minimize structural changes. Iron is transported by transferrin (Figure 10) whose binding site consists of two tyrosines, one aspartic acid and one histidine[129]. Figure 10.The Amino Acids that bind and hold iron in a N-terminus Transferrin lobe. Iron tris(bipyridine) Polymeric Metal Complexes is useful in biological applications because they are labile and may alter their inner coordination sphere in response to changes in pH and temperature or the presence of reactive oxygen species [130]. This presents a new triggered release because an iron PMC system that is initially inert when it is delivered can become labile when it interacts with cells or tissues with appropriate oxidizing environments. Additionally, some metals can function as molecular probes because they are chromophores or have properties that can be detected through analytical methods [130]. This allows the movement of the metal and its interactions with its environment and cells to be monitored. The regulation of iron metabolism (Bioiron) uses both DNA and RNA as targets, which contrasts with oxygen metabolism where DNA is the target. The molecular assembly of polytopic systems containing clathrochelate fragments was used to design novel antioxidants based on sterically hindered phenols. 2,6-Di(tert butyl)phenols are well known antioxidants which are widely used in various fields of food industry and pharmaceutics. Their antioxidant activity is determined by stability of the phenoxyl radicals formed upon their oxidation, the redox potential value, and the mechanism and reversibility of the electron transfer [131]. The incorporation of a metal ion in a phenol containing molecule is known to be an efficient way for stabilizing the phenoxyl radical formed upon its oxidation. The effect of the metal ion on the physicochemical characteristics of radical reaction products is determined by two main factors, steric factor (an increase in the structural rigidity of the molecule and steric hidrance of the reactive radical centers) and electronic factor (a decrease in the spin density on the radical fragment as a result of delocalization of the unpaired electron within the common electronic system of the complex) [132]. In addition, the central metal ions in these Hanan F. Abdel-Halim 284 complexes can initiate oxidation (in particular, through coordination of molecular oxygen and catalysis of hydroperoxide homolysis). Comparative study of the antioxidant activity was carried out for macrocyclic square bipyramidal iron(II) bis_dioximate and cage macrobicyclic iron(II) and tris-dioximates [133]. Two series of macrocyclic and macrobicyclic iron dioximate differing in the molecular geometry and the number of 2,6- di(tert_butyl)phenol substituents in them were prepared. Specifically, the macrocyclic iron bis_dioximate, FeD 2 (BF 2 )2Py 2 ,where D 2 is the methyl[3,5-di(tertbutyl) 4- hydroxyphenyl]glyoxime dianion, contained two fragments of this type, whereas the molecules of cage iron trisdioximates contained one or six sterically hindered phenolic groups [134]. Oleic acid was used as the substrate as a model of autoxidation of lipids by molecular- oxygen. The liquid phase oxidation of oleic acid is a radical chain process giving hydroperoxide as the primary product, which then decompose to yield oxidative destruction products (mainly, carbonyl compounds). Iron(II) tris_dioximate clathrochelate exhibits a much higher antioxidant activity than bis_dioximate macrocycles [135]. Thus, encapsulation of the metal ion in macrobicyclic iron(II) trisdioximate results in inhibition of accumulation of hydroperoxides and their decomposition products.The most pronounced antioxidant properties were observed for the complexes containing six 2,6_di(tertbutyl)phenol residues. The level of peroxidation of unsaturated fatty acids was measured based on accumulation of carbonyl compounds formed upon hydroperoxide decomposition ,and the effect of macrobicyclic phenol containing iron trisdioximate on the lipid peroxidation was studied in vitro . The high antioxidant activity of the clathrochelate iron trisdioximate compared to their macrocyclic bis_dioximate analogs is attributable to the possibility of incorporating additional antioxidant phenolic groups into the molecules of macrobicyclic complexes (Figs 11,12). Figure 11. General view of the iron(II) hexaphenolic clathrochelate. Review: Transition Metals in Medicine 285 The encapsulated metal ion provides high stability of the phenoxyl radicals formed, and the steric hindrance of the metal ion encapsulated in the cavity of the macrobicyclic clathrochelate tris_dioximate ligand prevents its involvement in dioxygen coordination and activation. In addition, the efficiency of inhibition of oxidation processes in the cells is determined by inclusion of clathrochelates with lipophilic peripheral substituents into the lipid bilayer of the cell membrane .Complexes with an encapsulated metal cation (in particular, radioactive ion) can be used as radiopharmaceutical and pharmaceutical agents for diagnostics and therapy. Figure 12. General view of the iron(II) monophenolic clathrochelate. It is important that the formation of the clathrochelate bridging fragment, whose stability is comparable with a covalent bond stability, between the boronic linkers according to Scheme 20 does not affect other functional fragments (amino, thiol, and carboxy groups). This system can be used for immobilization and affinity binding of macromolecules, antibodies, and enzymes, substrate linking to the active sites of these enzymes, and fluorescence probes.A promising application of clathrochelate linkers is mimicking of ligases and binding of nucleotide sequences to a single stranded DNA template. Macrobicyclic cobalt(II) polyamine complexes with apical groups functionalized with polycyclic aromatic substituents were synthesized as a new type of DNA intercalators. It was assumed that these systems would demonstrate a synergistic effect in DNA binding both through intercalation of planar apical fragments and through electrostatic interaction of the cationic macrobicyclic complex with the DNA poly-anion [136,137]. The use of clathrochelate complexes as protease inhibitors , probably, the ellipsoidal shape of their molecules allows one to inhibit the HIV protease active site. Analysis of the shape of molecules and crystal packings for adamantly containing clathrochelates in which the formation of their crystal lattices is mainly governed by the dispersion van der Waals interactions between the hydrophobic peripheral parts of the molecule and depends primarily on the overall geometry of the molecule [138]. PLATINUM Metal complexes which undergo ligand substitution and redox reactions is likely to mean that the active species are biotransformation products of the administered complex. 28 Id as to w gr ch A bo be co Fi Fi (a [P [1 D 86 dentification o s drugs. Resistance • reduce • strong metallo • repair o The drug c o two ammoni was discovered rowth of bacte Under phy hanging the Aminophosphin ond is relative etween the sub ontrolled by th igure 13. Struct igure 14. Struct I’st way of an aqua liga PtCl(H 2 O)(NH 138]. Of the b DNA)(NH 3 ) 2 ] + , of these active mechanism w ed transport ac binding to in othionein. of platinated l cisplatin (Figu ia ligands and d by chance i eria and using siological con ligands on ne ligands bin ely labile on bstituents on t he substituents ture of Cis-plati ture of Pt(II)dia f acting is as f and), in a p H 3 ) 2 ] + is itself ases on DNA, , crosslinking Hanan e species will which have bee cross the cell m nactivating th lesions on DN ure 13 ) conta d two chloride in an experim platinum elec nditions cispla Pt(lI) to am nd strongly to account of th the N atoms. T s on N ,by the in. aminocyclohexa follows ,one o process terme f easily displa , guanine is pr can occur via F. Abdel-Hal lead to the m en recognized membrane. hiolate ligands NA by enzymes ins a square-p ligands with ment looking a ctrodes.[139 ] atin does not a mino phosph o Pt(II) but in he high trans Thus chelate ri size of the ch ane. of the chloride ed aquation. aced, allowing referred. Subs a displacement im ore effective u d are as follow s inside the c s . planar platinum a cis-ligand c at the effect attack the DN hines allows n bischelated influence of P ing opening in helate ring, by e ligands is slo The aqua l g the platinum sequent to form t of the other c use of metal c ing: ell, e.g. gluta m(II) center c conformation. of electric fie NA base thymi this to be cis complexe P and steric i n these comple the pH [140]. owly displace igand in the m atom to bin mation of [PtC chloride ligand compounds athione and coordinated Its activity elds on the ine (T), but achieved. es the Pt-N interactions exes can be . ed by water e resulting nd to bases Cl(guanine- d, typically Review: Transition Metals in Medicine 287 by another guanine. Cisplatin crosslinks DNA in several different ways, interfering with cell division by mitosis. Cellular resistance to cisplatin (cis diamminedichloroplatinum(II)) can be overcome by changing the ammine ligands to 1,2-diaminocyclohexane (DACH) and Pt(lV) analogues It is therefore of much interest to investigate how the structures of amine ligands affect the reactivity of platinum complexes [141]. Intracellular hydrolysis has long been thought to be an important process for the activation of chloro Pt anticancer diamine complexes (Figure 14). Changing the ammine ligands can markedly affect the rate of hydrolysis and the pK, values of the resulting aqua complexes. ['H,I5N] NMR spectroscopy allows the detailed pathways of reactions of cisplatin (and other ammine and amine complexes) to be followed. The GG chelate is known to be an important adduct in cells. The selectivity of Pt for GG sequences is related to the high electron density at such sites (most easily oxidized sites of DNA). Molecular modeling studies demonstrate that H-bonding between the NH 3 ligands and carbonyl groups on DNA play a major role in determining the orientation of the Pt-Cl bonds and their accessibility. Molecular mechanics calculations show that although the chloride ligand in the monofunctional adduct faces outward, away from the helix, the aqua ligand which replaces it after hydrolysis faces inwards on account of its strong H-bonding properties. cisplatin does not attack the DNA base thymine (T), but changing the ligands on Pt(lI) to amino phosphines allows this to be achieved. Aminophosphine ligands bind strongly to Pt(II) but in bischelated cis complexes the Pt-N bond is relatively labile on account of the high trans influence of P and steric interactions between the substituents on the N atoms. Thus chelate ring opening in these complexes can be controlled by the substituents on N, by the size of the chelate ring, by the pH. The mechanism of action of Pt is that DNA is the target. In another word platinum- containing anticancer drugs are alkylating agents which means that they react with the nitrogenous bases in DNA strands to form crosslinkges within and between strands. The primary biological target appears to be the interaction with nucleic acids, and therefore studies of the interaction of platinum amine compounds (both active and inactive ones) with nucleic acids and nucleic acid fragments are of great interest. Studies on mononucleotides have made clear that a strong preference exists for platinum binding at guanine-N7 sites. Investigations on oligonucleotides have shown that, when two neighboring guanines are present, chelation of the cis-Pt(NH 3 ) 2 unit (cisplatin) is strongly preferred above all other possibilities. Studies on DNA ( in vivo and in vitro) have made clear that similar binding modes occur in DNA and oligonucleotides, and that after cisplatin binding the DNA structure is distorted in the same way as double-stranded oligonucleotides. Some of the most promising compounds, considered today, are Pt(NH)2(CBDCA), (CBDCA = 1,1-dicarboxylatocyclobutane), now also called paraplatin, and CHIP (cis,cis- ,trans-dichlorodihydroxobis(isopropylamine)platinum(IV).) Some examples are presented in (Figure 15). Especially the CBDCA derivative is promising because of its low toxicity. Hanan F. Abdel-Halim 288 Figure 15. Structure of Cisplatin derivatives. During the last decade large number of Pt(II) and Pt(IV) compounds were prepared, they have made clear that Pt compounds with anti-tumor activity have to fulfil all of the following structural requirements: • The two amine ligands in the Pt-compound should be in a cis-orientation. In a didentate chelating ligand, this geometric requirement is automatically fulfilled. The general formulae should be cis-Pt(II)X 2 (Am) 2 and cis-Pt(IV)Y 2 X 2 (Am) 2 . However, the number of variations studied in the case of Pt(IV) is still limited. • The ligands X, usually anions, should consist of groups that have intermediate bindingstrength to Pt(II), or that are - for other reasons - easily leaving (i.e. by enzymatic action). Examples are:Cl-, S04 2- ,citrate(3-), oxalate(2-) and other carboxylic acid residues. For the Pt(IV) compounds, the Y group is often OH. The amine ligands, either monodentate or didentate, should have at least one N-H group, i.e. possess a hydrogen-bond donor function . All compounds with both amine ligands lacking such a H-bond donor property, were found to be inactive. The role of this N—H group in the biological activity, however, is far from being understood. It could be either kinetic (i.e. play a role in the approach of the DNA), or thermodynamic (e.g. give an additional (de)stabilization after binding to the biological target DNA;vide infra). However, also steric effects and/or a role in transport through the cell wall cannot be excluded. Molecular modelling studies demonstrate that H-bonding between the NH 3 ligands and carbonyl groups on DNA play a major role in determining the orientation of the Pt-Cl bonds and their accessibility. In addition molecular mechanics calculations show that although the chloride ligand in the monofunctional adduct faces outward, away from the helix, the aqua ligand which replaces it after hydrolysis faces inwards on account of its strong H-bonding properties[142]. In 2004, a further platinum drug, oxaliplatin (Figure 16) achieved worldwide clinical acceptance. The clinical advantage of oxaliplatin is that it has a different spectrum of activity, in particular, it is effective against colorectal cancer, a disease not treatable using cisplatin or carboplatin(Figure 17) [143], in addition to its activity against some cisplatin-resistant cancers. The alternate diamine ligands used in heptaplatin and lobaplatin do not confer these same effects. Review: Transition Metals in Medicine 289 Figure 16. Structure of Carboplatin and Oxaliplatin. Figure 17. Structure of Nedaplatin (top right) and Lobaplatin (bottom). It is clear from the activity of oxaliplatin, satraplatin, and picoplatin that modifying those ligands on platinum that are retained in the DNA adduct can affect the way the compound acts in the biological system. Hanan F. Abdel-Halim 290 SUMMARY The equilibrium of metal ions is critical for many physiological functions, particularly in the central nervous system, where metals are essential for development and maintenance of enzymatic activities, mitochondrial function, myelination, neurotransmission as well as learning and memory. Due to their importance, cells have evolved complex machinery for controlling metal-ion homeostasis. However, disruption of these mechanisms, or absorption of detrimental metals with no known biological function, alter the ionic balance and can result in a disease state, including several neurodegenerative disorders such as Alzheimer's disease. Understanding the complex structural and functional interactions of metal ions with the various intracellular and extracellular components of the central nervous system, under normal conditions and during neurodegeneration, is essential for the development of effective therapies. Accordingly, assisting the balance of metal ions back to homeostatic levels has been proposed as a disease-modifying therapeutic strategy for Alzheimer's disease as well as other neurodegenerative diseases [144]. Metal metabolism is emerging as an exciting area of cell biology and a potential site for therapeutic interventions. Normal metal metabolism appears to maintain free metal ion concentrations at a very low level and to deliver metals very selectively to their sites of action, while maintaining tight control over their reactivity. Trials to reduce metal toxicity by delivering metal compounds to the tissues, cells and receptors are rapidly emerging. To better understanding the progressing happened in the field of pharmaceuticals[145,146]. REFERENCES [1] M. Gerken. Chemistry 2810 Lecture Notes : Metal ions in biology and medicine. [2] P., J. Sadler ; Z., Guo. Metal complexes in medicine: Design and mechanism of action. Pure & Appl. Chem., 70, 1998, 863-871. [3] Metals in Medicine: Targets, Diagnostics, and Therapeutics, Natcher Conference CenterNational Institutes of HealthBethesda, Maryland, U.S.A. 2000, 28-29. [4] B., George; E., E., Conn; R., H., Doi; and P., K., Stumpf. Outlines of Biochemistry. New York: John Wiley and Sons, Inc., 1978. [5] C., Liu and L., Wang .Dalton Trans., 2009, 227-239 [6] M., Chandra; A., Sachdeva; S., K., Silverman . DNA-catalyzed sequence-specific hydrolysis of DNA .Nature Chemical Biology 5, 2009 ,718 – 720. [7] S., D., Aust; L., A., Morehouse; C., E., Thomas. Role of metals in oxygen radical reactions. J. of Free Radicals in Biology & Medicine. 1, 2003, 3-25. [8] L., A., Finney; T. V. O'Halloran. Transition Metal Speciation in the Cell: Insights from the Chemistry of Metal Ion Receptors. Science. 300 , 2003, 931-936. [9] C.,Davis; J.B.Vincent. Chromium in carbohydrate and lipid metabolism. J. Biological Inorganic chemistr, 2,1997,675-679. [10] R., A., Anderson. Nutrient Requirements and Functions Laboratory, USDA Beltsville Human Nutrition Research Center, Beltsville, Maryland, USA, 20705. Chromium as a Dietary Supplement. Review: Transition Metals in Medicine 291 [11] B., Stoecker. Ph.D .Essentials of Chromium Bioavailability. [12] J. Challem. Stop Prediabetes Now: The Ultimate Plan to Lose Weight and Prevent Diabetes . [13] JB.,Vincent. Elucidating a biological role for chromium at a molecular level. Acc Chem Res. 33,2000, 503–510. [14] W., Cefalu; A.D.,Bell-Farrow; Z.Q., Wang. Effect of chromium picolinate on insulin sensitivity in vivo. J. Trace Elem. Exp. Med. 12, 1999 ,71-83. [15] S.,Davies; J., McLaren-Howard; A., Hunniset; M., Howard. Age-related decreases in chromium levels in hair, sweat, and serum samples from 40,872 patients implications for the prevention of cardiovascular disease and type II diabetes mellitus. Metabolism, 46, 1997 ,469-473. [16] R.A.,Anderson;N.,Cheng; N.A.,Bryden. Beneficial effects of chromium for people with diabetes. Diabetes. 46, 1997,1786-1791. [17] AD., Dayan; AJ., Paine .Mechanisms of chromium toxicity, carcinogenicity and allergenicity: review of the literature from 1985 to 2000. Hum. Exp. Toxicol. 20, 2001. 439-451. [18] U.S. EPA (U.S. Environmental Protection Agency). 1984. Health Assessment Document for Chromium. Environmental Criteria and Assessment Office, U.S. Environmental Protection Agency, Research Triangle Park, NC. EPA 600/8-83-014F. NTIS PB 85-115905. [19] U.S. Air Force. 1990. Chromium. In: The Installation Restoration Program Toxicology Guide.Wright-Patterson Air Force Base, OH, pp. 72-1 to 72-81. [20] P.,Nettesheim; M., J., Hanna; D., Doherty; R., Newell; A.,Hellman. Effect of calcium chromate dust,influenza virus, and 100 R whole-body X-radiation on lung tumor incidence in mice. J Natl Cancer Inst. 47, 1971,1129-1138. [21] M.,Costa; K., Salnikow; W.,Peng; J., Sutherland; M., Tang; C., Huang; X. Shi . National Institute of Occupational Safety and Health, Morgantown, West Virginia. [22] T.,Suksrichavalit;S.,Prachayasittikul;C.,Nantasenamat;C.,Isarankura;V.,Prachayasittiku l. Copper complexes of pyridine derivatives with superoxide scavenging and antimicrobial activities. European Journal of Medicinal Chemistry, 44, 2009, 3259- 3265.J., A., Drewry ; P., T., Gunning. Recent advances in biosensory and medicinal therapeutic applications of zinc(II) and copper (II) coordination complexes . Coordination Chemistry Reviews. 255, 2011, 459-472 . [24] Y., Rayssiguier ; E., Gueux ; L., Bussiere . J Nutr. 123, 1993, 1343-1348. [25] J.,R.,J., Sorenson. Prog Med Chem. 26 , 1989, 437-568. [26] H.,H.,A., Dollwet; J.,R.,J., Sorenson. Historic uses of copper compounds in medicine, Trace Elements in Medicine 2, 1985, 80 - 87. [27] [27] J., J., Sorenson; L., W., Oberley; R., K., Crouch; T., W., Kensler; V., Kishore; S., W., C., Leuthauser; T., D., Oberley; A., Pezeshk. Pharmacologic activities of copper compounds in chronic diseases Biological Trace Element Research, 5 , 257-273. [28] H.H.A. Dollwet and J.R.J. Sorenson, Historic uses of copper compounds in medicine, Trace Elements in Medicine. 2, 1985, 80 - 87. [29] L.M. Klevay; L. Inman; L.K. Johnson. Metabolism 33,1984,1112-1118. L.M. Klevay. Med Hypothesis,. 24,1987, 111-119. [30] L.M. Klevay, Med Hypothesis, 1987; 24: 111-119. Hanan F. Abdel-Halim 292 [31] Y. Rayssiguier; E. Gueux; L. Bussiere. J. Nutrition.123,1993, 1343-1348. [32] L.M. Klevay. Biol. Tr. Elem. Res. 16,1988 51-57. [33] E.,Broun;A., Greist ;G., Tricot;R., Hoffman . Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression. J.AMA,264, 1990,1441-3. [34] R., Jacob; J., Skala ; S., Omaye; J.,Turnlund. Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. J. Nutr,117, 1987,2109-15. [35] S. Aiser ; G. Winston. Copper deficiency myelopathy. [Review]. Journal of Neurology, 257, 2010, 869-881. [36] M. Johnson; J. Fischer; S. Kays; Crit Rev Food Sci Nutr , 32,1992, 1-31. [37] P. Baleuska; E. Russanov; T. Kassabova; Int J Biochem. 13, 1981, 489-493. [38] G., Multhaup; A., Schlicksupp; L., Hesse; D., Beher; T., Ruppert; C., L., Masters; K., Beyreuther. The Amyloid Precursor Protein of Alzheimer's Disease in the Reduction of Copper(II) to Copper(I). Science. 271 ,1996, 1406-1409 [39] L,.J., Taylor; M.,L., Hinners; S.,J., Ritchey. Am J Clin Nutr . 33,1980, 1077-1082. [40] H.H., Sandstead. Requirements and toxicity of essential trace elements, illustrated by zinc and copper. Am. J. Clin. Nutr. 61, 1995 (suppl):62S-4S. [41] J.R., J., Sorenson. J. Pharm. Pharmac. 2, 1977, 450-452. [42] E., Frieden. Clin. Physiol. Biochem. 4,1986,11-19. [43] J.,R.,J., Sorenson ; V. Kishore. Tr. Elem. Med. 1,1984, 93. [44] R., Milanino; A., Conforti; L., Franco. Agents and Actions .16,1985, 504-513. [45] A.,S., Gissen. Copper: The Maligned Mineral. 1994 issues of VRP's Newsletter. [46] J.,Bland: Copper Salicylates and Complexes in Molecular Medicine. Int Clin. Nutr. Review, 4, 1984, 130-134. [47] J.,R.,J., Sorenson. Copper Chelates as possible Active Metabolites in the Antiarthritic and Antiepileptic Drugs. J. Applied Nutrition 32, 1980,4-25. [48] M.,Hodak; R., Chisnell. Cu2+ Binding to the Prion Protein: Functional Implications and the Role of Copper. Online publication in Proceedings of the National Academy of Sciences. SCIENCE BLOG 2009. [49] Y. Rayssiguier ; E. Gueux ; L. Bussiere. J. Nutr. 123,199 ,1343-1348. [50] L.,G., Strause; P., Hegenauer; R.,C., Saltman. J. Nutr. 116,1986, 135. [51] E., Frieden. Caeruloplasm. In: "Biological Roles of Copper." CIBA Foundation Symposium-79. Exerpta Medica. Amsterdam. 1980. 93. [52] R.,J.,R., Sorenson. (ed.), Biology of Copper Complexes. Humana Press, Clifton, NJ. 1987. [53] R.,Moss: Shadow Falls on Anti-Angiogenic Drugs. Cancer Decisions Newsletter, 2009. [54] D., Beyersmann. Effects of carcinogenic metals on gene expression. Toxicol Lett. 127,2002 , 63-8. [55] D. G.,Barceloux. Manganese Review. J. Toxicol. Clin. Toxicol. 37,1999, 293-307. [56] N., Kumar. Copper deficiency myelopathy (human swayback). Mayo Clinic Proceedings. 81, 2006,1371-1384. [57] C.,Guo; P., Chen;, M.,Yeh,; D., Hsiung ; C., Wang.Cu/Zn ratios are associated with nutritional status, oxidative stress, inflammation, and immune abnormalities in patients on peritoneal dialysis. Clinical Biochemistry. 44, 2011, 275-280. [58] P.,Hedera; A., Peltier; J. K., Fink; S., Wilcock; Z., London; G. Brewer. Myelopoly- neuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown Review: Transition Metals in Medicine 293 origin II. The denture cream is a primary source of excessive zinc. [Article]. Neurotoxicology (Amsterdam), 30, 2009,996-999. [59] E., Mocchegiani; R., Giacconi; C., Cipriano. Zinc-bound metallothioneins as potential biological markers of ageing Review. Brain Res Bull. 55, 2001,147-53. [60] E.,Mocchegiani; M.,Muzzioli; R.,Giacconi. Zinc, metallothioneins, immune responses, survival and ageing. Biogerontology Review. 1, 2000,133-43. [61] N.,A.,Thornberry; Y.,Lazebnik. Caspases: enemies within. Science Review. 281, 1998,1312-6. [62] H.,Tapiero; K.,D., Tew. Trace elements in human physiology and pathology: zinc and metallothioneins Review. Biomed Pharmacother. 57, 2003 ,399-411. [63] M.,Seve; F.,Chimienti; A.,Favier. Role of intracellular zinc in programmed cell death Review.. Pathol Biol. 50, 2002, 212-21. [64] E.,Mocchegiani; R .,Giacconi; C., Cipriano. Metallothioneins (I+II) and thyroid-thymus axis efficiency in old mice: role of corticosterone and zinc supply. Mech Ageing Dev. 123, 2002 ,675-94. [65] R.J.P .,Williams. The biochemistry of zinc. Polyhedron. 6, 1987, 61-69. [66] A.,Butler. Acquisition and utilization of transition metal ions by marine organisms. Science, .281, 1998,207-209. [67] E., A., Keiter; R., L., Keiter. Inorganic Chemistry: Principles of Structure and Reactivity 4th ed., vol. 1 1993 Harper Collins College Publishers New York. [68] W., Bode; F. X., Gomisruth; R., Huber; R.,Zwilling; W.,Stocker. Structure of astacin and implications for activation of astacins and zinc-ligation of collagenases. Nature (Lond.) 358, 1992,164-167 [69] F., A.,Cotton; G.,Wilkinson. Advanced Inorganic Chemistry: A Comprehensive Text 5th ed., vol. 1. 1988 John Wiley & Sons New York. [70] R., G., Pearson. J. Am. Chem. Soc. 85, 1963m3533-3539. [71] B., L., Vallee; D., S., Auld. Cocatalytic zinc motifs in enzyme catalysis. Proc. Natl. Acad. Sci. U.S.A. 90, 1993a ,2715-2718. [72] F., H., Arnold; B., L., Haymore. Engineered metal-binding proteins: purification to protein folding. Science . 252, 1991,1796-1797. [73] J., E., Coleman. Zinc proteins: enzymes, storage proteins, transcription factors, and replication proteins. C .,Richardson; J. N. Abelson; A.,Meister; C.,Walsch T. eds. Annual Review of Biochemistry 1992:897-946 Annual reviews Inc Palo Alto, CA. [74] B., L.,Vallee; D., S.,Auld. Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry. 29, 1990b,5647-5659. [75] D., W.,Christianson; J., D., Cox. Catalysis by metal-activated hydroxide in zinc and manganese metalloenzymes. Annu. Rev. Biochem.68,1999,33-37. [76] B.,Lovejoy; A.,Cleasby; A., M., Hassell; K.,Longley; M., A., Luther; D.,Weigl; G.,McGeehan; A., B., McElroy; D.,Drewry; M., H., Lambert; S., R ., Jordan. Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor. Science.263, 1994,375-377. [77] D., N., Silverman; S.,Lindskog. The catalytic mechanism of carbonic anhydrase: implications of a rate-limiting protolysis of water. Acc. Chem. Res. 21, 1988.30-36. [78] B., L., Vallee; A .,Galdes. The metallobiochemistry of zinc enzymes. Adv. Enzymol. Relat. Areas Mol. Biol. 56 ,1984,283-430. Hanan F. Abdel-Halim 294 [79] B., L., Vallee ; J., E., Coleman ; D., S., Auld. Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains. Proc. Natl. Acad. Sci. U.S.A. 88, 1991, 999-1003. [80] J., C., Spurlino ; A., M., Smallwood; D., D., Carlton; T., M., Banks ; K. J.,Vavra; J., S., Johnson ; E., R., Cook; J., Falvo; R. C., Wahl; T. A., Pulvino; J. J., Wendoloski; D., L. , Smith .1.56 Å structure of mature truncated human fibroblast collagenase. Prot. Struct. Funct. Genet. 19,1994 ,98-109. [81] D ., S.,Bryce. Zinc-deficiency: the neglected factor. Chem. Br. 25, 1989,783-786. [82] R. Powell . The Antioxidant Properties of Zinc Saul. Journal of Nutrition. 130, 2000,1447-1454. [83] N .,Sugino; A.,H.,Karube; A., Sakata; S.,Takiguchi ; H.,Kato. Different mechanisms for the induction of copper-zinc superoxide dismutase and manganese superoxide dismutase by progesterone in human endometrial stromal cells. Hum Reprod. 17,2002,1709–14. [84] A. Prasad; B.,Bao; F.,Beck; O.,Kucuk; F.,Sarkar. Antioxidant effect of zinc in humans. Free Radic Biol Med .37,2004, 1182–90. [85] S.,L.,Best ; P.,J., Sadler. Gold Bulletin, .29,1996, 87-93. [86] P.,Greim;K.,Takahashi; H.,Kalbacher; E.,Gleichman. The antirheumatic drug disodium aurothiomalate inhibits CD4+ T cell recognition of peptides containing two or more cysteine residues. Journal of Immunology. 155,1995,1575–1587. [87] I., Ott .Review On the medicinal chemistry of gold complexes as anticancer drugs. Coordination Chemistry Reviews. 253, 2009, 1670-1681. [88] R.,Hewer; M., Coyanis;T., Traut; M., Mphahlele; J., Coates; E.,Van Der Lingen. Investigating the biomedical applications of gold. World Gold Conference 2009, The Southern African Institute of Mining and Metallurgy. [89] Bau, R. "Crystal Structure of the Antiarthritic Drug Gold Thiomalate (Myochrysine): A Double-Helical Geometry in the Solid State". Journal of the American Chemical Society, 120, 1998, 9380–1. [90] I. Schroter and J. Strahle. Chem. Ber. 124, 1991,2161-2164. [91] A.A. Isab and P.J. Sadler. J. Chem. Soc., Dalton Trans. 135-141 ,1982. [92] J.R. Roberts, J. Xiao, B. Schleisman, D.J. Parsons and C.F. Shaw 111. Inorg. Chem. 35, 1996,424-433. [93] M.T. Razi, G. Otiko and P.J. Sadler. ACS Sym. Ser. 209, 1983,371-384 . [94] J. Chaudiere and A.L. Tappel. J. Inorg. Biochem. 20, 1984,313-325. [95] D. Schuhmann, M. Kubickamuranyi, J.Mirtschewa, J. Gunther, P. Kind and E. Gleichmann. J. Immunol. 145, 1990,2132-2139. [96] S.L. Best, T.K. Chattopadhyay, M.I. Djuran, R.A. Palmer, P.J. Sadler; K. Varnagy. JCS Dalton Trans. 1997, 2587-2596. [97] P., J., Sadler and Z., Guo. Metal complexes in medicine: Design and mechanism of action. Pure & Appl. Chem. 70, 1998, 863-871. [98] C.J.,Mirabelli; R.K., Johnson; C.M., Sung; L.,Faucette; K.,Muirhead; S.T.,Crooke. Evaluation of the in vivo antitumor activity and in vitro cytotoxic properties of auranofin, a coordinated gold compound, in murine tumor models. Cancer Research. 45, 1985, 32–39. [9 [1 [1 [1 [1 [1 [1 [1 [1 [1 [1 [1 [1 [1 [1 [1 [1 99] C.J.,Mira Snug; S.T of gold(I) 100] R.V.,Pari A.M.,Els ((dimethy 101] R.G.,Buc R.V.,Pari [dimethyl 1996. 520 102] C.F.,Shaw complexe 1986.pp. 103] T.,Amaga new gold Japan. 62 104] A., Casin H.H.; L molecula study. J. B 105] S.P., Fric 2007, 49 106] C.,Gabbi Bulletin. 107] R.,Hewer LINGEN 2009, Th 108] S., Wan character carbothio 109] D., Jocke 2011. 110] H.,Sakura diabetes m 111] A K.,Sriv compoun 112] K.H.,Tho J. of Inor 113] S.,Verma glucose/in 114] A.B.,Gol Insulin-D ,2000 ,40 115] G.S.,Kell Rev. 5, 20 R abelli; R.K.,Jo T.,Crooke. Co )coordination ish; B.P., H ome; S.P.,F ylamino)methy ckley; A.M ish; B.P.,Ho lamino)methy 08 . w; A., Beery es with bridg 213–216. ai; T.K., Miya d(I) complexe 2, 1989, 1078– ni; Kelter; C .,Messori. Ch ar mechanisms Biol.Inorg. Ch cker. Metal b 903–4917. ani; A.,Casin 40, 2007, 73– r; M.,Coyanis N. Investigatin e Southern Af ng; W., Sha rization and cy oamide derivat ers. Reverse ai. A new co mellitus. The C vastava; M. Z nds. Diabetic M ompson; C., O rg. Biochem. 1 a; M.C.,Cam; nsulin system dfine; et al., Dependent Dia 00-10. ly. "Insulin R 000, 109. Review: Transi ohnson; D.T. orrelation of th complexes. Jo Howe; J.P.,W Fricker. Chem yl)phenyl)gold .,Elsome; S owe; L.R.,K yl]phenylgold( y; G.C.,Stocc ging dithiolat amoto;H., Ich es linked to –1080. C.,Gabbiani, C hemistry, ant s of novel gold hem., 2009, in based drugs: ni; L.,Messor –81. s; M.,Traut; T ng the biomed frican Institute ao ; H., Li ; ytotoxicity of tives Europea degenerative oncept: The Chemical Rec Z. Mehdi. Insu Medicine. 22, Orvig. Vanadiu 00, 2006,1925 J.H.,McNeill. : Vanadium. J "Metabolic E abetes Mellitu Resistance: Lif ition Metals in ,Hill; L.,Fauc he in vitro cyto ournal of Med Wright; J.,Ma mical and d(III). Inorgan S.P.,Fricker; Kelland. An (III) complex o. Anti-tumo te ligands. In hida; Y.,Sasak pyrimidines. C.,Cinellu;M.A tiproliferative d(III) compou n press. from serendip ri. Gold com T., M phahlel dical applicati e of Mining an C., Liu ; K the gold (III) n Journal of M diabetes natu use of vanad cord. 2,2002,2 ulino-mimetic 2004, 2-13. um in diabete 5-1935. Nutritional fa J. of the Amer. Effects of Va us: In Vivo an festyle and N n Medicine cette; G.R.,G otoxic and in dicinal Chemis ack; R.G.,Pr biological s nic Chemistry G.R.,Hende ntitumor pro xes. J. of Me or activity of norganica Ch ki. Preparation Bulletin of th A.,Minghetti;G properties, unds for cance pity to design mpounds as a e; M., Coates ions of gold.W nd Metallurgy K., Wang ; complexes of Medicinal Che urally (Opini dium complex 37-248 . and anti-diab s: 100 years f actors that can . College of N nadyl Sulfate nd In Vitro S Nutritional Inte Girard; G.Y.,K vivo antitumo stry, 29, 1986 ritchard; R.G studies of . 35, 1996. 16 erson; B.R. operties of edicinal Chem f two binucle himica Acta, n and crystal s he Chemical G.,F regona; tumor select r treatment: a n. Dalton Tra anticancer dr s; J., and E.,V World Gold C . J., Zhang . f 4,5-dihydrop emistry, in Pre on) .Natural xes in the tre etic effects of from phase 0 n favorably in Nutrition. 17, 1 e in Humans Studies," Meta erventions," A 295 Kuo; C.M., or activities 6.213–216. G.,Buckley; dichloro(2 59 . .,Theobald; some-2- mistry. 39, ear gold(I) vol. 123, structure of Society of D.,Fiebig; tivity, and systematic ansactions, rugs. Gold VAN DER Conference Synthesis, pyrazole-1- ess,2011 news.com, eatment of f vanadium to phase 1. fluence the 998,11-18. with Non- abolism, 49 Altern Med Hanan F. Abdel-Halim 296 [116] R. B.,Kreider. "Dietary Supplements and the Promotion of Muscle Growth with Resistance Exercise," Sports Med. 27,1999, 97-110. [117] R.,Liasko; A.,Kabonsot; S.,Karkabounas;M.,Malamas; A.J.,Tasiopoulos ; D., Stefanou; P.,Collery ; A.,Evangelou. Beneficial effects of a Vanadium complex with cysteine, administered at low doses on benzo(α)pyrene-induced leiomvosarcomas in Wistar rats. Anticancer Reaserch, 18, 1998, 3609-3613. [118] Aureliano, M. (Ed), Vanadium Biochemistry, Research Signpost, Kerala, 2007. [119] Aureliano, M. and Gândara, R. (2005) Decavanadate contribution to vanadium toxicity, J. Inorg. Biochem. 99: 979-985. [120] Ramos, S., Manuel, M., Tiago, T., Duarte, R. O., Martins, J., Gutiérrez- Merino, C.,. Moura, J.J.G., Aureliano, M. (2006) Decavanadate interactions with actin inhibit G- actin polymerisation, J. Inorg.Biochem.100, 1734-1743. [121] Soares, S.S. Henao, F., Aureliano, M, Gutiérrez-Merino C. (2008) Vanadate induces necrotic cell death in neonatal rat cardiomyocytes through mitochondrial membrane depolarization, Chem. Res. Toxicol. 21, 607-618. [122] Tiago, D.M., Cancela, M.L, Aureliano M., and Laize, V. (2008) Vanadate proliferative and anti- mineralogenic effects are mediated by MAPK and PI-3K/ras/Erk pathways in a fish chondrocyte cell line, FEBS Lett., 582, 1381-1385. [123] Kustin, K., Pessoa, J.C., Crans, D.C. (Eds.) Vanadium: The versatile metal, 974 ACS Symposium Series, Washington, DC., 2007. [124] Anderson BF, Baker HM, Dodson EJ, et al. (April 1987). Structure of human lactoferrin at 3.2-A resolution. Proc. Natl. Acad. Sci. U.S.A. 84 , 1769–73. [125] Dickerson, R. E., and Geis, I. (1983). Hemoglobin: Structure, Function and Evolution. Menlo Park, CA: Benjamin/Cummings. [126] H. R.Horton; L. A .,Moran; R. S.,Ochs,; J. D .,Rawn; and K. G. Scrimgeour, (2002). Principles of Biochemistry , 3rd edition. Upper Saddle River, NJ: Prentice Hall. [127] E.W. Dijk, B.L. Feringa, G. Roelfes Top. Organomet. Chem. 25, 2009,1. [128] Transferrin Structure". St. Edward's University. 2005. Retrieved 2009. [129] P. S Corbin.; M. P.Webb,; J. E McAlvin,.; , C. L Fraser. “Biocompatible Polyester Macroligands: New Subunits for the Assembly of Star-Shaped Polymers with Luminescent and Cleavable Metal Cores” Bio-macromolecules, 2, 2001,223-232. [130] V. A. Roginskii. Phenolic Antioxidants: Reactivity and Efficiency, Nauka, Moscow, 1988 . [131] E. R. Milaeva; Ross. Khim. Zh. Mendeleev Chem.J., 20 ,2004 . [132] E. R. Milaeva; Izv. Akad. Nauk. Ser. Khim., 2001,549. Russ. Chem. Bull., Int. Ed., 2001, 50, 573]. [133] D. B. Shpakovskii; E. R. Milaeva; A. V. Fionov; A. V. Dolganov; T. V.Magdesieva;A.S.Belov;Ya.Z.,Voloshin.Abstrs.Int.Conf."KLASTERY2006"("CLUS TERS 2006), Astrakhan, 2006, P: 90. [134] N. M. Emanuel; E. T. Denisov; Z. K. Maizus. Chain Oxidation of Hydrocarbons in the Liquid Phase, Nauka, Moscow, 1965. [135] R. J. Geue; B. Korybut_Daszkiewicz; A. M. Sargeson. Chem. Commun., 1996, 1569. [136] P. M. Angus; A. M. T. Bygott; R. J. Geue; B. Korybut_Daszkiewicz; A. W. H. Mau; A. M. Sargeson; M. M. Sheil; A. C. Willi. Chem. Eur. J., 3,1997, 1283. Review: Transition Metals in Medicine 297 [137] Y. Z. Voloshin; O. A. Varzatskii; A. S. Belov; A. Y. Lebedev; I. S. Makarov; M. E. Gurskii; M. Y. Antipin; Z. A. Starikova; Y. N. Bubnov. Inorg. Chim. Acta, 360, 2007, 1543. [138] B. Rosenberg. In Cisplatin, Chemistry and Biochemistry of a Leading Anticancer Drug,B. Lippert (Ed.), Wiley-VCH, Weinheim 1999. [139] N. Margiotta; A. Habtemariam; P.J. Sadler. Angew. Chem. Int. Ed. Engl. 36, 1997,1185-1 187 [140] L.R. Kelland; C.F.J. Barnard; I.G. Evans; B.A. Murrer; B.R.C. Theobald; S.B. Wyer; P.M. Goddard; M. Jones; M. Valenti;A. Bryant; P.M. Rogers; K.R. Harrap. J. Med. Chem. 38, 1995,3016-3024. [141] F. Reeder; F. Gonnet; J. Kozelka; J.C., Chottard. Chem. Eur. J.. 2, 1996, 1068-1076 . [142] P. Beale; I. Judson; A. O’Donnell. Br. J. Cancer 88, 2003,1128. [143] J. Holford; S. Y. Sharp; B. A. Murrer; M. Abrams; L. R. Kelland. Br. J. Cancer, 77, 1998, 366 . [144] J. A., Duce; A. I., Bush. Biological metals and Alzheimer's disease: Implications for therapeutics and diagnostics.Progress in Neurobiology,92, 2010, 1-18. [145] P. J., Sadler ; Z., Guo .Metal complexes in medicine: Design and mechanism of action. Pure & Appl. Chem., 70, 1998, 863-871. [146] E., Luk;L.T., Jensen; V.C., Culotta. The many highways for intracellular trafficking of metals. J. Biol. Inorg. Chem. 8, 2003,803–809. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 7 APPLICATION OF TRANSITION METALS AS ACTIVE COMPOUNDS IN SEPARATION TECHNIQUES Iwona Rykowska * and Wiesław Wasiak Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka, Poznań, Poland INTRODUCTION Among important factors related with an efficiency of analytical methods, a possibility of selective determination and preconcentration of the analytes makes it possible to determine the compounds at very low concentration levels (ppb, ppt, or even ppq). While determining the most adequate separation system, one must take into consideration several criteria towards optimum choice of both mobile and stationary phase according to physico-chemical properties of the analytes under study. Recently, separation techniques using transition metals as active compounds are of growing importance. This chapter is a survey of such applications of transition metals, divided to the following four parts: • metal complexes as components of column packings as well as liquid stationary phases in gas chromatography, • optical-active complexes of transition metals in the determination of the enantiomers by means of chromatographic methods, • sorbents containing metals to be applied for the SPE (Solid Phase Extraction) technique, • immobilized Metal Ion Affinity Chromatography IMAC applied for a separation of the proteins and peptides. Electron-donor complexes (EDA), known also as charge-transfer complexes, are created in both liquid phase and in a solution with some organic compounds, by cations of transition * Corresponding Author Iwona Rykowska and Wiesław Wasiak 300 metals characterized by a deficit of electrons. The metal cations creating above-mentioned EDA complexes were successfully applied to the modification of packings for gas chromatography. Such packings may be categorized as the two below-described groups, later described in detail: • liquid super-selective phases, for which an inorganic salt or a complex is dissolved in one of classical liquid stationary phases (e.g., AgNO 3 in glycol ethylene, HgBr 2 in glycol polyethylene, etc.), • super-selective adsorbents, for which transition metals are applied as: 1) a salt or another compound deposited at carrier surface, 2) porous inorganic salt, 3) an oxide of a transient metal, 4) metal-organic polymer, 5) salt of transition metal chemically bonded to the carrier surface. The second part of the chapter is devoted to the optical-active metal complexes. Such complexes are of growing importance in the chemistry, from both analytical and preparative points of view, in particular in the analysis of pharmacological preparations. Among the techniques capable of a separation of enantiomers as well verification of their optical purity, chiral chromatography is one of the most effective. This technique has been developed rapidly since an introduction of chiral stationary phases (CSP). A separation of enantiomers by means of chromatographic techniques and chiral stationary phases is based on a creation of transition diastereoisomeric complexes of a selector molecule, being a part of CSP or chiral mobile phase, and a molecule of the compound under separation (a selectand). Ligand-exchange chromatography LEC is a technique capable of a separation of enantiomers of free amino acids and their derivatives, amino-alcohols, hydroxyl-acids as well as some other classes of chiral compounds, which, in turn, are capable of a creation of complexes with ions of transition metals (M) and ligands (L) rooted in the stationary or mobile phase. The coordination complexes are created only in the case the ligand is a donor of the electrons, to fill unfilled orbitals d of transition metals. The most frequently applied for LEC ions are the following: Cu, Ni, Co, Zn, Mg, and Cd, due to the fact that their complexes are kinetically labile. Some examples of optically active complexes of metals for the separation of enantiomers by means of the chromatography will be given in the text. The third part of the chapter is devoted to applications of Solid Phase Extraction SPE. SPE is a method of growing-importance for an isolation and concentration of organic micro- pollutants and metals from water samples. Most of the currently used sorbents are based on silica modified with n-alkyl groups, including C 8 and C 18 ones. Current research is concentrated on more and more perfect sorbent, to be applied in SPE for a better determination of the analytes from complex matrices, and a higher recovery rate. By means of an immobilization of transition metals on a polymer or silica-gel, it is possible to preconcentrate the compounds that are able to create strong covalent bonds with metals. A desorption of an analyte is provoked by a change of pH or an introduction of a ligand that, in turn, creates a stronger bond with a metal in comparison with the compounds analyzed. Some examples of such sorbents will be given in the text. The last part of the chapter is devoted to applications of Immobilized Metal Ion Affinity Chromatography (IMAC). The isolation and separation of protein and peptide mixture is not Application of Transition Metals as Active Compounds in Separation Techniques 301 an easy procedure. IMAC is increasingly often applied to perform this task. Affinity chromatography relies on the specific interactions between amino acids, their reactive groups in peptides and transition metal ions. Those ions are immobilized by chelating compound on the bed, forming specific adsorbents that bind proteins and peptides. The chapter presents both theoretical and practical information about a possibility of an application of metals as active elements in the separation techniques. It is demonstrated that such metals may be effectively applied for chemistry, medicine, environmental research, and any other field characterized by a need for a selective determination and preconcentration of the analytes. As such, the proposed subject is very important and thus merits complex research and discussion. METAL COMPLEXES AS COMPONENTS OF COLUMN PACKINGS AS WELL AS LIQUID STATIONARY PHASES IN GAS CHROMATOGRAPHY Transition-metal complexes, chemically bonded with the carrier surface or dissolved in a liquid stationary phase, can create labile complexes with selected organic compounds. These complexes are also called charge-transfer complexes [1, 2]. The capability of some cations to form complexes with the molecules showing electron-donor properties is widely used in chromatographic separations. Such a capability may be interpreted on the grounds of the standard acid-base theory. From the point of view of the chromatographic analysis, the interactions among the analytes and the packings are of great importance. In case of liquid stationary phases, two basic mechanisms of the molecular-based interactions are identified: unspecific interactions by means of van der Waal’s forces, and specific interactions that in turn require a transfer of electrons between interacting molecules. In general, the origin of the adsorption interactions between an adsorbate molecule and the solid surface of an adsorbent are similar. A creation of covalent bonds or interactions among strong acids and bases, with resulting durable and stable products, is of no practical importance in case of chromatographic process. Only quite weak interactions, with bonding energy at the level of a few kcal/mol, are suited to this goal [3]. All the specific interactions taking place either in a liquid phase or on a solid surface can be explained on the basis of updated concept of Lewis acid-base interactions. Bases (electron donors) are species that can donate an electron pair to acids (electron acceptors). In terms of molecular orbital theory, electron donor-acceptor interactions can be classified according to the interacting molecular orbitals (Table 1), where n are nonbonding orbitals (e.g., unshared electron pairs, σ and π are bonding (occupied) orbitals, and σ* and π* are antibonding (empty) orbitals. The underlined interactions in Table 1 play an important role in chromatographic separations of organic compounds [3]. Iwona Rykowska and Wiesław Wasiak 302 Table 1. Classification of EDA interactions Donor orbital Acceptor orbital N σ* π* n n – n n - σ* n - π* σ σ - n σ - σ* σ - π* π π - n π - σ* π - π* In electron-donor-acceptor complexes, the metal stands for the acceptor, while the organic compounds containing π bond or free electrons n become the donors. Some examples of donors and acceptors of electrons are classified in Table 2. Table 2. Examples of donors and acceptors of electrons Compounds Examples n-Donors Aliphatic amines, pyridine, sulfides, ketones, ethers, and all neutral organics with nonbonding electron pairs π -Donors Olefines, aromatics, azaarenes alkanes, peralylpolysiloxanes σ-Donors Alkanes, peralylpolysiloxanes n-Acceptors Monoatomic cations (e.g., Pd +2 , Ag +2 , Cu +2 , etc.) π -Acceptors Alkynes, alkenes, or aromatics with electron-withdrawing substituents (e.g., CN, Cl, etc.) σ-Acceptors Halogenes, halogenated alkanes (e.g., CH 2 Cl 2 , CHCl 3 ) In this review of the application of EDA (electron-donor-acceptor) interactions to chromatography, we stay apart from organic complexes (e.g., π-π* or n-n*) and put stress on coordination complexes of some metal cations with organic ligands. The role of the d-block metal may be explained according to the charge-transfer theory [3]. The metal must be coordinatively unsaturated, and as such it may interact with an adsorbate showing electron- donor capabilities. Besides the stability of complexes created, complexation kinetics is important as well. Chromatographic retention depends on the stability of EDA complexes formed between the stationary phase and the solute. Ideas about the formation of EDA complexes in the gas phase or dilute solutions are based on Mulliken’s theory of charge-transfer complexes [3]. Despite the fact that the energy of formation of the complexes is of order of a few kcal·mol -1 and the retention is a result of several types of intermolecular interactions, such as, for example, the formation of EDA complexes, the formation hydrogen bonds, and the influence of steric effects, one can point out the cases where complexation is the process that determines the retention of the analyte. Some examples of electron donors and acceptors were given by Nondek [3]. The molecular complexes are substances with well-defined stochiometry and geometry. Such complexes are formed by the interaction of two or more component molecules or ions (Figure 1). Since the complex formation is highly selective, depending on the structure of the complexing species as well as on the temperature or polarity of environment (as for the HPLC Application of Transition Metals as Active Compounds in Separation Techniques 303 case), the utilization of such complexes in chromatography has resulted in many selective separations of mixtures of species of similar chemical structure and boiling point, such as constitutional, configurational, isotopic, and optical isomers. SiCH 2 CH 2 CH 2 C C C O O M Cl CH 3 CH 3 SiO 2 Figure 1. Schema of a packing with chemically bonded metal complexes. The factors influencing the stability of a complex with respect to selected ligands are the following: • valence, electronic structure, and radius of central metal ion, • spatial arrangement of overlapping orbitals of central ion and ligands, • basicity of ligands, • “internal” electric effects or ligands transmitted through the central ion, • steric effects due to direct contact between the atoms of different ligands, • “external” effects due to changes in the outer coordination sphere. A large number of the above-mentioned factors makes it possible to control the retention in order to obtain the required separations. In many cases, depending on the circumstances, the same molecules may play the role of either donor or an acceptor. Polycyclic aromatic hydrocarbons (PAH) are an example of such behavior: PAHs are donors of the electrons towards picrinian acid and tri-nitro-benzene, while acceptors towards N-dimethyloaniline. In large molecules, such as pharmaceuticals, biologically active compounds and synthetic colorants, few independent acceptor and donor centers may be pointed out. Low-molecule unsaturated and aromatic hydrocarbons are usually weak donors and very weak acceptors. Their capability of acting as donor/acceptor is increasing together with the number of double bonds >C =C <, or, as in case of WWA, number of aromatic rings. Multi-ring aromatic hydrocarbons are good electron donors. A substitution of a hydrogen atom by a substituent capable of increasing a density of electrons in the ring, such as alkylo-, alkoxylo- or amino group, increases a capability of a molecule to act as a donor of π electrons. On the other hand, aromatic or unsaturated compounds containing few substituents removing the electrons from the ring, such as - NO 2 , - CN and - Cl, are good acceptors, e.g., 1,3,5-trinitrobenzene, tetracyjanoethylene and similar compounds. A difference between the complexing in liquid stationary phase and at the surface of liquid sorbent aims in the fact, that: • large surface concentration of the complexing ligands may be a reason for creation of the complexes of “extraordinary” geometry or stechiometry, Iwona Rykowska and Wiesław Wasiak 304 • limited mobility of the adsorbed or chemically bonded with carrier surface acceptors and donors of the electrons is a reason of existence of steric hindrance in turn troubling the process of complex creation. In gas chromatography, organic and coordination complexes are being enumerated (e.g., π- π* or n-n*), created among cations of the metals and organic ligands. Besides the stability of the created complexes, kinetics of the complexing process is important as well. A capability of an easy and fast disassembly of the complexes and their fast rebuilding is a necessary condition for the application of such complexes in separation processes. Besides the fact that the energy of the creation of the complexes is at the level of a few kcal/mol, and the retention is a combined result of few types of interactions among molecules, such as a creation of EDA complexes, hydrogen bonds and steric effects, some cases may be pointed out when the complexation is the key process for the retention of an analyte. Metal cations creating electron-donor-acceptor complexes can be applied as modifiers for gas chromatography packings. Such modified packings are classified into the following two groups. 1) Liquid super-selective phases, where inorganic salt or a complex is dissolved in one of the classic liquid stationary phases, such as AgNO 3 in ethylene glycol; 2) Super-selective adsorbents, where a transition metal is applied in the form of [3]: • salt or another compound present on the carrier surface, • porous inorganic salt, • transition metal oxide, • organometallic polymer, • salt of a transition metal chemically bonded to the silica surface. The above-mentioned super-selective phases and adsorbents are usually applied to the separation of compounds differentiated by small structural changes, i.e., cis-trans isomers. As already mentioned, cations of the transient metals, capable of EDA complexation, may be applied as an active compound of a stationary phase in gas chromatography. The very first work devoted to this topic was published by Bradford, Hervey and Chalkey [4]. These authors applied a solution of AgNO 3 in polyethylene glycol to separate butene-1 and isobutane. Cation Ag + creates a π complex with olefin. Due to the fact that the stability of such complex depends (among others) on the steric factor, it is possible, by means of this method, to separate the compounds of the same or similar boiling temperatures, on condition that these compounds differ by geometric architecture (even in the minimum way). Among several metals, silver is the metal most widely used in gas chromatography. The systems with Ag as an active metal have been widely investigated and described. Based on the research results, the following conclusions may be drawn [5, 6]: • Usually, one olefin molecule coordinates at a single silver ion, forming a planar complex with triangular structure. • Alkyl substitution at the double bond usually decreases the stability of complexes despite if the basicity of olefin is enhanced. The steric effects are predominating for trans-olefins. Application of Transition Metals as Active Compounds in Separation Techniques 305 • The deuteration of a >C =C < bond increases its basicity and consequently the stability of the complex. • The most stable diene complexes are formed by 1,5-diene systems. • With endo-cycloolefins, the stability constant increases with increasing ring strain of olefin, which is released via complexation. • The stability of silver-olefin complexes also depends on the anion of silver salt - BF 4 - > ClO 4 - >> NO 3 - in concentrated solutions. According to Dewar [7], the bond between an olefinic ligand and metal ion, such as Ag + , is formed by donation of electrons from the filled π−orbital of the olefin to the vacat s orbital of Ag + and back donation of d electrons from the metal ion to the antibonding π*-orbital of the olefin. The bonding in the complex will be affected by the availability of electrons in the filled π−orbital and the ease of overlap of these orbitals. So both polar and steric factors determine the stability of the silver ion-olefin complexes. In fact, the steric effects have been found to be strong and in many cases are sufficient to explain the influence of structure on the stability constants. According to these basic principles, the chromatographic applications of silver-olefin complexing, they can be classified as follows: 1) Chromatographic separations of hydrocarbon mixtures (saturates, olefins, aromatics). 2) Selective separations of olefins: • monounsaturated hydrocarbons, • polyunsaturated hydrocarbons: dienes, • terpenes, • pheromones. Many examples of argentation chromatography are presented and discussed by D. Cagniant in his book entitled Complexation Chromatography [3]. A separation of cis and trans isomers is a well-described example of the usability of the Ag compounds in gas chromatography [8, 9]. By means of column packed with saturated solution of AgNO 3 in polyethylene glycol over Celit, Cope at al. [10] separated a mixture of cis- and trans- olefins. By an application of a solution of AgNO 3 in tetraethylene glycol, it was possible to determine equilibrium of cis- and trans- cyclenes (C 9 -C 12 ) [11]. However, an application of a higher temperature for this experiment is difficult to explain, as it is widely known that such column is not stable in the temperatures above 65 °C. Besides Ag + cation, an application of some other cations of transient metals was also investigated, with the metals as solutions creating stationary phases for the gas chromatography. Such cations as Hg 2+ , Cu 2+ , Ni 2+ , Pd 2+ , Pt 4+ , Rh + and Rh 2+ may be enumerated there. Compounds of mercury were detected as of particular importance towards a separation of oxygen-containing compounds, such as ethers, esters, and ketones [12]. The compounds of nickel, palladium, platinum and copper are characterized by especially strong interactions with organic compounds containing nitrogen. Capronines of nickel, copper and other metals have been applied to separate methyl esters of the amino acids and their N-trifluorooctanes [12]. Complexes of Ni, Pd, Pt and Cu with N-dodecylosalicyloaldimine we proposed to separate primary and secondary amines and paraffins [12]. Stearates of Mn, Co, Iwona Rykowska and Wiesław Wasiak 306 Ni, Cu and Zn we also applied to separate amines [13, 14]. Very interesting results in the area of a separation of olefins were reported by Gil-Av and Schurig. They proposed an application of rhodium (I) β-diketonate as a solution in squalane [15-17]. Different compounds of lantanes were also applied to the separation of some organic compounds. The authors of the work [18], while taking a research on packings containing β- diketonate of Eu 3+ dissolved in squalane, reported a affinity of such systems to such compounds as n-alkens-1, alcohols, ketones, esters and ethers. Kowalski determined a polarity and selectivity of polydimethylsiloxane stationary phases containing organic chelates of the following lanthanides [19]: Pr, Eu, Dy, Ho and Yb. The phases under study were characterized by a high selectivity towards nucleophilic compounds containing the following functional groups: - N=, - OH, ≡C- O- C≡ The second group of super-selective packings is based on adsorbents. The metal compounds are present there in the solid form [12] as (1) a salt or another compound present on the carrier surface, (2) porous inorganic salt, (3) transition metal oxide, (4) organometallic polymer, or (5) salt of a transition metal chemically bonded to the silica surface. Corresponding groups of super-selective adsorbents are enumerated below. Salt and metal complexes present on the carrier surface have been used in gas chromatography since 1962 [20]. Sawyer et al. published several results of the research devoted to a separation of compounds by means of salts and such carriers as Porasil and Al 2 O 3 . Different salts have been applied, both of transient metals and main groups (CoSO 4 , Cr 2 (SO 4 ) 3 , LaCl 3 , NaCl, Na 3 PO 4 , Na 2 SO 4 ). The authors put special attention to specific interactions of olefins and aromatic compounds with inorganic salts, drawing a conclusion that such compounds in particular interact strongly with the packings containing transient metals [21]. Interesting separation capabilities are shown in case of complexes of such transient metals as Fe, Ni, Co, Cr, Zn, Cu with phthalocyanate, to be applied as adsorbents. Such compounds are characterized by high thermal resistance, and thus may be applied to separate the compounds of high boiling temperature [22, 23]. Porous salts used as adsorbents are prepared in a thermal process, removing a part or a whole of the complexing element from the complexing salt. For example, Cu(Py) 2 (NO 3 ) 2 is synthesized from Cu(Py) 4 (NO 3 ) 2 in the temperature up to 85°C, and Cu(Py)SO 4 from Cu(Py) 4 SO 4 in 100°C. A similar method is applied to remove ammonia, water, dipyrydyl and o-phenanthroline from the complexing salts of copper, and water from the hydrated salts of cadmium and magnesium [21]. The above-described adsorbents, characterized by high uniformity of the pores and high thermal resistance, have been applied to separate compounds belonging to different groups. Cation of copper (II) interacted more strongly with non-bonding pair of electrons of a nitrogen molecule, more weakly with the pair of electrons of an oxygen molecule, and created π complexes with olefins. To separate alkanes, alkenes and alkines, anhydrous chlorides of vanadium, manganese, and cobalt have been applied [24]. Transition metal oxides have been applied as adsorbents mainly in the separation of light hydrocarbons and permanent gases. These oxides were applied as: Application of Transition Metals as Active Compounds in Separation Techniques 307 • fractions of the granulation adequate for the chromatographic packings, • porous adsorption layers at the internal surface of a capillary column, • surface adsorption layers on a glass or metal balls of adequate granulation, • adsorption layers at the carrier surface (Al 2 O 3 ). A lot of effort has been devoted to the application of iron oxides to separate light hydrocarbons. It was shown that α-Fe 2 O 3 may be applied to a fast separation of isomers of such group of organic compounds. Cr 2 O 3 has been proposed to separate oxygen and nitrogen [21]. Research on adsorption of benzene, pentane, hexane and other compounds showed high energetic homogeneity of the surface of Ni(OH) 2 and Co(OH) 2 as well as hydrogenised derivatives of these compounds. Also, an application of Fe(OH) 3 to separate the blasy-furnace gases has been investigated [12]. Zeolites with cations of transient metals, being crystallic aluminosilicate, are characterized by high ordering of their structure and a capability of ion exchange. These compounds were mainly applied, in the area of gas chromatography, to separate low-boiling- temperature hydrocarbons. These zeolites strongly interact with olefins. Irreversible adsorption of H 2 ,CO and unsaturated hydrocarbons was detected on AgX zeolite as a result of chemisorption on reduced molecules of silver [21]. The zeolites with ions Na + replaced by Ag + or Cd + strongly interacted with carbon monoxide and olefins [21]. Zeolites substituted with Ni +2 cations are characterized by high affinity for carbon monoxide, thus may be applied to complete separation of this gas from a mixture of inert gas. Other research was concentrated on an application, for gas chromatography, of the zeolites containing cations of zinc, cadmium, and manganese [25, 26]. Metalloorganic polymers are a group of adsorbents with high potential impact taking into account selectivity and thermal resistance. In case of that group of compounds, it is possible to obtain a packing with required pore size, specific volume, and other physical parameters. An introduction of a metal to an organic molecule may increase the selectivity of the adsorbent towards given groups of compounds. For example, an introduction of a molecule of silver or mercury may increase the affinity for olefins, while an introduction of nickel - affinity for amines [12]. The last group of super-selective adsorbents comprises salts of a transition metal chemically bonded to the silica surface. Authors of the review [27] summarized current state- of–the-art and recent advances in the application of metal complexes as adsorbents and liquid stationary phases in gas chromatography. Particular stress was put on stationary phases with β-diketonate group, and nitrogen-containing functional groups (e.g., ketoimine, amine). Such groups show electron-acceptor properties, and due to this fact, they can be permanently bonded to metal cations. Such packings can be used as selective stationary phases for analysis of electron-donor compounds. β-Diketonates were a subject of many research projects in field of chromatography. Complexes of transition metals and β-diketonates are used in gas chromatography for two basic purposes. On one hand, metal β-diketonates, due to their high volatility, are used for the analysis of metals [28,29] and, on the other hand, due to their ability to form adducts with additional ligands, β-diketonates can be used as selective adsorption centers in complexation gas chromatography. Iwona Rykowska and Wiesław Wasiak 308 β-Diketonate complexes of transition metals are of great interest to complexation gas chromatography. In Table 3, are sample applications of β-diketonates for the separation of nucleophilic compounds. Table 3. Sample applications of β-diketonates for the separation of nucleophilic compounds [27] No Packing Separated compounds Reference No 1 n-nonylo-β-diketonate M=Cu(II), Ni(II), Al(III), Zn(II), Be(II) alkenes, aromatic hydrocarbons, ketones, alcohols [30,31,] 2 Rh (CO) 2 β-diketonates Olefins [32] 3 (CO) 2 trifluoroacetylcamphorate M=Rh olefins, esters, alcohols, aldehydes [33,34,35] 4 M=Cu(II), U(II), Fe(III) p-, o-, m-nitroaniline, herbicides, [36] 5 7 3 O F C C C O C 7 3 O C F C C O C Eu Eu H H [Eu(dihed)] x ketones, aldehydes, esters, ethers, thioethers [37, 38] 6 R O Eu O O O O O X X ethers, ketones, alcohols, esters [39] 7 Ln O O 2 1 R R O O 2 1 R R O O 2 1 R R alcohols, ketones, ethers, esters [40, 41] Application of Transition Metals as Active Compounds in Separation Techniques 309 No Packing Separated compounds Reference No 8 O O R R = CH 3 , CF 3 , C 3 F 7 , C 6 H 5 M =Ni(II), Cu(II), La(III), Zn(II) O O R M O O R M O O R amines, alcohols, ketones, esters, ethers, compounds containing sulphur [42- 44] 9 2 2 2 6 SiO O Si CH CH C H PPh 4 2 Cu (acac) 2 . or 2 2 2 6 SiO O Si CH CH C H PPh 4 2 Ni (acac) 2 . alkenes, ketones, ethers, nitroalkanes [45,46] 10 Ni O N 3 3 H C H C O N CH CH 2 1 R R 3 3 ketones, amines, alcohols [47] 11 3 MX= 2 O O Si Si(CH ) C MX OEt O C 3 2 Si C O O CH CH 3 2 2 2 Co(acac) , Co(hfac) , Ni(acac) , Ni(hfac) ketones, cyclic and aromatic hydrocarbons, ethers and tioethers [48-56] 12 7 3 F C 3 7 C F O O O O M=La(III), Cu(II), Zn(II) nitro aromatic, nitrate ester, piroxide explosives [57] Iwona Rykowska and Wiesław Wasiak 310 Apart from the applications of β-diketonates discussed above, another group of gas chromatography packings came into attention, namely those based on ketoimines. Iminoketonates are one of the possible products of acetylacetone reactions with different reagents. Complexes of transition metals with β-ketoimines formed in such a way are characterized by high volatility, and this fact enables efficient use of iminoketonates in the analysis of metals by gas chromatography [58, 59]. Due to coordinative unsaturation, additional ligands can be inserted in the unoccupied coordinative positions of metal iminoketonates. They form adducts with Lewis bases through intermolecular bonds. Pyridine bases were separated by the use of nickel (II) N,N’-ethylene-, N,N’-trimethylene-, and N,N’- phenyl-bis(acetylacetimine) dissolved in squalane [60]. Complexes of copper (II) with bis(β- diketone) were applied by Zhang et al. [61] to separations of position isomers of selected aromatic hydrocarbons. Silica modified by ketoimino groups bonded to chlorides of copper (II) and nickel (II) were used by Wawrzyniak and Wasiak as adsorbents for capillary PLOT (porous layer open tubular) columns [62,63]. The specific interactions between the adsorbent and adsorbate molecules (linear and branched hydrocarbons, cyclic and aromatic hydrocarbons) were characterized by retention parameters. Rykowska and Wasiak, in a series of publications [64-70], have presented results of their studies of the application of complexes of copper(II) and chromium(III) chemically bonded with silica surface by ketoimino groups. Structures of such packings are presented in Figure 5. The packings were investigated from the point of view of characterization of specific interactions, as well as determination of the influence of the interactions on retention parameters. Since electron-donor interactions are influenced by several factors, both originated from the packings and from adsorbate molecules, several adsorbates differing in their electron-donor abilities and configurations were tested. These adsorbates included, among others, aliphatic hydrocarbons, both linear and branched [65, 66, 69], aromatic and cyclic hydrocarbons [66, 69, 70], halogenated hydrocarbons, ethers and thioethers [64, 67, 69]. While investigating the influence of the structure and the configuration of the adsorbate molecules on the specific interactions, particular attention was paid to the following factors: quantity, types and positions of unsaturated bonds in a molecule, number and types of substituents and the presence of heteroatoms (S, O) in the molecule. In Table 4 are sample applications of β- ketoimines for the separation of nucleophilic compounds. Chemically bonded phases containing amine groups are of great importance to GC and HPLC [71-73]. They show electron-donor-acceptor properties, and, therefore, they can form stable complexes with metal cations. Chemically bonded chelates have been used as selective adsorbents in complexation reactions in gas chromatography in order to separate different organic compounds such as hydrocarbons, alcohols, and amines. Khuhawar et al. [74] used Ni(II) chelate complexes to separate saturated aromatic hydrocarbons, heteroaromatic aldehydes, amines, ketones and alcohols. Dithiocarbamates bound to the support surface have also been used as chemically bonded phases [75]. The complexes of dithiocarbamates and such metals as cadmium, copper, and zinc were studied with the aim of applying them to the separation of dialkyl sulfides. Application of Transition Metals as Active Compounds in Separation Techniques 311 Table 4. Sample applications of β-ketoimines for the separation of nucleophilic compounds No Packing Separated compounds Reference No 1 Ni (II) N,N’-ethylene-, N,N’-trimethylene-, and N,N’-phenyl-bis(acetylacetimine) dissolved in squalane Pyridine bases [60] 2 Complexes of Cu (II) with bis(β-diketone) Isomers of selected aromatic hydrocarbons [61] 3 The silica modified by ketoimino groups bonded to chlorides of Cu (II) and Ni (II) Linear and branched hydrocarbons, cyclic and aromatic hydrocarbons [62,63] 4 Complexes of Cu (II) and Cr (III) chemically bonded with silica surface by ketoimino groups Aliphatic hydrocarbons, both linear and branched, aromatic and cyclic hydrocarbons, halogenated hydrocarbons, ethers and thioethers [64-70] In [76, 77] some results of research on using polyamine complexed with copper(II) and chromium(III) for analysis of nucleophilic compounds by complexation gas chromatography were described. These packings were tested in order to verify their usefulness for the analysis of aliphatic and aromatic nucleophilic compounds [76], aliphatic and aromatic halogenated hydrocarbons, ethers, thioethers and esters [77]. Results of the retention studies as well as chromatographic analysis have proved that the phases investigated can be successfully applied to complexation gas chromatographic analyses of mixtures of organic compounds including geometric isomers [76]. Cu(II) and Co(II) chelates of dithiooxamide, linked via propylene ether to silica, were prepared, and their application to separation of C 1 –C 4 hydrocarbons was reported by Akapo [78], who claimed that the Co(II) complexes enable a better separation of olefins than for the Cu(II) chelates. Akapo has also determined and characterized retention parameters for such a group of light hydrocarbons. In Table 5 are sample applications of amine groups for the separation of nucleophilic compounds. Separation of higher olefins (C 5 and higher) and their isomers have been carried on transition metal complexes of bonded silica with the carrier groups –CN, -SH, -NH 2 , and PPh 2 [79-84]. Iwona Rykowska and Wiesław Wasiak 312 Table 5. Sample applications of amine groups for the separation of nucleophilic compounds No Packing Separated compounds Reference No 1 Ni(II) chelate complexes aromatic hydrocarbons, heteroaromatic aldehydes, amines, ketones and alcohols [74] 2 The complexes of dithiocarbamates and such metals as cadmium, copper, and zinc dialkyl sulfides [75] 3 Polyamine complexed with Cu (II) and Cr (III) aliphatic and aromatic nucleophilic compounds , aliphatic and aromatic halogenated hydrocarbons, ethers, thioethers and esters [76, 77]. 4 Cu (II) and Co (II) chelates of dithiooxamide C 1 –C 4 hydrocarbons [78] OPTICAL-ACTIVE COMPLEXES OF TRANSITION METALS IN THE DETERMINATION OF THE ENANTIOMERS BY MEANS OF CHROMATOGRAPHIC METHODS The separation of enantiomers by gas chromatography can be performed in two modes. 1. Indirect Methods Enantiomers are converted off-column into diastereomeric derivatives by a chemical reaction with an enantiomerically pure resolving agent; further subsequent gas chromatographic separation of the diastereomers is achieved using a conventional chiral stationary phase. 2. Direct Method Gas chromatographic separation of the enantiomers is achieved using a chiral stationary phase (CSP) containing a resolving agent of high (but not necessarily 100%) enantiomeric purity. While the indirect method involves the formation of diastereomers before separation, the direct method relies on the different diastereomeric molecular association between the chiral, Application of Transition Metals as Active Compounds in Separation Techniques 313 non-racemic stationary phase (named selector) and the chiral analyte (selectand). Since diastereomers usually possess different physical properties, an unintended discrimination may arise during detection when using the indirect method. Also, fractionation may occur as the result of incomplete recovery, decomposition and losses during work-up, isolation and sample handling. Furthermore, the racemization and kinetic resolution must be absent in the formation of diastereomers by the indirect method. Enantiomer separation by gas chromatography is mainly performed on three types of CSPs: • chiral amino acid derivatives via hydrogen bonding [85-88], • chiral metal chelates via coordination (complexation gas chromatography) [89-91], • cyclodextrin derivatives via inclusion [92,93]. Three principal CSPs, distinguishable by the mode of selector-selectand interaction (i.e., hydrogen bonding, coordination and inclusion), have been thoroughly investigated using GC [94]: • chiral separation on non-racemic chiral amino acid derivatives via hydrogen- bonding, • chiral separation on non-racemic chiral metal coordination compounds via complexation, • chiral separation on biogenic cyclodextrin derivatives via (inter alia) inclusion. Pioneering work in the field of chiral separation by the gas chromatography in general was done by Gil-Av and co-workers [95]. They developed the first chiral GC phases based on an amino acid derivative, N-trifluoroacetyl – L – isoleucine lauryl ester [96] and N-trifluoroacetyl – L – valyl – L – valine cyclohexylester and resolved N-trifluoroacetyl amino acids on these columns (Figure 2). F C C C COOR' N 3 * R H H O R = sec-butyl R' = dodecyl Figure 2. Structure of N-trifluoroacetyl – L – isoleucine lauryl ester. At the beginning, the selectors were based on non-volatile liquids or some compounds dissolved in squalane or polysiloxane. Later, these compounds were chemically bonded to polysiloxane (such type of a stationary phase is usually known under common name Chirasil). The method of chemical bonding of a selector has been applied for the first time in the synthesis of Chirasil-Val [97-99] (Figure 3). Recently, this approach has been broadened for the complexation gas chromatography by the synthesis of Chirasil-Metal [100] (Figure 4), Iwona Rykowska and Wiesław Wasiak 314 and, for the inclusive gas chromatography by the synthesis of Chirasil-Dex [101,102] (Figure 5). A valine diamide was linked to polysiloxanes yielding Chirasil-Val phase [103], which found broad application for chiral separation of amino acids and other compounds after transformation into volatile derivatives. O C C HN 2 R CH H Si C NH Bu n t H Me O CH Me O Si O Me Me * Figure 3. Structure of Chirasil-Val. 2 C F 2 Si n CH O Si O CH CH 3 3 CH 3 2 CH O Ni / O 3 7 O Figure 4. Structure of Chirasil-Metal. Schurig [104] introduced the principle of complexation gas chromatography using a dicarbonyl rhodium(I)-3-trifluoroacetyl-(1R)-camphorate (Figure 6) dissolved in squalane as CSP (Chiral Stationary Phases) and resolved (used for the enantiomeric separation of the chiral olefin) 3-methylcyclopentane on this phase. Later, a series of 1,3-diketonate bis chelates of manganese(II), cobalt(II) and nickel(II) derived from perfluoroacetylated terpene- ketones were investigated as CSPs [105]. A limiting factor of coordination-type CSPs is the low temperature range of operation 25 to 120 ° C. To increase the thermal stability, an immobilized polysiloxane-based phase (Chirasil-Nickel) was developed [106]. Fi Fi in at ga in co ch ad Applicati igure 5. Structu igure 6. Coordin Many chira nvestigated in Lipkowitz tomic-level m A compreh as chromatog nclude those ontaining opti A good sur haracterization dvances in in ion of Transiti ure of Chirasil-D Dicarbony nation-type chir al phases succ super- and sub discusses th olecular mode hensive survey raphy was pe by Schurig e cally active lig rvey of differe n of inorganic norganic chro ion Metals as O Si CH CH 3 (CH O) 3 (CH O Dex. l rhodium(I)-3 ral stationary ph cessfully appli b-critical fluid heoretical asp eling [110]. y of different erformed by S et al., who s gands to the se ent techniques c complexes w omatography Active Comp 2 Si n (CH O H H 3 3 CH 3 O ) 6 O) 7 (OC β - CD 3-trifluoroacet hases. ied in HPLC o d chromatogra ects of diffe t techniques u Schurig in 20 successfully a eparation of e s used in gas c was made by S that took pla ounds in Sepa 2 ) 3 O 8 3 CH ) 7 tyl-(1R)-camp or GC chroma aphy [106-109 rent separatio used in enanti 002 [111]. Ot applied metal nantiometric p chromatograph Shepherd [112 ace from 199 aration Techni phorate atography have 9]. on principles ioselective com ther studies in l-β-diketonate pairs [33-35]. hy for the sepa 2]. The review 92 through e iques 315 e been also based on mplexation n this area e polymers aration and w covers the early 2003, Iwona Rykowska and Wiesław Wasiak 316 concerning separations of isomers, chiral complexes, or species that bind to metal complexes via molecular recognition that affects their migration rates. Table 6. Surveys and other important publications in the field of optical-active complexes of transition metals in the determination of the enantiomers by means of chromatographic methods Authors Title Ref. 1 W. Linder Recent development in HPLC enantioseparation—a selected review [113] 2 V. Schurig Enantiomer analysis by complexation gas chromatography: scope, merits and limitations [114] 3 V. Schurig Separation of isotopic and enantiomeric compositions by complexation gas chromatography [115] 4 G. Gűbitz Separation of drug enantiomers by HPLC using chiral stationary phases—a selective review [116] 5 V. Schurig Enantiomer separation by gas chromatography on chiral stationary phases (Review) [117] 6 J. Bojarski, Hassan Y. Aboul-Enein Recent applications of chromatographic resolution of enantiomers in pharmaceutical analysis [118] 6 S. Allenmark, V. Schurig Chromatography on chiral carriers [119] 7 J. Bojarski Recent progress in chromatographic enantioseparations [120] 8 H.Y. Aboul-Enein, M.I. El-awady, C.M. Herda, P.J. Nicholas Application of thin-layer chromatography in enantiomeric chiral analysis—an overview [121] 9 V. Schurig Separation of enantiomers by gas chromatography [122] 10 F. Gasparrini, D. Misiti, C. Villani HPLC chiral stationary phases based on low- molecular-mass selectors [123] 11 G. Gűbitz, M. Schmid Chiral separation by chromatographic and electromigration techniques. A review [124] 12 V. Schurig Chiral separations using gas chromatography [125] 13 V. Schurig Practice and theory of enantioselective complexation gas chromatography [111] 14 G. Gűbitz, M. Schmid Chiral separation principles. [126] 15 Oi Naobumi Development of practical Chiral stationary phases for chromatography and their applications [127] 16 H. Lingfeng, T. Beesley Applications of enantiomeric gas chromatography: A review [128] 17 V. Šunjić Separation of enantiomers by chromatography as a vehicle for chiral catalysis. Abridged review [129] 18 K.K. Chandrul, B. Srivastava Enantiomeric separation in pharmaceutical analysis: A chromatographic approach [130] Application of Transition Metals as Active Compounds in Separation Techniques 317 In Table 6, a list of the references is given, related with surveys and other important publications in the field of optical-active complexes of transition metals in the determination of the enantiomers by means of chromatographic methods. SORBENTS CONTAINING METALS TO BE APPLIED FOR THE SPE (SOLID PHASE EXTRACTION) TECHNIQUE These sorbents contain some metals immobilized on a carrier surface, i.e., a polymer or a silica gel. They are characterized by a high selectivity, and they are usually applied for the isolation and preconcentration of the compounds of similar chemical structure. Some organic compounds can form very strong covalent bonds with metal ions. To trap these compounds, the metal ions can be dissolved in aqueous solution, but a more advantageous approach is to immobilize them on a polymer or silica gel-type support. A covalent bond between the internal orbitals of a metal ion and the functional groups of the support can serve for this immobilization. Other orbitals of the metal ion must remain free after its immobilization, to bind the ligands from the mobile phase. Besides accumulated analytes, other competitive ligands and metal ions as well as inorganic ions are usually also present in the aqueous sample. This fact has to be taken into account to establish the sorption conditions properly. Analytes will be eluted by change of pH value and introduction of a ligand, which forms stronger bonds with the metal ions into the system. Another possibility is to flush the analytes out with a solution of a competitive metal ion. The main sorbents used for trace enrichment purposes have been enumerated in a survey [131] and some other publications [132,133]. Metal-loaded sorbents are a suitable tool when the selectivity is of prime importance. Unfortunately, they can be used only for classes of compounds that can form covalent bonds with metal ions. As for SPE technique, and similar–liquid chromatography, these sorbents have their “dedicated” application areas. Continuously, the research is undertaken to broaden these areas. IMMOBILIZED METAL ION AFFINITY CHROMATOGRAPHY IMAC APPLIED FOR A SEPARATION OF THE PROTEINS AND PEPTIDES In 1975, Porath et al. [134] introduced a new type of chromatography, at the beginning named “metal chelate chromatography,” but later renamed to “immobilized metal (ion) affinity chromatography” (IMAC). The authors described the use of immobilized zinc and copper metal-ions for the fractionation of proteins from humana serum. Since the set of work was published describing the immobilization of metal ions using a chelating agent covalently attached to a stationary support, to purify proteins [134, 135], there have been several modifications and adaptations of this technique over the years. IMAC is a group-specific affinity separation technique, based on specific interactions between molecules in solution and metal ions fixed to solid support. This technique is based on the principle of coordinate covalent bonding chemistry. Metal ions (e.g., Ag + Al 3+ , Ca 2+ , 3 C w su bi ch [1 an A ph pr su an st [1 th (e de si do im am ag ch tr pe in N sc ID de Fi 18 Cr 3+ , Ni 2+ , Cu 2 with ligands an urface-exposed iomolecules a helate complex The classif 136], who pos nd soft, based Al 3+ , Ca 2+ , Fe hosphates fou refer sulfur. In ulfur. The mo nd Fe 3+ , espe tability under 137]. Electron-do hat are attach electron-pair a epending on th ites are norma onor groups fr As a chro mmobilized m mino acids ac gent, multide hromatograph ridentate, e.g., entadentate, e nvestigated sin NTA and TED chematic repre DA, NTA an entation of the IDA igure 7. Continu Iw 2+ , Zn 2+ , Co 2+ nd electron-don d atoms of re bound to m x. fication system stulated that m on their prefe 3+ ) show a p und in phosph ntermediate m ost commonly ecially Ni 2+ , w r chromatogra onor atoms n hed to the ch acceptors) for he number of ally occupied b rom protein. omatographic metal-ion chela ccessible at th entates are ic products. F , iminodiaceti .g., N,N,N’-yr nce immobiliz D are by far t esentation of nd TED, illus e chelator incr A (Iminodiacet ued. wona Rykows + , Eu 3+ , Fe 3+ , nor groups of nitrogen, su metal chelates, m cited by m metal ions can erential reactiv preference for orylated prote metal ions Ni 2+ used metal-io which provide aphic conditio itrogen, oxyg romatographic rming metal f occupied coo by water mole technique, ate complexes he surface of p most popula Four different c acid (IDA), ris-carboximet zed metal affin the most wid the octahedra strating the d reases. tic acid) Tride ska and Wiesła , Hg 2+ , La 3+ , M f biomolecules ulfur and ox weakly bound most authors i be divided in vity towards n r oxygen-cont eins. Soft met + , Cu 2+ , Zn 2+ , C ons are the tr es a coordina ons, borderlin gen and sulfur c support are chelates, whi ordination bon ecules and can the IMAC p to interact w protein via co arly used in t types of den , tetradentate, thyl ethylene nity chromatog dely used chel al coordination decrease in av entate; three re aw Wasiak Mn 2+ ), being s. In biomolec xygen, potent d ligands are d n the IMAC nto three categ nucleophiles. T taining group tal ions such a Co 2+ , coordina ansition ones, ation number ne polarizabil r present in th e capable of ch can be bi nds. The remai n be exchange procedure re with the side-ch oordinative int n research w ntates: bidenta e.g., nitrilotr diamine (TED graphy was ex lating compou n of metal ion vailable prote emaining coor electron accep cules, electron tially phosph displaced from field is that gories: hard, in The hard metal ps such as ca as Cu 2+ , Ag + , ate nitrogen, o , Cu 2+ , Ni 2+ , Z of six, elect lity and redo he chelating c coordinating identate, tride ining metal co ed with suitabl lies on the hain moieties teractions. Fo works and c ate, e.g., salic riacetic acid (N D), have been xploited [138, unds. Figure n Me with the ein-binding si rdination sites ptors, react donors are horous. As m the metal of Pearson ntermediate l ions (e.g., arboxyls or Hg 2+ , etc., oxygen and Zn 2+ , Co 2+ , rochemical ox stability compounds metal-ions entate, etc., oordination le electron- ability of of specific or chelating commercial cylaldehyd, NTA), and thoroughly 139]. IDA, 7 shows a e chelectors ites as the Application of Transition Metals as Active Compounds in Separation Techniques 319 NTA (Nitrilotracetic acid) Tetradentate; two remaining coordination sites TED (Tris(carboxymethyl)ethylenediamine Pentadentate); one remaining coordination site * Indicates coordination sites available for protein binding Figure 7. Schematic representation of IDA, NTA and TED metal chelation. A very simplified representation of the capacity and selectivity of various chelating ligands and intermediate metal ions is shown in Figure 8 [140]. Selection of the supporting matrix is the first important consideration in affinity systems. To be adequate for IMAC, the matrix must show the following characteristics [138,139]: • easy to derivatize, • high hydrophilic character and extremely low non-specific adsorption, • high porosity to allow high amount of ligand immobilization, • fairly large pore size and narrow pore size distribution, • functional surface groups (hydroxyl, carboxyl, amide, etc.), 32 Fi di se ca T an in as in to se pr ap an m of ta IM 20 • physic conditi • allow t • permit • provid igure 8. Chelati Two chara ifferent ligand econd, binding an be carried o hree different nd pH adjustm nvestigated [1 ssumed that th nfluencing the Since its in ool. The numb eawater, separ roducts and pr In recent y pplications. IM nd characteri macromolecule f this principle arget proteins f In Table 7 MAC. Iw ally, chemica ions, the use of high regeneration e a stable bed ing ligands and acteristics of t ds. First, the s g between the out by changi t elution princ ment. Ligand r 41-144], but he value of th retention of li ntroduction by ber of uses is l ration of enant rotein purifica ears, IMAC h MAC has been ze natural o es [141-147]. H e in not only g from complex 7 are some ref wona Rykows ally, thermally h flow rates, of columns w with no shrin metal ions: spe the metal-liga strength of the immobilized ng the conditi ciples are use retention using most studies he conditional igand on the I y Porath in 197 arge and inclu tiomeric form ation. has experience n employed in organic ligand Hundreds of p group separatio x biological sa ferences are g ska and Wiesła y, and mechan without degene nking or swelli ecificity vs. adso and bond can e metal-ligand metal ions an ions and there d in IMAC: c g Fe, Co, Cd a have examin l stability con IMAC column 75, IMAC has udes the isolat ms of amino ac ed a rapid expa n combination d from aquat papers have sin ons, but also a amples [140]. given to the l aw Wasiak nically stable ration of the m ing during the orption [140]. be used for d bond varies nd the ligand i efore breaking competitive el and Ni as imm ned Cu-bindin nstant with Cu n [141-146]. s developed in tion of metal-b cids, tetracycli ansion into a v with hyphena tic environm nce been publ as highly selec iterature (mai under a wid matrix, chromatograp successful sep from ligand-l is reversible. T g the metal-lig lution, strippi mobilized meta g ligands. Mo u is the domi nto a robust an binding compo ine removal fr variety of env ated technique ments and oth ished, describ ctive purificati inly surveys) de range of phic run. paration of ligand, and The elution gand bonds. ing elution, als has been ost authors nant factor nd versatile ounds from rom animal vironmental es to isolate her natural bing the use ion tool for devoted to Application of Transition Metals as Active Compounds in Separation Techniques 321 Table 7. IMAC-related publications Authors Title Ref. 1 J. Porath, B. Olin Immobilized metal ion affinity adsorption and immobilized metal ion affinity chromatography of biomaterials: serum protein affinities for gel- immobilized iron and nickel ions [148] 2 E. Sulkowski Purification of proteins by IMAC [149] 3 A.J. Fatiadi Affinity chromatography and metal chelate affinity chromatography [150] 4 J. Porath IMAC—Immobilized metal ion affinity based chromatography [151] 5 E. Sulkowski The saga of IMAC and MIT [152] 6 J. Porath Amino acid side chain interaction with chelate- liganded crosslinked dextran, agarose, and TSK- gel, A mini review of recent work [153] 7 F.H. Arnold Metal-affinity separations—A new dimension in protein processing [154] 8 J.W. Wong, R.L. Albright, N.H. Wang Immobilized Metal Ion Affinity Chromatography (IMAC) Chemistry and Bioseparation Applications [155] 9 J. Porath Immobilized metal ion affinity chromatography [136] 10 T.T. Yip, T.W. Hutchens Immobilized metal ion affinity chromatography [156] 11 R.D. Johnson, F.H. Arnold Multipoint binding and heterogeneity in immobilized metal affinity chromatography [157] 12 S.A. Lopatin, V.P. Varlamov A new trend toward using metal chelates in affinity chromatography of proteins (review) [158] 13 Ki Gedal L. Immobilized metal ion affinity chromatography [159] 14 J. Zouhar Affinity Chromatography of Proteins on Immobilized Metal Ions [160] 15 G.S. Chaga Twenty-five years of immobilized metal ion affinity chromatography: past, present and future [140] 16 V.Garberc-Porekar, V. Menart Perspectives of immobilized-metal affinity chromatography [161] 17 N.T. Mrabet, M.A. Vijayalakshmi, Immobilized metal-ion affinity chromatography: from phenomenological hallmarks to structure- based molecular insights [162] 18 E.K.M. Ueda, P.W. Gout, L. Morganti Current and prospective applications of metal ion-protein binding [137] 19 S.Y. Suen, Y.C. Liu, C.S. Chang Review: Exploiting immobilized metal affinity membranes for the isolation or purification of therapeutically relevant species [139] Iwona Rykowska and Wiesław Wasiak 322 Table 7. (Continued) Authors Title Ref. 20 E. Zatloukalova Immobilized metal ion affinity chromatography and its application [163] 21 X. Sun, J.F. Chiu, Q.Y. He Application of immobilized metal affinity chromatography in proteomics [164] 22 J. Arnau, C. Lauritzen, G.E. Petersen, J. Pedersen Current strategies for the use of affinity tags and tag removal for the purification of recombinant proteins [138] 23 R. Gutiẽrreze, E.M. Martin del Valle, M.A. Galản Immobilized metal-ion affinity Chromatography: status and trends [165] 24 D.V. Kurek, S.A. Lopatin, V.P. Varlamov Prospects of application of the chitin-binding domains to isolation and purification of recombinant proteins by affinity chromatography [166] 25 Rex E. Shephard Chromatographic and related electrophoretic methods in the separation of transition metal complexes or their ligands [112] CONCLUSION The chapter presents both theoretical and practical information about a possibility of an application of metals as active elements in the separation techniques. Such topics were described: metal complexes as components of column packings as well as liquid stationary phases in gas chromatography, optical-active complexes of transition metals in the determination of the enantiomers by means of chromatographic methods, sorbents containing metals to be applied for the SPE (Solid Phase Extraction) technique, and Immobilized Metal Ion Affinity Chromatography (IMAC) applied for a separation of the proteins and peptides. It was demonstrated that such metal compounds may be effectively applied for chemistry, medicine, environmental research, and any other field characterized by a need for a selective determination and preconcentration of the analytes. REFERENCES [1] E.N. Gurjanowa, I.P. Goldsztajn, I.P. Romm, Donoro-akceptornaja zwjaz., Izd. Chemia, Moscow 1973. (in Russian) [2] I.J. Krickaja, J. Usp. Chim. 41 (1972) 2160. [3] D. Cagniant (Ed.) Complexation Chromatography, Marcel Dekker Inc., New York, 1992. [4] W.B. Bradford, D. Harvey, D.E. Chalkey, J. Inst. Petroleum, 4 (1955) 80. [5] H. Hosoya, S. Nagakura, Bull. Chem. Soc. Jpn., 37 (1964) 249. [6] M.A. Muhs, F.T. Weiss, J. Am. Chem. Soc., 84 (1962) 4697. [7] M.J.S. Dewar, Bull. Soc. Chim. Fr., 18 (1951) C71. [8] J.S. Shabtai, J. Herling, E. Gil-Av, J. Chromatogr., 2 (1959) 406. Application of Transition Metals as Active Compounds in Separation Techniques 323 [9] J. Herling, J.S. Shabtai, E. Gil-Av, J. Chromatogr., 8 (1962) 349. [10] A.C. Cope, E.M. Acton, J Am. Chem. Soc., 80 (1958) 355. [11] A.C. Cope, P.T. Moore, W.R. Moore, J. Am. Chem. Soc., 82 (1960) 1744. [12] W. Szczepaniak, J. Nawrocki, Chemia Analityczna (Poland), 19 (1974) 375. [13] D.W. Barber, C.S.G. Philips, G.F. Tusa, A. Verdin, J. Chem. Soc., (1959) 18. [14] R.C. Castells, J.A. Cataggio, Anal. Chem., 42(1970) 1268. [15] V. Schurig, E. Gil-Av, Anal. Chem., 3 (1971) 2030. [16] V. Schurig, J.L. Bear, A. Zlatkis, Chromatogr., 5 (1972) 301. [17] V. Schurig,, R.C. Chang, E. Gil-Av, F. Mikes, Chromatogr., 6 (1973) 223. [18] E.T. Kowalska, W.J. Kowalski, J. Chromatogr., 19 (1984) 301. [19] W.J. Kowalski, Chromatographia, 34 (1992) 266. [20] C.G. Scott, Gas Chromatogr., Intern. Symp., 4 (1962) 36. [21] W. Szczepaniak, J. Nawrocki, W. Wasiak, Chromatogr. 12 (19790 559. [22] J.J. Franken, C. Vidal-Madjar, G. Guichon, Anal. Chem., 43 (1971) 2034. [23] C. Vidal-Madjar, G. Guichon, J. Chromatogr. Sci., 9 (1971) 664. [24] R.L. Grob, E.J. Mc Gonigle, J. Chromatogr., 59 (1971)13. [25] F. Wolf, H. Schmidtke, Z. Phys. Chem.. (Leipzig), 257 (1976) 1061. [26] F. Wolf, H. Schmidtke, Z. Phys. Chem.. (Leipzig), 257 (1976) 1073. [27] I. Rykowska, W. Wasiak J. Chromatogr., 1216(2009)1713. [28] S. Dilli, E. Patsalides, Aust. J. Chem. 29 (1986) 2369. [29] K. Robards, E. Patsalides, S. Dilli, J. Chromatogr. A, 411 (1987)1. [30] D.J. Mc Ewen, Anal. Chem., 38(1966) 1047. [31] G.P. Cartoni, A. Liberti, R. Palombari, J. Chromatogr. A, 20(1965) 278. [32] V. Schurig, E. Gil-Av, Anal. Chem., 3 (1971) 2030. [33] V. Schurig, Chromatographia, 13 (1980) 263. [34] V. Schurig, R.C. Chang, E. Gil-Av, F. Mikes, Chromatographia, 6 (1973) 223. [35] V. Schurig, R.C. Chang, A. Zlatkis, J. Chromatogr. A, 99 (1974) 147. [36] T. Seshardi, V. Kampschultz, A. Kettrup, Fresenius, Z. Anal. Chem., 360 (1980) 124. [37] J.E. Picker, R.E. Sievers, J. Chromatogr. A, 203 (1981) 29. [38] J.E. Picker, R.E. Sievers, J. Chromatogr. A, 217 (1981) 275. [39] E.T. Kowalska, W.J. Kowalski, Chromatographia, 19 (1984) 301. [40] W. J. Kowalski, J. Chromatogr. A, 349(1985) 457. [41] W. J. Kowalski, Chromatographia, 31(1991) 168. [42] T.J. Wenzel, W. Lawrance, J. Chromatogr. A, 396 (1987) 51. [43] T.J. Wenzel, P.J. Bonasia, T. Brewitt, J. Chromatogr. A, 637 (1989) 171. [44] T.J. Wenzel, K.J. Towsend, J. Chromatogr. A, 637 (1993) 187. [45] W. Wasiak, J. Chromatogr. A, 547 (1991) 259. [46] W. Wasiak, J. Chromatogr. A, 653 (1993) 63. [47] M.Y. Khurawar, A. Memon, M.I. Bhanger, J. Chromatogr. A, 715 (1995) 366. [48] W. Wasiak, W. Urbaniak, I. Obst, R. Wawrzyniak, Acta Chromatogr. 1 (1992) 56. [49] I. Rykowska, R. Wawrzyniak, W. Wasiak, Chem. Anal. (Warsaw), 39 (1994) 335. [50] W. Wasiak, I. Rykowska, Chem. Anal. (Warsaw) 40 (1995) 731. [51] W. Wasiak, I. Rykowska, J. Chromatogr. A, 723 (1996) 313. [52] W. Wasiak, I. Rykowska, J. Chromatogr. A, 773 (1997) 209. [53] W. Wasiak, I. Rykowska, Acta Chromatogr., 7 (1997) 88. [54] Wasiak, I. Rykowska, Chromatographia, 48 (1998) 284. Iwona Rykowska and Wiesław Wasiak 324 [55] I. Rykowska, W. Urbaniak, Chem. Papers, 62 (2008) 268. [56] W. Wasiak, A. Voelkel, I. Rykowska, J. Chromatogr. A, 690 (1995) 83. [57] S.D. Harvey, T.J. Wenzel, Chromatogr., 1192 (2008) 212. [58] S. Dilli, E. Patsalides, Aust. J. Chem. 29 (1986) 2369. [59] K. Robards, E. Patsalides, S. Dilli, J. Chromatogr. A, 411 (1987)1. [60] J. Masłowska, G. Bazylak, Collect. Czech. Chem. Commun., 54 (1985) 1530. [61] H. Zhang, X. Yuan, R. Fu, J. Chromatogr. A, 809 (1998) 65. [62] R. Wawrzyniak, W. Wasiak, J. Sep. Sci., 28 (2005) 2454. [63] R. Wawrzyniak, W. Wasiak, Chromatographia, 59 (2004) 205. [64] W. Wasiak, I. Rykowska, Anal. Chim. Acta, 378 (1999) 101. [65] I. Rykowska, W. Wasiak, Chem. Anal. (Warsaw), 46 (2001) 489. [66] I. Rykowska, W. Wasiak, J. Chromatogr. Science, 39 (2001) 1. [67] I. Rykowska, W. Wasiak, Anal. Chim. Acta, 451 (2002) 271. [68] W. Wasiak, I. Rykowska, A. Voelkel, J. Chromatogr. A, 969 (2002) 133. [69] I. Rykowska, W. Wasiak, Chem. Anal. (Warsaw), 48 (2003) 495. [70] Rykowska, W. Wasiak, Chem. Anal. (Warsaw), 49 (2004) 707. [71] O. Bordelanne, M.H. Delville, G. Felix, Chromatographia, 52 (2000) 51. [72] A.G.S. Prado, C. Airoldi, J. Coll. Interface Sci., 236 (2001) 161. [73] C.R. Silva, I. Jardim, C. Airoldi, J. High Resolut. Chromatogr., 22 (1999) 1030. [74] M.Y. Khuhawar, A.A. Memon, M.I. Bhanger, J. Chromatogr. A, 715 (1995) 336. [75] C.F. Yeh, S.D. Chyuch, W.S. Chen, I.D. Fang, C.Y. Liu, J. Chromatogr. A, 630 (1993) 275. [76] I. Rykowska, S. Smyka, W. Urbaniak, W. Wasiak, J. Chromatogr. A, 844 (1999) 239. [77] Rykowska, W. Wasiak, Chromatographia, 51 (2000) 623. [78] S.O. Akapo, Anal. Chim. Acta, 341 (1997) 37. [79] W. Wasiak, W. Szczepaniak, Chromatographia, 18 (1984) 205. [80] W. Wasiak, Chromatographia 22 (1986) 147. [81] W. Wasiak, Chromatographia 23 (1987) 423. [82] W. Wasiak, Chromatographia 23 (1987) 427. [83] W. Wasiak, J. Chromatogr. A, 547 (1991) 259. [84] W. Wasiak, W. Urbaniak, J. Chromatogr. A, 757 (1997) 37. [85] W.A. Kőnig, J. High Resolut. Chromatogr., 5 (1982) 588. [86] R. Straub, M. Pfister, H. Arm, J. Chromatogr., 585 (1991) 195. [87] D. Chambaz, W. Haerdi, J. Chromatogr., 600 (1995) 203. [88] V. Vaccher, P. Berthelot, M. Debaert, J. Chromatogr., 715 (1995) 361. [89] V. Schurig, Chromatographia, 13 (1980) 263. [90] V. Schurig, J. Chromatogr., 441 (1988) 135. [91] Ch. Boberg, T. Norin, L. Rakos, J. Chromatogr., 585 (1991) 111. [92] M. Jang, V. Schurig, J. High Resolut. Chromatogr., 16 (1993) 289. [93] V. Schurig, H.P. Nowotny, J. Chromatogr., 441 (1988) 155. [94] P. Schreier, A. Bernreuther, M. Huffer, Analysis of Chirac organic molecules, Walter de Gruyter, Berlin, Germany, 1995. [95] E. Gil-Av, B. Feibush, R. Charles-Sigler, Tetrahedron Lett., 8 (1966) 1009. [96] E. Gil-Av, B. Feibush, Tetrahedron Lett., 9 (1967) 3345. [97] H. Frank, G.J. Njcholson, E. Bayer, J. Chromatogr. Sci., 15 (1977) 174. [98] T. Saeed, P. Sandra, M. Verzele, J. Chromatogr., 186 (1980) 611. Application of Transition Metals as Active Compounds in Separation Techniques 325 [99] H. Rotzche, Stationary phases in gas chromatography, Elsevier, Leipzig 1991. [100] W.A. Kőnig, I. Benecke, J. Chromatogr., 209 (1981) 91. [101] V. Schurig, D. Schmalzing, J. High Resolut. Chromatogr., 13 (1990) 713. [102] M. Jung, V. Schurig, J. Microcol. Sep., 5 (1993) 11. [103] H. Frank, G.J. Nicholson, E. Bayer, Angew. Chem. Int. Ed Engl., 17 (1978) 363. [104] V. Schurig, Angew. Chem. Ed Engl., 16 (1977) 110. [105] V. Schurig, W. Burkle, K. Hintzer, R. Weber, J. Chromatogr. A, 475 (1989) 23-44. [106] V. Schurig, D. Schmalzing, M. Schleimer, Angew. Chem. Int. Ed Engl., 30 (1991) 987. [107] G. Terfloth, J. Chromatogr. A, 906 (2001) 301. [108] K.L. Williams, L.C. Sander, J. Chromatogr. A, 785 (1997) 149. [109] P. Petersson, K.E. Markides, J. Chromatogr. A, 666 (1994) 381. [110] K. B. Lipkowitz, J. Chromatogr. A, 906 (2001) 417. [111] V. Schurig, J. Chromatogr. A, 965 (2002) 315. [112] Rex E. Shepherd, Coord. Chem. Rev. 247 (2003) 147. [113] W. Linder, Chromatographa, 24 (1987) 97. [114] V. Schurig, J. Chromatogr. A, 441 (1988) 135. [115] V. Schurig, Anal. Proceedings (London) 26 (1989) 202. [116] G. Gűbitz, Chromatographia, 30 (1990) 555. [117] V. Schurig, J. Chromatogr. A, 666 (1994) 111. [118] J. Bojarski, Hassan Y. Aboul-Enein, Biom. Chromatogr., 10 (1996) 297. [119] S. Allenmark, V. Schurig, J. Mater. Chem. 7 (1997) 1955. [120] J. Bojarski, Chem. Anal., 42 (1997) 139. [121] H.Y. Aboul-Enein, M.I. El-Awady, C.M. Herda, P.J. Nicholas, Biomem. Chromatogr., 13 (1999) 531. [122] V. Schurig, J. Chromatogr. A, 906 (2001) 275. [123] F. Gasparrini, D. Misiti, C. Villani, J. Chromatogr. A, 906 (2001) 35. [124] G. Gűbitz, M. Schmid, Biopharm. Drug Dispos., 22 (2001) 291. [125] V. Schurig, Trends Anal. Chem. (TRAC), 21 (2002) 647. [126] G. Gűbitz, M. Schmid, Methods in Molecular Biology, 243 (2003) 1. [127] Oi Naobumi, Chromatography, 26 (2005) 1. [128] H. Lingfeng, T. Beesley, J. Liq. Chrom. & Related Technol., 28 (2005) 1075. [129] V. Šunjić, Croat. Chem. Acta, 82 (2009) 503. [130] K.K. Chandrul, B. Srivastava, J. Chem. Pharm. Res., 2 (2010) 923. [131] I. Liška, J. Krupčik, P.A. Leclerc, J. High Res. Chromatogr., 12 (1989) 577. [132] C.E. Goewie, P.K. Kwakman, R.W. Frei, U.A. Th. Brinkman, W. Maasfeld, T. Seshadri, A. Kettrup, J. Chromatogr. A, 284 (1984) 73. [133] M.W. Nielen, R. Bleeker, R. W. Frei, U.A. Th. Brinkman, J. Chromatogr. A, 358 (1984) 393. [134] J. Porath, J. Carlsson, I. Olsson, G. Belfrage, Nature, 258 (1975) 598. [135] J.R. Everson, H.E. Parker, Bioinorg. Chem., 4 (1974) 15. [136] J. Porath, Protein Expression Purif., 3 (1992) 263. [137] E.K.M. Ueda, P.W. Gout, L. Morganti, J. Chromatogr. A, 988 (2003) 1. [138] J. Arnau, C. Lauritzen, G.E. Petersen, J. Pedersen, Protein Expr. And Purificat., 48 (2006) 1. [139] S.Y. Suen, Y.C. Liu, C.S. Chang, J. Chromatogr. B, 797(2003) 305. [140] G.S. Chaga, J. Biochem. Biophys. Chromatogr., 49 (2001) 313. Iwona Rykowska and Wiesław Wasiak 326 [141] I. Paunovic, R. Schulin, B. Nowack, J. Chromatogr. A, 1100 (2005) 176. [142] S. Sharma, G.P. Agarwal, Anal. Biochem., 288 (2001) 126. [143] F.C. Wu, R.D. Evans, P.JJ. Dillon, Anal. Chim. Acta, 452 (2002) 85. [144] F.C. Wu, R.D. Evans, P.JJ. Dillon, Anal. Chim. Acta, 464 (2002) 47. [145] A.R.S. Ross, M.G. Ikonomou, K.J. Orians, Mar. Chem., 83 (2003) 47. [146] R.W. Vachet, M.B. Callaway, Mar. Chem., 82 (2003) 31. [147] R.G. Pearson, In: Rearson, R.G., editor. Hard and soft acids and bases. Stroudsburg, PA: Hutchington & Ross; 53 (1973) 67. [148] J. Porath, B. Olin, Prot. Express. Purif., 3 (1983) 263. [149] E. Sulkowski, Trends Biotechnol., 3 (1985) 1. [150] A.J. Fatiadi, Crit. Rev. Anal. Chem., 18 (1987) 1. [151] J. Porath, TRAC-Trends Anal. Chem., 7 (1988) 254. [152] E. Sulkowski, Bioessays, 10 (1989) 170. [153] J. Porath, J. Mol. Recognit., 3 (1990) 123. [154] F.H. Arnold, Bio-Technol., 9 (1991) 151. [155] J.W. Wong, R.L. Albright, N.H. Wang Sep. Purif. Methods 20 (1991) 49. [156] T.T. Yip, T.W. Hutchens, Mol. Biotechnol., 1 (1994) 151. [157] R.D. Johnson, F.H. Arnold, Biotechnol. Bioeng., 48 (1995) 437. [158] S.A. Lopatin, V.P. Varlamov, Prikl. Biokhim. Microbiol., 31 (1995) 259. [159] Ki Gedal L., Immobilized metal ion affinity chromatography. In: Janson J-C, Rydĕn L, eds. Protein Purification: Principles, High-Resolution Methods, and Applications. 2nd ed. New York: John Wiley & Sons, Inc., (1998) 311. [160] J. Zouhar, Chem. Listy, 93 (1999) 683. [161] V. Garberc-Porekar, V. Menart, J. Biochem. 49 (2001) 335. [162] N.T. Mrabet, M.A. Vijayalakshmi, Immobilized metal-ion affinity chromatography: from phenomenological hallmarks to structure-based molecular insights. In: Vijayalakshmi M.A. ed. Biochromatography: Theory and Practice. London: Taylor & Francis, Ltd., (2002) 272. [163] E. Zatloukalova, Chemicke Listy, 98 (2004) 254. [164] X. Sun, J.F. Chiu, Q.Y. He, Expert Rev. Proteomics, 2 (2005) 649. [165] R. Gutiẽrreze, E.M. Martin del Valle, M.A. Galản, Separ. & Purf. Reviews, 36 (2007) 71. [166] D.V. Kurek, S.A. Lopatin, V.P. Varlamov, Applied Biochem. and Microbiol., 45 (2009) 1. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 8 CHROMIUM PIGMENT Mohammad Fikry Ragai Fouda 1 , Hanan F. Abdel-Halim 2 and Samia Abdul Raouf Mostafa 3 1 Professor of Inorganic Chemistry, National Research Center, Cairo, Egypt 2 Ph.D Inorganic Chemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt 3 Associate Professor Inorganic Chemistry, National Research Center, Cairo, Egypt INTRODUCTION Discovery of the Chromium Chromium is the 21st element in the earth's crust in relative abundance, ranking with V, Zn, Ni, Cu, and W, with atomic numder 24, It belongs to Group VI B of the periodic table whose other members are molybdenum and tungsten. Its neighbors are vanadium and manganese. It was first isolated and identified as a metal by the French chemist, Vauquelin, in 1798 working with a rare mineral, Siberian red lead (crocoite, PbCrO 4 ). He chooses to name it chromium, from the Greek word chroma meaning color, because of the wide variety of brilliant colors displayed by compounds of the new metal. Chromium metal in its purest form (99.96% chromium) is produced in limited quantities by vapor deposition from anhydrous chromium iodide. Commercial chromium metal is produced either by electrolysis of a chromium-containing electrolyte or by aluminothermic reduction of pure chromic oxide. Nowadays, the chromium metal, different chromium alloys and chromium compounds were produced, on a large scale, for uses in various industrial applications [1]. 1 E.mail address:
[email protected] 2 Email address:
[email protected] 3 Email address:
[email protected] Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al. 328 Occurrence and Mining of Chromite Ore The only commercial ore, chromite, has the ideal composition FeO.Cr 2 O 3 , i.e. 68% Cr 2 O 3 , 32% FeO or ca. 46% chromium- Actually the Cr/Fe ratio varies considerably and the ores are better represented as (Fe,Mg)0.(Cr,Fe,Al) 2 O 3 . Table 1 gives the classification of chromite ores. Table 1. Composition of chromite ores[1] Grade Composition Ratio Cr:Fe metallurgical, high Cr 46% Cr 2 O 3 min. >2:1 chemical, high Fe 40 to 46% Cr 2 O 3 1.5 to 2:1 refractory, high Al >20% Al 2 O 3 >60% A1 2 O 3 + Cr 2 O 3 Chromite deposits occur in olivine and pyroxene type rocks and their derivatives. Geologically they appear in stratiform deposits several feet thick covering a very wide area and are usually mined by underground methods. Podiform deposits, i.e. isolated lenticular, tabular, or pod-shaped bodies ranging in size from a kilogram to several million tons are mined by both surface and underground methods, depending on size and occurrence. Most chrome ores are rich enough for hand sorting. However, fines or lower-grade ore can be effectively concentrated by gravity separation methods yielding products as high as 50% Cr 2 O 3 with the Cr/Fe ratio of the original ore usually unchanged. Decreasing world supplies [2] of high-grade lumpy ore and increasing availability of high-grade fines and concentrates has increased the use of three agglomeration methods, (a) briquetting with a binder, (b) production of an oxide pellet by kiln firing, and (c) production of aprereduced pellet by furnace treatment. Manufacture of Chrome and Chrome Compounds The two primary industrial compounds of chromium made directly from chromite ore are sodium chromate and sodium dichromate. Secondary chromium compounds produced in substantial quantity include potassium chromate and dichromate, ammonium dichromate, chromic acid (chromium (VI) oxide), and various formulations of basic chromic sulfate used principally for leather tanning. The production processes of chromium and different chromium alloys; and chromium compounds (such as potassium chromate and dichromate, ammonium dichromate, chromic acid, basic chromic sulfate) from different grades of chromite ores were extinsively studied by numerous authers[3, 4]. Uses of Chromium Compounds Chromite ore used for production of some inorganic chemicals and pigments. These compounds are widely used in various industrial purposes such as metal finishing and Chromium Pigment 329 corrosion control pigments, allied products, leather tanning, textiles, wood preservation, drilling muds, catalysts and intermediates. Chromium compounds are essential to many industries. The major uses are metal finishing and corrosion control, pigments and allied products, leather tanning and textiles , wood preservation, drilling muds and other uses ( e.g: catalysts, intermediates) [5]. METAL FINISHING AND CORROSION CONTROL The most important use of chromium compounds in metal finishing is that of chromic acid in chromium plating [6,7]which consumes most of the chromic acid produced. Unlike most metals, chromium is best plated from solutions in which it is present as an anion in a high oxidation state. The use of the lower oxidation states is confined to the electrolytic production of chromium metal. Chromate performs two major applications in corrosion control. The first is conversion sealing pretreatments for metal alloys of iron, aluminum, zinc, copper, and magnesium. The second application is as leachable inhibitive pigments in many primer formulations. Both of these uses of chromate compounds produce strong corrosion inhibiting effects. Trialkoxysilanes and similar silicon compounds are currently the subject of intensive research due to the need of “green” technology in the metal-finishing and the adhesive industries. PIGMENTS Chromium pigments can be further classified into chromate color pigments based on lead chromate, chromium oxide greens and corrosion inhibiting pigments based on difficulty soluble chromate. An excellent discussion of these pigments is given in a recent encyclopedia [8]; an older reference is also useful [9]. Lead Chromate Pigments The Chemical compositions of these pigments in addition to their analytical specifications are summarized in the Table2. PbCrO 4 PbMoO 4 PbSO 4 also known as chromium-molybdenum, molybdenum red, orange molybdenum, Pigment Red 104. The main compounds are lead chromate acid and a small amount of lead and molybdenum lead sulfate solution formation of the orange-red approximate composition of inorganic pigments for PbCrO 4 69%:80%, PbSO 4 9%:15%. Look for the light orange-red powder, molybdenum (chromium) bright red. The impermeability of a better color and fragmentation. Hiding and excellent brightness, high crushing strength worse. For sodium, sodium molybdenum, sodium nitrate and lead to raw materials, crystal formation of the mixed precipitation making it stable, according to that system in molybdenum lead chromate, adjusting the ratio of raw materials, control of the reaction temperature and time, the different colors available products. Mainly used in the coatings, plastics and inks, but there are restrictions on heavy metals in the area not to be applied. Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al. 330 Table 2. Chemical composition and analytical specifications for chromate color pigments [11,12] PbCrO 4 , % PbSO 4 , % Other components, % Primrose chrome yellow theoretical 77.3 22.7 ASTM spec, min 50 actual min 52.0 4.2 max 82.7 25.9 Lemon chrome yellow theoretical 72.7 27.3 ASTM spec, min 65 actual mm. 52.4 17.4 max. 68.8 39.0 medium chrome yellow theoretical 100.0 ASTM spec, min 87 actual mm. 82.4 nd max. 98.2 nd chrome orange theoretical 59.2 PbO.40.8 ASTM spec, min 55 actual 58.2 PbO, 39.4 molvbdate orange theoretical 82.3 2.8 PbMoO 4 , 14.9 ASTM spec, min 70 lead silicochromate theoretical 50.0 SiO 2 , 50.0 Chromium Oxide Greens These pigments comprise both the pure anhydrous oxide Cr 2 O 3 , and hydrated oxide, or Guignet's green [13] Corrosion Inhibiting Pigments These pigments derive their effectiveness from the low solubility of chromate. The major pigment of this group is zinc chromate or zinc yellow; others include zinc tetroxychromate, basic lead silicochromate, strontium chromate, and barium potassium chromate [14]. The chemical composition of some of these pigments is shown in Table 3. Table 3. Analytical specification and composition (percent by weight) of corrosion inhibiting pigments [12,14] CrO 2 ZnO Other MO H 2 O combined SO 3 Other zinc chromate type I, low sulfate theoretical 45.8 37.2 10.8 K 2 O 6.2 ASTM spec. 41min. 35-40 max. K 2 O 0.2 max. 0.1 max. Cl typical 45.0 36.0 10.0 6.0 0.05 type n, regular ASTM spec. 41min. 35-40 13max. K 2 O 3.0 max. 0.8 max. C1 typical 44.0 38.0 10.0 6.0 1.0 zinc tetroxychromate typical 17.0 71.0 10.0 0 strontium chromate theoretical ASTM spec. 44min. 47min. SrO 0.2 max. 0.1 max. C1 typical 47.0 49.0 0.2 Basic lead silico- chromate ASTM spec. 5.1-5,7 46-49 PbO 0.2 max. 45.5- 48.5 SiO 2 typical 5.4 47.0 47.0 Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al. 332 LEATHER TANNING Although compounds of chromium (VI) are the most important commercially chromium compounds the bulk of the applications in the textile and tanning industries depend on the ability of chromium (III) to form stable complexes with proteins, cellulosic materials, dyestuffs, and various synthetic polymers. The chemistry is complex and still imperfectly understood in many cases. The common denominator is the coordinating ability of chromium (III). The chromium tanning of leather is one step in a complicated series of operations leading from the raw hide to the finished product. Chrome tanning is the most important tannage for all hides except heavy cattle hides, which are usually vegetable, tanned. In heavy shoe uppers and soles, chrome tanned leather is frequently given a vegetable retan to produce chrome retan leather. The annual consumption of hides by the leather industry appears to be decreasing [15]. Some thermoresistant pigments having spinel and tin sphene structure were synthesized using as chromophore (Cr 3+ ) source leather wastes with 6.5% Cr 2 O 3 content. This particular chromium source brings a series of advantages, as: burning of the organic components supplies in situ a part of the necessary energy of the synthesis and the chromophore is well dispersed in the reaction mixture. The complete burning of the wastes without the emission of polluting compounds requires the reaction mixture to be introduced in the oven at temperatures above 800 °C [16]. IN TEXTILE INDUSTRY Sodium dichromate and various chromic salts are employed in the textile industry [17, 18]. The former compounds are used as an oxidant and as a source of chromium; for example, to dye wool and synthetics with mordant acid dyes, oxidize vat dyes and indigosol dyes on wool, after-treat direct dyes and sulfur dyes on cotton to improve washfastness and oxidize dyed wool. Premetallized dyes are also employed. These are hydroxyazo or azomethine dyes in which chromium or other metals are combined in the dye. A typical premetallized dye is designated Chromolan Black NWA (CI 15711). The commercial product also contains some-of the 1:1 chelate. There are numerous patents covering dark pigment compositions containing iron and chromium. For example, U.S. Pat. No. 2,187,822 (I. G. Farben) relates to a process of producing a brown pigment having the formula 3K 2 O.11Fe 2 O 3 .16CrO 3 .12H 2 O. In this pigment, the weight ratio of the oxides of chromium and iron is approximately 1:1. U.S. Pat. No. 3,561,989 (Bayer) relates to a black enamel having a corundum structure in the form of Fe 2 O 3 and containing 66 to 95 parts by weight of Cr 2 O 3 per 100 parts of Fe 2 O 3. No mention is made of its possible use in vinyl or other polymers for house siding. Instead its suggested uses are limited to enameling and glazing. U.S.Pat. No. 3,528,839 (Bayer) covers a black pigment containing copper, iron, and chromium in a spinel structure and having higher temperature stability, high tinting strength, good light fastness and resistance to weathering. The atomic weight ratio of copper to chrome and iron is 0.25-0.5 and the ratio of iron to chrome is 0.25-0.5 [19]. Another use of chromium Chromium Pigment 333 compounds is in the production of water- and oil resistant coatings on textiles, plastic, and fiberglass. Trade names are Quilon, Volan, and Scotchgard [20,21]. CHROMIUM PIGMENTS AS WOOD PRESERVATION The recent increase in the use of chromium compounds in wood preservation may be largly due to the excellent results achieved by chromated copper arsenate (CCA), available in three modifacations under a variety of trade names. The treated wood is free from bleeding, is paintable and of an attractive olive-green color. Thus CCA is widely used, especially in treating utility poles,building lumber, and wood foundations. Chromium compounds are also used in fire- retardant formulations where their function is to prevent leaching of the fire retardant from the wood and corrosion of the equipment employed.[22]. CCA protects wood used aboveground, in contact with the ground, or in contact with freshwater or seawater. Wood treated with CCA (commonly called green treated) dominated the treated wood market from the late 1970s until 2004. Chromated copper arsenate has been phased out voluntarily for most applications around residential areas and where human contact is prevalent. The allowable uses for CCA are discussed in more detail in the Recommended Guidelines section. The three standardized formulations are: CCA Type A, CCA Type B, and CCA Type C. CCA Type C (CCA–C) is the formulation used by nearly all treatment facilities because of its resistance to leaching and its demonstrated effectiveness. CCA–C is comprised of 47.5 percent chrom-ium trioxide, 18.5 percent copper oxide, and 34.0 percent arsenic pentoxide dissolved in water. CCA–C has decades of proven performance. It is the reference preservative used to evaluate the performance of other waterborne wood preservatives during accelerated testing. Because it has been widely used for so many years, CCA–C is listed in AWPA standards for a wide range of wood products and applications. The minimum retention of CCA–C in wood ranges from 0.25 pounds per cubic foot (4 kilograms per cubic meter) in aboveground applications to 2.5 pounds per cubic foot (40 kilograms per cubic meter) in marine applications. Most ground-contact applications require minimum retentions of 0.4 pounds per cubic foot (6.4 kilograms per cubic meter). Critical structural applications require minimum retentions of 0.6 pounds per cubic foot (9.6 kilograms per cubic meter). It may be difficult to obtain adequate penetration of CCA in some difficult-to-treat species. The chromium serves as a corrosion inhibitor. CHROMIUM PIGMENTS AS CATALYSTS A more important minor use of chromium compounds is in the manufacture of catalysts, consuming about 1500 metric tons of sodium dichromate equivalents annually. Chromium catalysts are used in a great variety of reactions, including hydrogenations, oxidations.and polymerizations. Most of the details are proprietary and many patents are available [23-25] Chromia-alumina catalysts are prepared by impregnating y-alumina shapes with a solution of Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al. 334 chromic acid, ammonium dichromate, or chromic nitrate, followed by gentle calcination. Zinc and copper chromites are prepared by coprecipitation and ignition, or by thremal decomposition of zinc or copper chromates, or organic amine complexes therefore many catalysts have spinel-like structures [26]. Back in the 1940s as well as in the paint industry of today, the term Zinc Chromate does not refer to a paint color, but rather a protective coating. Another route of preparation of these compounds by heating the nitrates of chromium and the desired metal at 1000 c. A Through investigation were carried out by monitoring reaction products at numerous temperatures.the products were tested as pigments according to the usual method of testing in that respect[27]. Zinc chromate is a corrosion resistant agent that is added to certain coatings. Even today, chromate finishes including zinc chromate provide superior corrosion resistance. Additionally, zinc chromate is highly toxic thus protecting the surface from proliferation of organic matter. In the aircraft industry of the 1940s, zinc chromate was used as an anti-corrosive barrier primer; it could be described as a sort of painted-on galvanizing. It has been developed by Ford Motor Company by the late 1920s, subsequently adopted in commercial aviation and later by the US Military. Official USAAC notes mention successful application of zinc chromate primer starting from 1933, but it has not been adopted as standard until 1936. Because zinc chromate is all about corrosion protection, the precise coloring of it is and has not been considered as important as the chemical composition. In the official notes of the period, the name zinc chromate is often accompanied by the name of particular manufacturer, thus mentioning Ford zinc chromate, DuPont zinc chromate or Berry Brothers zinc chromate. This means that the actual color of zinc chromate coating may have varied from batch to batch or manufacturer to manufacturer without it being viewed as an issue. The 'native' tone of zinc chromate crystalline salt is a bright greenish-yellow. When put into a vehicle with binders to make paint, this color would be the raw result. Such raw zinc chromate primer would also give a semi-translucent coating, not very opaque like a pigmented paint or lacquer. This property becomes especially interesting when we consider that aircraft factory instructions often called for just one protective coat of primer. As a consequence, the color of the underlying surface might have a significant effect on the final appearance. For example, raw zinc chromate applied on the white background would look yellow, while applied to bare metal aluminum it would look more like apple green. Similarly, any pigment might be added to the raw paint mixture to go with the zinc chromate, thereby modifying the color. Some of today's mixtures use iron oxide -- giving that rusty red appearance you can often see on prefabricated steel beams in highway and building construction. Sometimes, zinc chromate was mixed with Lamp Black paste to give a bit more UV resistance (zinc chromate is very sensitive to photolitic reactions) and more durability in high wear areas. Mixing with black gave greener tones, which, depending on the amount of black added could run from apple greens to medium olive greens[28]. Thermochromism of art-known compositions of rubies d-elements (Al 2-x Cr x O 3 ) and spinels (MgAl 2-x Cr x O 4 ), as well as of the claimed ones, is stipulated not by the phase transition with the temperature changes, but with the change in ligands field force. Color change takes place with chromium concentration increase on account of aluminium atoms Chromium Pigment 335 with chromium atoms substitution, which is accompanied by lattice deformation due to greater radius of chromium atoms against aluminium atoms. Hereupon, the phenomenon of such thermochromism is known for chromium only. If chromium concentration in these compounds is not high, they have pink color. At high chromium concentrations the color of these compounds is green. Pink crystals have thermochromism : upon heating their color gradually changes from pink at low temperatures to green at high temperatures. However, this change takes place very slowly within wide range of temperatures from 200 to 900 ◦C. Within the range of temperatures from room temperature to about 400 ◦C, which is the most substantial for warning a customer, change of color in rubies and spinels is not sufficient for using them as thermochromic components of the coatings. Spinel Structured Pigments Spinels are ternary oxides with the general formula AB 2 O 4 , where A and B are cations occupying tetrahedral and octahedral sites respectively. These oxides exhibit interesting electric, magnetic and catalytic properties [29-32], depending on their nature, charge, and distribution of ions at interstices [33]. CuCr 2 O 4 crystallizes as a tetragonally distorted spinel structure. Its distortion is related to the cooperative Jahn-Teller effect of Cu 2+ at the tetrahedral sites [34]. The substitution of tetrahedral Cu 2+ ions by any bivalent cation does not affect the distribution of cations in the substituted spinel oxides [35,36]. Site preference energies for oxide spinels indicate that Ni 2+ and Cr 3+ occupy octahedral sites, although Cr 3+ is also capable of forcing Ni 2+ into tetrahedral positions [35]. The most widely used method for the preparation of spinels involves solid-state reaction of mechanically mixed metal oxides at high temperatures [37,38]. The Pechini method[39,40], based on polymeric precursors, can be used to prepare spinels and it does not require high temperature calcinations and permits good stoichiometric control as well as reproducibility. This method consists of the formation of a polymeric resin between a metallic acid chelate and polyhydroxide alcohol by polyesterification. This study is focused on the preparation of solid solutions of copper chromites doped with nickel by the Pechini method, and the investigation of the effect of heat treatment on particle size and morphology. X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) patterns were used to reveal the structural properties of the materials formed. According to group theory, spinel type oxides should exhibit four IR bands υ 1 - υ 4 [41,42]. In this investigation measurements were carried out up to 500 cm -1 , thus limiting the study to the high frequency bands (υ 1 and υ 2 ) of the IR spectrum. Since these bands are nearly insensitive to changes in the bivalent cation [37], they should not be significantly affected when Cu 2+ from CuCr 2 O 4 is substituted by another bivalent cation. The infrared spectra are shown in( Figure 2) Both, υ 1 at 665 cm -1 , and υ 2 at 580 cm -1 are related to bonds of the internal tetrahedra and octahedra of the structure of Cu 0.8 Ni 0.2 Cr 2 O 4 . The broadening of these bands is probably due to the presence of more than one type of cation [42]. Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al. 336 Figure 1. Infrared absorption pattern of the polymeric precursor and powders calcined at 500 o C, 700 o C and 900 o C for 4 hours. Due to their excellent resistance to temperature, light, weather and chemicals, spinel black pigments are eminently suitable for pigmenting highly heat resistant lacquers (e.g. based on silicone resins) and Coil-Coat-Lacquers. For these applications they are sometimes mixed with white pigments for obtaining a variety of grey shades. They are also suitable for colouring plastics, porcelain enamels and ceramic glazes. Oxidic mixed phase pigments having a spinel structure have been known for a long time. The crystal structure of the colourless mineral spinel, MgAl 2 O 4 ,offers numerous possibilities of substitution of the magnesium and aluminium, in particular by colour producing transition metals such as vanadium, chromium, manganese, iron, cobalt, nickel and copper, mixed oxides of the general formula AB 2 O 4 being thereby obtained in a wide variety of colour shades .Mixed phase pigments are normally produced by subjecting an intimate mixture of the metal oxides, or of compounds which form the metal oxides when heated, to a solid state reaction at temperatures of from 800° to 1400° C. and then grinding the product. Black pigments based on copper-chromium spinels CuCr 2 O 4 have achieved particular technical importance. They are frequently modified by the incorporation of iron and/or manganese in the spinel lattice[43]. The black pigments according to the invention are distinguished by the fact that they have substantially lower brightnesses L* when brightened by a white pigment than pigments which have been produced by conventional processes. This brightness L* may serve as measure of the tinting strength of the pigments. A low L* value indicates that the black pigment has a high absorption capacity for visible light and is therefore particularly efficient in imparting colour to other substances. Chromium Pigment 337 The preparation of spinel black pigments by annealing a mixture of oxides, hydroxides and/or carbonates of copper, chromium and manganese, optionally with the addition of mineralizing agents, at temperatures of from 750° to 900° C has been invented. After the addition of the copper and chromium component, a homogeneous suspension is prepared with intensive stirring and the reaction time increased by decreasing the temperature. Production and characterisation of pigments by using less expensive raw materials such as limonite and chromite was undertaken. The resulting pigments were characterised by using X-ray diffraction (XRD) and UV-Vis spectrophotometer. The colour of glazed tiles containing 3 wt.% pigment change from dark brown to light brown depending on the calcination temperature and limonite content. With pigments prepared with 50% limonite content calcined at 1250 °C, the chocolate brown colour was obtained corresponding to the commercial brown pigments. An iron-chromium black pigment was synthesised from a mixture of pure chromium (III) oxide (Cr 2 O 3 ) and iron (III) oxide (Fe 2 O 3 ) powders and was used to determine possible interactions between a pigment and a transparent glaze. The interactions were studied using a scanning electron microscope (SEM) attached with an energy dispersive X-ray spectrometer (EDX). The results showed that black pigment particles give brown colour to the glaze. EDX analysis on pigment crystals embedded in the glaze clearly showed that Zn and Mg diffused into pigment crystals and caused a change of colour from black to brown [44]. Brown ceramic pigment has also been studied. The pigment was synthesized by adding Al 2 O 3 and MgO dopants in small quantities, below 3 wt%. Analysis has shown the stabilization of two corundum structures with a compositions close to Cr 0.50 Fe 1.50 O 3 and Al 0.30 Cr 1.70 O 3 , plus a spinel structure with composition close to MgCr 2 O 4 . This new way of preparation may lead to significant savings in costs [45]. Another invention in the preparation of a mixed-phase pigment was based on iron oxide and chromium oxide by heating a mixture of the oxides, hydroxides or oxide hydroxides of iron and of chromium at from 600° to 1100° C .The essential feature of this invention is that a mixture of transparent α-iron oxide having an orthorhombic bipyramidal crystal structure and a chromium(III) hydroxide, which has been applied onto the transparent iron oxide by precipitation with an alkali, preferably sodium carbonate, is heated. The pigments according to the invention give deep colorations and are readily dispersible. Mixed-phase pigments based on iron oxide and chromium oxide belonging to the (Fe,Cr) 2 O 3 are used in the form of chrome iron brown, and demand for them in the plastics industry for coloring construction components, eg. window profiles, is growing since they possess excellent fastness properties. However, the tintorial properties, such as particLe fineness, dispersibility and color yield, of the chrome iron brown pigments commercially available to date have not so far completely met the high requirements set by the plastics industry. Mixed-phase pigments are manufactured in general by reacting the oxide components in the solid state at from 800° to 1400° C. This method of production results in pigments which have a very large particle diameter and extensive sintered fractions .The use of particularly finely divided oxides, hydroxides, or other compounds to produce a good mixture in aqueous suspension did not result in any substantial improvement, nor were sufficient improvements achieved by using mixtures, such as hydroxides or carbonates, which were prepared by co- precipitation of aqueous salt solutions. Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al. 338 Processes which lead to homogeneous brown products of the general composition (Fe, Cr) 2 O 3 , in which decomposed iron and chromium compounds are ignited at fairly high temperatures, are also known .The mixture of the transparent α-iron oxide and the chromium(III) hydroxide is obtained by precipitating a solution of a chromium(III) salt in the presence of the iron oxide with an alkali, preferably sodium carbonate or potassium carbonate. Precipitation is carried out at from room temperature to 95°C., preferably from 40° to 80° C. The precipitate (the mixture) is filtered off, washed and dried, and the dry mixture is then heated in a conventional manner at from 600° to 1100° C. Heating is effected by a conventional method, for example in a bogie hearth furnace, a rotary tube furnace or a similar furnace. The hue of the pigments is altered from pale brown through medium brown to deep dark brown shades by increasing the amount of chromium oxide. To a lesser extent, the tinctorial properties of the products are also influenced by the temperature during heating (calcining temperature). In the system ZnO–Fe 2 O 3 –Cr 2 O 3 the ability of iron to occur on both the tetrahedral and octahedral sites of the spinel structure leads to a versatile system yielding a variety of related shades [46,47]. Brown spinel pigments based on zinc chromite which are iron-free and exhibit an atomic ratio of chromium to zinc in a range of 1 to greater than 0.5 up to 2 are disclosed. Preferred pigments additionally contain manganese, in which instance the atomic ratio of Mn to Cr is a maximum of 0.2. The production of the pigments involves a firing process of a powder mixture consisting of the oxides the metals, or precursors thereof, contained in the pigment. Instead of previously known grayish-brown unattractive products, attractive brown pigments are obtained by means of the selected molar ratio and a baking temperature above 1200° C. The novel pigments can be used in the presence of glass frits even at firing temperatures above 1200° C. to 1500° C. and are suitable for a common firing of ceramic carrier and decoration. The novel brown spinel pigments based on zinc chromite which, in contrast to previously known pigments of this type, are iron-free. The production of the pigments of the invention is carried out in a manner which is generally known for spinel pigments but in which the baking temperature of the powder mixture is above the known range. The novel pigments can be used for ceramic decorations which can be fired or baked on in a high- temperature firing. Spinel pigments based on zinc chromite are known; however, in many respects they do not meet the qualities desired by manufacturers of ceramic decorations. Zinc chromite of the formula ZnCr 2 O 4 is a spinel in which the Zn 2 + ions occupy the tetrahedral positions and the Cr 3 + ions the octahedral interstices of the cubically densest packing of oxygen atoms. ZnCr 2 O 4 is normally a greenish-gray product and is coloristically unattractive. This brown pigments are obtained by means of the insertion of iron into the spinel lattice of the zinc chromite. A disadvantage of these brown spinel pigments is their limited temperature stability in the presence of glass frits, which also applies to many other iron-containing spinels. Such pigments discolor during the firing on of decorative colors produced from them onto ceramic products with increasing firing temperature. Such pigments are therefore not satisfactorily suitable for applications which require firing temperatures above 1200° C., especially above 1300° C. to 1500° C., such as e.g. new porcelain firing methods in which the unfired ceramic carrier and a decorative layer applied onto it are fired in a single firing cycle. It is assumed that chromium is partially in the tetravalent form in the lattice of the spinels of the present Chromium Pigment 339 invention and that zinc ions occupy positions of the chromium for the purpose of the charge equalization. Normally, the zinc oxide which is not bound in the spinel lattice does not result in any disturbances when the pigments are used. However, excess ZnO can be dissolved out or leached out of the pigment with an acid wash as required. The pigments can additionally contain other metals in a limited amount in the spinel lattice aside from the components Cr 2 O 3 and ZnO for modifying the shade and/or for stabilizing the shade in the case of very high firing temperatures, with the stipulation that the brown color remains preserved. The term "limited amount" denotes an atomic ratio of these other metals to chromium of a maximum of 0.2. These modifying metals are preferably manganese, but metals inserted in the spinel such as Mg, Ti, Al, Sn, Ni, Co and V can also modify the shade. Pigments of the invention which essentially contain only Cr 2 O 3 and ZnO exhibit a slight color shift toward green in glazes as the firing temperature increases--this can be recognized by an "a" value in the L, a, b colorimetric system which decreases and, if applicable, becomes negative. This color shift can be eliminated by means of the insertion of manganese into the spinel lattice. Especially preferred pigments of the invention contain essentially only oxides of chromium, zinc and manganese and exhibit an atomic ratio of Cr to Zn to Mn of 1:0.75 up to 2:0.01 up to 0.15. The term "precursors of metal oxides" denotes compounds which are converted into oxides below the firing temperature, e.g. sulfates, oxide hydrates, carbonates, oxalates. Preferred pigments which do not exhibit any color shift to green even at the high firing temperatures of decorative systems containing these pigments and glass frits can be produced in that the powder mixture to be fired consists essentially of Cr 2 O 3 , ZnO and an Mn compound from the series MnO , MnO 2 , Mn 2 O 3 or a permanganate with the atomic ratio of Cr to Zn to Mn being 1:0.75 up to 2:0.01 up to 0.15. The term "essentially" signifies that the powder mixture can additionally contain mineralizers which are not inserted into the spinel lattice as well as impurities stemming from the raw materials used [48]. A gray vinyl polymer material having improved tolerance to sunlight and other sources of infra red radiation. The vinyl polymer contains an inorganic pigment composed of chromium oxide (Cr 2 O 3 ) and iron oxide (Fe 2 O 3 ) wherein the weight ratio of the oxides is about 3:1. The pigment may be blended with titanium dioxide (TiO 2 ) to give a continuous spectrum of shades ranging from dark gray to light gray. The pigment is prepared by co-calcining the oxides of chromium and iron in finely divided form (-325 mesh) at a relatively low (900°- 950° C.) temperature followed by grinding of the co-calcined product to 99% -325 mesh. The pigment useful in the present invention contains between 40 and 60% by weight of chromium, present in oxide form and between 25 and 12% by weight of iron, also present as the oxide. A more preferred range is between 48 and 52% chromium and between 19 and 16% iron. In a highly preferred embodiment of the invention, the chromium is present as 49.8% and the iron as 17.6%. This represents 73.91% as Cr 2 O 3 and 26.09% as Fe 2 O 3 [49] . Grayish-green ZnCr 2 O 4 spinel that an attractive brown spinel pigment is obtained by means of the elevation of the firing temperature and the selection of the molar ratios of the initial components. It was also surprising that the incorporation of a small amount of manganese into the pigment distinctly increases the color stability at very high temperatures. The novel brown spinel pigments obtainable in accordance with the method of the present invention can be used for coloring and decorating ceramic products known in the art such as porcelain, earthenware and stoneware in the presence of glass frits which are known Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al. 340 in the art. The firing temperatures can be in the customary range of usually 700° to 1100° C. or above thereby. The temperature is a function in particular of the pigment composition and also the softening range of the glass frits present in the decoration system used. The temperature stability and glaze stability of the pigments of the present invention also permit firing temperatures above 1200° C. and especially above 1300° to 1500° C. This unexpected advantage makes it possible to also use the pigments in so-called high-temperature firing methods, in which the ceramic carrier and the decoration are fired simultaneously in a single firing procedure [50]. Valences of chromium were directly related to the color of the pigments. The valences were dependent on the Ti/Sn ratio in sphene-type (CaTiSiO5-CaSnSiO5), perovskite-type (CaTiO3-CaSnO3) and rutile-type (TiO2-SnO2) matrices mother crystals . Results of XPS showed that chromium ions doped in CaSnSiO5 and CaSnO3 matrices existed Cr4+, causing reddish purple color. With substitution of Ti for Sn in these matrices, the fraction of trivalent chromium increased and the color changed from reddish purple through purple red, red brown and finally to brown. A similar valence change of chromium was observed in the rutile-type pigments that changed lilac through brown to ocar colors. Purple red color was achieved in 2mol% Cr-doped sphene- and perovskite-type pigments containing 20mol%Ti [51]. The tie-lines delineating intercrystalline ion-exchange equilibria between MgAl 2 O 4 - MgCr 2 O 4 spinel solid solution and Al 2 O 3 -Cr 2 O 3 solid solution with corundum structure have been determined at 1473 K by electron microprobe and X-ray diffraction (XRD) analysis of equilibrated phases. The tie-lines are skewed to the solid solution 0.7MgAl 2 O 4 -0.3MgCr 2 O 4 . The lattice parameters and molar volumes of both the solid solution series exhibit positive deviations from Vegard's and Retger's laws, respectively. Activities in the spinel solid solution are derived from the tie-line information and thermodynamic data on Al 2 O 3 -Cr 2 O 3 solid solution available in the literature. Activities of Mg 0.5 CrO 2 and Mg 0.5 AlO 2 in the spinel solid solution exhibit strong positive deviations from Raoult's law over most of the composition range. However, activity of Mg 0.5 CrO 2 exhibits mild negative deviation for compositions rich in Mg 0.5 CrO 2 . The activity-composition relationship in the spinel solid solution is analyzed in terms of the intracrystalline exchange of cations between the tetrahedral and octahedral sites of the spinel structure. The intracrystalline ion exchange is governed by site preference energies of the cations. The difference between the Gibbs energy of mixing calculated using the cation mixing model and the experimental data is taken as a measure of the strain contribution arising from the difference in the radii of Al 3+ and Cr 3+ ions. The large positive strain enthalpy suggests the onset of immiscibility in the spinel solid solution at low temperatures. The computed critical temperature and composition for phase separation are 802 (±20) K and X MgCr2 O 4 = 0.46 (±0.02), respectively[52]. Solid Solution Pigments An investigation of the reaction products of aluminium hydroxide-chromium nitrate mixtures at 200° and 1000°C with molar ratios 9:1, 8:2, 7:3, 6:4, 5:5 and 4:6 was carried out. The products resulting at 200°C were characterized by XRD, IR and diffuse reflectances spectra (DRS) as mixtures ofhexavalent chromium compounds with general formula Al 2 O 3 Al n (OH) 3n−2 -iCrO 4 , Al 2 (OH) 4 CrO 4 ,Al 2 CrO 4 ) 2 Cr 2 O 7 , and Al 2 O 3 Cr 2 (CrO 4 ) 2 -Cr 2 O 7 . Upon heating at 1000°C for 12 h transformation into (Al 1−x Cr x O 3 ) solid solutions took place. The Chromium Pigment 341 compositions were estimated from plots of lattice parameter values versus compositions of mixed crystals. The solid solutions were examined in order to test their suitability as pigments in comparison with the well-known green chromium oxide pigments. They showed a high degree of stability towards water, organic solvents, acids, alkalis, light and heat and had in addition reasonable hiding power. Their good properties indicate that they can be used as satisfactory pigments for coating applications [53]. The presence of these hexavalent chromium compounds was verified by the presence of a charge transfer band in the UV region in addition to the presence of characteristic vibrational bands in the IR region. The chromates and dichromates are converted into definite solid solutions of Cr 2 O 3 in A1 2 O 3 and vice versa on heating above ca. 480°C. The composition of such crystalline solid solutions is estimated from the plot of lattice parameter values versus composition of Al x Cr 2−x O 3 mixed crystals [54-56]. Thermal decomposition of aluminium nitrate and chromium nitrate was carried out. The decomposition products of these salts at 250, 350, 500, 750 and 1000 ° C were characterized by means of chemical analysis, IR, diffuse reflectance and X-ray diffraction. The same studies were also carried out on three mixtures of aluminium and chromium nitrates with molar ratios 3 :1, 1:1 and 1:3, where two intermediates were produced from each mixture in the temperature range 375–475 °C. These were AlCrO 3 Al(OH)CrO 4 , Al 2 O 3 Al 3 (OH) 7 CrO 4 Al 0.67 Cr 1.33 O 3 Al 2 (CrO 4 ) 2 Cr 2 O 7 , Al 2 (OH) 4 CrO 4 Al 1.33 Cr 0.67 O 3 Cr 2 (CrO 4 ) 2 Cr 2 O 7 , AlCrO 3 Al (OH)CrO 4 .The dichromates or chromates with an Al/Cr ratio of less than 1 are transformed to corresponding solid solutions of Al 2 O 3 , in Cr 2 O 3 at about 500 °C, whereas those with an Al/Cr ratio of more than 1 are transformed to solid solutions of Cr 2 O 3 in Al 2 O 3 at temperatures above 750 °C. The corresponding solid solutions of the above-mentioned dichromates and chromates are (Al 0.5 Cr 0.5 ) 2 O 3 , (Al 0.83 Cr 0.17 ) 2 O 3 (Al 0.33 Cr 0.67 ) 2 O 3 , (Al 0.67 Cr 0.67 ) 2 O 3 (Al 0.17 Cr 0.832 O 3 , (Al 0.5 Cr 0.5 ) 2 O 3 [57]. TOXICITY OF CHROMIUM COMPOUNDS Chromium (Cr)-doped materials have been widely investigated as ceramic pigments. Malayaite pigment chemical formula (CaSnSiO 5 ) is one of the important red pigments used in the ceramic and polymer industries. These industries use Cr ions as the active chromosphere agent. (1) Cr(VI) is recognized as a carcinogenic and mutagenic agent. In addition, Cr(VI) leads to liver damage, pulmonary congestion, and causes skin irritation, resulting in ulcer formation. Because of its high toxicity (acute and chronic) and carcinogenicity, Cr (VI) needs to be controlled. Cr-containing waste is recycled as a secondary raw material in the ceramic industry, which could help reduce the quantity. In the literature, many solutions are indicated for reuse of the wastewater; most of them are the preparations of green chromium oxide (Cr 2 O 3 ) and lead chromate (PbCrO 4 ) [58]. The toxicity associated chromium (VI) is mainly due to generation of reactive oxygen species (ROS) with subsequent oxidative deterioration of biological macromolecules. Both nickel and chromium can generate free radicals (FR) directly from molecular oxygen in a two step process to produce superoxide anion and in continued process, produce highly toxic 34 hy an be cy m w ye C so by ap ce fr cy so ch re gr pr ce ag as ch pl pa to st ch ch ph th on br m so ge ch 24 re in H da ch 42 ydroxyl radic ntioxidant enz Also they eing always th ytotoxicity, ch more than the without metabo ellow and ch Cr(VI) pigment oluble Cr(VI) y decreased c pply to the cy ells. The activ requency of S ytotoxicity of oluble Cr(III) hromium accu emains firmly rowth medium robably bound ell membrane greement with ssays in bacte hromium carc Hexavalent laying an imp articulate Cr(V o induce tumo tudy shows th hromosome da hromate-induc hosphorylated he cells. In add nly observed reaks observe mechanisms of Lead chrom o in humans. enotoxicity is hromosomes o 4-h exposure. educed surviva nduced a dose HFF cells exhib amage observ hromatids [62 Mohammad al. The pro-o zymes and dep differentially he most affect hromite is part poorly solubl olizing cell c hromite, but s ts. When BHK to Cr(III) by c cytotoxicity. T ytotoxic effect vity of chromit CE, is due to Cr(III), much than with th umulated in th bound to the m. Chromium d to the cell m and reduced i h those obtain ria and carcin inogenisis is p t chromium C portant role in VI) compound ors in experim hat zinc chrom amage and DN ced breaks, M d, indicating th dition, our dat in the G2/M ed in G1 an f zinc chromat mates are resp It induces ne s unknown. E of Chinese ham At 0.4 μg/cm al of CHO cel e-dependent 4 bited higher se ved for both ce ].To test for p d Fikry Ragai F oxidative effec plete intracellu inhibit macro ted. Among C ticularly activ e Cr(VI) com cultures, solub significant am K cells are tre cell metabolite The same dif ts on mitosis te, the only Cr o contaminatio h higher chrom he same con he cells durin e cells, even w m accumulated membrane, wh in the cell nuc ed with the sa nogenicity test proposed. Cr(VI) is a re n its carcinoge d, has been sho mental anima mate induced NA double str MRE11 expre hat the DNA ta show that z phase popula nd S phase c e toxicity and piratory carcin eoplastic trans Examination t mster ovary (C m 2 , 0.8 μ/cm 2 lls to 86%, 62% 4–19-fold incr ensitivity in bo ell types was particle dissolu Fouda, Hanan cts are compo ular glutathion omolecular sy Cr (III) compo e, and inhibits mpounds. Prein bilizes consid mounts are als eated with suc es is seen with fferences betw of HEp cells r(III) pigment on with solubl mium levels ar ncentrations o ng treatments when they are d in the cells ereas some of cleus. The res ame Cr(VI) an ts in rodents. A espiratory tox enic potential own to be carc ls, but its gen concentration rand breaks in ession was in double strand zinc chromat ation, with no cells. These carcinogenes nogens in expe sformation in the effect of CHO) and hum 2 , 2 μg/cm 2 a %, 2% and < rease in the p oth cytotoxicit primarily ach ution effects, n.F.Abdel-Hali ounded by fa ne [59,60]. yntheses in B ounds, which s cell growth a ncubation in g erable amoun so obtained fr h preincubate h all Cr(VI) co ween Cr(VI) s and the clas capable of sig le Cr(VI). In re detected in f soluble Cr( with Cr(VI) e incubated fo after treatme f the Cr(VI) is ults of the pre nd Cr(III) com A re-evaluatio xicant and car . Zinc chrom cinogenic in e notoxicity is n-dependent in n human lung c ncreased and d break repair te -induced do o significant a data will aid is [61]. erimental anim cultured cell lead chrom man foreskin and 8 μg/cm 2 1% respective ercent metaph ty and clastog hromatic lesio CHO cells we im et al. ct that they a BKH cells, tha generally hav and DNA syn growth mediu nts of Cr(VI) from the mos d solutions, re ompounds, ac and Cr(III) c togenic effect gnificantly inc contrast to th the cells incu (VI). 50% an and Cr(III) re or up to 48 h ent with Cr(II s transported t esent investiga mpounds in mu on of the mec rcinogen, with mate a water in epidemiology poorly under ncreases in cy cells. In respo ATM and A r system was ouble strand b amount of dou d in understa mals and susp s but the mec mate on the in fibroblasts (H lead chromat ely. These con hases with da genicity. The s ns affecting o ere treated for also inhibit at of DNA ve very low thesis even um, with or from zinc t insoluble eduction of ccompanied compounds ts on CHO creasing the e very low ubated with nd 75% of espectively h in normal II) is most through the ation are in utagenicity hanisms of h solubility nsoluble or studies and rstood. Our ytotoxicity, onse to zinc ATR were initiated in breaks were uble strand anding the ected to be chanism of ntegrity of HFF) after a te particles ncentrations amage. The spectrum of one or both r 24 h with ei cl pa di co in fo ch C so hu ab su is C th ge in cr da ab in re ro pr ad ce m m ca as re nm de ex w (R of in ch w m ither clarified larified mediu articles for 2 issolution into onsistent with nternalization or lead chroma Lead chro hromatid exch CHO cells, po olubility of le uman lympho berrations wer However,C urvival signali s metabolically Cr(IV), and Cr( he cell membr enetic damage ntracellular re rosslinks, oxi amage induce berrant cell nstability, infl esponsible for ole in Cr(VI) rogression is a dvantages, and ells. This revi mechanisms in mechanisms in ascades in resp There is an sThe capacity eaction was de m. At stoichio ependent on th xcess of GSH were required RBC) with an f the original ncubated with Sephadex G hromate ( 51 Cr( was bound to molecular fract medium that um that had b 24 h. No dam o ionic lead h a previous of the particle ate induced ca mate caused hange in hum ossibly due to ad chromate i ocytes appear re induced by Cr(VI)-induced ing pathways. y reduced by (III). Cr(III) h rane, thereby t e leading to g duction of Cr dized bases, ed by Cr(VI) cycle checkp lammatory re r the balance o ) carcinogene a result of con d ultimately le ew is based o ncluding Cr(V n survival afte ponse to Cr(V n intracellular of glutathione etermined spec ometric condit he solution's p H (100- or 100 to reduce 1 excess of of N amount. This 62 mM diethy G-100 chroma (VI)) showed hemoglobin tions. Howev Chrom t had been in been pre-cond mage was det and chromate s study in w es. These resu arcinogenesis [ dose-related man lymphocyt o the relative in tissue cultu rs to be entir potassium chr d inflammato Cr(VI) enter agents includ has a weak mem trapping it wit genomic insta r(VI) include abasic sites, can lead to points, dysre sponses, and of cell surviva esis. Several nsecutive gene ead to the con on studies that VI)-induced d er chromium VI) genotoxicit r redox pathw e (GSH) to red ctrophotometr tions (molar ra pH. It was mu 00-fold) accel molecule of Na 2 CrO 4 (10 m depletion of ylmaleate (DE atography of ly a strong affin whilst only er, incubation mium Pigmen ncubated for 2 ditioned by C tected in thes e did not con which scanni ults suggest th [63]. increases in tes. No increa e insensitivity ure medium. T rely due to t romate but not ory/immunolo s the cell thro ding ascorbate mbrane perme thin the cell w ability. Struct DNA adduct and DNA in dysfunctional gulated DNA the disruptio al and cell de lines of evid etic/epigenetic nversion of no t provide a gl death-resistanc exposure, and ty. way in the met duce Cr(VI) to rically by follo atio Cr(VI)/G uch slower at p erated the rea chromate. I mM) decrease GSH was sim EM), a well kn ysates from hu nity of 51 Cr for minor amoun ns of prepared nt 24 h with lead HO cells trea se cells, indic ntribute to th ing electron hat clastogenes chromosome ase in DNA d y of the CHO The mutageni the chromate t lead chloride ogical respon ough non-spec e, glutathione eability capaci where it can bi tural genetic l ts, DNA-stran nter- and intr l DNA replic A repair me on of key reg eath, which m dence have in changes that ormal human c impse into Cr ce, the involv d the activatio tabolism of th o Cr(III) in vit owing the abs SH of 1:3) the pH 7.4 than at action. In any Incubation of d the GSH co milar to that ob nown GSH dep uman RBC in r hemoglobin: nts of 51 Cr w d lysates (as d chromate p ated with lead cating that ex he genotoxicit micrographs sis may be a m e aberration damage was o O cells and t city of lead c ion since ch e [64]. nses, and alt cific anion cha , and cysteine ity and is unab ind to DNA an lesions produc nd breaks, DN rastrand cross cation and tra chanisms, m gulatory gene ay all play an ndicated that provide cellul cells to malign r(VI) carcinog vement of D on of surviva he carcinogen tro was investi orption of Cr( e reduction w t pH values be case, 3 GSH f human red b ontent of the ce btained when pleting agent. ncubated with 97% of the ap were found in opposed to in 343 particles, or d chromate xtracellular ty. This is illustrated mechanism and sister- observed in the limited hromate in hromosome teration of annels, and e to Cr(V), ble to cross nd produce ced by the NA-protein slinks. The anscription, microsatelite e networks n important neoplastic lar survival nant cancer genicity via DNA repair al signaling chromate igated. The (VI0 at 370 was strongly elow 5. An molecules blood cells ells to 10% RBC were radioactive pplied dose n the low- ntact cells) 34 w (p re m po fl ac sh PI nu ph in va as co ru ch an So co ox is gr in by so of ox m a ox sk [1 [2 A 44 with 10 mM N probably GSH eduction of Cr metal. The toxic olyrhiza by m uorescence tr ccording to th how a decreas I ABS , which is umber of ac hotochemistry nto the electro aries within pl s a decrease i omplex [65]. B unny nose, no hromium (VI) nd even death ome people ar onsisting of se Cr (VI) is n xidizing agent The main r s Cr (V). Chro rowths. In the n small quantit y a tissue, the ome of the fin During the f the relatively Animal stu xidation state man and labora correlation be xidant directly kin surface is d 1] J. L. Mor 2] P. R. Gra Use", Iron A. H. Sully- Mohammad Na 2 51 CrO 4 ma H-Cr-complexe r(VI) to Cr(III effects of Cr means of the c ransients wer he JIP-test wh se in yield for s the combinat ctive reaction y ( Po ) and (3 on transport ch lant populatio in the number Breathing high sebleeds, and ) can cause sto h. Skin contac re extremely s evere redness a not a very stab t (therefore ve reason why Cr ome (V) is a k body, the acid ties of Cr (V) e Cr (V) will p e capillaries in passage out, y safe Cr (III) udies also sho is very toxic atory animals etween exposu y on the skin damaged. rning, Chromiu abfield, "Chrom n and Steel M and E. A. Bra d Fikry Ragai F arkedly raised es), probably I), the latter be have been st chlorophyll a re recorded i hich can quan r primary pho tion of the ind n centers pe 3) efficiency w hain (ψ 0 ), dec ns. The main r of active rea h levels of chr ulcers and ho omach upsets ct with certain sensitive to ch and swelling o ble state when ery fast in reac r (VI) is so to known carcino dity and action . However, as pass out. The n the kidneys, Cr (VI) will c and complete w that Cr (VI by the oral r [67]. Studies o ure to Cr (VI) surface or it REF um, U. S. Bur me Ore Sourc Metallurgy, 197 andes, Chromiu Fouda, Hanan the chromium indicative of eing regarded tudied on the (Chl a) fluor in vivo with tify the photo otochemistry, dexes of three er absorption with which a t creased due to targets of Cr, action centers romium (VI) c oles in the nas and ulcers, c n chromium (V hromium (VI) of the skin hav n compared to cting, unlike C oxic is that one ogen and will n of enzymes s the size of th only place wh intestines or l continue to ox ly unsafe Cr ( I) is generally route. Chromi of workers in and lung canc can be absorb FERENCES r. Mines Rpt. M ces and Availa 75, 16-26; 197 um, Plenum P n.F.Abdel-Hali m content of f a role of G as the ultima e photosynthet rescence trans high time r osystem II beh Po . The perf e independent (RC/ABS), trapped excito o Cr treatment according to t s and damage can cause irrita sal septum. Ing convulsions, k VI) compound or chromium ve been noted. o Cr (III). The Cr (III) and like e of the reduc lodge in any t on Cr (VI) wi his is normally here the Cr (V lungs. xidize anything (V) behind [66 y more toxic t um(VI) cause the chrome pi cer [68]. Chro bed through th S MCP-1,1977. ability with Em 75, 27-35. Publ. Corp. Ne im et al. low-molecula GSH in the in ately toxic spe tic activity of sient O-J-I-P. resolution and havior. Cr tre formance inde parameters, ( (2) yield o on can move a t. Chromate the JIP-test, ca to the oxyge ation to the no gesting large a kidney and liv ds can cause s m (III). Allergi . e Cr (VI) is a v ely to form co ction products tissue to form ill promote the y too large to V) is likely to g it can, leavin 6]. than Cr (III), es hepatotoxic igment industr omium (VI) ca he skin, espec mphasis on Me ew York, 2nd ar fractions ntra-cellular cies of this f Spirodela The Chl a d analyzed ated plants ex of PSII, 1) the total of primary an electron sensitivity an be listed en-evolving ose, such as amounts of er damage, skin ulcers. ic reactions very strong omplexes). of Cr (VI) m cancerous e formation be adopted lodge is in ng deposits but neither city in both ry revealed an act as an cially if the etallurgical ed., 1967 . Chromium Pigment 345 B. L. Rollinson, The Chemistry of Chromium, Molybdenum and Tungsten, 21, Pergamon Texts in Inorganic Chemistry ,1975. [3] O. Kirk, Encyclopedia of Chemical Technology, 3rd ed., part 6 John Wiley& sons. New York, 1979. [4] W. H. Hartford, Chromium, in A. J. Bard, ed.. Applied Electrochemistry of the Elements, Marcel Dekker, New York, Oct. 1977 . [5] F. A. Loewenheim and M. R. Moran Faith, Keys, and dark's Industrial Chemicals. 4th ed., Wiley-mterscience, New York, 716-721,1975 . [6] T. C. Patton, Pigment Handbook, 1, Wiley-mterscience, New York, 1947 . [7] C. H. Love, Important Inorganic Pigments, Hobart, Washington, D. C.1947 . [8] Inorganic Chemicals, Report M28A (76)-14, U. S. Bureau of the Census, Washington, D. C. (1977) . [9] Ref.9.pp., 357-389. [10] W. H. Hartford in F. D. Snell and L. C. Ettre, eds., Encyclopedia of Industrial Chemical Analysis, part 17, John Wiley & sons. New York, 197- 201,1973 . [11] Ref 9, pp., 351-357. [12] Ref.9, pp., 843-861. [13] R. A. Smith, Quo Vadis Chromium, Producers Council of Canada, Toronto, (copies available from Allied Chemical Corp.) Syracuse, New York, (1976). [14] R.I. Lazău, Cornelia Păcurariu , D. Becherescu and R. Ianoş. Ceramic pigments with chromium content from leather wastes .J. of the European Ceramic Society 2007, 27, 1899-1903. [15] M. J. Udy, Chromium, Chemistry of chromium and its compounds, vol 1, Reinhold Publishing Co., New York, pp., 283-301, 1956 . [16] H. A. Lubs, The Chemistry of Synthetic Dyes and Pigments, Robert E. Krieger Publishing Co., Huntington, N. Y., pp. 153, 160, 161, 247, 258, 261, 284, 426, (1972). [17] Brown spinel pigments based on zinc chromite, method of their production and use [18] United States Patent 5254162 [19] R. F. Her, Wemer-type chromium complexes. U. S. 2,683, 1954.156 . [20] T. S. Reid, Chromium coordination complexes of saturated perfluoromono- carboxylic acids. U. S. 2,662,835, 1953. [21] Ernst and Ernst, Proc. Am. Wood Preservers Assoc. 73, 186,1977. [22] Ref. 18, pp.283-422. [23] Chemical Sources USA, Directories Publishing Co., Flemington, N. J., 1977. [24] Chemical Week 1979 Buyers'Guide Issue, McGraw-Hul, New York, 1978. [25] 1976-1977 OPD Chemical Buyers' Directory, SchneU Publishing Co., New York, (1976). [26] M.F.Fouda,R.S.Amin and S.A.Moustafa,E.A.Yousseff and A.Ismail;Preparation and Characterization of Chromites As Safe Pigments Suitable For Practical Applications,To be published elsewhere. [27] Combustion and Flame. Rubies and Spinels As Chromium Coloring, Materials, 1970, 14,73-83. [28] P.,Nathawan; VS.,Darshane . Structural, Transport, magnetic and infrared studies of the oxidic spinels Co 2-X Ti 1-X Fe 2X O 4 . Journal of Physics. 1988, 21,3191-3203. Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al. 346 [29] VM.,Vlasenko; VL.,Chernobrivets. Methane chlorination on spinel copper-chromium catalyst in the presence of oxygen. Russian Journal of Applies Chemistry. 1998; 71,1393-1396. [30] E.,Erran; F.,Trifino; A.,Vaccari ; M.,Richter . Structure and reactivity of Zn-Cr mixed oxides Role of non-stoichiometry in the catalytic synthesis of methanol. Catalysis Letter. 1989, 3,65-72. [31] MSC., Câmara; PN., Lisboa-Filho; MD., Cabrelon; L., Gama; WA., Ortiz; CO., Paiva- Santos; ER., Leite; et al. Synthesis and characterization of Li 2 ZnTi 3 O 8 spinel using the modified polymeric precursor method. Materials Chemistry and Physics. 2003, 82,68- 72. [32] McClure D. The distribution of transition metal action in spinels. Journal of Physical Chemistry Solids. 1957, 3,311-317. [33] Roy S, Ghose J. Synthesis and studies on some cooper chromite spinel oxide composites. Materials Research Bulletin. 1999, 34,1179-1186. [34] Jendrzejewska I. Influence of nickel substitution on the crystal structure of CuCr 2 Se 4 . Journal of Alloys Compounds. 2000, 305.90-92. [35] I.,O., Kozlowska ; J.,Kopyczok; HD.,Lutz; TH.,Stingl. Single-crystal structure refinement os spinel-type CuCr 2 Se 4 . Acta Crystallographica Section C - Crystal Structure Communications. 1993, 49,1448-1449. [36] Preudhomme J, Tarte P. Infrared studies of spinels-III. The normal II-III spinels. Spectrochimica Acta Part A: Molecular Spectroscopy. 1971, 27,1817-1835. [37] S.,Chokkaram ; R.,Srinivasan;,DR., Milbrun ; HB.,Davis .Conversion of 2-octanol over nickel-alumina, cobalt-alumina, and alumina catalysts. Journal of Molecular Catalysis A: Chemical. 1997, 121,157-169. [38] M P .,Pechini. US Patent. 3330697, 1967. [39] PA .,Lessing .Mixed-cation powders via polymeric precursors. American Society Ceramic Bulletin. 1989, 68,1002-1007. [40] HD., Lutz; G.,Waschenbach; G.,Khiche; H., Hacuseler . Latice vibration-spectra .33. far-infrared reflection spectra, to and lo phonon frequencies, optical and dielectric- constants, and effective charges of the spinel-type compounds MnCr254, FeCr254, CoCr254, ZnCr254, CdCr254, HgCr254, ZnCr25E4, CdCr25E4, HgCr25E4, MnIn254, FeIn254, CoIn254, NiIn254, CdIn254, HgIn254. Journal of Solid State Chemistry. 1983, 48,196-208 . [41] D.,Basak; J ,Ghose. Infrared studies on some substituted copper chromite spinels. Spectrochimica Acta Part A: Molecular Spectroscopy. 1994, 50,713-718. [42] P. A. Lewis. Pigment Handbook, John Wiley & Sons, New York 1988, 2nd Edition, Volume 1, 777-784. [43] E., Ozel and S., Turan. Production and characterisation of iron-chromium pigments and their interactions with transparent glazes . Journal of the European Ceramic Society, 23, 2003, 2097-2104 . [44] Á. G. De la Torre; M. A. G. Aranda ; L., León-Reina; J. Pérez.International Journal of Applied Ceramic Technology Ceramic Pigments and the European REACH Legislation: Black Fe 2 O 3 –Cr 2 O 3 , a Case Study.2010 [45] S., H., Murdock ;R., A., Eppler. Zinc Iron Chromite Pigments. J. American Ceramic Society. 1988 71,212–214. [4 [4 [4 [4 [5 [5 [5 [5 [5 [5 [5 [5 [5 [6 46] Preparatio States Pa 47] Brown sp United St 48] Pigment red reflec 49] Brown sp .United S 50] K.,MASA Pigment 2000,108 51] K.,T., Ja MgO-Al 2 metallurg 52] M. F. R. character Pigments 53] M.F.R. F of reacti different hexavalen Agency f 88/10, 19 54] EPA web 1998. 55] M. F. R character temperatu 56] Z., Le; P malayaite PAPER)( 57] Al Ame. Possible 2009, 2 ,4 58] P., T. LaP Paint Par A., L., Ho S. Jeevar chromoso and Appl 60] [62] J.J. Thallium human ex in the ch 1988, 71, on of a mixed tent 4643772. pinel pigment tates Patent 52 consisting of ctance gray vin pinel pigment States Patent 5 AHIRO;U.,HI by Substituti 8,478-481. acob ;C.K.,Be 2 O 3 -Cr 2 O 3 at gy and materia Fouda ; R. S. rization of (Al s. 1991, 15,299 Fouda, R.S. Am on products temperatures nt chromium. for Toxic Sub 989. bsite. Toxicol R. Fouda, R rization of re ures, Thermoc P., Zhenbang; e pigments fr (Report) Journ A Comprehen Antioxidant 43 -50. Puma; J., M., rticles .Regula olmes ;J. L. Y rajan; W., T., ome instability lied Pharmaco McAughey, A m: Toxicity, E xposure. Biolo hromate pigm , 317-322. Chrom d-phase pigme ts based on z 254162. a mixture of c nyl compositio ts based on z 254162. DERO;T., MI ion of Ti for ehera. Spinel- 1473 K. Me als processing, . Amin;M. A. l 1−x Cr x ) 2 O 3 sol 9-306. min and M.M. of aluminium s. Thermochi . CAS No. 1 bstances, U.S logical U.S. E R. S. Amin eaction produ chimica Acta. ; Y., Chao; T from wastewa nal of the Air & nsive Review (Allium Sativ Fox and E., C atory Toxicolo Young ;Q., Qin Wallace; D., y and DNA do ology, 2009, 23 A.M. Samuel, Environmental ogical indicat ment producti mium Pigmen ent based on ir zinc chromite, chromium oxi on. United Sta zinc chromite INORU.Color r Sn. Journal corundum eq etallurgical an , Science 2000 Abd El-Ghaf lid solutions a . Selim. Therm m hydroxyace mica Acta. 18540-29-9, T S. Public Hea Environmental and M. M. ucts of al-nitr 1989, 141, 27 T., Xike; Z., ater containin & Waste Man w on Nickel ( vum Linn) D C. Kimmel. Ch ogy and Pharm n ;K., Joyce; S Hammond an ouble strand br 34, 293-299 . P.J. Baxter a l and Health or Biological ion industry. nt ron oxide and method of th ide and iron o ates Patent 462 ,method of th r Modification l of the Cera quilibria and a nd materials t 0, 31, 1323-1 ffar . Preparati as inorganic gr mal and spectr etate-chromium 1989,144, 1 Toxicological lth Service, R l Protection A Selim. Ther rate-Cr-nitrate 77-291. Suxin.Synthes ng low chrom nagement Asso (II) And Chr efenses.Kusal hromate Conc macology, 200 S. C., Pelsue ;C nd J. P. Wise reaks in huma and N.J. Smit Impact, and monitoring o Science of T chromium ox heir productio oxide useful in 24710. heir productio n of Chromium amic Society activities in t transactions. B 332 . ion and physic reen pigments roscopic chara m nitrate inte 141-150. [55] Profile for C Report No. A Agency,Washi rmal and spe e interaction sis of Chrom mium(VI).(TE ociation, 2010 romium VI T l K.Das. en J centration Bia 01,33, 343-34 C., Peng ;S.,S . Zinc chroma an lung cells .T h. Lead, Chro Regulation S of occupationa The Total En 347 xide United on and use n high infra on and use m-Tin Pink of Japan. the system B, Process cochemical s. Dyes and acterization eraction at ]review of Chromium. ATSDR/TP- ington DC, ectroscopic at various mium-doped CHNICAL . Toxicities – J Med Sci. s in Primer 49. H., Xie; S., Wise ;A. ate induces Toxicology omium and Sources of al exposure nvironment, Mohammad Fikry Ragai Fouda, Hanan.F.Abdel-Halim et al. 348 [61] J., Wise; J., Leonard and S., R. Patierno. Clastogenicity of lead chromate particles in hamster and human cells. Mutation Research/Genetic Toxicology, 1992, 278, 69-79 .G., R. Douglas; R.D.L. Bell; C.E. Grant; J.M. Wytsma and K.C. Bora. Mutation Research/Genetic Toxicology, 1980, 77,157-163. [63] Effect of lead chromate on chromosome aberration, sister-chromatid exchange and DNA damage in mammalian cells in vitro. K.,J. Appenroth, J. Stöckel, A. Srivastava and R. J. Strasser. Environmental Pollution, 2001, 115, 49-64 . [65] Multiple effects of chromate on the photosynthetic apparatus of Spirodela polyrhiza as probed by OJIP chlorophyll a fluorescence measurements. Combustion and Flame. 1970,14, , 3-83. [67] P .,Nettesheim; Jr.,Hanna; DG.,Doherty ; RF.,Newell; A.,Hellman .Effect of calcium chromate dust, influenza virus, and 100 R whole-body X-radiation on lung tumor incidence in mice. J Natl Cancer Inst. 1971, 47, 1129-1138. [68] R ,Frentzel-Beyme. Lung cancer mortality of workers employed in chromate pigment factories. A multicentric European epidemiological study. J Cancer Res Clin Oncol,1983. 105, 183-188. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 9 TRANSITION METALS: BIOINORGANIC AND REDOX REACTIONS IN BIOLOGICAL SYSTEMS Marisa G. Repetto 1 * and Alberto Boveris 2 1 General and Inorganic Chemistry 2 Laboratory of Free Radical Biology (PRALIB; UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina ABSTRACT Transition metals are elements located in the middle section of the periodic table within groups 3 and 12 that have incomplete inner electron shells and are, in terms of the outermost electron shell, intermediate between the most and the least electropositive in the series of elements. All the transition metals have certain properties in common: they have a partially filled d-shell, as elements and in their compounds, except Zinc (Zn); they are all metals, malleable and ductile; they have high melting and boiling points; and their ions form complexes and colored compounds (except scandium, and Zn) with various coordination numbers and geometries. These elements have more than one electron shell capable of acting with different oxidation numbers, they can accept or give various numbers of electrons per atom. This wealth of electron mobility is highly effective in conducting electricity, so transition metals are good conductors either as pure metal or as alloys. Physically mixed with silica, transition metals generate semiconductors, the essential part of transistors and chips. Due to their strong atom bonding, these metals are useful in metallurgy for their ductility and malleability and in industrial catalysis, where the transition metals participate with their mobile electrons in the reaction without affecting the metal lattice. A limited amount of transition metals is present in biological organisms, where they are part of essential and vital proteins and enzyme active centers. In this way, small amounts of the transition metals constitute minerals necessary for life. The more important processes and reactions in mammals derived directly from their aerobic life, i. e., oxygen transport in blood, cellular respiration and inactivation of the * Corresponding Author: Prof. Dr. Marisa G. Repetto. Department of General and Inorganic Chemistry. School of Pharmacy and Biochemistry. University of Buenos Aires. Junin 956. Buenos Aires 1113AAD, Argentina.TEL: 54-11-4964-8249; FAX: 54-11-4508-3653; E-mail:
[email protected] Marisa G. Repetto and Alberto Boveris 350 radical superoxide and hydrogen peroxide, occur at transition-metal centers. However, transition metals became toxic to cells at elevated tissue concentrations. The understanding of the metabolism of oxygen free radicals in mammalian cells has shown that transition metals, notably iron (Fe) and copper (Cu), and in a lower proportion Chromium and vanadium, undergo redox cycling, involving the Fenton-like production of superoxide anion, hydrogen peroxide and hydroxyl radicals, while cadmium, mercury, and nickel deplete the endogenous cytosolic antioxidants, reduced glutathione and protein-bound sulphydryl groups, resulting in both cases in toxicity of the transition metals. The cytoxicity of the transition metals is currently explained by the sequential stages of reversible oxidative stress and irreversible oxidative damage. Oxidative breakdown of biological phospholipids and protein macromolecules occurs in most cellular membranes including mitochondria, microsomes, peroxisomes and plasma membrane. The toxicity of transition metals in mammals generally involves neurotoxicity, hepatotoxicity and nephrotoxicity. Specific differences in the toxicities of metal ions derive from the differences in chemical properties, electronic configuration and oxidation-reduction potentials. The two more important redox-active biometals, Fe and Cu, promote lipid peroxidation by hydrogen peroxide decomposition and direct homolysis of endogenous hydroperoxides. The understanding of the effects of transition metal ions on biomolecules is relevant to prevent oxidative damage and toxicity in biological systems. In this chapter, we highlight the current understanding and some of the new insights into bioinorganic chemical reactions and into the functions and toxicity of transition metals. INTRODUCTION The transition metals are the group of metals in the middle section of the Periodic Table of Elements, in groups 3 to 12. They are considered as divided in three groups: the first row, the second row and the third row transition metals. There are in total 38 transition metals, including such common metals as iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), silver (Ag), gold (Au), and mercury (Hg). These metals have similar chemical properties, easily alloy with other metals, and have useful properties for metallurgy and industrial catalysis [1-4] (Figure 1). Figure 1. Transition metals’ classification in the Periodic Table. Elements in white background are trace and essential elements, necessary for living organisms; in dark gray, very toxic elements; in intermediate gray, moderate toxic; in clear gray, low toxic; and in black, radioactive elements. Transition Metals 351 Due to their malleability and ductility, conductive electrical properties, and catalytic properties, transition metals are used in building construction, as electricity conductors, and as industrial catalysts. TRANSITION METALS: PHYSICAL PROPERTIES AND USES Transition metals have useful structural properties. Elements such as Cu and Fe can be bent into different shapes, while remaining strong enough to support significant weights. This makes the transition metals good to be used in building and appliance construction. The bonding of the atoms in the metal lattice is very strong in transition metals. As a result, transition metals are strong metals, with high melting and boiling points, and high density. Well-known and representative transition metals are Fe, Cu, Ag, Au and Hg [1]. The ease of bending and the property of stretching without breaking are advantages of transition metals. These metals are known for being ductile (they can be stretched) and malleable (they can be hammered into various shapes) [1]. Transition metals are commonly used to create alloys, which are combinations of metals and/or non-metallic substances. Many well-known substances are alloys made of transition metals. Fe is combined with carbon and a variety of other substances to make steel, and the inclusion of chromium (Cr) makes it stainless steel. Cu makes up several well-known alloys: it is mixed with Zn to create brass, combined with tin to form bronze and mixed with Ni to form cupro-Ni, which is often made into coins [2]. Transition metals have a wealth of electrons in inner electron layers that are also incomplete, in such way that the atoms easily take or release a number of electrons per atom. The easy electron mobility in transition metals is the property that gives the basis for their two main uses: electricity and heat conductors and industrial catalysts. Transition metals such as Cu, Zn and Au can be stretched out into wires to transmit electricity. Conducting wires in the power lines are commonly made of Cu. Additionally, many light bulbs have filaments made of tungsten, which has a very high melting point [3]. Three transition metals, in particular Fe, cobalt (Co) and Ni, are capable of producing a magnetic field; the metals and their compounds are paramagnetic; and they are affected by magnetic fields. Given this versatility, transition metals are used to create materials that are intentionally responsive or unresponsive to magnetic fields. Furthermore, Fe, Co and Ni are used to create ferromagnetic solids, objects that create a magnetic field. Compass needles and bar magnets, for example, are ferromagnetic [4]. Transition metal compounds (often oxides) of Cu, Fe, Cr and Co are used as pigments for artwork; they give bright colors to stained glass and ceramics and pottery glazes. Unlike alkali metals like potassium and sodium, many of the transition metals are not reactive to water or oxygen. When they do form salts, the resulting substance is often colored. The compounds used in making pigments and other coloration involve transition metals oxides and salts. Fe, Cu, Cr and titanium (Ti) are transition metals used widely in the pigmentation of substances, such as foods and artistic supplies. For example, Ni chloride is green, and Ti chloride is purple [2, 3]. Transition metals are widely used in the production of semiconductors. A semiconductor is a material with electrical conductivity due to electron flow (as opposed to ionic conductivity), intermediate in magnitude between that of a conductor and that of an insulator. Marisa G. Repetto and Alberto Boveris 352 They are used for manufacturing modern electronics, including computers, telephones, radio, TV sets and many other devices, such as transistors, solar cells, many kinds of diodes including the light-emitting diode, the silicon controlled rectifier, and digital and analog integrated circuits. Recent studies have increased our understanding of the nanotoxicity of the metal oxide particles used in semiconductor materials. People who work in the production or in recycling computers are at the greatest risk for a toxic exposure to heavy and transition metals, such as lead (Pb), Cr, Cd (Cd) and Hg. The toxic chemicals in computers are linked to many health problems: Hg can cause permanent brain damage, and reproductive and developmental harm; Cd is known to cause cancer. The oxides of the transition metals of the fourth period are widely used in industry and biotechnology. Recent studies and reports indicate that the toxicity of the nanoparticles of these metals is compellingly related to oxidative stress and oxidative damage. The phase of oxidative stress and damage is followed by alteration of calcium (Ca) homeostasis, by inflammatory responses, and by abnormal cellular signaling and gene expression. The precise physicochemical properties that make the toxicity of nanoparticles have yet to be defined, but may include element-specific surface catalytic activity (e.g., metallic or semiconducting properties), and nanoparticle uptake or dissolution. Nanoparticles are frequently applied directly on human body for purposes such as diagnostics. Toxicological literature reveals a trend, including several transition metal oxides (TiO 2 , CuO and ZnO, oxides of Cr, manganese (Mn), Fe, Co, Ni, Cu, and Zn), which are widely used in industry [5]. Some transition metals and transition metal oxides and compounds are used as industrial catalysts to speed up reaction rates. Due to their strong atom bonding, transition metals participate in the catalyzed reactions forming adducts with their mobile electrons without affecting the metal lattice, with catalyst recovered from the process. In the hydrogenation of vegetable oils to turn them into saturated fats (with higher melting point), Ni is used as a catalyst so the hydrogen molecule can effectively join a carbon-carbon double bond [4]. Another example is given by automobiles that have an emissions-control device called a catalytic converter. This device contains a screen of platinum or palladium, along with the metal rhodium. The presence of the transition metal, along with the heat of combustion generated by the automobile engine, causes the exhaust coming from the internal combustion engine to be broken down from partially burned hydrocarbon compounds into less harmful compounds such as water vapor and carbon dioxide [2]. THE ABUNDANCE OF THE FIRST ROW TRANSITION METALS IN THE EARTH’S CRUST Transition metals are present in the solid crust of the planet at significant levels. Fe is the fourth most abundant element in the earth crust (after oxygen, silicon, and aluminium) at 6.2% or 62000 ppm, making it the commonest transition metal. V and Cr are present at the similar levels of 126 and 122 ppm, respectively. About 19.4 and 9.5 million tonnes are produced annually of Cr and V. Mn is the twelfth most abundant element, and the fourth most abundant transition element at 1060 ppm in the earth crust. Over 300 minerals contain Mn, of which 12 are important commercially. Ni is the seventh most abundant transition metal and twenty-second most abundant element at 99 ppm. Zn is present at 76 ppm, and about six Transition Metals 353 million tonnes are produced each year. Cu is present at 68 ppm in the earth crust and has several important ores, as well as being found native. About eight million tonnes are produced annually. Co is present at 29 ppm and is only the thirtieth most abundant element and apart from scandium (Sc), at 25 ppm, is the most rare of the first row transition elements. Only a few important ores exist, although over 200 Co-containing minerals are known, and about 33,000 tonnes are produced annually. About 30% of this is used to produce chemicals for the ceramic and paint industries [2]. ELECTRONIC CONFIGURATION AND CHEMICAL PROPERTIES OF TRANSITION METALS All the transition metal atoms in a row of the Periodic Table have the same arrangement of electrons in the outer orbital shell of the metal atom, and an inner orbital of the metal atom fills with electrons moving from left to right across the row. The outer orbital is already filled, so the atom adds or loses electrons without greatly changing properties such as atomic radius [2]. The most commonly studied transition metals are the first row transition metals, and their electronic configuration is given in Table 1. Cr and Cu are particularly popular ones, as they do not fill the outer shell in the order one would expect. When forming ions, they all start by losing the 4s electron first, then the 4d electrons. Table 1. Electronic configurations of the transition metals of the first row of the Periodic Table of Elements Name Atomic Number Electronic Configuration Sc Scandium 21 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s 2 , 3d 1 Ti Titanium 22 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s 2 , 3d 2 V Vanadium 23 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s 2 , 3d 3 Cr Chromium 24 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s 1 , 3d 5 Mn Manganese 25 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s 2 , 3d 5 Fe Iron 26 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s 2 , 3d 6 Co Cobalt 27 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s 2 , 3d 7 Ni Nickel 28 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s 2 , 3d 8 Cu Copper 29 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s1, 3d 10 Zn Zinc 30 1s 2 , 2s 2 , 2p 6 , 3s 2 , 3p 6 , 4s 2 , 3d 10 Transition metals are, according to their standard reduction potentials (Table 2), good reducing agents (except Cu). These ions transfer 2 electrons of the subnivel s, and additional electrons of the incomplete subnivel d (Table 1). The standard reduction potential of the first row transition elements is given in Table 2. Marisa G. Repetto and Alberto Boveris 354 Table 2. Standard reduction potentials of the transition metals of the first row of the Periodic Table of Elements (298 K). The ionic aqueous concentrations of ions are 1 M Name E 0 (V) Sc (3+) - 2. 08 Ti (2+) - 1. 63 V (2+) - 1. 18 Cr (2+) - 0. 91 Mn (2+) -1. 19 Fe (2+) - 0. 44 Co (2+) - 0. 28 Ní (2+) - 0. 25 Cu (2+) + 0. 34 Zn (2+) - 0. 76 BIOLOGICAL PROPERTIES OF TRANSITION METALS Twenty-three elements of the Periodic Table are present in the bodies of humans and mammals, have known physiological functions and hence, they can be considered as bioelements. From these bioelements, eleven are classified as trace elements (V, Cr, Mn, Fe, Co, Cu, Zn, molybdenum (Mo), selenium (Se), fluoride (F), iodine (I)) because of their limited quantity in humans and their essentiality for life. Seven of these elements belong to the period 4 of the periodic table (Cr, Mn, Fe, Co, Cu, Zn, Mo), indicating an optimal relationship between nucleus size and electron availability of the elements to interact with bioorganic molecules in living systems (Figure 1). All of these elements are considered as micronutrients, which are needed by the human body in small concentrations (less than 100 mg/day) and are essential components of biological structures [6]. Transition metals of the first row account for a good part of the trace elements, indeed six out of eleven elements, and all of them have known biochemical and physiological functions. Fe plays a decisive role in the most important functions of the aerobic life of mammals and humans participating in oxygen delivery to the tissues by blood haemoglobin, oxygen utilization in cell mitochondria by cytochromes and cytochrome oxidase, and hydrogen peroxide removal by catalase. Fe is found in four classes of proteins: hemoproteins (hemoglobin, myoglobin, cytochromes, catalase), Fe-sulfur enzymes (aconitase, fumarate reductase), proteins for Fe storage and transport (transferrin, lactoferrin, ferritin, hemosiderin), and other enzymes that contain Fe or –Sfe, such as activated NAD(P)H dehydrogenase, succinate dehydrogenase, alcohol dehydrogenase, cyclooxigenases) [7]. Cu is in way similar to Fe, an essential part of the active center of essential enzymes: cytochrome oxidase for cell and tissue respiration and Cu,Zn-superoxide dismutase (Cu,Zn-SOD), where the reversible redox change Cu 2+ - Cu 1+ is the mechanism for the dismutation reaction. Cu has been recognized as necessary for the development of connective tissue, nerve coverings, and bone [8]. Zn is involved in the activity of about 100 enzymes, for example, RNA polymerase, carbonic anhydrase, angiotensin I and superoxide dismutase, in the latter case with a Transition Metals 355 structural role [9]. Manganese is the active redox component of mitochondrial superoxide dismutase (Mn-SOD). It has been associated with bone development and with amino acid, lipid and carbohydrate metabolism [10]. In enzymes, the transition metals participate in catalytic processes as constituents of enzyme active sites; as stabilizers of enzyme tertiary or quaternary structure; or associated in forming complexes with the substrate. Metal cations are effective as intermediates in oxidation-reduction processes by reversible changes in their oxidation state, transferring or receiving electrons to or from the substrate or cofactor [6]. A free radical is “any chemical species capable of independent existence that possesses one or more unpaired electrons” [11]. Stable compounds have even numbers of electrons, paired in orbital with opposite spins, the magnetic fields of which cancel each other out. A free radical has either an odd number of orbital electrons, with one unpaired or pairs of electrons of the same spin isolated singly in separate orbital. The presence of one or more unpaired electrons causes physically that the species is slightly attracted to a magnetic field and chemically that exhibits a high reactivity. Molecular oxygen is, in fact, a biradical, having two unpaired electrons with parallel directions of the spin in these unpaired electrons. Molecular oxygen, in spite of the biradical nature, is quite unreactive and is kwon as a sluggish radical. Cations of the bioelements Cu, Fe and Mn have unpaired electrons that allow their participation in redox reactions involving mostly one electron loss (oxidation) or gain (reduction). This condition would allow classifying these bioelements as free radicals’ however, when the concepts of one unpaired electron and high reactivity are linked, the free radical concept applies to organic molecules and not to metal ions. Most of the toxic effects of these transition metals are related to their capacity of catalyse the initiation of free radical reactions by the decomposition of hydroperoxides, allowing the propagation of free radical chain reactions and tissue damage [6, 11, 12]. The role of the biometal depends on its chemical structure and on the reaction medium: Fe and Cu ions act as pro-oxidants and as antioxidants; Co and Zn are, in general, antioxidants, preventing the catalytic participation of redox metals in free radical reactions, by replacing these metals [6-14]. Other trace transition metals that are important for human physiology are Co (component of cobalamine or vitamin B 12 ) [15], Mo (electron transfer agent in enzymes such as xanthine oxidase and sulphite reductase) [16]; and Cr and V, related to glucose and lipid metabolism and ion pumps [17]. In biological systems, these bioelements are mostly conjugated or bound to proteins forming metalloproteins, or to smaller molecules, such as phosphates, phytates, polyphenols and other chelating compounds [6]. THE TOXIC EFFECTS OF TRANSITION METALS Transition metals at increased levels are clearly toxic and sometimes lethal for biological systems from isolated cells to whole organisms. There are no metabolic pathways for the detoxification of transition metals and it is not easy to establish clear separations among essentially, health benefits and toxicity [6]. The metals Fe and Cu are considered trace elements, and the metals Co and Ni are known as ultra-trace elements, considering their presence in low and very low quantities, Marisa G. Repetto and Alberto Boveris 356 respectively, in humans. The biological activity of these transition metals is associated with the presence of unpaired electrons that favour their participation in redox reactions. They are part of important enzymes involved in vital biological processes. However, these transition metals (Fe, Cu, Co and Ni), as all the other transition metals, become toxic to cells when they reach elevated tissue concentrations, mainly producing cellular oxidative stress and damage [12]. Recent studies have shown that some transition metals, for instance, Fe, Cu, Cr, and V, undergo redox cycling, involving the production of reactive oxygen species (superoxide anion, hydrogen peroxide and hydroxyl radicals), while other metals, for instance, Cd, Hg, and Ni, deplete the cytosolic endogenous antioxidants, such as reduced glutathione and protein-bound sulphydryl groups, resulting in both cases in toxicity of the metals. Irreversible oxidative damage to biological macromolecules, such as proteins, RNA and DNA, and to cellular membranes is considered the mechanism of the cellular and tissue toxicity of the transition metals. In all cases, the irreversible phase of oxidative damage is preceded by the reversible phase of oxidative stress, in the reduction level of key redox pairs (NADH/NAD; NADPH/NADP; GSH/GSSG) is shifted towards oxidation. Some transition metal ions, notably those of Fe and Cu, catalyze Fenton-like reactions with homolysis of the hydroperoxide –O-O- bond and generation of hydroxyl radical (HO . ) especially in the membranes of subcellular fractions, such as mitochondria, microsomes, plasma membranes and peroxisomes. Biological systems have developed proteins that have the ability to recognize and combine with the toxic metal, not allowing it to participate in toxic reactions, with a second function of transporting and delivering it at distance [6, 12]. Concerning transition metal toxicity, there are clear examples and evidences. Fe intoxication produces oxidative damage to biomolecules, cells, tissues and organs. Increased Fe storage has been associated with colorectal cancers in humans, genetic hemochromatosis and hepatocellular tumors [7]. Cu toxicity is associated with liver damage, neurodegenerative disease, and gastrointestinal effects characterized by abdominal pain, cramps, nausea, diarrhea, and vomiting [18]. Zinc toxicity, which includes interference with Cu and Fe status and functions, reduces immune function, promotes neurodegeneration, increases cell hydroperoxide concentrations, and reduces the levels of HDL [19]. Manganese toxicity as been reported in human brains, and as a cause of Parkinson-type syndrome [20]. Metal toxicity is used with chemotherapeutic purposes: the drug cis-Platinum is utilized in treatment of cancer [2]. OXIDATIVE DAMAGE ASSOCIATED WITH TRANSITION METALS The mechanism of biological damaged caused by oxygen free radicals and related species has been the focus of scientific interest for many years [11, 21-34]. The spectrum of reactive oxygen species that are considered responsible for biological toxicity include the intermediates of the partial reduction of oxygen, superoxide radical (O 2 - ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radicals (HO . ), peroxyl radical (ROO . ), the intermediate of lipid peroxidation process, and singlet oxygen ( 1 O 2 ) [12]. Superoxide radical exhibits low chemical reactivity in vitro [11] by itself is not a deleterious agent, but rather serves as a source, through its dismutation product, H 2 O 2 , of secondary highly reactive and toxic species, such as Transition Metals 357 HO . radicals, and even singlet oxygen [27]. Hydroxyl radicals are formed mainly by the Haber-Weiss reaction that implies the homolytic scission of hydrogen peroxide (Eq. 1): O 2 - + H 2 O 2 → O 2 + HO· + HO - (1) However, the in vitro data indicate that this reaction would not proceed significantly in vivo because the rate constant of the reaction is lower than that of the dismutation reaction. Nevertheless, a modification of the Haber-Weiss reaction, as Fenton-like reactions, in which O 2 - and H 2 O 2 are bound to a Fe-hemoprotein and that utilizes the redox cycling ability of Fe to increase the rate of reaction, is more feasible in vivo [11, 27, 30]. This type of reaction mechanism is frequently used to explain the toxic effects of redox-active metals where M (n)+ is usually a transition metal ion. The original Fe-catalyzed Haber-Weiss mechanism has been extended to other transition metals (Fe, Co, Cr, Co and others) as chemical pathways that lead to HO . radical formation (Eq. 2 and 3): M (n) + + O 2 - → M (n-1) + + O 2 (2) M (n-1) + + H 2 O 2 → M (n) + + HO· + HO - (3) The in vivo production of HO· in a Haber-Weiss reaction, with M (n)+ as an ionic form of Fe, Co, Cr, Co, is the current hypothesis in the field [20]. Interestingly, the intracellular concentration of redox active transition metals is either low or negligible: free Fe 2+ is 0. 2 to 0. 5 μM and the pool of free Cu 2+ is about a single ion per cell. However, trace (nM) levels of cellular and circulating active transition metal ions seem enough for the catalysis of a slow Fenton reaction in vivo at the physiological levels of hydrogen peroxide (H 2 O 2 , 0. 1-1. 0 μM) [27]. As said, the Haber-Weiss reaction, a well-known abiotic reaction, affords the current hypotheses in the field [19]. Hydroxyl radical (HO . ) production is the From a molecular point of view hydroxyl radical (HO·) generation, formed from H 2 O 2 and Fe 2+ by the Fenton reaction, has been considered for a long time as the likely rate-limiting step for physiological process of lipid peroxidation [11, 25, 27]. This process involves free radical-mediated reactions, in which the initiation reaction is provided by HO . attack to allylic carbons in unsaturated phospholipids with hydrogen abstraction and generation of alkyl radicals (R . ). The propagation reactions are given by the addition of molecular O 2 to the alkyl and carbon centered free radical (R . ) to form oxyradicals (ROO . ) and the reaction in which ROO . abstract another hydrogen from another allylic carbon, yielding stable hydroperoxide (ROOH) and the R . radical, with the capacity to keep the chain process as long as unsaturated fatty acids and oxygen are present. The stable products of the lipid peroxidation process are the hydroperoxides (ROOH), a series of aldehydes, among them, 4-HO-nonenal and malonaldehyde; this latter, is usually measured by its reaction with thiobarbituric acid (TBARS). The toxicity of the sum of reactive oxygen species comes from their ability to oxidize a large number of cellular constituents, such as phospholipids, proteins and DNA. The role of metal transition ions in promoting lipid peroxidation by H 2 O 2 homolysis has been recently studied in phospatidylcholide and phospatidylserine mixed (PC/PS). Phospholipid oxidation was assessed by TBARS production [12]. The Fe 2+ -H 2 O 2 -mediated lipid peroxidation takes place by a pseudo-second order process, and the Cu 2+ -mediated Marisa G. Repetto and Alberto Boveris 358 process by a pseudo-first order reaction. Co 2+ and Ni 2+ by themselves do not induce lipid peroxidation. Nevertheless, when they are combined with Fe 2+ , a Fe 2+ -H 2 O 2 -mediated lipid peroxidation process is stimulated (Ni) or inhibited (Co) [12]. Iron Fe is the most abundant transition metal in the body (about 4 g in human adults), almost all in the form of hemoproteins and Fe-sulfur centers. Free Fe concentrations are particularly low (0. 2 to 0. 5 μM) [31], mainly as Fe 2+ due to the biological reduction by O 2 - and ascorbic acid [28]. Superoxide radicals are able to reduce the Fe 3+ of ferritin and some Fe-sulphur centres to Fe 2+ , making Fe 2+ readily released [11]. It has been considered for a relatively long time that the main source of HO· formation in aerobic cells is the Fenton reaction (ΔEº = + 0. 307 V), with H 2 O 2 homolyzed and reduced (Eq. 4): Fe 2+ + H 2 O 2 → [Fe(II)H 2 O 2 ] → Fe 3+ + HO - + HO (4) An alternative explanation for the Fenton reaction postulates the formation of an oxidizing Fe(IV) species, as FeO 2+ or Fe(IV)=O. These perferryl intermediates are thought of as powerful oxidants, similar to HO· but distinguishable from it. In the Fenton reaction, HO . derives exclusively from H 2 O 2 and not from H 2 O [35]. Transition metal ions also stimulate Fe 2+ -mediated lipid peroxidation by the reductive cleavage of endogenous lipid hydroperoxides (ROOH) of membrane phospholipids to the corresponding alkoxyl (RO·) and peroxyl (ROO·) radicals in a process that is known as ROOH-dependent lipid peroxidation (Eqs. 5 and 6): Fe 2+ + ROOH → RO· + OH - + Fe 3+ (5) Fe 3+ + ROOH → RO 2 · + H + + Fe 2+ (6) The mechanisms of these two reactions appear to involve the formation of Fe(II)-Fe(III) or Fe(II)-O 2 -Fe(III) complexes with maximal rates of HO· radical formation at a ratio Fe(II)/Fe(III) of 1 [11]. At low level of H 2 O 2 , Fe 2+ induces lipid peroxide decomposition, generating peroxyl and alkoxyl radicals and favouring lipid peroxidation [12]. Copper Cu is an essential element, as it is part of the active center of cytochrome oxidase, the enzyme responsible for O 2 uptake in mammalian cells [27], with a content of about 80 mg in human adults. The Cu + ion is considered an effective catalyst for the Fenton reaction (Eq. 5), and Cu 2+ and Cu + are known for their capacity to decompose organic hydroperoxides (ROOH) to form RO . and ROO· (Eqs. 7 to 9) [11, 12, 36]. Transition Metals 359 Cu + + H 2 O 2 → [Cu(I)-H 2 O 2 ] → Cu 2+ + HO - + HO (7) Cu + + ROOH → RO· + OH - + Cu 2+ (8) Cu 2+ + ROOH → RO 2 · + H + + Cu + (9) Cu + , as well as Fe 2+ promoted lipid peroxidation in phospholipid liposomes by homolysis of H 2 O 2 with HO· generation and by scission of ROOH with RO . and ROO . production and by altering liposome surface structure [12]. The process of lipid peroxidation has been recognized as free radical-mediated and physiologically occurring [11, 27] with the supporting evidence of in situ organ chemiluminescence [37]. The main initiation reaction is understood to be mediated by HO· (Eq. 2) or by a ferryl intermediate, both with the equivalent potential for hydrogen abstraction from an unsaturated fatty acid and formation of an alkyl radical (R·) (Eq. 10): HO· + RH → H 2 O + R (10) The metal ions Fe 2+ and Cu 2+ , which are bound to proteins, are reduced by ion O 2 - , yielding the reduced metal-protein complex. This reduced complex reacts with H 2 O 2 in a Fenton reaction to yield locally the secondary HO· radicals. These HO· radicals react at the specific site with the protein, impairing its activity. In this site-specific mechanism, the O 2 - radical ion plays a dual role: reduction of the protein bound metal ion and production of H 2 O 2 by dismutation [11]. Cu forms high affinity complexes with amino acids, short oligopeptides, and proteins, and the role of Cu, as Cu + -macromolecule complexes in enhancing biological damage has been suggested [38]. Reduced Cu ions in the complex react with H 2 O 2 in a Fenton reaction (Eq. 11): Cu + -protein + H 2 O 2 → [Cu(I)-protein-H 2 O 2 ] → Cu 2+ -protein + HO - + HO (11) The site-specific Fenton mechanism explains the enhancement of biological damage due to transition metal ions by reducing agents [11, 12, 37, 38]. The toxicity of Cu and Fe in biological systems may come clearer by increasing the concentration of the ions and by providing reducing agents (for instance, ascorbate). Recent experiments by the authors (unpublished results) show that the property of Fe 2+ and Cu 2+ of promoting lipid peroxidation, as shown by Figure 2, is reproduced in vivo. The two transition metals, Fe 2+ and Cu 2+ were injected to rats (FeCl 2 , 0. 3-60 mg/kg rat; CuSO 4 , 5- 30 mg/kg rat; i. p.), and in situ liver chemiluminescence was determined after 16 hs. The intensity of surface organ chemiluminescence, expressed as counts/second (cps) indicates and measures the steady-state concentration of 1 O 2 in the organ. For the physiological condition, the measured photon emission corresponds to 10 -16 M 1 O 2 . Singlet oxygen is by-product of lipid peroxidation and its level directly measures the rate of lipid peroxidation. Both transition metal ions were able to increase in situ and in vivo liver chemiluminescence: Fe 2+ by a factor of 4. 9 and Cu 2+ by a factor of 1. 6. These effects depended on the transition metal content of Marisa G. Repetto and Alberto Boveris 360 the organ (Figure3). Thus, the two transition metals increased the physiological rate of lipid peroxidation. Cu and Fe toxicity primarily affect the liver because it is the first site of these metals deposition after they enter the blood. Other organs, notably the brain, are later reached. Figure 2. Phospholipid oxidation and lipid peroxidation (expressed as TBARS) on phospholipid liposomes (0. 5 mg/mL, PC/PS) in the metal and H 2 O 2 -promoted process at different Fe 2+ and Cu 2+ concentrations (H 2 O 2= 10 μM). For statistical analysis, p<0. 05 with respect to control was used. Figure 3. Dependence of the in situ chemiluminecence emission with Fe 2+ and Cu 2+ liver content, after 16 hours of acute treatment with the metal. The data show mean ± SEM. For statistical analysis, p<0.05 with respect to control was used. Transition Metals 361 The spontaneous chemiluminescence of in situ organs provides a quantitative determination of the steady-state concentrations of molecules in excited states, since these molecules give off photons in the process of returning to the ground state. Photons are quantitatively determined at the organ surface by the single photon counting. The spectral analysis of organ chemiluminescence and the effects of trap and quenchers indicate that the light emission from mammalian organ under physiological and in pathological situation of oxidative stress is mainly related to singlet oxygen (dimol emission) and secondarily to excited carbonyl groups [25, 27]. Inactive redox metals, such as Hg and Cd, displace Fe and Cu from their intracellular binding sites and accelerate, in a Fenton reaction, the production of reactive oxygen species. Nickel and Cobalt The divalent cations of Ni and Co are able to promote, similarly to Fe 2+ and Cu 2+ , in the metal-catalyzed peroxidation of cellular phospholipids. Although not clear yet, it is generally considered that Fenton-type reactions may be involved in the toxic effects of these metals in vivo. The oxidative effects are ascribed to the Ni(III)-Ni(II) complex and to the oxene species (NiO) 2+ that are formed at neutral pH [39]. Ni 2+ does not promote lipid peroxidation in the presence of hydroperoxides but it does in the presence of Fe 2+ /H 2 O 2 mixtures, in such conditions is oxidized to Ni 3+ and reduced back to Ni 2+ by cellular reductant as O 2 - , in a Haber/Weiss-type reaction [40, 41]. Co ions, Co 2+ , do not promote phospholipids peroxidation directly and showed an almost negligible pro-oxidant effect in the presence of Fe 2+ /H 2 O 2 . Co 2+ may act as pro-oxidant through its capacity to replace redox-active metals from in their binding sites in hemoproteins. The possibility that Co 2+ -mediated free radical generation contributes to cobalt toxicity was studied by EPR spin trapping, and it was found that O 2 - is formed in the reaction of H 2 O 2 with Co 2+ , a reaction inhibited when Co 2+ was chelated with ADP, EDTA or citrate [26]. The observed effects of Co 2+ and Ni 2+ in vivo are better explained by their structural binding to liposomes and cell surfaces. The current hypothesis is that ions with redox capacity stimulate Fe 2+ -initiated lipid peroxidation, but ions without redox capacity increase Fe 2+ - initiated lipid peroxidation by increasing lipid packing, bringing phospholipid acyl chains closer together, thus favoring the propagation steps of lipid peroxidation [12, 42]. Recent results showed that Co 2+ and Ni 2+ by themselves do not induce lipid peroxidation. Nevertheless, when they are combined with Fe 2+ , Fe 2+ -H 2 O 2 -mediated lipid peroxidation is stimulated in the presence of Ni 2+ and inhibited in the presence of Co 2+ [12]. The concept of oxidative stress describes an imbalance between the physiological rate of oxidant production and the velocity of antioxidant defence system. The whole purpose of the antioxidant defence is the maintenance of biological oxidative damage at a minimum [21-23]. A difference is made between oxidative stress as a reversible situation and oxidative damage as an irreversible situation, but the limit is not clear. The difference is similar to the one between reversible and irreversible cell injury in classic cell pathology [24]. Marisa G. Repetto and Alberto Boveris 362 In free radical-mediated chain reactions, the increase in the steady state concentration of any intermediate species produces: (a) an increase in the reaction rate of all the reactions that are downhill; (b) an increase in the steady state concentrations of all downhill intermediates; and (c) a decrease in the steady state concentration of the antioxidants in the system. An alternative and more chemical definition is the consideration of intracellular oxidative stress as a situation where increases in the steady state concentrations of any intermediate produces an increase in oxidant intermediates, an increase in the chain reaction rate, and a decrease in intracellular antioxidants [23]. A growing body of evidence indicates that transition metal cytotoxicity is likely exerted through oxidative stress and oxidative damage as precursors of cellular damage leading to apoptosis or necrosis [11, 12, 19, 25-28]. The physiological generation of the products of the partial reduction of oxygen, O 2 - and H 2 O 2 , constitute the biological basis of the process of lipid peroxidation in mammalian cells. The lipid peroxidation of membrane phospholipids induced by reactive oxygen species leads to membrane damage and is considered one of important mechanisms for the onset of several pathologies [12]. Oxidative damage and the triggering of oxidant-responsive transcription factors could be involved in the neurotoxicity of certain metals. Zn, Fe and Cu are essentials elements required for the functions of various enzymes and cellular proteins in the central nervous system [11]. High Zn levels in the brain have been implicated in the oxidative damage to cell components, with an effect that is initiated by the increase in intracellular oxidant concentrations. In a second step, the reactive oxygen species trigger redox-sensitive transcription factors involved either in cell proliferation mechanisms or in apoptosis [19]. Even though the mechanism is not elucidated, mitochondria may have a central role in the neuronal death caused by Zn toxicity, enhancing mitochondria O 2 - and H 2 O 2 production that leads to cell death. Apoptotic or necrotic neuronal death will depend on the amount of oxidant generated. Moderate production of oxidants seems to lead to apoptosis while high amounts of oxidants trigger the necrotic pathways [29, 30]. TRANSITION METALS, NEURODEGENERATION AND TUMOR PROMOTION Neurodegeneration and Neurodegenerative Diseases Increasing evidence indicates that multiple biochemical and cellular factors are involved in metal-induced toxicity. Two main mechanisms are currently considered: a Haber-Weiss reaction, likely to be the mechanism for redox active metals; and a depletion of major sulfhydryls, reduced glutathione and protein –SH groups, likely to be the mechanism for the metals that are redox active. The cellular and tisular levels of transition metals are apparently determined by regulatory proteins and metallochaperons that control metal capture, transport and storage. The major consequences of metal dyshomeostasis are mitochondrial dysfunction, oxidative stress, and mitochondrial genomic damage, which enhanced activation of the apoptotic machinery [43]. Transition Metals 363 Oxidative stress and oxidative damage have been reported in familial amyotrophic lateral sclerosis, Alzheimer’s, and Parkinson’s diseases. The series of observed changes include glycation, protein oxidation, lipid peroxidation, depletion of antioxidants, and nucleic acid oxidation [44-49]. There are also consistent observations of the impaired functioning of mitochondrial complex I (NADH CoQ10 reductase), with consequent aggregation and accumulation of α- synuclein [49]. Mitochondria are targets of metal toxicity, and in many cases, a close link between metal-induced oxidative stress and damage and mitochondrial dysfunction has been established [33, 51-53]. The mitochondria of Fe-treated rats show lower respiratory control in association with higher resting (state 4) respiration. The mitochondrial uncoupling elicited by Fe-treatment does not affect neither the phosphorylation efficiency nor ATP levels, indicating a mild degree of uncoupling in Fe overload [54]. Alzheimer’s disease is characterized by a selective loss of neurons in hippocampus and frontal cortex and by the presence of neurofibrillary tangles, neutrophil threads, and β- amyloid peptide (Aβ)-rich senile plaques. The brains of Alzheimer’s-diseased patients are characterized by the accumulation of Fe within senile plaques and neurofibrilary tangles, and also by lowered expression of the transferrin receptor. As a consequence, these brains are subject to high levels of oxidative stress. It has been claimed that Fe promotes Aβ amyloid deposition and affects the enzymatic processing of the amyloid precursor protein [43, 55]. As for Parkinson’s disease, dopaminergic cell loss and disease progression are accompanied by the accumulation of high Fe levels, associated with aggregation of α- synuclein (especially the mutated form found in familial Parkinson’s disease). The Fe accumulation in substantia nigra (with up to 255% increases) results in oxidative stress, oxidative damage, decreased reduced glutathione levels, and increased dopamine neuronal toxicity [43]. The Fe-induced oxidative damage to mitochondria contributes to the cellular death mechanisms, arising from a diminished respiratory chain activity and ATP production. The significant reduction in transferrin levels, observed in patients with Alzheimer’s and Parkinson’s diseases, is a contributory factor to increased Fe concentrations [43, 56]. Increased contents of Cu in the human body, especially in the central nervous system, exert toxic effects with metabolic disturbances. The increased Cu levels have been implicated in many diseases, including microbial infections, cancer and neurodegenerative disorders. These copper metabolism disorders include Menkes and Wilson diseases, and neurodegenerative disorders like familial amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s diseases [43]. The aggregation of Aβ is promoted by Cu, and its neurotoxicity depends on catalytically generated H 2 O 2 by Aβ-Cu complexes. Moreover, the characterization of Cu 2+ interacting with α-synuclein demonstrated that this metal is effective in accelerating protein aggregation at physiologically relevant concentrations without altering the resultant fibrillar structures [43]. The Cu 2+ -complex is reduced by ascorbate, GSH or NADPH and reacts with H 2 O 2 to generate HO . (recognized by immediate amino acid oxidation). Another proposed mechanism is that Aβ aggregation promoted by Cu inhibits cytochrome oxidase α-ketoglutarate dehydrogenase activities in mitochondria. The higher reduction state increases superoxide production through a single-electron transfer to molecular oxygen, particularly at respiratory complex I. Both the Cu deficiency and the Cu Marisa G. Repetto and Alberto Boveris 364 overload are associated with neurodegeneneration and result in oxidative stress and oxidative damage. These effects are associated with mitochondrial dysfunction due to decreased activity of cytochrome c oxidase and to the increased production of reactive oxygen species, which, in turn, triggers mitochondria-mediated apoptotic neurodegeneration [56, 57]. Membrane-bound α-synuclein may play a role in fibril formation. Over expression of α- synuclein impairs mitochondrial function and increases oxidative stress. The prion protein has a neuroprotective function by acting as antiapoptotic factor that inhibits the mitochondria- mediated apoptosis, by preventing the formation of the permeability pore of the inner mitochondrial membrane [43, 50]. Oxidative stress promotes aggregation and accumulation of Aβ and α-synuclein, both characteristics of Alzheimer’s and Parkinson’s diseases, respectively [43, 50]. Oxidative stress and damage induce chemically modified forms of Aβ (generation of soluble covalently-linked oligomers of the protein). Interaction of these oligomers and Cu, further promote the aggregation of Aβ, which is the core component of extracellular amyloid plaques, a central pathological hallmark of Alzheimer’s disease. Cu deregulation is also implicated in the hyperphosphorylation and aggregation of tau, the main component of neurofibrillary tangles, which is also a pathological hallmark of this disease [43, 50-52]. Oxidative damage has been proposed to favour the aggregation of α-synuclein in sporadic Parkinson’s disease. Inhibition of complex I creates an environment of oxidative stress that ultimately leads to aggregation of α-synuclein with the consequent neuronal death. Complex I dysfunction, also called “complex I syndrome” results in complex I inactivation, reduced O 2 uptake and ATP formation, increased O 2 - formation, oxidative stress and lipid peroxidation, events that lead to neuronal depolarisation and contribute to excitotoxic neuronal injury [43, 50, 52]. In the brain, Zn is found at higher concentrations in hippocampus and frontal cortex, with lesser amounts in cerebellum. This metal is associated with glutamate in excitatory neurons. Upon stimulation, glutamate and Zn are released into the synapse, where Zn is thought to play a role in stabilizing the neurotransmitter, reaching high levels at the synaptic area and entering post-synaptic neurons via Ca channels, competing with Ca [58]. Several diseases, such as global ischemia or epilepsy, are related to Zn-mediated neuronal death, and they induce a rapid delivery of Zn from storage vesicles in excitatory pre-synaptic buttons and bounds to metallotionein. The binding of Zn to this enzyme is thought to be one of the most important mechanisms of Zn homeostasis. The mechanism involved in Zn-induced neuronal degeneration is not completely elucidated. Increasing evidence suggests that Zn toxicity induces cell death by impairing mitochondrial function and decreasing cell energy production through different mechanisms: inhibition of the electron transport chain by Zn [59], inhibition of energy production and induction of mitochondrial depolarisation [60], inhibition of the α-ketoglutarate complex of the tricarboxylic cycle in rat liver mitochondria [61], reversible inhibition of electron transport chain at the bc 1 -complex [62], and inhibition of oxygen consumption and reduction of transmembrane potential in brain mitochondria [63]. Neuronal death due to Zn toxicity mainly involves the mobilization and redistribution of this metal located in the brain, rather than a participation of exogenous Zn [43, 58]. Transition Metals 365 In familial amyotrophic lateral sclerosis, the general concept is that upon mutation, SOD 1 (Cu,Zn-SOD) is partially misfolded and binds copper improperly. Inadequately buffered copper ions trigger aberrant metal chemistry leading to oxidative stress and to induction of cell death [48, 64, 65]. Considering the organs affected, the toxicities produced by transition metals are mainly associated with apoptosis and generally involve neurotoxicity, hepatotoxicity, and nephrotoxicity [43]. Tumor Promotion Increased Fe levels promote already-initiated hepatocarcinogenesis, enhance cell proliferation and deplete intracellular antioxidants, such as ubiquinone [29]. Cu toxicity is associated with liver injury by generating reactive oxygen species and causes tumour promotion, possibly by inducing oxidative DNA damage. Oxidative stress- related effects are involved in Cu-induced tumour promotion and Fe-induced enhancement, causing cytokine imbalance and enhanced lipid peroxidation [29]. Many carcinogenic metals, including Cd, Cr, and to a lesser extend Ni, form complexes with thiols preferentially to any other functional group. The proposed mechanisms of carcinogenesis associated with toxic metals involve free radical generation by Fenton-like reactions, metal-induced thiyl radical generation, metal-induced DNA damage and inhibition of DNA repair, and impairment of phosphorylation/desphosphorylation controlled by signal transduction, involving nuclear factor-kappa β, activator protein-1 and mitogen-activated protein kinases [66]. Cr and Cd are well-known carcinogens. Cr is an essential transition metal that reacts with H 2 O 2 and other organic hydroperoxides to form reactive oxygen species. Due to its ability to change oxidation numbers from +2 to +6, Cr has a complex redox chemistry and can participate in a multitude of cellular interactions. Hexavalent Cr (Cr 6+ ) is a potent teratogen and is considered the most carcinogenic form of Cr. The hexavalent form of Cr is a potent inducer of apoptosis. The hexavalent form is easily reduced in cells to the trivalent state by ascorbate, NADPH and GSH; the trivalent form is redox active and able to interact with peroxides. For example, Cr 5+ interacts with H 2 O 2, generating HO . in a Fenton-type reaction [31]. Partially reduced Cr is able to interact with DNA and cellular macromolecules. Cd is frequently associated with lung cancer in humans. Cd is an abundant, non-essential element that increases lipid peroxidation in tissues soon after Cd exposure, but does not appear to generate free radicals by itself [31]. Ni is a long-term recognized human carcinogen that forms compounds with oxidation states –1 to +4, with the prevalent form of +2. The main recognized biochemical effects of Ni 2+ are the interference in DNA repair [66] and the promotion of lipid peroxidation and protein carbonyl formation [63, 66]. CONCLUSION The toxicity of transition metal ions in biological systems is a complex process that involves Haber-Weiss-like production of reactive oxygen species with the participation of redox active metals as Fe, Cu, Cr, and V. However, for redox inactive toxic metals, such as Marisa G. Repetto and Alberto Boveris 366 Cd, Zn, Co, Ni, and Hg, depletion of cells’ major antioxidants, reduced glutathione and protein-bound sulfhydryls provide the molecular mechanism for the overall toxic manifestations. Mounting evidence indicates that multiple mechanisms participate in production of free radicals and reactive oxygen species in the toxicity of transition metals. Concerning the cellular mechanisms for transition metal toxicity, increased production of free radicals, decreased reduced thiol status, increased lipid peroxidation, and impairment of the cellular antioxidant defense systems have been proposed, and it seems that all of them, redox active and inactive metals, participate in the phenomenon. The bulk of the studies on the relationship of transition metals with the protein markers of the most common neurodegenerative diseases strongly support the hypothesis that an aberrant redox reactivity of these metals may be implicated in neuronal death. A tight regulation of neuronal transition metal homeostasis is essential to the integrity of normal brain functions. The understanding of the effects of physiological and pathological levels of transition metal ions on neurons is relevant to prevent oxidative damage in highly sensitive brain areas (hippocampus and frontal cortex). REFERENCES [1] Chang, R. Chemistry. Ninth edition. Mexico: McGraw Hill; 2007. [2] Housecroft, C.E. & Sharpe A.G. Inorganic Chemistry. Second edition. United Kingdom: Pearson Education; 2006. [3] Atkins, P. & Jones, L. Chemical principles. The quest for insights. Third edition. United States, New York: Freemand and CO; 2005. [4] Orgel, L.E. An introduction to transition-metal chemistry. Ligand field theory. Second edition. United Kingdom, London: Methuen and CO; 1975. [5] Wern Huang, Y. Wu, Chi-heng. & Aronstam, R. (2010) Toxicity of transition metal oxide nanoparticles: recent insights from in vitro studies. Materials, 3, 4842-4859. [6] Fraga, C.G. (2005) Relevance, essentially and toxicity of trace elements in human health. Mol Asp Med, 26, 235-244. [7] Fraga, C.G. & Oteiza, P. (2002) Iron toxicity and antioxidant nutrients. Toxicol, 180, 23-32. [8] Vir, S. & Rana, S. (2008) Metals and apoptosis: recent developments. J Trace Elem Med Biol, 22, 262-284. [9] Zago, M. Verstraeten, S. & Oteiza, P. (2000) Zinc in the prevention of Fe 2+ -initiated lipid and protein oxidation. Biol Res, 33,143-150. [10] Davis, C.D. & Greger, J.L. (1992) Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. Am J Clin Nutr, 55, 747-752. [11] Halliwell, B. & Gutteridge, J. (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J, 219, 1-14. [12] Repetto, M.G. Ferrarotti, N.F. & Boveris, A. (2010) The involvement of transition metal ions on iron-dependent lipid peroxidation. Arch Toxicol, 84, 255-262. [13] Oteiza, P.I. Olim, K.L. & Fraga, C.G. (1995) Zinc deficiency causes oxidative damage to proteins, lipids and DNA in rat testes. J Nutr, 123, 823-829. Transition Metals 367 [14] Oteiza, P.I. Clegg, M.S; Zago, M. & Keen, C.L. (2000) Zinc deficiency induces oxidative stress and AP-1 activation in 3T3 cells. Free Radic Biol Med, 28, 1091-1099. [15] Kobayashi, M. & Shimizu, S. (1999) Cobalt proteins. Eur J Biochem, 261, 1-9. [16] Rajagoplan, K.V. (1988) Molybdenum: an essential trace element in human nutrition. Annu Rev Nutr, 8, 401-427. [17] Vincent, J.B. (2004) Recent advances in the nutritional biochemistry of trivalent chromium. Proc Nutr Soc, 63, 41-47. [18] Waggoner, D.J. Bartnikas, T.B. & Gittin, J.D. (1999) The role of copper in neurodegenerative disease. Neurol Dis, 6, 221-230. [19] Oteiza, P.I. Mackenzie, G.G. & Verstraeten, S.V. (2004) Metals in neurodegeneration: involvement of oxidants and oxidant-sensitive transcription factors. Mol Asp Med, 25, 103-115. [20] Auschner, M. (2000) Manganese: brain transport and emerging research needs. Environ Health Perpect, 108, 429-432. [21] Boveris, A. Repetto, M.G. Bustamante, J. Boveris, A.D. & Valdez, L. (2008) The concept of oxidative stress in pathology. In: Alvarez S. & Evelson P. (Eds.), Free Radical Pathophysiology (first edition, 1-17). Kerala, India: Research Signpost. [22] Sies, H. (1991) Oxidative stress: from basic research to clinical application. Am J Med, 91, 31-38. [23] Halliwell, B. & Gutteridge, J. (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J, 219, 1-14. [24] Repetto, M.G. & Ossani, G. (2008) Sequential histopathological and oxidative damage in different organs in choline deficient rats. In: Alvarez S. & Evelson P. (Eds.), Free Radical Pathophysiology (first edition, 433-450). Kerala, India: Research Signpost. [25] Cadenas, E. (1989) Biochemistry of oxygen toxicity. Annu Rev Biochem, 58,79-110. [26] Carter, D. (1995) Oxidation-reduction reactions of metal ions. Environ Health Perspect, 103, 17-20. [27] Chance, B. Sies, H. Boveris, A. (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev, 59,527-605. [28] Fang, Y. Yang, S. & Wu, G. (2002) Free radicals, antioxidants and nutrition. Nutrition, 18, 872-879. [29] Mizukami, S. Ichimura, R. Kemmoci, S. Wang, L. Taniai, E. Mitsumori, K. & Shibutani, M. (2010) Tumor promoting by copper-overloading and its enhancement by excess iron accumulation involving oxidative stress responses in the early stage of a rat two-stage hepatocarcinogenesis model. Chem Bio Int, 185, 189-201. [30] Repetto, M. Ossani, G. Monserrat, A. & Boveris, A. (2010) Oxidative damage: The biochemical mechanism of cellular injury and necrosis in choline deficiency. Exp Mol Pathol, 88, 143-149. [31] Valko, M. Rhodes, C. Moncol, J. Izakovic, M. & Mazur, M. (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact, 160,1- 40. [32] Boveris, A. & Fraga, C. (2004) Oxidative stress in aging and disease. Mol Aspect Med, 25, 1-4. [33] Navarro, A. & Boveris, A. (2004) Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging. Am J Physiol Reg Comp Integr Physiol, 287, 1244-1249. Marisa G. Repetto and Alberto Boveris 368 [34] Ossani, G. Dalghi, M. & Repetto, M.G. (2007) Oxidative damage and lipid peroxidation in the kidney of choline-defficient rats. Front Biosci, 12, 1174-1183. [35] Lloyd, R. Hanna, P. and Mason, R. (1997). The origin of the hydroxyl radical oxygen in the Fenton reaction. Free Radic Biol Med, 22, 885-888. [36] Klotz, O. Kronche, D. Buchczyk, D. & Sies, H. (2003) Role of copper, zinc, selenium and tellurium in the cellular defense against oxidative and nitrosative stress. J Nutr, 133, 1448-1451. [37] Boveris, A. Cadenas, E. Reiter, R. Filipkowski, M. Nakase, Y. & Chance, B. (1980) Organ chemiluminescence: noninvasive assay for oxidative radical reactions. Proc. Natl Acad Sci USA, 177, 347-351. [38] Shinar, E. Navok, T. & Chevion, M. (1983) The analogous mechanisms of enzymatic inactivation induced by ascorbate and superoxide in the presence of copper. J Biol Chem, 25, 14778-14783. [39] Kasprzak, K. Sunderman, F. & Salnikow, K. (2003) Nickel carcinogenesis. Mut Res, 533, 67-97. [40] Krezel, A. & Bal, W. (2004) Studies of Zn (II) and Nickel (II) complexes of GSH, GSSG and their analogs shed more light on their biological relevance. Bioinorg Chem Appl, 2, 293-305. [41] Salnikow, K. & Kasprzak, K. (2005) Ascorbate depletion: a critical step in nickel carcinogenesis. Environ Health Perspect, 113, 577-564. [42] Verstraeten, S. Nogueira, L. Schreier, S. & Oteiza, P. (1997) Effect of trivalent metal ions on phase separation and membrane lipid packing: role in lipid peroxidation. Arch Biochem Biophys, 338, 121-127. [43] Kozlowski, H. Janck-Klos, A. Brasun, J. Gaggelli, E. Valensin D. & Valensin, G. (2009) Copper, iron, and zinc ions homeostasis and their role in neurodegenerative disorders (metal uptake, transport, distribution and regulation). Coord Chem Rev, 253, 2665-2685. [44] Gatto, E. Carreras, M.C. Pargament, G. Reides, C. Repetto, M. G. Llesuy, S. Fernandez Pardal, M. & Poderoso, J. (1996) Neutrophil function nitric oxid and blood oxidative stress in Parkinson’s disease. Mov Disord, 11, 261-267. [45] Famulari, A. Marschoff, E. Llesuy, S. Kohan, S. Serra, J. Dominguez, R. Repetto, M. G. Reides, C. & Sacerdote de Lustig, E. (1996) Antioxidant enzymatic blood profiles associated with risk factors in Alzheimer’s and vascular diseases a predictive assay to differentiate demented subjects and controls. J Neurol Sci, 141, 69-78. [46] Gatto, E. Carreras, C. Pargament, G. Riobó, N. Reides, C. Repetto, M.G. Fernandez Pardal, N. Llesuy, S. & Poderoso, J. (1997) Neutrophyl function nitric oxide and blood oxidative stress in Parkinson’s Disease. Focus Parkinson’s Dis, 9, 12-14. [47] Repetto, M. Reides, C. Evelson, P. Kohan, S. Sacerdote de Lustig, E. & Llesuy, S. (1999) Peripheral markers of oxidative stress in probable Alzheimer’s patients. Eur J Clin Invest, 29, 643-649. [48] Fiszman, M. D´Eigidio, M. Ricart, K. Repetto, M.G. Llesuy, S. Borodinsky, L. Trigo, R. Riedstra, S. Costa, P. Saizar, R. Villa, A. & Sica, R. (2003) Evidence of oxidative stress in Familial Amyloidotic Polyneuropathy Type 1. Arch Neurol, 60, 593-597. [49] Domínguez, R. Marschoff, E. Guareschi, E. Repetto, M.G. Famulari, A. Pagano, M. & Serra, J. (2008) Insulin, glucose and glycated haemoglobin in Alzheimer’s and vascular Transition Metals 369 dementia with and without superimposed Type II diabetes mellitus condition. J Neur Transm, 115, 77-84. [50] Opazo, C. Barría, M.I. Ruiz, F.H. & Inestrosa, N.C. (2003) Copper reduction by copper binding proteins and its relation to neurodegenerative diseases. Biometals, 16, 91-98. [51] Navarro, A. Bández, M. Gómez, C. Sánchez-Pino, M. Repetto, M. & Boveris, A. (2010) Effects of rotenone and pyridaben on complex I electron transfer and on mitochondrial nitric oxide synthase functional activity. J Bioenerg Biomembr, 42, 405- 412. [52] Navarro, A. Boveris, A. Bandez, M.J. Sanchez-Pino, M.J. Gomez, C. Muntane, G. & Ferrer, I. (2009) Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkinson’s disease and in dementia with Lewy bodies. Free Radic Biol Med, 46, 1574-1580. [53] Navarro, A. & Boveris, A. (2009) Brain mitochondrial dysfunction and oxidative damage in Parkinson's disease. J Bioenerg Biomembr, 41, 517-521. [54] Pardo Andreu, G.L. Inada, N.M. Vercesi, A.E. & Curti, C. (2009) Uncoupling and oxidative stress in liver mitochpndria isolated from rats with acute iron overload. Arch Toxicol, 83, 47-53. [55] Wan, L. Nie, G. Zhang, J. Luo, Y. Zhang, P. Zhang, Z. & Zhao, B. (2011) Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease. Free Radic Biol Med, 50, 122- 129. [56] Spencer, W. Jeyabalan, J. Kichambre, S. & Gupta, R. (2011) Oxidatively generated DNA damage after Cu(II) catalysis of dopamine and related catecholamine neurotransmitters and neurotoxins: Role of reactive oxygen species. Free Radic Biol Med, 50, 139-147. [57] Rossi, L. Lombardo, M. Ciriolo, M. & Rotilio, G. (2004). Mitochondrial dysfunction in neurodegenerative diseases associated with Copper imbalance. Neurchem Res, 29, 493- 504. [58] Choi, D.W. & Kob, J.Y. (1999) Zinc and brain injury. Annu Rev Neurosci, 21, 347-375. [59] Dineley, K.E. Votyakova, T.V. & Reynolds, I.J. (2003) Zinc inhibition of cellular energy production: implications for mitochondria and neurodegeneration. J Neurochem, 85, 563-570. [60] Sensi, S.L. Yin, H.Z. Carriedo, S.G. Rao, S.S. & Weiss, J.H. (1999) Preferential Zn 2+ influx through Ca 2+ permeable AMPA/kainite channels triggers prolonged mitochondrial superoxide production. Proc Natl Acad Sci, USA, 96, 2414-2419. [61] Brown, A.M. Cristal, B.S. Effron, M.S. Shestopalov, A.I. Ullucci, P.A. Sep, K.F. Blass, J.P. & Copper, A.J. (2000) Zn 2+ inhibits alpha-ketoglutarate-stimulated mitochondrial respiration and the isolated alpha-ketoglutarate dehydrogenase complex. J Biol Chem, 275, 13441-13447. [62] Lorusso, M. Cocco, T. Sardanelli, A.M. Minuto, M. Bononi, F. & Papa, S. (1991) Interaction of Zn 2+ with the bovine-heart mitochondrial bc1 complex. Eur J Biochem, 197, 555-561. [63] Galaris, D. & Evangelou, A. (2002) The role of oxidative stress in mechanisms of metal-induced carinogenesis. Crit Review Oncol Hematol, 42, 93-103. Marisa G. Repetto and Alberto Boveris 370 [64] Carri, M.T. Ferri, A.B. Cozzolino, M. Calabrese, L. & Rotilio, G. (2003) Neurodegeneration in amyothropic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals. Brain Res Bull, 61, 365-374. [65] Ozcelick, D. & Uzun, H. (2009) Copper intoxication; antioxidant defenses and oxidative damage in rat brain. Biol Trace Elem Res, 127, 45-52. [66] Hartwig, A. Asmuss, M. Ehleben, I. Herzer, U. Kostelac, D. & Pelzer, A. (2002) Interference by toxic metal ions with DNA repair processes and cell cycle control: molecular mechanisms. Environ Health Perspect, 110, 797-799. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 10 HYDRODESULFURIZATION OF DIBENZOTHIOPHENE OVER VARIOUS COMOP/AL 2 O 3 SULFIDE CATALYSTS PREPARED FROM CO AND MO PHOSPHORIC ACIDS Masatoshi Nagai * 1 , Yuki Nakamura 1 and Shoji Kurata 2 1 Graduate School of Bio-applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24 Nakamachi, Koganei, Tokyo, Japan 2 Criminal Investigation Laboratory, Metropolitan Police Department, Chiyoda-ku, Tokyo, Japan ABSTRACT The activities of the CoMoP/Al 2 O 3 catalysts prepared by different preparation methods using Mo and Co phosphoric acids were studied for the hydrodesulfurization (HDS) of dibenzothiophene at 513 K and a total pressure of 2.0 MPa. The sulfided CoMoP/Al 2 O 3 catalyst using the consecutive impregnation method with calcination exhibited a higher conversion (62 % at 7.5 h) than those prepared by seven other methods. The sulfided catalyst is prepared by calcination of the catalyst impregnated with a Co phosphoric acid solution after drying the catalyst impregnated with a Mo phosphoric acid solution on alumina. The sulfided catalysts, made by the drying method after both a consecutive impregnation and simultaneous methods using Co and Mo solutions, was less active than the catalysts with calcination during the HDS. The sulfiding pretreatment of the CoMo phosphorus precursors was more useful for the HDS than the reduction. From the XPS analysis, the catalysts with calcination and subsequent impregnation had the higher ratios of Co/(Co+Mo) and S/(Co+Mo) than those prepared by the other methods. The composition of the active catalyst was CoMo 1.4 S 2.9 P 0.57 (CoMoS 2 ‧Mo 0.4 P 0.57 ) before the reaction probably due to the formation of the CoMoS slab stacking. Keywords: Dibenzothiophene; HDS; Co and Mo Phosphide; XPS * Corresponding author: E-mail address:
[email protected] Masatoshi Nagai, Yuki Nakamura and Shoji Kurata 372 1. INTRODUCTION Hydrodesulfurization (HDS) has been of considerable attention for the past decade to reduce the high sulfur levels to below 10 ppm and is being developed as a deep HDS catalyst. It is generally accepted that the addition of phosphorus promotes the HDS activity of NiMo/Al 2 O 3 during the HDS of dibenzothiophene and 4,6-dimethyldibenzothiophene (4,6DMDBT) due to the stacking formation of the active species [1-3,30,31], formation of strong acid sites [4-8], surface active site distribution [9-12], and decrease in coke formation [13,14]. The addition of 2.7% phosphorus to NiMo/Al 2 O 3 has been reported to cause the formation of a highly dispersed NiPS 3 of NiMo/Al 2 O 3 [15] and of a "Ni-(thio)phosphate phase" [16] of CoNiMo/Al 2 O 3 . For the CoMo catalysts, the phosphorus-doped CoMo catalyst acted as a 3-fold more active catalyst compared to the phosphorus-free CoMo catalyst. The CoMo catalyst prepared using citric acid and phosphoric acid without calcination (only drying) was reported to be very active during the HDS [17]. Furthermore, the cobalt and molybdenum phosphides are reported to be active for the HDS and hydrodenitrogenation [15,18-21]. However, there are few studies regarding the preparation methods of the Co-Mo phosphide from the compounds of Co and Mo containing phosphorous in the starting material and their HDS active catalysts. In this study, the CoMo phosphides supported on alumina were prepared and sulfided using six impregnation methods, such as the consecutive and simultaneous methods of cobalt and molybdenum phosphoric acids and two subsequent procedures of drying and calcination. Two reduced catalysts were prepared. The change in the compositions of the sulfided CoMoP/Al 2 O 3 catalysts before and after the reaction were discussed on the basis of the obtained X-ray photoelectron spectroscopy (XPS) results. 2. EXPERIMENTAL 2.1. Catalyst Preparation A cobalt molybdenum phosphide (mole composition, CoO:MoO 3 :P 2 O 5 = 3.1:17.9:2.7) supported on Al 2 O 3 was prepared using four different successive impregnation methods and two simultaneous solutions methods containing the Co and Mo phosphoric acids (Fig. 1). In the first successive impregnation method (Mo first and Co after), alumina was injected into an aqueous solution of (NH 4 ) 3 PO 4 ⋅12MoO 3 ⋅3H 2 O and dried at 393 K and then oxidized at 773 K for 5 h. An aqueous solution of Co 3 (PO 4 ) 2 ⋅8H 2 O and a 0.1 M HNO 3 solution was added to the solid which was then dried at 393 K (Cat 5) and calcined at 773 K for 5 h (Cat 1). In the second method (Co first and Mo after), alumina was introduced into the aqueous solution of Co 3 (PO 4 ) 2 ⋅8H 2 O and dried at 393 K, then the aqueous solution of (NH 4 ) 3 PO 4 ⋅12MoO 3 ⋅3H 2 O was added to the dried solid. This precursor was dried at 393 K (Cat 6) and calcined at 773 K for 5 h (Cat 2). In the third simultaneous method (Co-impregnation of Co and Mo), the aqueous solutions of (NH 4 ) 3 PO 4 ⋅12MoO 3 ⋅3H 2 O and Co 3 (PO 4 ) 2 ⋅8H 2 O were mixed with Al 2 O 3 , followed by drying at 393 K (Cat 4) and calcining at 773 K for 5 h (Cat 3). The catalysts were pretreated by two presulfidation methods of Cat1-Cat6 and pre-reduction of Cats 1 and 5. For the reduction of the calcined catalysts (Cat 1 and Cat 5 before sulfidation), the catalysts were cooled in a stream of He from 773 to 623 K (Cat 7) or heated from 393 to 623 K in the stream Hydrodesulfurization of Dibenzothiophene … 373 of He (Cat 8). The former catalyst (Cat 7) and the latter (Cat 8) were reduced in a stream of H 2 at 623 K for 3 h. All the catalysts (Cat 1-Cat 6) were sulfided in 10% H 2 S/H 2 at 4 L/h and 623 K for 3 h. In a separate experiment, the Mo compound without phosphorus ((NH 4 ) 6 Mo 7 O 24 ⋅4H 2 O) and phosphoric acid were mixed instead of (NH 4 ) 3 PO 4 ⋅12MoO 3 ⋅3H 2 O and then prepared with alumina compared to the activity of Cat 1. Consecutive and Simultaneous Impregnation Figure 1. Catalyst names based on the consecutive impregnation methods. 2.2. HDS Activity Measurement and Characterization The HDS of dibenzothiophene was carried out using a fixed-bed microreactor, which was packed with1.0 g of the sulfided catalyst, in a high-pressure flow system. The solution of 1.0 wt% dibenzothiophene in xylene was introduced into the reactor at the flow rate of 10 mL/h with flowing hydrogen at 4 L/h, 513 K and a total pressure of 2 MPa. Hydrogen was dried by passing it through a Linde 13X molecular sieve trap. The feed and reaction products were quantitatively analyzed using an FID gas chromatograph with a DB-5 (30 m x 0.248 mm, J&W) capillary culumn. The changes in the surface compositions of the catalysts before and after the reaction were determined using XPS. The catalyst was not exposed to air during the procedure from the catalyst pretreatment to the XPS measurement. The XPS spectra of the Mo 3d , Co 2p , P 2p , and S 2p lines before and after the reaction were obtained using a Shimadzu ESCA 3200 spectrometer with monochromatic MgK α exciting radiation. The binding energy values for MoP dry CoP C alc D r y 6 2 3 K C onsec M oP 1 MoP dry CoP C alc D r y 6 2 3 K C atalyst MoP CoP C alc 2. Sim ultaneous D r y 6 7 3 K ＋ C onsec C oP 1 C onsec C oP 2 Sim ultaneous 3 Sim ultaneous 4 C onsec M oP 2 773 K 773 K 773 K 1. C onsecutive Sulf R e d 6 2 3 K Sulf 623 K 623 K Sulf R e d 6 2 3 K 623 K C at 1 Sulf 623 K Sulf 623 K Sulf 623 K C at 7 C at 5 C at 8 C at 2 C at 6 C at 3 C at 4 Masatoshi Nagai, Yuki Nakamura and Shoji Kurata 374 the catalysts were referenced to the Al 2p line of Al 2 O 3 at 74.7±0.2 eV. The baseline corrections for the Co 2p 3/2 and Mo 3d peaks were carried out using the Shirely method. 3. RESULTS AND DISCUSSION 3.1. Catalyst Preparation The HDS of dibenzothiophene on Cat 1-Cat 6 is shown in Fig. 2. Cat 1 exhibited a conversion of approximately 62% and was similar to or slightly higher than that for Cat 2. The conversion for Cat 5 and Cat 6, dried in spite of the calcination of Cat1 and Cat 2, were 0.38 and 0.3, respectively, and less active than Cat 1 and Cat 2. This result showed that the drying process probably neither fully activated the Mo species to combine the phosphorus with Al 2 O 3 during the incomplete decomposition of (NH 4 ) 3 PO 4 ⋅12MoO 3 ⋅3H 2 O nor decompose Co(PO 4 ) 2 to CoP, Co 2 P or Co with heating [22]. Furthermore, the catalysts from the drying method did not completely form Co and Mo oxides that produced the low active species. The catalysts (Cat 3 and Cat 4) based on the simultaneous method were less active. The Cat 3, based on the simultaneous method, with calcination exhibited a conversion of 15%. The mixture of the aqueous solution of Mo and Co caused the precipitation to form large particles on alumina on heating. The conversion factor for Cat 5 at 7.5 h was the same value (38%) as Cat 4. The catalysts made by the drying method had a middle level of activity between the catalysts formed by the consecutive method with calcination (Cat 1 and Cat 2) and the simultaneous method with calcination (Cat 3). Figure 2. HDS of dibenzothiophene over various 623 K-sulfided CoMoP/Al 2 O 3 catalysts at 513 K and a total pressure of 2.0 MPa. (■) Cat 1, (□) Cat 2, (▲) Cat 3, (△) Cat 4 , (●) Cat 5, and (○) Cat 6. 0 2 4 6 8 10 12 0.0 0.2 0.4 0.6 0.8 1.0 C o n v e r s i o n / - Time on stream / h Hydrodesulfurization of Dibenzothiophene … 375 Table 1. Reaction products and selectivity of the desulfurization and hydrogenation at 8 h Concentration [mmol/L] Selectivity [-] Catalyst BP a Conc. CHB b Conc. THDBT c Conc. BCH d Conc. BP/CHB BP/(THDBT+ CHB+BCH) Cat 1 34.1 3.49 0 0 9.78 9.78 Cat 5 18.2 4.75 0.624 0.224 3.85 3.25 Cat 2 31.6 3.74 0.200 0.150 8.43 7.70 Cat 6 14.7 2.52 0.553 0.117 5.84 4.61 Cat 3 7.26 0.487 0.324 0 14.9 8.95 Cat 4 19.4 2.33 0.440 0.106 8.32 6.74 a Biphenyl, b cyclohexylbenzene, c tetrahydrodibenzothiophene, and d bicyclohexyl. Figure 3. Selectivity of biphenyl to cyclohexylbenzene, tetrahydrodibenzothiophene, and bicyclohexyl. (■) Cat 1, (○) Cat 2, (▲) Cat 5, (△) Cat 6. The selectivities of biphenyl to cyclohexylbenzene, tetrahydrodibenzothiophene, and bicyclohexyl are shown in Table 1 and Fig. 3. No tetrahydrodibenzothiophene and bicyclohexyl were observed for Cat 1, but they were formed at about 0.15 and 0.2 mmol/L for Cat 2. The biphenyl selectivity for Cat 1 and Cat 5 (selectivity for the C-S hydrogenolysis) was higher than those for the Cat 2 and Cat 6 catalysts as shown in Fig. 3. Based on the results, the second impregnation of CoP was preferred to the C-S hydrogenolysis due to the creation of Co on the surface and the binding with the Mo sulfides. Manoli et al. [23] reported that phosphorus modifies the catalytic behavior in several ways; i.e., increases the Mo 4+ abundance [17], increases the number of Lewis acid sites, and subsequent enhancement of the direct desulfurization rate [4]. Although the dried Cat 5 and Cat 6 catalysts exhibited lower activities than Cat 1 and Cat 2, they contained a concentration of tetrahydrodibenzothiophene 0 2 4 6 8 0 3 6 9 12 B P N / ( C H B + T H D B T + B C H ) / - Time on stream / h Masatoshi Nagai, Yuki Nakamura and Shoji Kurata 376 2-3 times higher than that for Cat 2. The drying method before sulfidation promoted the hydrogenation activity of the CoMoP/Al 2 O 3 catalysts. Furthermore, phosphorus addition could promote the hydrogenation pathway of HDS as suggested from the promotion for NiMo/MCM-41 [24]. Although Cat 3 and Cat 4 exhibited a high biphenyl selectivity of 9, it might contain a higher error because of the low conversion (below 20%). The simultaneous mixing of the Co and Mo phosphoric acids likely caused a buildup of the active species or participated with the Mo and Co phosphoric acid particles to form large particles. The effect of the reduction treatment instead of sulfidation was carried out using Cat 7 and Cat 8 reduced at 623 K (Fig. 4). These catalysts were less active at conversions below 18 % after a 3-h run. Although the 623 K-reduced catalyst was the most active of the NiMo phosphorus catalysts reduced at 573-923 K in the dibenzothiophene HDS as reported in a previous paper [25], the sulfided catalyst was more active than the reduced NiMo/Al 2 O 3 catalysts. Tetrahydrodibenzothiophene and bicyclohexyl were scarcely observed. The selectivity of biphenyl to cyclohexylbenzene (approximately 10) for the reduced catalysts was similar to that for the sulfided catalysts, but the conversion for the reduced catalysts was lower than that for the sulfided catalysts. The reduction treatment was not useful for the activity improvement due to the hard sulfidation of the CoP and MoP formed by reduction. The sulfidation treatment should have a good catalyst consisting of a phosphorus containing CoMo catalyst. Figure 4. The effect of the reduction treatment for Cats 1, 2 ,and 3 reduced at 623 K. (■) Cat 7 and (●) Cat 8. 3.2. Difference between Mo Phosphide and Mo with Phosphorus Addition In order to determine the difference in the HDS activity between the Mo compound containing phosphorus ((NH 4 ) 3 PO 4 ⋅12MoO 3 ⋅3H 2 O) and the Mo compound without 0 2 4 6 8 10 12 0.2 0.4 0.6 0.8 1.0 C o n v e r s i o n / - Time on stream / h Hydrodesulfurization of Dibenzothiophene … 377 phosphorus ((NH 4 ) 6 Mo 7 O 24 ⋅4H 2 O) for the preparation procedures of the precursors, the catalyst to which were separately added Mo and phosphorus ((Mo+P)+ Co) was prepared. The separately added-phosphorus catalyst had the same high or slightly higher HDS rate than Cat 1 (Fig. 5A). It appeared that the calcination procedure separated the Mo phosphorus from phosphorous oxide which probably bonded to the alumina. Lewis and Kylk [7] reported that molybdena on P/Al 2 O 3 is more easily sulfided than that on Al 2 O 3 , in particular molybdena bonded to the phosphorus-OH group is readily sulfided [7,8]. Furthermore, Quartararo et al. [6] suggested that the phosphorus addition decreased the activity by the formation of the AlPO 4 or Al 2 (MoO 4 ) 3 , phase, but promoted the activity by the formation of Mo-O-P species in MoP-Al such as heteropolymolybdate species (PMo 12 O 40 3 − ) [26]. Based on this result, the preparation of the catalyst containing both Mo and phosphorus was not related to the HDS activity, but the second impregnation of Co phosphoric acid and calcination is useful for the formation of the active species for HDS. In addition, the biphenyl/cyclohexylbenzene selectivity of Cat 1 had a higher selectivity for biphenyl to cyclohexylbenzene than that for the catalyst prepared without the phosphorus Mo compound (Fig. 5B). Tetrahydrodibenzothiophene and bicyclohexyl were not observed for Cat 1, but were observed for the separately-added phosphorus catalyst. Consequently, the catalyst containing both Mo and phosphorus (Cat 1) preferred the C-S hydrogenolysis selectivity probably due to the formation of sulfided (cobalt-decorated) heteropolymolybdate on the Al 2 O 3 surface. Figure 5A. The HDS for the phosphorus-added catalyst vs. Cat 1. (■) Cat 1 and (●) phosphorus-added ((Mo+P)+Co) catalyst. 0 2 4 6 8 10 12 0.0 0.2 0.4 0.6 0.8 1.0 C o n v e r s i o n / - Time on stream / h Masatoshi Nagai, Yuki Nakamura and Shoji Kurata 378 Figure 5B. The selectivity for biphenyl to cyclohexylbenzene. (■) Cat 1 and (●) phosphorus-added ((Mo+P)+Co) catalyst. 3.3. Composition of the Catalyst by XPS The ratios of Co, sulfur, and phosphorus to (Co and Mo) before and after the reaction are shown in Table 2 and Fig. 6. The catalysts with calcination and the consecutive impregnation (Cat 1 and Cat 2) had the higher ratios of Co/(Co + Mo) and S/(Co + Mo) before and after the reaction. The Co/(Co + Mo) ratios for Cat 1 and Cat 2 were higher than those of Cat 5 and Cat 6. This result indicated that the calcination of the catalysts increased the Co amount on the surface. From the XPS analysis, the presence of phosphorus on the support surface forced the formation of octahedral Co 2+ species and irregular oxide Mo 6+ particles [27] as well as improved the cobalt phase dispersion in the oxide precursor state of the catalyst [28]. Furthermore, the Co/(Co+Mo) ratio after the reaction was higher than that before the reaction. The Co atoms of all the catalysts came to the surface from the inside during the reaction. The catalyst from the second impregnation of CoP contained more phosphorus than the first impregnation of the CoP catalysts before and after the reaction. The gradual decrease in phosphorus is due to the release of phosphorus from the Al 2 O 3 surface at the total pressure of 2.0 MPa and hydrogen flow rate of 4 L/h. Furthermore, Cat 1 and Cat 2, by calcination before sulfidation, exhibited a higher S/(Co+Mo) ratio than Cat 5 and Cat 6 by drying before sulfidation. This is probably because the Co and Mo oxides were more readily sulfided than CoP and MoP. The sulfidation of the cobalt promoted catalysts would increase the extent of stacking of the molybdenum disulfide layers [2,3]. The binding energies of the oxides with alumina were lowered by compensation of the phosphorus bonded with alumina, and 0 2 4 6 8 10 12 0 3 6 9 12 15 B P N / C H B / - Time on stream / h Hydrodesulfurization of Dibenzothiophene … 379 consequently, the Mo oxides were liberated and readily sulfided by hydrogen sulfide. Furthermore, after sulfiding at 623 K, the Co-Mo-S phase is most likely still to be associated with the AlPO 4 species [29]. Mangnus et al. [30] reported that the cobalt sulfide species are formed upon sulfiding of the CoO, Co 3 O 4 , cobalt nitrates or cobalt species surrounded by a small number of phosphates. Co 3 (PO 4 ) 2 8H 2 O is also reported to sulfide to a minor extent below 800 K. The composition of the active Cat 1 was CoMo 1.4 S 2.9 P 0.57 (CoMoS 2 ·Mo 0.4 P 0.57 ). The composition of Cat 1 had decreased Mo, S, and P contents in the catalyst and became CoMo 1.2 S 1.4 P 0.4 after the reaction. Table 2. XPS results for Cats 1, 2, 3 and 4 before and after the reaction Co/(Co+Mo) Mo/(Co+Mo) S/(Co+Mo) P/(Co+Mo) br ar br ar br ar br ar Cat1 a 0.425 0.451 0.575 0.549 1.22 0.746 0.244 0.182 Cat2 a 0.464 0.512 0.536 0.488 1.14 0.964 0.085 0.044 Cat5 b 0.233 0.419 0.767 0.523 0.824 0.791 0.097 0.087 Cat6 b 0.317 0.411 0.683 0.589 0.889 0.787 0.081 0.068 a calcination before sulfidation. b drying before sulfidation. Figure 6 Surface composition of sulfided CoMoP/Al 2 O 3 prepared by the consecutive methods by XPS. ( ) Cat 1 and ( )Cat 2. CONCLUSION The catalysts made by the consecutive impregnation method using Co and Mo phosphoric acids exhibited higher conversion than those made by the other methods. The catalysts with drying after the Co and Mo impregnation and the catalysts prepared by the Co /(Co+Mo) S /(Co+Mo) P /(Co+Mo) 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 Catalyst A t o m i c r a t i o / - Masatoshi Nagai, Yuki Nakamura and Shoji Kurata 380 simultaneous method were less active. From the XPS analysis, the Co/(Co+Mo) ratio after the reaction was higher than that before the reaction. The Co atoms migrated to the surface from the inside during the reaction. The Co and Mo oxides in Cat 1 and Cat 2 with calcination before sulfidation exhibited a high S/(Co+Mo) ratio and were more readily sulfided than CoP and MoP. The catalysts (calcination) made by the second Co impregnation of phosphoric acid had a higher ratio of P/(Co+Mo) than the catalysts prepared by the other methods, resulting in stacking of the CoMoS slabs, which were prepared from the sulfidation of cobalt-decorated heteropolymolybdate species (PMo 12 O 40 3 − ). The catalyst contained CoMo 1.4 S 2.9 P 0.57 before the reaction which was active for dibenzothiophene HDS. REFERENCES [1] D. Ferdous, A. K. Dalai, J. Adjaye, L. Kotlyar, Appl. Catal. A: Gen. 294 (2005) 80. [2] D. Frdous, A. K. Dalai, J. Adjaye, J. Mol. Catal. A: Chem. 234 (2005) 169. [3] M. Villarroel, P. Baeza, F. Gracia, N. Escalona, P. Avila, F. J. Gil-Llambías, Appl. Catal. A: Gen. 364 (2009) 75. [4] D. Ferdous, A. K. Dalai, J. Adjaje, Appl. Catal. A: Gen. 260 (2004) 137, 153. [5] E. J. M. Hensen, V. H. J. de Beer, J. A. R. van Santen J. Catal. 215 (2003) 353. [6] J. Quartararo, J.-P. Amoureux, J. Grimblot, J. Mol. Catal. A: Chem. 162 (2000) 353. [7] J. M. Lewis, R. A. Kydd, J. Catal. 136 (1992) 478. [8] S.M.A.M. Bouwens, J.P.R. Vissers, V.H. J. de Beer, R. Prins, J. Catal. 112 (1988) 401. [9] T. Koranyi, Appl. Catal. A: Gen. 239 (2003) 253. [10] J. M. Lewis, R. A. Kydd, P. M. Boorman, P. H. van Rhyn, Appl. Catal. A: Gen. 84 (1992) 103. [11] S. Sigurdson, V. Sundaramurthy, A. K. Dalai, J. Adjaye, J. Mol. Catal. A: Chem. 291 (2008) 30. [12] S. Eusbouts, J.N.M. van Gestel, J.A.R. van Veen, V.H.J. de Beer, R. Prins, J. Catal. 131 (1991) 412. [13] A. Spojakina, S. Damyanova, L. Petrov, Z. vit, Appl. Catal. 56 (1989) 163. [14] S. K. Maity, G. A. Flores, J. Ancheyta, M. S. Rana, Catal. Today 130 (2008) 374. [15] A. Andreev, Ch. Vladov, L. Prahov, P. Atanasova, Appl. Catal. A: Gen. 108 (1994) L97. [16] M. W. J. Crajé, V. H. J. de Beer, A. M. van der Kraan, Catal. Today 10 (1991) 337. [17] T. Fujkawa, Top. Catal. 52 (2009) 872. [18] S.T. Oyama, J. Catal. 216 (2003) 343. [19] A. W. Burns, K. A. Layman, D. H. Bale, M. E. Bussell, Appl. Catal. A: Gen. 343 (2008) 68. [20] C. Stinner, R. Prins, Th. Weber, J. Catal. 202 (2001) 187;191 (2000)438: [21] F. Sun, W. Wu, Z. Wu, J. Guo, Z. Wei, Y. Yang, Z. Jiang, F. Tian, C. Li, J. Catal. 228 (2004) 298. [22] P. J. Mangnus, J. A. R. van Veen, S. Eijsbouts, V. H. J. de Beer, J. A. Moulijn, Appl. Catal. 61 (1990) 99. [23] J.-M. Manoli, P.Da Costa, M. Brun, M. Vrinat, F. Mauge, C. Potvin, J. Catal. 221 (2004) 365. Hydrodesulfurization of Dibenzothiophene … 381 [24] J. M. Herrera, J. Reyes, P. Roquero, T. Klimova, Microporous Mesoporus Mat. 83 (2005) 283. [25] M. Nagai, T. Fukiage, S. Kurata, Catal. Today 106 (2005) 201. [26] D. Nicosia, R. Prins, J. Catal. 234 (2005) 414. [27] B. Pawelec, T. Halachev, A. Olivas, T. A. Zepeda, Appl. Catal. A: Gen. 348 (2008) 30. [28] S.M.A.M. Bouwens, A.M. van der Kraan, V.H. J. de Beer, R. Prins, J. Catal. 128 (1991) 559. [29] P. J. Mangnux, A.D. van Langeveld, V. H. J. de Beer, J. A. Moulijn, Appl. Catal. 68 (1991) 161. [30] P. J. Mangnux, V. H. J. de Beer, J. A. Moulijn, Appl. Catal. 67 (1990) 119. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 11 MIXED TRANSITION METAL ACETYLIDES WITH DIFFERENT METALS CONNECTED BY CARBON-RICH BRIDGING UNITS: ON THE WAY TO HETERO-MULTIMETALLIC ORGANOMETALLICS * Heinrich Lang † and Alexander Jakob Technische Universität Chemnitz, Fakultät für Naturwissenschaften, Institut für Chemie, Lehrstuhl für Anorganische Chemie, Chemnitz, Germany ABSTRACT The chemistry of mono- and bis(alkynyl) transition metal complexes, modified ferrocenes, functionalized alkynyls, diaminoaryl NCN pincer molecules (NCN = [C6H2(CH2NMe2-2,6)2]-), and 1,4- and 1,3,5-substituted benzene derivatives towards diverse metal fragments will be discussed and serves to understand the manifold and sometimes unexpected reaction behavior of such species. Interesting novel (hetero)bi- to undecametallic compounds with often uncommon structural motifs are formed in which the respective transition metal building blocks are connected by carbon-rich p-conjugated organic and/or inorganic bridging units. The reactions based on the modular molecular “Tinkertoys” approach depend upon the steric and electronic properties of the metal centers and ligands involved, which also will be discussed. The electrochemical behavior of such 1-dimensional molecular wire molecules, coordination polymers, star-like structured and dendritic oriented transition metal systems, respectively, is presented as well. * A version of this chapter also appears in Organometallic Chemistry Research Perspectives, edited by Richard P. Irwin, published by Nova Science Publishers, Inc. It was submitted for appropriate modifications in an effort to encourage wider dissemination of research. † Heinrich Lang: E-mail:
[email protected] Heinrich Lang and Alexander Jakob 384 INTRODUCTION The coordinative and covalent linking of modular constructed transition metal building blocks to generate heteromultimetallic assemblies increasingly gained interest during the last years because such species may offer diverse applications in, for example, the field of electroluminescence, information storage materials and photochemical molecular devices [1]. Also, they are of interest since they may be used as representative model compounds in the fundamental study of electron-transfer and photoinduced energy-transfer processes [1]. One possibility to synthesize such complexes includes the principle of molecular manufacturing [2, 3]. This generally requires the prior preparation of multifunctional organic molecules which allow the stepwise synthesis of multitopic organometallic assemblies. In particular, as different binding sites of the bridging ligands reactive groups such as acetylides, phosphines, N,N,(N)-donor systems (N,N,(N) = bi- or tri-dentate Lewis-base), … can be used to control the synthesis of multimetallic complexes. In this respect, metal-containing alkynyls have been studied extensively due to their rigid structures, their stability and, for example, their rich spectroscopic, photophysical and electrochemical properties [1d, 4]. Examples of such connectivities are 1,4-diethynyl benzene [5, 6], 1,3,5-triethynyl benzene [7, 8], 1-ethynyl- 4diphenylphosphino benzene [9], 5-ethynyl-2,2´-bipyridine [10] and 2,5-bis(alkynyl) thiophenes [11, 12]. Based on these cores mainly homometallic assemblies have been synthesized, while only less is known about heteromultimetallic transition metal species. In context with this background we focuse in this chapter on the synthesis of heterodi- to heterohexametallic transition metal complexes, a hitherto barely explored class of compounds, supported by applying multitopic organometallic and organic building blocks. This article is a continued amendment of recently published reviews in this field of chemistry by one of the authors including recent developments made in organometallic p-tweezer chemistry [13]. Bis(alkynyl) transition metal complexes of type RC=C-[M]-C=CR with [M] = 12 - 16 valence electron complex fragment, R = singly-bonded organic or organometallic group [13, 14], have recently been applied as organometallic bidentate chelating ligands (organometallic p-tweezers) for the stabilization of low-valent metal fragments M'Ln (M' = element of groups 1, 2, 4, or 6 – 12 of the periodic table of the elements; L = neutral or ionic organic or inorganic 2-electron donor ligand; n = 1, 2, 3, 4) [14]. In the thus accessible heterobimetallic {[M](µ-s,p-C=CR)2}M'Ln tweezer molecules the alkynyl groups RC=C act as s-donors to M and as p-donors to M', and hold the metals M (preferentialy an early transition metal atom, such as Ti, Zr or Hf) and M' (vide supra) in close proximity to each other [14]. Synergistic and cooperative effects between M and M' are observed and apparently, these complexes show a versatile reaction chemistry and many applications [14]. Mixed Transition Metal Acetylides with Different Metals Connected … 385 A further extensively investigated chelating ligand in organometallic chemistry is the potentially η3-chelating, monoanionic diaminoaryl pincer molecule NCN (NCN =[C6H3(CH2NMe2-2,6)2]-) [13, 15]. Together with related diphosphino- and disulfido- arylanions many pincer metal complexes are accessible, which possess a remarkable stability, and at the same time show excellent catalytic properties [15]. Recently, this approach could be successfully extended to synthesize pincer main-group element compounds [15]. Functionalized ferrocenes can act as bidentate chelating ligands towards many diverse transition metal and main-group element entities [16]. In addition, the ferrocene moiety is an exceptional building block in the preparation of, for example, multimetallic coordination complexes which provide interesting electronic, optical and/or magnetic properties [17]. Moreover, ferrocenes are very robust materials and show a versatile and interesting redox chemistry associated with, for example, polycarbon or related ligands derived from polyynes, since ferrocenes are excellent organometallic one-electron reservoirs [17]. Although, ferrocene celebrated its 50th anniversary six years ago [18], it still is a fountain of youth for the synthesis of new types of transition metal complexes with specific properties. The concept of “molecular Lego®” was independently established by Michl [2a] and Stoddart [3a]. Individual functionalized inorganic, organic and/or organometallic molecules can be Heinrich Lang and Alexander Jakob 386 considered as modular “Tinkertoys” and can be assembled according to a specific building design to give new complexes with unique chemical head structures. This construction process should be reversible. The thus prepared parts can be maintained until the next “molecular Lego®” process starts anew. Herein we focus in the following on the use of mainly mono and bis(alkynyl) transition metal complexes, ferrocenes, NCN pincer molecules, 1,4-/1,3,5-substituted benzenes, functionalized acetylenes etc. as molecular “Tinkertoys” in the modular synthesis of heteroatomic multinuclear assemblies with up to six different transition metal atoms. (For other organic and/or inorganic connecting units, such as carboxylates, halides and pseudohalides see refs. [13, 15, 18]). In this respect, special attention will be paid to the most recent rersults from our group and others. We hope that we will be able to give new impetus to the path-breaking and rapidly developing field of multiheterometallic organometallic chemistry and applications of the systems. Therefore, this chapter is divided into two sections (i) 102 Heinrich Lang and Alexander Jakob RECENT DEVELOPMENTS IN ORGANOMETALLIC π-TWEEZER CHEMISTRY, and in particular, (ii) MULTIHETEROMETALLIC TRANSITION METAL COMPLEXES. In all organometallic systems different transition metals are spanned by carbon-rich π- conjugated organic and/or inorganic units, allowing (more or less) electronic communication between the metals along the bridging entities. However, clusters, or (linear) transition metal complexes with direct metal-metal interactions will not be considered [19]. RECENT DEVELOPMENTS IN ORGANOMETALLIC π-TWEEZER CHEMISTRY Complexes of type RC≡C-[M]-C≡CR ([M] = 12 – 16 valence electron complex fragment, R = singly-bonded organic or organometallic group) (type A molecule) [14n] with their two alkynyl units act towards different metal fragments as organometallic bidentate chelating ligands, or like the motto “an old principle but a new name” as organometallic π- tweezers to afford heterobimetallic species of type B – G in which the respective metals M and M’ are bridged by alkynyl ligands (Scheme 1) [14n]. The structures adopted by complexes B - G strongly depend on the relative affinity of the metals M and M′ for electron density. If one metal atom (e.g., M) is more electrophilic than the other (M′), then the alkynyl ligands RCβ≡Cα will preferentially bind to M through the α atoms. This results in the formation of type B species in which both alkynyl ligands are σ- bound to M and π-coordinated to the second metal M′. This is the preferred structure for many early-late heterobimetallic complexes [14n]. In most complexes of the latter type, e. g., {[Ti](μ-σ,π-C≡CR)2}M′X ([Ti] = (η5-C5H5)2Ti, (η5-C5H4Me)2Ti, (η5-5H4SiMe3)2Ti, ...; M′= Cu, Ag, Au, ..; X = neutral or ionic inorganic or organic 2-electron donor ligand; M′ = Ni, Co: X = CO, PR3, ...) the metals M′ within the tweezer framework have coordination number 3 and possess a planar environment [14]. Mixed Transition Metal Acetylides with Different Metals Connected … 387 Scheme 1. Interconversion of alkynyl coordination modes in type A – G molecules [14n]. If the metals M and M′ are competitive in their affinities towards the alkynyl ligands RC≡C, or if steric factors prevent the formation of type B tweezer complexes, then structural type C or D species are formed. In these molecules, the ligands RC≡C are more evenly shared, either with both metals, μ-bridged by both alkynyl ligands (type C) or with each metal σ-bonded by one alkynyl unit and π-coordinated to the other (type D) [14]. In view of the fact that the two alkynyl ligands in type B molecules are held in close proximity by [M], coupling reactions between the two RC≡C ligands are possible, forming molecules of type E and G [14f, r, aa]. Steric and electronic effects appear to play an essential role in determining the feasibility of the carbon-carbon bond forming reactions, as small changes in the alkynyl-bonded groups R or in the ancillary ligands of M and M′ can induce or prevent these reactions. The state-of-the-art in the field of organometallic π-tweezer chemistry until 2000 is depicted in Scheme 1. Many examples to date confirm this picture [14n]. While in the beginning of this chemistry we have been increasingly attracted by the use of type A molecules as organometallic chelating ligands [14n], we recently became interested in the application of such systems to study, for example, electron transfer [14i, h, s, v, x], to create Heinrich Lang and Alexander Jakob 388 self-assembled monolayers (SAMs) [20], and to prepare 1-dimensional molecular wire molecules, which can be used in molecular electronics to span metal surfaces/electrodes [20]. Regarding these topics, special attention was drawn to low-valent alkynyl-stabilized organo-copper(I) and -silver(I) compounds in which the respective metals possess a planar surrounding [14]. While the use of alkyne- and alkynyl-stabilized inorganic and organic group-11 metal fragments have lately been reviewed in detail [14], we focus here on recent results obtained in the field of electron transfer. Since the path-breaking and pioneering work of Creutz and Taube in early 1969 [21], there has been a rapidly growing interest in the preparation as well as chemical and physical properties of homo- and heterobimetallic organometallic and metal organic assemblies in which the respective transition metals are connected by organic and/or inorganic (carbonrich) π-conjugated bridging units [22, 23]. As this, many redox-active model compounds have been synthesized, such as (η5-C5H5)(η5-C5H4)Fe-C≡C-Pt(dppe)(R) (1) [22t] (dppe = diphenylphosphino ethane; R = aryl), [(η5-C5H5)Fe(η5-C5H4-C≡C-η5-C5H4)Co(η5- C5H5)]+ (2) [24], trans-(PEt3)2(Ph)Pt-C≡C-C6H4-C≡C-MLn (3a, MLn = Ru(Cl)(Ph2PCH2PPh2)2; 3b, MLn = Ru(η5-C5H5)(PPh3)2, …) [6b], (η5-C5Me5)(dppe)Fe- C≡C-C≡C-Fe(η5-C5Me5)(dppe) (4) [22w, y], and [(η5-C5Me5)(NO)(Ph3P)Re-C≡C- C≡C-C≡Mn(η5-C5H5)(CO)2]+ (5) [23p, 25] in which a molecular wire consisting of an all- carbon C2-, C4- or C5-chain bridges the two metals M and M′ (M/M′ = Fe/Fe, Re/Mn, Fe/Co, Fe/Pt), giving rise to an electronic coupling through three, five or even six bonds. Further examples of molecular wire molecules are, for example, (R′2PCH2CH2PR′2)(RC≡C)Mn-C≡C-C≡C-Mn(C≡CR)(R′2PCH2CH2PR′2) [26] (6) (R = SiEt3, SiiPr3, SitBuMe2; R’ = Me, Et), (η5-C5H4Me) (Me2PCH2CH2PMe2)Mn=C=C=Mn-(Me2PCH2CH2PMe2)(η5-C5H4Me) (7) [27], (η5-C5H5) (NO)(Ph3P)Re-(C≡C)n-Re(η5-C5H4-Me)(NO)(PPh3) (8) (n = 1 – 10) [28], [trans-(R-4- C6H4)(Ph3P)2Pd←N∩N→Pd(PPh3)2(C6H4-4-R)]m+ (9) (N∩N = 4,4'-bipy, C6H4-1,4-(C≡N)2, (C6H4-4-C≡N)2, C5H4N-CH=CH-C6H4-CH=CH-C5H4N, …; R = Me(O)CS, m = 2; R = Ph3P, m = 4) and [(R-4-C6H2(CH2NMe2-2,6)2)Pt←N∩N→Pt(C6H2(CH2NMe2-2,6)2-4-R]2+ (10) [20]. In 10 the group-10 platinum redox termini can be adjusted in variable distances to each other by the connecting entities N∩N [20]. Besides these species, further binuclear assemblies with two different redox sites in close proximity were synthesized containing the cyano acetylide ligand as bridging unit. The isomeric heterobimetallic Fe-Ru complexes (η5-C5H5)(Ph3P)2Ru-C≡C-C≡N-Fe(η5- C5H5)(dppe) (11) and (η5-C5H5)(dppe)Fe-C≡C-C≡N-Ru(η5-C5H5)(PPh3)2 (12) are readily available [29], and the electrochemical response of each complex is characterized by two oxidation waves found at 0.62 and 1.22 V (11) and at 0.66 and 1.37 V (12), respectively [29]. IR spectro-electrochemical investigations of the respective mono cationic species revealed a noteworthy decrease in the energy of the ν(C≡C, C≡N) vibrations, which is consistent with a contribution from the ligand to the redox active orbitals. [29] In addition, a intense NIR band is observed at ν = 9600 cm-1 (ε = 5600 M-1 cm-1) for [(η5-C5H5)(Ph3P)2Ru-C≡C-C≡N- Fe(η5- C5H5)(dppe)]+, while for [(η5-C5H5)(dppe)Fe-C≡C-C≡N-Ru(η5-C5H5)(PPh3)2]+ a band at ν = 9600 cm-1 (ε = 5600 M-1 cm-1) is typical [29]. From oxidation potentials of model alkynyl and cyano complexes featuring the (η5-C5H5)(dppe)Fe and Ru(η5- Mixed Transition Metal Acetylides with Different Metals Connected … 389 C5H5)(PPh3)2 fragments, respectively, it looks like that initial oxidation of these two assemblies takes place at the iron ion [29]. Examples of another type of binuclear compounds are shown in Figure 1. It must be noted that since the first generation of the mixed-valence of diferrocenyl acetylene in 1974 [30], the interest in these sandwich complexes has significantly increased [31], because the ferrocenyl moiety is robust in its neutral and oxidized form. It also was shown that oligoyne and polyyne chains can be stabilized next to the direct linking of sp carbon atoms to the metals (vide supra) by joining the triple-bonded systems to the ligand periphery as typical for the molecules represented in Figure 1. The electrochemical response of these systems has been selectively reported with a focus on the variation of the connecting unit and the nature of the metal groups [32]. There it is found that the doubly bridged diiron species (ΔE = 0.25 V) exhibit two sequential one electron oxidations with greater separation in the E1/2 potentials than the singly bridged analogues [32]. From NIR studies it is assumed that the doubly bridged ferrocenes are more strongly coupled than the singly bridged ones [32]. The binuclear cobalt complex shown in Figure 1 possesses two potentials at 0.846 and 0.947 V in the cyclic voltammogram [33]. Apparently, in the radical cationic state the two cobalt atoms interact via the butadiyne chain. Although the complexes gave no ESR signals, the cyclic voltammetric results are in good agreement with a valence-trapped species. Figure 1. Selected oligometallic complexes featuring acetylide-based connecting ligands [32, 33]. Diethynyl di- and triferrocenyls have also been considered as potential connecting units. [34] Interactions between the remote ferrocenyl redox probes through the Fcn core (n = 1, 2, 3) were investigated [34]. However, it was found that the interpolation of the Fc2 moiety does not impede electronic communication between the two Fc units, although more attention is apparent with the Fc3 entity. This means that the terminal groups and the oligo-ferrocene skeleton act almost independently. For an excellent review on this topic see ref. [29b]. Next to the high variety of late-late transition metal complexes (vide supra), also a number of early-late species, e.g. (η5-C5H5)(Me3P)2Ru-C≡C-Zr(η5-C5H5)2(Cl) (13) are known [23l]. Further examples of this family are depicted in Figure 2. Complexes 14 - 16 are suited to transport electrons along the organic π-system between the redox-active metal termini. Heinrich Lang and Alexander Jakob 390 Figure 2. Organometallic π-tweezer molecules with (benzene tricarbonyl) chromium (14), ferrocenyl (15, 16) and ruthocenyl (15) (redox-active) termini [14n, v, w, aa, 35 - 38]. Cyclic voltammetric studies of 14 show a reversible wave at E0 = -1.6 V (ΔE = 100 mV) which can be assigned to the Ti(IV)/Ti(III) redox couple [35]. For the (η6-C6H5)Cr(CO)3 unit the appearance of irreversible oxidation waves is typical [39]. Replacement of this fragment in 14 by less electron withdrawing groups such as ferrocenyl or ruthocenyl units affords the organometallic π-tweezers [Ti][(C≡C)mMc][(C≡C)nM′c] (15a, m = n = 1, Mc = M′c = Fc; 15b, m = n = 1, Mc = M′c = Rc; 15c, m = n = 2, Mc = M′c = Fc; 15d, [Ti] = (η5- C5H5)2Ti, m = n = 2, Mc = M′c = Fc; 15e, m = n = 2, Mc = Fc, M′c = Rc; 15f, m = 1, n = 2, Mc = M′c = Fc; 15g, m = 1, n = 2, Mc = Rc, M′c = Fc; Fc = (η5-C5H4)Fe(η5-C5H5), Rc = (η5-C5H4)Ru(η5- C5H5)) (Figure 2) [14v, x, aa]. Oxidation of 15 leads to an instantaneously coupling of the acetylide-ferrocenyl or –ruthocenyl entities Mc(C≡C)m and M′c(C≡C)n to give the appropriate all-carbon complexes by an electron transfer from Ti- CC≡C to Mc or M′c across the π- conjugated acetylides (C≡C)m and (C≡C)n, respectively. The oxidatively induced coupling of the Mc(C≡C)m and M′c(C≡C)n moieties is not even averted when the alkynyl ligands in 15 are η2-coordinated to an additional transition metal fragment as given in, i. e., {[Ti](μ-σ,π- C≡CFc)2}CuBr (17) and {[Ti](μ-σ,π- C≡CFc)2}PdPPh3 (18) [14s, ee]. To prevent the metal-carbon cleavage in 15 the titanocene moiety was exchanged by [Pt] since Pt-C bonds are significant more stable than Ti-C ones. In cis-[Pt](C≡CFc)2 (16a, [Pt] = (bipy)Pt; 16b, [Pt] = (Ph3P)2Pt; 16c, [Pt] = (dppf)Pt; 16d, [Pt] = (bipm)Pt; bipy = 2,2'- bipyridine; dppf = 1,1’-bis(diphenylphosphino)ferrocene; bipm = 2,2’-bispyrimidine) a d8- electron configurated and hence, square-planar coordination of the Pt(II) ion is typical, which Mixed Transition Metal Acetylides with Different Metals Connected … 391 contrasts with the tetrahedral surrounding of the titanium(IV) ion in [Ti]. The electrochemical response of 16a and 16b shows two reversible one-electron oxidations centered on the Fc moieties at E0 = -0.1 V (ΔE = 180 mV) and +0.05 V (ΔE = 115 mV) for 16a and E0 = +0.1 V (ΔE = 200 mV) and +0.17 V (ΔE = 200 mV) for 16b. This indicates a moderate electronic interaction between the iron cores through the connecting organic chains and the platinum atom. Nevertheless, the electronic interaction found in 16a and 16b is stronger as in all-carbon Fc-C≡C-C≡C-Fc (ΔE = 100 mV) [37, 38]. Next to the two reversible oxidation processes, irreversible one-electron reductions are found at -1.55 and -2.19 V for 16b and at - 1.46 V for 16a, which can be assigned to the reduction of Pt(II) to Pt(0). The second reduction wave for 16a (Pt(I)/Pt(0)) is covered by the reversible reduction of the 2,2'-bipyridine ligand (bipy/bipy- = -1.78 V (ΔE = 140 mV), bipy-/bipy2- = -2.47 V (ΔE = 180 mV)) [37]. In addition, the electrochemical properties of cis-(dppf)Pt(C≡CFc)2, (16c) [{cis-(dppf)Pt- (C≡CFc)2}CuBr] (19a), and [{cis-(dppf)Pt(C≡CFc)2}AgOClO3] (19b) were investigated [40].Oxidation of 16c gives by an oxidative coupling of the FcC≡C fragments the all-carbon butadiyne FcC≡C-C≡CFc along with [(dppf)Pt]2+ (Figure 3) [40]. Figure 3. Cyclic voltammogram of 16c in dichloromethane at 25 °C, [nBu4N]PF6 supporting electrolyte (0.1 M), scan rate = 100 mV s-1. All potentials are referenced to the FcH/FcH+ redox couple (FcH = (η5-5H5)2Fe) with E0 = 0.00 V (ΔEp = 150 mV) [40]. The oxidatively induced coupling of the FcC≡C units is averted, when the alkynyl ferrocene ligands in 16c are π-bonded to a low-valent CuBr moiety, i.e., [{cis-(dppf)- Pt(C≡CFc)2}CuBr] (19a), which differs from the appropriate titanocene species (vide supra) [40]. When instead of the CuBr moiety the higher homologue of copper is used then again the Heinrich Lang and Alexander Jakob 392 coupling of the FcC≡C ligands takes place. Next to the formation of FcC≡C-C≡CFc the mononuclear cationic platinum compound [(dppf)Pt(L)(OH)]X (L = thf, CH3C≡N; X = Br, ClO4) along with elemental silver was produced. A detailed mechanism for the formation of the latter species is presented in ref. [40]. The higher oxidation potentials for the silver complexes as compared with the copper counter parts suggest that there is less stabilization of the silver in the bis(alkynyl) platinum complexes than in the copper-platinum-iron assemblies [40]. A similar behavior was found for cis-(dppf)Pt(C≡CPh)2 [41]. When the Fc units in 16 and 19 are replaced by Rc moities (Rc = (η5-C5H4)(η5-C5H5)Ru), then more stable compounds are obtained, which most likely is attributed to the higher oxidation potential of the Rc fragments. Extending the idea of connecting early-late and late-late transition metal building blocks from all-carbon to other carbon-rich μ-σ,π-conjugated organic bridging units enables the synthesis of a large variety of further organometallic compounds by applying the modular “Tinkertoy” approach. MULTIHETEROMETALLIC TRANSITION METAL COMPLEXES Within this Section the modular preparation of multimetallic transition metal compounds featuring two, three, four, five, or even six different redox active early and/or late transition metals will be discussed. This idea can be extended even to complexes of higher nuclearity (undecametallic systems) possessing a variety of two, three or four distinct metal atoms. Concertedly for all heteromultimetallic species is that the individual metals are bridged by π- conjugated carbon-rich organic and/or inorganic building blocks. To limit the scope of this article we focus in the following on the synthesis, reaction chemistry, structure and bonding of mainly multimetallic complexes based on mono- and bis(alkynyl) transition metal complexes, functionalized diaminoaryl NCN (NCN = [C6H2(CH2NMe2-2,6)2]-) and NN’N (NN’N = C5H3N(CH2NMe2-2,6)2) pincer molecules, modified ferrocenes as well as 1,4- and 1,3,5-substituted benzenes. (HETERO)BIMETALLIC TRANSITION METAL COMPLEXES Besides early-late organometallic π-tweezer complexes of structural type B (Scheme 1), also titanocene and zirconocene mono-acetylides enable the synthesis of a series of heterobimetallic compounds featuring early-late transition metal atoms [42]. Two selected examples based on a titanocene (η5-C5H4SiMe3)2Ti core are depicted in Figure 4 [44]. Replacement of the C5H4N→{Ru} and C6H4-4-C≡N→{Ru} coordination complex fragments in 20 and 21 by an organometallic sandwich moiety Fc (Fc = (η5-C5H4)(η5- C5H5)Fe) leads to [Ti](CH2SiMe3)(C≡CFc) (22). Compound 22 represents a mixed early-late transition metal molecule with a reasonable electron transfer between the reducible [Ti] and oxidizable Fc groups via a C≡C connecting unit [44, 45]. A further example is (η5- C5H5)2(Me3P)2Ru-C≡C-Zr(η5-C5H5)2(Cl) (13) in which the zirconium(IV) ion is directly linked with a ruthenium(II) fragment by an acetylide unit [46]. Likewise, {Pt}(C≡C-C6H4-4- Mixed Transition Metal Acetylides with Different Metals Connected … 393 C≡N) (23) ({Pt} = (C6H3(CH2NMe2-2,6)2)Pt) can act as starting source for the synthesis of linear heterobimetallic complexes of type {Pt}-C≡C-C6H4-4-C≡N→M'L (24a, M'L = {Pt}BF4; 24b, M'L = {Ru}; 24c, M'L = AuCl) [47]. Figure 4. Complexes 20 (left) and 21 (right) [44]. A series of supplementary heterobimetallic complexes based on Fc moieties is accessible by applying different synthesis methodologies. Sonogashira cross-coupling of ethynylferrocene (26) with 4-bromobenzonitrile or 5-bromo-2,2'-bipyridine afforded Fc- C≡C-C6H4- 4-C≡N (27) and Fc-C≡C-bipy (28), respectively. Treatment of 27 and 28 with {Pt}BF4, {Ru}N≡N{Ru}, (nbd)Mo(CO)4 (nbd = norbornadiene), Mn(CO)5Br, Ru(bipy)2Cl2 or (Et2S)2PtCl2 gave the appropriate binuclear complexes Fc-C≡C-C6H4-4-C≡N→M′L (29a, M′L = {Pt}BF4; 29b, M′L = {Ru}) and Fc-C≡C-bipy(M′L) (30a, M′L = Mo(CO)4; 30b, M′L = Mn(CO)3Br; 30c, M′L = Ru(bipy)2(PF6)2; 30d, M′L = PtCl2) in which a rigid-rod structured alkynyl benzonitrile entity spans the ferrocene and the M′L building blocks [13, 14a, 48]. Heterobimetallic iron-platinum and iron-palladium complexes based on the pincer functionalized ferrocene Fc-NCN (NCN = [4-C6H2(CH2NMe2-2,6)2]-) are available by the synthesis protocol shown in Scheme 3 [49, 50]. Compound 33b possesses the ability to reversibly bind sulfur dioxide and hence, can successfully be used as a gas sensor for the detection of SO2 (Scheme 3) [49, 50]. Related Fc- C≡C-NCNH (35) in which the NCNH and the Fc moieties are separated by an acetylide unit is accessible from FcC≡CH by applying the Sonogashira cross-coupling protocol. Lithiation of 35 and reaction of 35-Li with stoichiometric amounts of [(Et2S)2MCl2] (M = Pd, Pt) produced Fc-C≡C-NCN-MCl (36a, M = Pd; 36b, M = Pt) [49, 50]. The introduction of a PdI unit into ferrocene NCN pincer molecules is realizable by the oxidative addition of the carbon-iodide bond in Fc-NCN-I or Fc-C≡C-NCN-I to palladium (e. g., [Pd2(dba)3], dba = di(benzylidene) acetone). After appropriate work-up, complexes Fc-NCNPdI (33c) and Fc- C≡C-NCN-PdI (35c) could be isolated in good yields. Heinrich Lang and Alexander Jakob 394 Scheme 3. Synthesis of heterobimetallic 33a and 33b and their reaction behavior towards SO2 (formation of 34) [49, 50]. The influence of the connecting alkynyl-aromatic moieties has been considered through electrochemical measurements of closely related complexes (vide supra) with a metal-ligand combination and a range of ethynyl-aromatic bridging entities. (HETERO)TRIMETALLIC TRANSITION METAL COMPLEXES Recent work of our group has been concerned with (hetero)trimetallic complexes derived from organometallic π-tweezers {[Ti](μ-σ,π-C≡CR)2}M′X and {[Pt](μ-σ,π- ≡CR)2}M′X (R = singly-bonded organic or organometallic fragment; M′X = 12 – 14 valence electron transition metal building block; [Pt] = (bipy)Pt, …) (type B molecule) in which the M′X unit is complexed by both alkynyl ligands of the bis(alkynyl) transition metal fragments [Ti](C≡CR)2 and [Pt](C≡CR)2 [14n]. In complexes of type {[Ti](μ-σ,π- C≡CR)2}M′X the chelated metal atoms M′ and the [Ti](C≡CR)2 fragments are coplanar, while in {[Pt](μ-σ,π- C≡CR)2}M′X the M′ center is displaced from the plane defined by the Pt atom and the alkynyl ligands and hence, are non-planar [14n]. Within these studies a closely related series of diverse complexes with interesting properties could be prepared. An approach to transition metal complexes with linear heterotrimetallic assemblies is given by starting from the alkyne-stabilized copper(I) methyl compound {[Ti](μ-σ,π- C≡CR)2}CuCH3 (37a, R = SiMe3; 37b, R = tBu). Reaction of 37a and 37b with equimolar amounts of FcC≡CH produces upon loss of methane the appropriate copper(I) acetylide {[Ti](μ-σ,π-C≡CR)2}CuC≡CFc (38) in which a rigid-rod structured Ti-Cu-C≡C-Fc unit is present [14o]. Compounds similar to 38 can be obtained, when FcC≡CH is reacted with 4- ethynylbenzonitrile or 5-ethynyl-2,2′-bipyridine which contain further N-ligated Mixed Transition Metal Acetylides with Different Metals Connected … 395 sites. Thus formed {[Ti](μ-σ,π-C≡CR)2}CuC≡CR′ (39a, R′ = C6H4-4-C≡N; 39b, R′ = bipy) reacts with, for example, {Ru}N≡N{Ru} ({Ru} = RuCl2(NN′N); NN′N = [C5H3N(CH2NMe2-2,6)2]-) or (nbd)Mo(CO)4 to afford heterotrimetallic 40 (Ti-Cu-Ru) and 41 (Ti-Cu-Mo), respectively, (Figure 5) [14j, 48]. Figure 5. Trimetallic 40 (left) and 41 (right) (R = SiMe3, tBu) [14j, 48]. In 40 and 41 three different transition metals (TiCuRu, TiCuMo) are connected via σ,π- bound acetylides and datively-bound benzonitrile (40) and 2,2′-bipyridine (41) ligands. In 40 a linear Ti-Cu-C≡C-C6H4-C≡N-Ru-NN′N building block is characteristic as evidenced by single X-ray structure analysis [LIT]. A further example of a similar compound is [Ti](μ- σ,π-C≡CSiMe3)2}Cu-C≡N→Cr(CO)5 (42) which is accessible by treatment of the copper(I) cyanide {[Ti](μ-σ,π-C≡CSiMe3)2}CuC≡N (43) with the metal carbonyl Cr(CO)5(thf) in a 1:1 molar ratio [52]. However, the latter molecule could only be characterized spectroscopically, due to its great instability in solution at room temperature. A further effort to include metal atoms within organic connecting moieties is possible by treatment of the early-late titanium-copper and titanium-silver tweezers {[Ti](μ-σ,π- C≡CSi- Me3)2}M′X (44a, M′X = Cu(N≡CMe)BF4; 44b, M′X = AgFBF3) with Ph3PAuC≡N in a 1:1 molar ratio [52]. Complex 44a affords upon elimination of MeC≡N cationic 45 (Figure 6) in which the linear Cu-N≡C-Au-P arrangment is stabilized by the chelating effect of the organometallic π-tweezer [Ti](C≡CSiMe3)2. However, when 44b is reacted with the same gold(I) precursor then heterotrimetallic 46 is obtained (Figure 6) [52]. Figure 6. Complexes 45 (left) and 46 (right) (R = SiMe3) [52]. In 45 the copper(I) ion is tri-coordinate and shows a planar surrounding set-up by the η2- coordinated Ti(C≡CSiMe3)2 unit and the datively-bonded (Ph3P)AuC≡N building block counting to 16-valence electrons at the copper center, while in 46 the coordination number of silver(I) expands to four and an 18-valence electron fragment is formed [52]. Complex 46 displays a non-linear Ti-Ag-N≡C-Au array as required by the pseudo-tetrahedral geometry Heinrich Lang and Alexander Jakob 396 around silver(I). For the different coordination behavior of copper(I) and silver(I) towards Lewis-bases see refs. [14] and [53]. Although the reaction of [M](C≡CR)2 π-tweezers ([M] = [Ti], [Pt]; R = singly-bonded organic or organometallic ligand) with different metal sources in a 1:1 ratio results in the formation of heterobimetallic structural type B complexes (Scheme 1), an interesting class of oligometallic species is produced in a straightforward manner, when two equivalents of the organometallic π-tweezer [M](C≡CR)2 are allowed to react with copper(I) or silver(I) salts [M′X], forming molecules of type [{[M](μ-σ,π-C≡CR)2}2M′]X (47 – 50) (Table 1). In these complexes a single metal M′ (M′ = Cu, Ag) is tetrahedrally coordinated by two organometallic π-tweezer fragments [14]. However, it appeared that the counter-ion X must be a poor ligand, such as BF4 -, ClO4 - and PF6 - to prevent the formation of structural type B molecules. Complexes 47 - 50 are summarized in Table 1. The molecular solid state structures of selected species of multimetallic 47 - 50 were determined by single X-ray structure analysis. The cationic [{[M](μ-σ,π-C≡CR)2}2M′]+ part is set-up by two almost orthogonal positioned bis(alkynyl) transition metal fragments [M](μ- σ,π-C≡CR)2 which are connected by a d10 M′+ metal ion. All four RC≡C ligands are thereby η2-coordinated to M′+ forming a linear M-M′-M assembly. A characteristic feature of complexes 47 – 50 is the non-equivalent linkages of Cα and Cβ to M′ (M-Cα≡Cβ), which is even more pronounced as it is the case in type B molecules [14]. In 49c the copper ion lies only slightly out of the best Pt(C≡CCPh)2 plane to presumably minimize steric interactions between the phenylethynyl ligands and the dppe chelate, in 50b an asymmetric structure is typical, which means that the silver(I) ion is more closely situated to one Pt(C≡CCPh)2 fragment than to the other (Pt(1)–Ag 3.384 Å, Pt(2)–Ag 3.513 Å) [14, 54, 59]. Further possibilities to prepare 49a – 49c are presented in Scheme 4. The reactions shown there are based on the stoichiometry of the reactants cis-[Pt](C≡CPh)2 and [Cu(N≡CMe)4]X (X = BF4, PF6, ClO4) as well as on the temperature and the reaction time (Scheme 4) [14gg, 56, 57, 59]. It was found that, when cis-[Pt](C≡CPh)2 is reacted with [Cu(N≡CMe)4]X in the ratio of 3:2, pentametallic Pt3Cu2 (51) is formed in which three helically arranged cis- [Pt](C≡CPh)2 building blocks are connected by two copper(I) ions. In 51 the two outer [Pt](C≡CPh)2 entities are coordinated by only one copper atom. For this, we reacted 51 with a further type B molecule to obtain even higher oligomeric structures. To our surprise only trimetallic 49 could be isolated. However, treatment of cis-[Pt](C≡CPh)2 with the copper Table 1. Synthesis of Complexes 47 – 50 Compound [M] R M` X Refs. 47a (η5-C5H4SiMe3)2Ti Ph Cu BF4 14d, 87 47b (η5-C5H4SiMe3)2Ti Ph Cu PF6 14d, 87 47c (η5-C5H4SiMe3)2Ti F Cu BF4 14d 48a (η5-C5H4SiMe3)2Ti Ph Ag BF4 14d, 87 48b (η5-C5H4SiMe3)2Ti Ph Ag PF6 14d, 87 48c (η5-C5H4SiMe3)2Ti Ph Ag ClO4 14d, 87 48d (η5-C5H4SiMe3)2Ti Fca) Ag PF6 14w 48e (η5-C5H4SiMe3)2Ti Fca) Ag ClO4 14d 48f (η5-C5H5)2Ti C≡CFca) Ag PF6 14w 48g (η5-C5H4SiMe3)2Ti C≡CFca) Ag PF6 14w 48h (η5-C5H4SiMe3)2Ti Rcb) Ag PF6 14w 49a (bipy)Ptc) Ph Cu BF4 55, 59 49b (bipy`)Ptd) Ph Cu BF4 55, 59 49c (dppe)Pte) Ph Cu BF4 55, 59 49d (bppz)Ptf) SiMe3 Cu BF4 55, 59 49e (bipy)Ptc) Fca) Cu Br 61 49f (bipy)Ptc) Fca) Cu BF4 61 49g (dppf)Ptg) Ph Cu BF4 58 50a (bipy)Ptc) Ph Ag BF4 55, 59 50b (bipy)Ptc) Ph Ag PF6 55, 59 50c (bipy)Ptc) Ph Ag ClO4 55, 59 50d (bipy`)Ptd) Ph Ag BF4 55, 59 50e (bipy`)Ptd) Ph Ag PF6 55, 59 50f (bipy`)Ptd) Ph Ag ClO4 55, 59 50g (bipy)Ptc) Fca) Ag ClO4 61 Table 1. (Continued) Compound [M] R M` X Refs. 50h (bppz)Ptf) SiMe3 Ag ClO4 55, 59 50i (PPh3)2Pt Ph Ag ClO4 54 50j (PEt3)2Pt Ph Ag ClO4 54 50k (dppe)Pte) Ph Ag ClO4 54 50l (PPh3)2Pt t Bu Ag ClO4 54 50m (dppe)Pte) t Bu Ag ClO4 54 50n (dppf)Ptg) Ph Ag BF4 58 a) Fc = (η5-C5H4)Fe(η5-C5H5). b) Rc = (η5-C5H4)Ru(η5-C5H5). c) bipy = 2,2'-bipyridine. d) bipy' = 4,4'- dimethyl-2,2'-bipyridine. e) dppe = 1,2- diphenylphosphinoethane. f) bppz = 2,5-bis(2- pyridyl)pyrazine. g) dppf = 1,1'-bis(diphenylphosphino) ferrocene. Mixed Transition Metal Acetylides with Different Metals Connected … 399 source [Cu(N≡CMe)4]X and using the molar ratio of 2:1 at low temperature gave 52, a compound in which the copper(I) ion is π-bound by one PhC≡C ligand of individual cis- [Pt]C≡CPh)2 units, thus resulting in a linear alkyne-copper-alkyne arrangement (alkyne = midpoint of the C≡C triple bond). This complex can be considered as an intermediate in the formation of 49 (Scheme 4). Slowly warming a tetrahydrofuran solution containing this species to 45 °C, 52 smoothly rearranges via the formation of 53 and 54 to give 55 as evidenced by spectroscopic and single crystal X-ray diffraction studies [14gg, 45, 56 57, 58, 59]. When 49 is further reacted with one equivalent of [Cu(N≡CMe)4]X the incoming Cu(I) adds to the alkynyl ligands of 49 resulting in the formation of 55 (Scheme 4). In 55 two bis(alkynyl) platinum entities are linked by copper(I) ions, whereby two PhC≡C units, one associated with each platinum atom, are π-bonded to the group-11 metal copper. Scheme 4. Reaction chemistry of cis-[Pt](C≡CPh)2 towards [Cu(N≡CMe)4]X; formation of 49 and 51 – 55 [55, 57, 59]. Another possibility to synthesize trimetallic 50a is given by treatment of the platinumsilver species {cis-[Pt]( μ-σ,π-C≡CPh)2}AgFBF3 (56) with stoichiometric amounts of cis- [Pt](C≡CPh)2 as depicted in Scheme 5 [55, 57, 59]. The first step in the preparation of 50a involves the elimination of BF4 - from 56 upon addition of the organometallic chelate cis- [Pt](C≡CPh)2. Initially formed [{cis-[Pt](μ-σ,π- C≡CPh)2}2Ag]BF4 (57) contains two cis- [Pt](C≡CPh)2 moieties which are η2-coordinated to a silver(I) cation by all of the PhC≡C ligands. The two cis-[Pt](C≡CPh)2 units are oriented parallel to the platinum atoms on opposite sites. This complex isomerizes in solution to produce 58 and then 59, which afterward rearranges to give 50a. IR spectroscopic studies Heinrich Lang and Alexander Jakob 400 gave the first hint for the different bonding modes of the alkynyl groups in 56 - 59 and 50a. Additionally, the molecular solid state structures of these species were confirmed by single crystal X-ray structure determinations [14gg, 45, 56, 59]. Scheme 5. Synthesis of 50a by reacting 56 with cis-[Pt]C≡CPh)2 [55, 57, 59]. Trimetallic M2M′ compounds of type (M = Fe, M′ = Hg, Cd, Zn, Pd; M = Pd, Pt, M′ = Fe; …) can be synthesized in a straightforward manner by applying different synthesis methodologies [60, 61]. Treatment of two equivalents of FcC≡CH with mercuric acetate (Hg(OAc)2) in different solvents produced (FcC≡C)2Hg (60) along with acetic acid [60, 61]. The reaction mechanism is discussed in the light of the mercurated and non- mercurated reaction intermediates (depending on the solvents used), involving FcC(O)CH2HgX, FcC(OMe)=CH2, FcC(O)Me, and FcC(OAc)=CH2, whereby X appeared to contain another mercury atom [60a]. For comparison the reaction behavior of ethynylbenzene witht the same mercurating systems has also been investigated [60, 61]. Isostructural (FcC≡C)2M complexes (61, M = Cd; 62, M = Zn) are accessible in a much more straightforward reaction when FcC≡CLi is treated with MCl2 (M = Cd, Zn) in a 2:1 molar ratio [61]. After appropriate work-up, these complexes were obtained in good yield. In the latter molecules group-11 and group-12 transition metal atoms are linking two ferrocene ethynyl building blocks. Electrochemical studies, however, showed that between the FcC≡C units no coupling is observed [61]. A Fe2Pd trinuclear complex of composition [(Fc-C≡C-1-C6H4-4-C≡N)2 Pd(PPh3)2](OTf)2 (63) is available by the reaction of Fc-C≡C-1-C6H4-4-C≡N (64) with Pd(PPh3)2(OTf)2 [62]. Electrochemical studies of 63 showed that only one reversible redox couple is found for the Fc units and hence, no electron transfer via the connecting metal palladium atom takes place. Mixed Transition Metal Acetylides with Different Metals Connected … 401 As shown earlier Fc-NCNH pincer molecules can successfully be used in the synthesis of heterobimetallic complexes. The introduction of a further NCNH unit in Fc-NCNH opens the possibility to prepare the ferrocene-based trimetallic FeM2 complexes 68 and 69 (M = Pd, Pt) by starting from ferrocene 65 (Scheme 6). The reactions shown in Scheme 6 include metallation-transmetallation and oxidative addition processes [49, 63]. Scheme 6. Synthesis of FeM2 complexes 68, 69a and 69b from 65 [49, 63]. Replacing the NCN pincer unit in (η5-C5H4-NCN)2Fe sandwich compounds by diphenyl phosphino coordinating groups allows the synthesis of a series of trimetallic assemblies of structural type (η5-C5H4PPh2MLn)2Fe (MLn = M(CO)5: 70a, M = Cr; 70b, M = Mo; 70c, M = W; 71, MLn = (η6-C6H4-1-iPr-4-Me)RuCl2; 72a, MLn = AuCl; 72b, MLn = AuC≡Cbipy) [64, 65]. Molecules 72a and 72b can be used as starting materials for the preparation of complexes of higher nuclearity and of, e.g., coordination polymers [64]. Other trimetallic MM′2 metal complexes are {[(η5-C5H4PPh2)2CuCl]Ti(μ-σ,π- C≡CtBu)2}CuCl (73) [65], Pt[(μ-σ,π-C≡CPh)CdCl2]2 (74) [66], Pt[(C≡C-C6H4-2-C≡C- C6H4- 2-C≡C)HgCl2]2 (75) [67], (nBu3P)2(L)(CO)Ru(C≡CFc)2 (76a, L = CO; 76b, L = C5H5N; 76c, L = P(OMe)3) [68], (Ph2P(CH2)nPPh2)2Ru(C≡CFc)2 (77a, n = 1; 77b, n = 2) [69], (R3P)2Pt(C≡CFc)2 (78) [70], (R3P)2Pt(C≡C-Y-C≡CFc)2 (79a, Y = 1,4-C6H4; 79b, Y = 2,5- thiophene, …; R = alkyl, aryl) [12a, 71], and [(η5-C5H4terpy)Fe(η5-C5H4PPh2)]2MCl2 (80a, M = Pt; 80b, M = Pd; terpy = terpyridine) [61]. Trimetallic 80b can be used in the preparation of pentametallic complexes featuring three different transition metals, since it possesses with the terpy ligands further N-ligated coordination sites (see below). From 77 – 79 detailed spectroelectrochemical investigations were carried out. These complexes display a degree of electronic interaction between the metal-based redox groups located at the ligand termini. The electrochemical response of these systems has been selectively reviewed, with a focus on the Heinrich Lang and Alexander Jakob 402 variation in properties that accompany changes in the structure of the bridging ligand and the nature of the metal groups [69-71]. So far, trimetallic molecules with two different transition metals have been discussed. A straightforward synthesis method to prepare heterotrimetallic organometallic π-tweezer- based derivatives with three different metal atoms is depicted in Scheme 7 [14a, 48]. Scheme 7. Synthesis of heterotrimetallic 83 by subsequent treatment of 81 with HC≡CSiMe3 followed by complexation of 82 with [Cu(N≡CMe)4]ClO4 [14a, 48]. Compound 83 is accessible in a consecutive way by the alkynylation of FcC≡Cbipy(PtCl2) (81) with HC≡CSiMe3 in presence of diisopropyl amine and catalytic amounts of [CuI] to give FcC≡C-bipy[Pt(C≡CSiMe3)2] (82) which yields with [Cu(N≡CMe)4]BF4 the trimetallic Fe-Pt-Cu complex 83 (Scheme 7) [14a, 48]. The cyclic voltammogramms of 82 and 83 are shown in Figure 7. For heterobimetallic 82 two redox waves are observed for the bipy ligand at E0,1 = -1.59 V (ΔEp = 120 mV) and E0,2 = -2.24 V (ΔEp = 130 mV) in the cyclic voltammogram (Figure 7, top) which is typical for chelate-bonded bipy ligands in platinum transition metal chemistry [14a, 48]. The cyclic voltammogram of 82 also exhibits, as 81, a reversible oxidation for the ferrocene moiety at E0 = 0.17 V (ΔEp = 130 mV) showing that this unit is more difficult to oxidize than 81 and FcH, taken as standard [72]. Complexation of [CuFBF3] as given in 83 does not influence on the oxidation or reduction potentials of the FcC≡C-bipy[Pt(C≡CSiMe3) 2] moiety (Fe2+/Fe3+: E0 = 0.16 V (ΔEp = 120 mV); bipy: E0,1 = -1.60 V (ΔEp = 130 mV) E0,2 = -2.23 V (ΔEp = 120 mV). The coordinated copper(I) ion shows a irreversible reduction wave at Ep,red = -1.82 V (Figure 7, bottom). This observation may imply that the copper(I) reduction occurs initially resulting in fragmentation of FcC≡C-bipy{[Pt((μ-σ,π- C≡CSiMe3)2]CuFBF3}. A similar phenomenon was found for other organometallic π- tweezers, i.e. {[Ti](μ-σ,π-C≡CR)2}CuX [14a, 48]. In neutral 83 a Fc-C≡C-bipy unit is chelate-bonded to a Pt-Cu tweezer moiety. A similar structural motif is also found in [({[Ti](μ-σ,π-C≡CSiMe3)2}M')bipy-C≡CFc]X (85a, M' = Cu, X = PF6; 85b, M' = Ag, X = ClO4), where the 2,2'-bipyridine entity is coordinated to a heterobimetallic {[Ti](μ-σ,π-C≡CSiMe3)2}M'+ tweezer fragment [14a, 48]. In this Mixed Transition Metal Acetylides with Different Metals Connected … 403 molecule the group-11 metal ions copper and silver are chelate-bound by the organometallic π-tweezer [Ti](C≡CSiMe3)2 and the 2,2’-bipyridine ligand resulting in tetra-coordination at M'. These complexes are accessible by combining the mononuclear ferrocene acetylide FcC≡C-bipy (84) with heterobimetallic early-late {[Ti](μ-σ,π-C≡CSiMe3)2}M'X (M'X = Cu(N≡CMe)PF6; M'X = AgOClO3). While trimetallic 85a and 85b are stable in the solid state, they slowly start to decompose in solution on exposure to air, i. e., 85b gives metallic silver along with [Ti](C≡CSiMe3)2 [14a, 48]. Exemplary, the solid state structure of 85a was determined by single X-ray structure analysis. The result thereof is shown in Figure 6 [14a, 48]. Figure 6. ORTEP plot (30 % probability level) of 85a with the atom numbering scheme (the hydrogen atoms, the PF6 - counter ion, and the distortion of one Me3Si group are omitted for clarity). For selected bond distances (Å) and angles (°) see ref. [14a, 48]. Heinrich Lang and Alexander Jakob 404 Figure 7. Cyclic voltammograms of 82 (top) and 83 (bottom) in tetrahydrofuran at 25 °C, [nBu4N]PF6 supporting electrolyte (0.1 M), scan rate = 100 mV s-1. All potentials are referenced to the FcH/FcH+ redox couple (FcH = (η5-C5H5)2Fe) with E0 = 0.00 V (ΔEp = 150 mV) [14a, 48]. Heterotrimetallic 85a shows a pseudo-tetrahedral coordination geometry around Cu1 with two η2-coordinated Me3SiC≡C groups (C23-C24, C28-C29) and the chelate-bonded bipy ligand (N1, N2). Noteworthy to mention is the difference between Cu1-N1 (2.225(4) Å) and Cu1-N2 (2.044(4) Å) which verifies an asymmetrical chelate binding of the bipyridine ligand to Cu1. The large dissimilarity between Cu1-N1 and Cu1-N2 in 85a most probably can be ascribed to electronic effects resulting from the electron rich FcC≡C unit. For comparison, [FcC≡C-bipy{[Ti](μ-σ,π-C≡CSiMe3)2}Cu]PF6 (85a) was subjected to cyclic voltammetric studies (Figure 8). Mixed Transition Metal Acetylides with Different Metals Connected … 405 Figure 8. Cyclic voltammogram of 85a in tetrahydrofuran at 25 °C, [nBu4N]PF6 supporting electrolyte (0.1 M), scan rate = 100 mV s-1. All potentials are referenced to the FcH/FcH+ redox couple (FcH = (η5-C5H5)2Fe) with E0 = 0.00 V (ΔEp = 150 mV) [14a, 48]. The relevant electrode potentials of 85a are for the iron(II) ion E0 = 0.12 V (ΔEp = 150 mV), the reduction of the copper ion at Ep,red = -1.45 V and the reduction process bipy/bipy- at Ep,red = -2.67 V (Figure 8). The reduction of Cu(I) to Cu(0) is typical in Ti-Cu organometallic π-tweezer chemistry implying that in such complexes the reduction occurs initially at the Cu(I) ion resulting in fragmentation of the respective complexes (vide supra) [14a, 48]. However, when the cyclic voltammogram of 85a is measured only between -0.4 and -1.6 V (Figure 8, inlet) the cathodic reduction of Cu(I) is followed by reoxidation of Cu(0) (E0 = - 1.39 V, ΔEp = 120 mV) obviously without any change of the chemical identity of the molecule involved. In contrast, this is not the case for isostructural 85b, where instead of copper(I) a silver(I) ion is present. Next to the redox couples Fe2+/Fe3+ (E0 = 0.13 V, ΔEp = 145 mV) and bipy/bipy- (Ep,red = -2.66 V), respectively, an irreversible reduction peak for Ag(I)/Ag(0) is found at Ep,red = -1.26 V, i. e., no reoxidation peak is observed. In the second run the only observable potentials are those ones typical for free FcC≡C-bipy and [Ti](C≡CSiMe3)2 indicating that 85b fragmented into the starting materials. Related trimetallic compounds to 83 and 85 can be obtained, when the gold(I) and ruthenium(II) acetylides Ph3PAu-C≡C-bipy (86) and (η5-C5H5)(PPh3)2RuC≡C-bipy (87) are reacted with the organometallic π-tweezer {[Ti](μ-σ,π-C≡CSiMe3)2}M'X (M'X = Cu(N≡CMe)PF6, AgOClO3). After appropriate work-up, complexes [LnMC≡C- bipy{[Ti](μ- σ,π-C≡CSiMe3)2}M′]X (88a, LnM = (Ph3P)Au, M' = Cu, X = PF6; 88b, LnM = (Ph3P)Au, M' = Ag, X = ClO4; 89a, LnM = (η5-C5H5)(PPh3)2Ru, M’ = Cu, X = PF6; 89b, LnM = (η5- C5H5)(PPh3)2Ru, M' = Ag, X = ClO4) can be isolated as red solids in excellent yield [48, 64]. Heinrich Lang and Alexander Jakob 406 Table 2. Electrochemical Data of 82 – 85 a) Compd. Fe 2+ /Fe 3+ bipy/bipy.- b) bipy.-/bipy 2- b) M′+/M′ c) E 0 /V (ΔE p mV) E 0 (E p,red )/V (ΔE p /mV) E 0 /V (ΔE p /mV) E p,ox V E p,red /V E 0 /V (ΔE p /mV) 82 0.17 (130) -1.59 (120) -2.24 (130) - - - 83 0.16 (120) -1.60 (130) -2.23 (120) - -0.82 - 84 0.10 (194) -2.36 (200) -2.76 (430) - - - 85a 0.12 (150) -2.67 - -1.33 -1.45 -1.39 (120) 85b 0.13 (145) -2.66 - - -1.26 - a) In tetrahydrofuran. b) For electrode potentials of free bipy see ref. [73]. c) M′ = Cu, Ag. They are fairly stable molecules, both in the solid state and in solution. The chemical and physical properties of the latter compounds correspond to those of other gold(I) [74] and ruthenium(II) [75] acetylides. Another heterotrimetallic complex with a gold(I) acetylide unit is Ph3PAu-C≡C-NCN- Pt- C≡C-Fc (91), which can be obtained by combining Ph3PAu-C≡C-NCN-PtCl (90) with FcC≡CSnMe3 [74k]. Complex 91 represents a rigid-rod shaped molecular wire molecule in which the transition metals Au, Pt, and Fe are spanned by acetylide, cyclopentadienyl and phenylene units. A heterotrimetallic molecule featuring iridium, platinum and rhodium metals is 92, which is accessible by treatment of (NBu4)[{Ir-Pt}(C≡CSiMe3)2] with [Rh(cod)(acetone)x]+ (cod = cyclooctadiene) [76]. The molecular solid state structure of 92 proves the presence of the zwitter ion [(cod)Ir(μ-1κCα:η2-C≡CSiMe3)(μ-2κCα:η2-C≡CSiMe3)Pt-(μ-2κCα:η2- C≡CSi- Me3)2Rh+(cod)], resulting from the dinuclear anionic fragment [(cod)Ir(μ- 1κCα:η2- C≡CSiMe3)(μ-2κCα:η2-C≡CSiMe3)Pt(C≡CSiMe3)2]- which acts as a chelating dimetallo bidentate ligand towards the cationic [Rh(cod)]+ building block. One more heterotrimetallic complex is represented by (dppf)(η5-C5H5)Ru-C≡C-C5H4- N→W(CO)4PPh3 (93) in which a linear carbon-rich dimetalla Ru-C≡C-C5H4N-W segment is present [77]. Replacement of the 4-ethynyl-pyridine by a 1-ethynyl-4-diphenylphosphino Mixed Transition Metal Acetylides with Different Metals Connected … 407 benzene entity gives access to a further series of complexes, i. e. (dppf)(η5-C5H5)Ru- C≡CC6H4PPh2- MLn (94, MLn = AuCl; 95, MLn = (η5-C5Me5)RhCl2; 96, (cod)RhCl) [64]. Other trimetallic complexes featuring the dppf group as a basic building block are (dppf)Pt(C≡CPPh2MLn)2 (97a, MLn = AuCl; 97b, MLn = (η6-C6H4-1-iPr-4-Me)RuCl2) and (dppf)Pt[(C≡CPPh2)2MLn] (98a, MLn = PdCl2; 98b, MLn = PtCl2; 98c, MLn = Mo(CO)4) (Figure 9) which are accessible in consecutive reaction sequences as described in ref. [40]. Complex 98a was used as a catalyst in the Heck reaction of coupling iodobenzene with tert.- butylacrylate to give E-tert.-butyl cinnamate [40]. Figure 9. Complexes 97 (left) and 98 (right) [40]. The molecular solid state structures of 98a – 98c were established by single X-ray structure analyses showing that constraint Pt(C≡CP)2M' rings (M' = Mo, Pd, Pt) are present. This corresponds with the observation made that 98a is a very efficient catalyst in Heck reactions showing very high activities [40]. Examples of other heterotrimetallic complexes are [(η5-C5H4terpyMLn)Fe(η5- C5H4PPh2)]2M'Cl2 (M' = Pd: 99, MLn = Mo(CO)4; M' = Pt: 100, MLn = Mo(CO)4) [61]. Another possibility to synthesize heterotrinuclear transition metal assemblies is the use of (poly)phenyleneethynes as connecting units to span different metal ions [78]. Recently, 1,3,5- triethynylbenzene was introduced as core in organometallic chemistry to prepare symmetrical and unsymmetrical bridged transition metal complexes. Due to its geometry and active coordination sites this molecule allows to extend the core into three directions by using, e. g. dehydrohalogenation and C-C coupling reactions. In general, there has been symmetric homo-substitution around the benzene core based on iron, iridium, chromium, gold and platinum containing metal building blocks (i. e., C6H3-1,3,5-(Fe(η5-C5Me5)(dppe))3 (101)) [5i, 7b 79], while only less is known about unsymmetrical substituted complexes of 1,3,5- triethynylbenzene featuring, for example, trans-[Ru(dppm)2Cl], trans-[Os(dppm)2Cl], [Ru(η5-C5H5)(PPh3)2] (dppm = bis(diphenylphosphino)methane), and ferrocenyl end-grafted moieties [80]. These organometallic species are key molecules for the synthesis of metallodendrimers, megamers, and nanostructured materials [81], and play an importend role in homogeneous catalysis and in many electron-transfer processes [81]. However, only two examples are known in which three different transition metal fragments are unsymmetrical arranged around the periphery of a 1,3,5-triethynylbenzene core [8c, 82]. Heinrich Lang and Alexander Jakob 408 A suitable starting material for the preparation of additional heterotrinuclear σ-alkynyl complexes is the 1,3,5-ethynylbenzene core 1-(Fc-C≡C)-3,5-(HC≡C)2C6H3 (102) because alkynyl ferrocenes are known to be very robust to further reactions [8c]. Lithiation of 102 with LiN(SiMe3)2 followed by treatment with (bipy´)(CO)3ReCl (bipy´ = 4,4´-di-tert.-butyl- 2,2´-bipyridine) afforded heterobimetallic 1-(FcC≡C)-3-[(bipy´)(CO)3ReC≡C)]-5- (HC≡C)- C6H3 (103). Complex 103 possesses with the free alkynyl entity a further reactive site and therefore should have a great potential to introduce a third transition metal building block and hence, forms oligomeric structures based on a 1,3,5-trisubstituted benzene core. Thus, the reaction behavior of the disubstituted iron-rhenium assembly 103 towards diverse transition metal complexes was studied. The preferred synthetic method for the preparation of heterotrimetallic species was accomplished by the addition of the organometallic metal chloride (η5-C5H5)(Ph3P)2RuCl to 103 in presence of the ammonium salt [H4N]PF6 and the base KOtBu (Scheme 8). The analog osmium(II) complex could be prepared by the reaction of 103 with (η5-C5H5)(Ph3P)2OsBr in refluxing methanol in presence of [H4N]PF6 followed by deprotonation of the vinylidene intermediate [1-(FcC≡C)-3-[(bipy´)(CO)3ReC≡C)]-5-[(η5-C5H5)(Ph3P)2Ru=C=CH]C6H3]+ (104) by addition of sodium metal. After appropriate work-up, 1-(FcC≡C)-3- [(bipy´)(CO)3ReC≡C)]-5-[(η5-C5H5)(Ph3P)2MC≡C]C6H3 (105, M = Ru; 106, M = Os) could be isolated as orange powders in good yield [64]. A possibility to introduce a platinum building block exists in the reaction of 103 with (PPh3)2PtCl2 in refluxing chloroform in presence of diethylamine (Scheme 8) [64]. To avoid the formation of the corresponding platinum bis(acetylide) complex the use of an excess of (PPh3)2PtCl2 is required. 1-(FcC≡C)- 3-[(bipy´)(CO)3ReC≡C)]-5-[Cl(Ph3P)2PtC≡C]C6H3 (107) could be isolated as a yellow solid. The influence of connecting alkynyl-aromatic moieties has been considered through electrochemical measurements and is discussed in detail elsewhere [64]. A further series of trinuclear heterometallic complexes could be synthesized based on the 1,3,5-tri(ethynyl)benzene core as evidenced by [1,3-{Cl(PEt3)2PdC≡C}2-5-{(Me2bpy)(CO)3- ReC≡C}C6H3] (108) and [1-{Fc-C≡C}-3-{(CO)3Cr(η6-C6H5C≡C)}-5-{Ph3PAuC≡C}C6H3] (109) [83, 64]. For similar compounds see ref. [64]. Heterotrimetallic complexes based on the diphenylphosphino ferrocene building block are FcPPh2Au-C≡CRc (110), FcPPh2Au-C≡C[(η6-C6H5)Cr(CO)3] (111), and FcPPh2Au- C≡Cbipy[Mo(CO)4] (112) (Rc = (η5-C5H4)(η5-C5H5)Ru) [48, 64, 84]. Redox-active multinuclear ferrocenyl ethynyl phosphanes and their palladium and platinum complexes Ph3- nP(C≡CFc)n (113, n = 1; 114, n = 2; 115, n = 3) and [Ph3-nP(C≡CFc)n]M′X2 (M′ = Pd, X = Cl: 116a, n = 1; 116b, n = 2; 116c, n = 3; M′ = Pd, X = I: 117, n = 1; M′ = Pt, X = Cl: 118a, n = 1; 118b, n = 2; 118c, n = 3) were independently described by Baumgartner [85] and our group [84]. These ferrocenyl ethynyl phosphanes show an increasing number of ferrocenyl ethynyl units including the corresponding M′X2 complexes. Mixed Transition Metal Acetylides with Different Metals Connected … 409 Scheme 8. Reaction chemistry of 103; synthesis of heterotrimetallic 105 – 107 ((i) 1. LiN(Si-Me3)2, toluene, 25 °C, 2 h; 2. (bipy’)(CO)3ReCl, toluene, reflux, 5 h. (ii) M = Ru: (PPh3)2(η5-C5H5)RuCl, [H4N]PF6, KOtBu, CH2Cl2/MeOH, 5 h; M = Os: 1. (PPh3)2(η5-C5H5)OsCl, [H4N]PF6, MeOH, reflux, 3 h; 2. Na, MeOH, 25 °C, 1 h. (iii) cis-(PPh3)2PtCl2, CHCl3/HNEt2, reflux, 3 h) [64]. Solid state structures of this series of complexes were determined by X-ray structure analysis. The PdI2-based complex shows a favourable trans-configuration with almost linear alkynyl ligands. The thermal behavior of some of the newly synthesized compounds indicated their utility as potential precursors for magnetic ceramic nanomaterials [85]. Although they can successfully be used as catalysts in, for example, the Heck, Suzuki and Buchwald- Hartwig reaction [84, 86]. Electrochemical investigations of the ferrocenyl ethynyl phosphane ligands and the appropriate palladium and platinum complexes, respectively, revealed that the structural motif of the ligands Ph3-nP(C≡CFc)n does not support multistep redox processes within these materials. All assemblies showed single, reversible redox processes whose Heinrich Lang and Alexander Jakob 410 potential is influenced by the substitution pattern of Ph3-nP(C≡CFc)n and the respective complex geometries [84, 85]. Reaction of 118a with two equivalents of HC≡CFc in diisopropyl amine in presence of catalyic amounts of [CuI], or treatment of 118c with LiC≡CFc in a 1:2 molar ratio produced the nonametallic square-planar structured platinum(II) complex [(FcC≡C)Ph2P]2 Pt(C≡CFc)2 (119) in excellent yield [84]. In 119 a total of four ferrocene ethynyl groups are present. (HETERO)TETRAMETALLIC TRANSITION METAL COMPLEXES Organometallic π-tweezer complexes of structural type B (Scheme 1) can also successfully be used in the preparation of tetrametallic Ti2Ma′Mb′ species (Ma′ = Mb′; Ma′ ≠ Mb′; Ma′, Mb′ = Cu, Ag) [14, 87]. In this respect, halides, pseudohalides, dicarboxylates and, for example, nitrogen-based molecules have been utilized to connect tweezer-chelated copper(I) and silver(I) ions. For a detailed discussion on this topic see ref. [14b, e, 87]. The respective complexes may display metal-metal interactions, as the inorganic or organic connecting units permit rapid intramolecular electron transfer. The electrochemistry of selected complexes was studied by cyclic voltammetry. Semi-empirical calculations were additionally carried out. [14h] The results indicate a strong intramolecular interaction between the group-11 metals held in place by the organometallic bis(alkynyl) π- tweezers. Other tetrametallic MM′M2′′ compounds are {[M](μ-σ,π-C≡CFc)2}M′X ([M] = (η5- C5H4SiMe3)2Ti: 120a, M′X = Pd(PPh3); 120b, M′X = Ni(CO); 120c, M′X = CuBr; 120d, M′X = CuCl; 120e, M′X = CuOTf; 120f, M′X = CuCl2; 120g, M′X = ZnCl2; 120h, M′X = ZnBr2; 120i, M′X = AgCl; 120j, M′X = AgBF4; [M] = (bipy)Pt: 121a, M′X = CuBr; 121b, M′X = CuOTf; 121c, M′X = CuBF4; 121d, M′X = AgNO3; 121e, M′X = AgClO4; 121f, M′X = AgO2CCF3; [M] = [(Ph2PCH2PPh2)2Ru: 122, M′X = CuI) [14, 61]. They are impressive examples of mixed early-late transition metal complexes in which reducible and oxidizable groups are present in close proximity to each other. Their electrochemical behavior is discussed in detail in refs. [14] and [61]. Mixed Transition Metal Acetylides with Different Metals Connected … 411 Further heterotetrametallic compounds are 125a and 125b (Figure 10) which are accessible in a two-step synthesis procedure including the Sonogashira cross-coupling reaction of 1,1`-bis(ethynyl) biferrocene (123) with I-1-NCN-4-Br and the oxidative addition of (1,1`-Br-4-NCN-C≡C)2bfc (bfc = biferrocene) (124) to [Pd2(dba)3] and [Pt(tol)2(SEt2)]2, respectively, [88]. Figure 10. Biferrocene-based molecules 125a (M = Pd) and 125b (M = Pt) [88]. Cyclic voltammetric measurements of 125a and 125b show that the ferrocene moieties can be oxidized independently. The difference of the potentials of the Fe(II)/Fe(III) redox couples is 300 mV and is not affected by the NCN transition metal pincer [88]. Similar results are obtained for the biferrocene-based complexes bfc(PPh2MLn)2 (127a, MLn = Cr(CO)5; 127b, MLn = Mo(CO)5; 127c, MLn = W(CO)5; 128, MLn = (C6H4-1-iPr-4- Me)RuCl2; 129, MLn = AuCl), a series of complexes which can be prepared by the reaction of bfc(PPh2)2 (126) with two equivalents of the MLn sources M(CO)5(thf) (M = Cr, Mo, W), [(C6H4-1-iPr-4-Me)RuCl2]2, or (tht)AuCl [89]. Tetrametallic Fe2Au2 129 affords with HC≡CMc (Mc = Fc, Rc) in presence of [CuI] and diethylamine in tetrahydrofuran at room temperature bfc(PPh2Au-C≡C-Mc)2 (130a, Mc = Fc; 130b, Mc = Rc) (Scheme 9, route (i)) [90]. Under identical reaction conditions 129 reacted with a 20 % excess of 5-ethynyl-2,2´-bipyridine to give bfc(PPh2Au-C≡C-bipy)2 (131) (Scheme 9, route (ii)) which contains with the bipy ligand a further N-ligating unit and hence, was reacted with stoichiometric amounts of the heterobimetallic early-late tweezer molecule [{[Ti](μ-σ,π-C≡CSiMe3)2}Cu(N≡CMe)]PF6 (Scheme 9, route (iii)). On replacement of the weakly-bonded acetonitrile in the latter molecule by bipy octametallic 132 is formed which can be isolated after appropriate work-up in acceptable yield [90]. In 132 the bfc unit links the two heterotrimetallic Au-C≡C-bipy[{[Ti](μ-σ,π-C≡CSiMe3)2}Cu]+ building blocks and hence, represents a further example of a so far only barely discussed class of heterotetrametallic MM′M′′M′′′ complexes. A detailed investigation of possible photophysical properties and electronic interactions between the appropriate metal atoms of 132 is in progress in our laboratory. Heinrich Lang and Alexander Jakob 412 Scheme 9. Synthesis of heteromultimetallic 130, 131 and 132. ((i) 1. (tht)AuCl; 2. HC≡CMc, [CuI]/NEt3. (ii) 1. (tht)AuCl; 2. HC≡Cbipy, [CuI]/NEt3. (iii) [{[Ti]C≡CSiMe3}2Cu(N≡CMe)PF6]) [90]. The development of polynuclear ruthenium(II) terpyridine molecular wire molecules based on the biferrocene building block bfc were recently reported by Dong et al. [91]. The multinuclear supramolecules assembled from 1’,1’’’-bis(terpyridyl) biferrocene redox-active sub-units attached to Ru(II) ions were prepared by, for example, the reaction of bfc-terpy (133) and bfc(terpy)2 (134), respectively, with LRuCl3 (L = terpy, fc-terpy), LRuCl2(dmso) (L = bfc-terpy, dmso = dimethylsulfoxide) or RuCl2(dmso) in the appropriate ratios as outlined in Figure 11 [91]. Complexes Ru(bifc-terpy)(dmso)Cl2 (135), [Ru(terpy)(bifc-terpy)](PF6)2 (136), [Ru(bifc-terpy)2](PF6)4 (137), [bifc(terpy)2(Ru(terpy))2](PF6)4 (138), [bifc- (terpy)2(Ru(terpy-Fc))2](PF6)4 (139), [bifc(terpy)2(Ru(terpy-bifc))2](PF6)4 (140), [(Ru(terpy)) 2(bifc(terpy)2](PF6)6 (141), and [(Ru(terpy-Fc)2(bifc(terpy)2)2](PF6)6 (142) are thereby formed in good yield. The cyclic voltammograms of the ruthenium(II) coordinated bifc-terpy and fc- terpy species are dominated by the Ru2+/Ru3+ (E1/2 ≅ 1.35 V), Fe2+/Fe3+ (E1/2 ≅ 0.4 – 0.9 V), and the terpy (terpy-/terpy2- redox couples (E1/2 ≅ -1.2 – -1.4 V). The appreciable variations detected in the Fe2+/Fe3+ oxidation potentials indicated that this is an interaction between the respective spacer and the Ru2+ metal ions [91]. On the coordination of the 1,’1’’’-bis(terpyridyl) biferrocene 133 to a ruthenium(II) ion there is a red-shifted and more intense 1[(d(π)Fe)6] → 1[(d(π)Fe)5(π*terpy Ru)1] transition found in the visible region ([Ru(terpy)2]2+, [Ru(terpy)(bifc-terpy)]2+: ca. 510 nm; polynuclear ruthenium(II) 1,’1’’’-bis(terpyridyl) biferrocenes: ca. 570 nm) [91]. This shift indicates that there is a qualitative electronic coupling within the appropriate assemblies. The coordination of Ru(II) ions lowers the energy of the π*terpy orbitals giving a more red-shifted transition. Mixed Transition Metal Acetylides with Different Metals Connected … 413 Figure 11. Complexes 140 (left) and 142 (right) [91]. Further examples of heterotetrametallic MM′M′′M′′′ complexes with four different metals, based on organometallic π-tweezer units, can be obtained by joining heterobimetallic titanium-copper or titanium-silver tweezers with Fe-Pt or Fe-Au containing molecules (Figure 12). Thus, HC≡C-{Pt}-C≡C-Fc (143) ({Pt} = Pt(C6H2(CH2NMe2-2,6)2)) gives with {[Ti](μ- σ,π-C≡CtBu)2}CuCH3 on loss of CH4 complex 144 [51], while FcPPh2Au-C≡C-bipy affords with {[Ti](μ-σ,π-C≡CSiMe3)2}M′X (M′X = Cu(N≡CMe)PF6, AgClO4) tetrametallic 145 [92]. Figure 12. Complexes 144 (left) and 145 (right; 145a: M′ = Cu, X = PF6; 145b: M′ = Ag, X = ClO4) [51, 92]. Complexes 144 and 145 represent the first examples of heterotetrametallic transition metal complexes in which early and late metals are connected by π-conjugated organic bridging units. A striking feature of 144 is that all metals possess different coordination spheres: titanium shows a pseudo-tetrahedral environment, copper possesses a planar surrounding, platinum is square-planar coordinated and iron is part of a sandwich structure [51]. Based on the organometallic π-tweezer moiety [{[Ti](μ-σ,π-C≡CSiMe3)2}Cu]+ another heterotetrametallic species could be isolated from the reaction of {[Ti](μ-σ,π- C≡CSiMe3)2}- CuMe with (η5-C5H4CO2H)Fe(η5-C5H4PPh2Mo(CO)5) (146) [93]. The latter molecule is accessible by treatment of HO2C-fc-PPh2 (147) (fc = Fe(η5-C5H4)2) with M(CO)5(thf) [93]. The respective Ti-Cu-Fe-M complexes 148a - 148c (148a, M = Cr; 148b, M = Mo; 148c, M = W) are, however, very instable molecules both in the solid state and in solution and hence, can only be handled at low temperature without significant decomposition [93]. Heinrich Lang and Alexander Jakob 414 Isostructural systems to 148 can be obtained for the higher homologue of copper by combining [Ti](C≡CSiMe3)2 with equimolar amounts of the silver(I) salt [AgO2C-fc-PPh2] to give {[Ti](μ-σ,π-C≡CSiMe3)2}AgO2C-fc-PPh2 (149) [93]. Addition of M(CO)5(thf) to 149 produced the Ti-Ag-Fe-M complexes {[Ti](μ-σ,π-C≡CSiMe3)2}AgO2C-fc- PPh2M(CO)5 (150a, M = Cr; 150b, M = Mo; 150c, M = W), which are, when compared with 148a – 148c, even more reactive. They readily decompose in solution and on exposure to sun light on formation of metallic silver, the free π-tweezer [Ti](C≡CSiMe3)2 and other unidentified materials. When the FcPPh2Au entity in 145 (Figure 12) is replaced by the (η2-dppf)(η5-C5H5)Ru building block related tetranuclear complexes of type [(η2-dppf)(η5-C5H5)Ru-C≡Cbipy{[ Ti](μ-σ,π-C≡CSiMe3)2}M′]X (151a: M′ = Cu, X = PF6; 151b: M′ = Ag, X = ClO4) are accessible [64]. Extending the distance between the remote Fe-Ru and Ti-Cu fragments in 151 by an C≡C-1-C6H4-4-PPh2-Au moiety opens the possibility to create stable heteropentametallic transition metal complexes (see below). When the organometallic π-tweezer entity (vide supra) is substituted by mononuclear transition metal building blocks, such as Mo(CO)4 and Re(CO)3Cl, then tetrametallic [(η2-dppf)(η5-C5H5)Ru(C≡C)-1-(C6H4)-4-PPh2-Au- C≡Cbipy( MLn)] (152, MLn = Mo(CO)4; 153, MLn = Re(CO)3Cl) is formed in which four different metal atoms are bridged by organic carbon-rich connecting units [64]. Mixed Transition Metal Acetylides with Different Metals Connected … 415 Compounds of the latter type are formed by treatment of [(η2-dppf)(η5- C5H5)Ru(C≡C)-1- (C6H4)-4-PPh2-AuCl] (154) with HC≡C-bipy(Re(CO)3Cl) (synthesis of 152) or combining (η2-dppf)(η5-C5H5)Ru(C≡C)-1-(C6H4)-4-PPh2-Au-C≡C-bipy (155) with (nbd)Mo(CO)4 (synthesis of 153) [64]. An elegant approach to a novel Fe-Ru-Re-Rh tetrametallic complex, based on the 1,3- diethynyl-5-diphenylphosphino benzene core, is given by using a consecutive reaction methodology as presented in Scheme 10 including, dehydrohalogenation and carbon-carbon coupling reactions [64]. Scheme 10. Synthesis of heterotetrametallic 158 via the formation of 156 and 157, ((i) (bipy’)(CO)3ReC≡CH, [(PPh3)2PdCl2], [CuI], HNiPr2, reflux, 5 h; (ii) [nBu4N]F, thf, 25 °C, 1 h; (iii) (dppf)(η5-C5H5)RuCl, [H4N]PF6, KOtBu, CH2Cl2/MeOH, 25 °C, 3 h; (iv) [(η5-C5Me5)RhCl2]2, CH2Cl2, 25 °C, 1 h) [64]. Exemplary, the molecular solid state structure of 158 was solved by X-ray structure analysis, thus confirming the structural assignment made from spectroscopic data [64]. An ORTEP drawing of this species is depicted in Figure 13. Heinrich Lang and Alexander Jakob 416 Figure 13. ORTEP drawing of 158. Thermal ellipsoids are shown at the 50% probability level. For selected bond lengths (Å) and angles (°) see ref. [64]. (HETERO)PENTA- TO (HETERO)UNDECAMETALLIC TRANSITION METAL COMPLEXES Further examples of the modular “Tinkertoy” approach includes the synthesis of (hetero)penta- to nona-metallic complexes. An important family of “Tinkertoys” are halide-, pseudohalide-, cyanoacetylide-, heterocyclic- and/or di- and tricarboxylic acid-funtionalized transition metal building blocks. There are mainly three methods which can successfully be applied for the preparation of the title compounds. The first synthesis protocol includes the reaction of {[Ti](μ-σ,π- C≡CR) 2}CuMe with diverse organic and organometallic di- and tricarboxylic acids, owing to the instability of the alkyl-copper system, and is based on the preparation of 159 and 160 [14m, 94]. Mixed Transition Metal Acetylides with Different Metals Connected … 417 In the latter molecules organometallic π-tweezer units are connected by a 1,1'- errocenyldicarboxylate (159) or a 1,3,5-benzenetricarboxylic entity (160). However, electrochemical studies showed that the connecting carboxylates act as an impedance rather than a transmitter [14m, 94]. The 2nd and hence, more straightforward synthetic route to (hetero)multimetallic π- tweezer-based complexes is the reaction of {[Ti](μ-σ,π-C≡CSiMe3)2}M′X (M′ = Cu, Ag; X = ClO4, OTf) with the metal salts [MX2]- (M = Cu, Ag, Au; X = C≡N, OCN) (synthesis of 161a - 161e) or [Ag(C≡N)4]3- (synthesis of 162) in the ratios of 2:1 and 4:1, respectively [14h, gg, 52, 56, 87, 95]. Heinrich Lang and Alexander Jakob 418 Complexes 161a – 161e (161a, M = M′ = Cu, X = C≡N; 161b, M = M′ = Ag, X = C≡N; 161c, M = M′ = Ag, X = NCO; 161d, M = Ag, M′ = Cu, X = C≡N; 161e, M = Au, M′ = Cu, X = C≡N) are linear structured and contain the features typical for 1- dimensional molecular wire molecules. Complex 162 is one of the outstanding examples of a cross-shaped molecule in which four titanium-silver tweezer parts are linked by a [Ag(C≡N)4]3- core. In 162 each cyanide is datively-bound to a silver(I) center of an individual π-tweezer fragment. While the inner silver atom possesses a tetrahedral environment, the outer silver(I) ions are planar coordinated and hence, possess coordination number 3 [95]. Multiple π-tweezers can also be linked together by bipyridyl, 2,4,6-tri(2-pyridyl)-1,3,5- triazine (tpt) or pyridyl-functionalized porphyrin connecting units [96, 97]. With tpt, complexes 163a – 163d (M′ = Cu, X = PF6: 163a, R = Ph; 163b, R = SiMe3; M′ = Ag, X = ClO4: 163c, R = Ph; 163d, R = SiMe3) are formed, when {[Ti](μ-σ,π-C≡CR)2}M′X is reacted with tpt in the stoichiometry of 3:1. In a similar manner, heptametallic FeAu2Cu2Ti2 and FeAu2Ag2Ti2 molecules Fe(η5- C5H4PPh2AuC≡Cbipy-M′{(μ-σ,π-C≡CSiMe3)2[Ti]})2 (164a, M′ = Cu; 164b, M′ = Ag) are accessible by treatment of Fe(η5-C5H4PPh2AuC≡Cbipy)2 with two equivalents of {[Ti](μ- σ,π-C≡CSiMe3)2}M′X (M′X = Cu(N≡CMe)PF6, AgClO4) [64]. Pyridine-functionalized porphyrins allow the linkage of four organometallic π-tweezers as shown in 165a (M′ = Cu) and 165b (M′ = Ag). However, these molecules show a tendency to decompose in solution with formation of metallic copper or silver along with [Ti](C≡CSiMe3) 2 and the free porphyrin [97]. Mixed Transition Metal Acetylides with Different Metals Connected … 419 The reaction chemistry of 165a and 165b towards diverse transition and main-group element salts is in progress in our labortories. Ferrocene-based multimetallic species of type MxM′y are [Ph((η5-C5H5)Fe(η5- C5H4))2P]AuC≡CAu[P((η5-C5H5)Fe(η5-C5H4))2Ph] (166) [98], (FcC≡C-C≡CFc)2Os2(CO)6 (167) [32c] and (FcC≡C)2Os3(CO)9 (168) [32c]. As an instance, the pentametallic complex 171, a bipyramidal supramolecular cage based on rhodium and platinum atoms must be mentioned [99]. This compound is accessible by the consecutive reaction of 4-ethynyl-pyridine with tBuLi followed by its addition to (Me3tacn)RhCl3 (Me3tacn = N,N′,N′′-trimethyl-1,4,7-triazacyclononane) giving the facial octahedral complex (Me3tacn)Rh(C≡Cpy) (169), condensation of which with the squareplanar species cis-(dcpe)Pt(NO3)2 (170) (dcpe = 1,2-bis(dicyclohexylphosphino)ethane) results in a self-assembled trigonal-bipyramidal cage with Rh(III) and Pt(II) ions occupying the vertics. Multinuclear NMR analyses and single X-ray structure determination of 171 are consistent with the proposed structure. Heinrich Lang and Alexander Jakob 420 A star-shaped ruthenium complex (176) with five ferrocenyl end-grafted arms bridged by the trans- platinum fragments Pt(PEt3)2 represents an example of a undecanuclear Fe5Pt5Ru assembly containing three different metals [100]. This complex can be synthesized by starting from the novel heteropolytopic penta(4-ethynyl)cyclopentadiene C5(C6H4-4-C≡C-TIPS)5(Br) (TIPS = tri(iso-propyl)silyl) (172) (Scheme 11). Ruthenium was subsequently condicted to 172 affording 173 (Scheme 11). Compound 173 reacts with potassium tris(indazolyl)borate (= KTIB) and than with tetra-butylammonium fluoride (= TBAF) to yield 174, bearing five free HC≡C terminal groups. These end-grafted units are available for coordination and hence, 174 was reacted with the ethynyl-ferrocenyl platinum fragment Fc-C≡C-Pt(PEt3)2Cl (175) in presence of [CuI] in Et2NH as solvent (Scheme 11). In a quintuple coupling of 175 with 174, complex 176 was isolated. Oxidation of the five centers in 176 occurs simultaneously at a potential of 0.31 V followed by the oxidation of the Ru(II) ion at 0.60 V. However, the platinum atoms were not oxidized within the potential window of –1.8 to +1.5 V used. Finally, after preforming a partial oxidation of the Fc units, no intervalence transition between Fe2+/Fe3+ was observed, thus confirming the absence of electronic communication between the electro-active ferrocenes [100]. Even the synthesis of heteropenta- and heterohexametallic complexes with the metals rhenium, iron, ruthenium, gold, copper and titanium is possible. Complex [(η2-dppf)(η5- C5H5)RuC≡C-1-C6H4-4-PPh2-Au-C≡C-bipy{[Ti](μ-σ,π-C≡CSiMe3)2}Cu]PF6 (179) is accessible in a consecutive reaction sequence by using (η2-dppf)(η5-C5H5)RuC≡C-1-C6H4- 4- PPh2-AuCl (177) as key starting material [64, 101]. The newly synthesized compounds and the overall synthetic strategy employed are shown in Scheme 12. Compound 177 reacts with 5-ethynyl-2,2´-bipyridine, whereby this compound is added in a 20 % excess, in presence of [CuI] and diethylamine to give (η2-dppf)(η5-C5H5)RuC≡C-1-C6H4-4-PPh2-Au-C≡C-bipy (178) (Scheme 12, route (i)). This molecule contains with the 2,2´-bipyridine ligand a Nligating unit and hence, was reacted with stoichiometric amounts of the heterobimetallic Mixed Transition Metal Acetylides with Different Metals Connected … 421 early-late tweezer molecule [{[Ti](μ-σ,π-C≡CSiMe3)2}Cu(N≡CMe)]PF6 (Scheme 12, route (ii)). On replacement of the copper-bonded acetonitrile in the organometallic π- tweezer part by bipyridine, complex 179 is formed which could be isolated after appropriate work-up in 92 % yield. Complex 179 is surprisingly a very stable species in which five different transition metals are brought in close proximity to each other by connecting C5H4PPh2, C≡C, C6H4, and bipyridine units. Scheme 11. Consecutive synthesis of 176 from 172 [100]. Scheme 12. Synthesis of trimetallic 178 and pentametallic 179 (route (i): tetrahydrofuran, 25 °C, 3 h; (ii): tetrahydrofuran, 25 °C, 2 h) [64, 101]. Heinrich Lang and Alexander Jakob 422 The formation of heteropentanuclear 179 was evidenced from spectroscopic studies and ESI-TOF mass spectrometric investigations. The ESI-TOF spectrum shows a prominent ion peak at m/z 1963.4 (100 %) corresponding to [179-PF6]+. Moreover, comparison of the Mixed measured isotope pattern of 179 with the calculated one confirms the elemental composition and charge state (Figure 13). Figure 13. Comparison of the measured (bottom) and calculated (top) isotope pattern of the ion peak [179-PF6]+ in the ESI-MS spectrum of 179 [64, 101]. The bipyridine building block in [(η2-dppf)(η5-C5H5)RuC≡C]-1-[(4,4´-tBu2-2,2´- bipy)(CO)3ReC≡C]-5-[PPh2AuC≡Cbipy]C6H3 (180) as bidentate binding site allows the preparation of Fe-Ru-Re-Au-Mo- and even Fe-Ru-Re-Au-Cu-Ti-based assemblies as outlined in Scheme 13. Addition of (nbd)Mo(CO)4 yields heteropentanuclear 181 upon replacement of nbd by bipy. Heterohexanuclear 182 is formed in a straightforward manner, when 180 is treated with [{[Ti](μ-σ,π-C≡CSiMe3)2}Cu(N≡CMe)]PF6 [64]. Within this reaction the coordination number at copper is changed from three (planar) to four (tetrahedral). The synthesis protocol developed to prepare heteromultinuclear 181 and 182 is directed to the use of modular shaped organometallic building blocks (vide supra) [64]. This allowed for the first time the synthesis of such unique complexes in which acetylenic and aromatic groups are connecting the different metal atoms. Mixed Transition Metal Acetylides with Different Metals Connected … 423 Scheme 13. Synthesis of heteropentametallic 181 and heterohexanuclear 182 [(i) (nbd)Mo(CO)4, dichloromethane, tetrahydrofuran, 25 °C, 8 h; (ii) [{[Ti](C≡CSiMe3)2Cu(N≡CMe)]PF6, tetrahydrofuran, 25 °C, 2 h] [64]. The reports on the synthesis of transition metal complexes in which five different metals such as Fe, Ru, Au, Cu and Ti (complex 179), Fe, Ru, Re, Au and Mo (complex 181) or even six different metal atoms (Fe, Ru, Re, Au, Cu, Ti; complex 182) are spanned by carbon-rich bridging units demonstrate that such large heteronuclear assemblies can be synthesized in a straightforward manner by using the modular “Tinkertoy” approach. This procedure allows a fair control over the structure and composition of such molecules. A detailed investigation of possible photophysical properties and electronic interactions between the appropriate metal atoms of 179, 181 and 182 is in progress in our laboratory. The identities of all described complexes within this article have been confirmed by elemental analysis, IR, 1H, 13C{1H} and 31P{1H} NMR spectroscopy. From selected samples the ESI-TOF mass spectra were measured and the solid state structures determined by single X-ray structure analysis. In this respect, IR and NMR (1H, 31P{1H}) spectroscopy allows to monitor the progress of the reactions and verifies the structure and composition of the final assemblies. CONCLUSION This chapter addresses the chemistry of mono- and bis(alkynyl) transition metal complexes, diaminoaryl NCN and NN’N pincer molecules (NCN = [C6H2(CH2NMe2-2,6)2]-; NN’N = [C5H3N(CH2NMe2-2,6)2]), modified ferrocenes and biferrocenes towards diverse metal complex fragments and serves to understand the manifold and sometimes unexpected Heinrich Lang and Alexander Jakob 424 reaction behavior of such systems. Interesting unique (hetero)bi- to (hetero)undecametallic compounds with often uncommon structural motifs are formed in which the respective transition metal building blocks are connected via π-conjugated carbon-rich organic and/or inorganic bridging units. The reactions based on the modular “Tinkertoys” approach depend on the steric and electronic properties of the metal atoms and ligands involved. Despite the large quantity of experimental work carried out in this field of chemistry, the exact factors which control the formation and/or interconversion of the structures in the (hetero)multimetallic complexes is still an open question and will continue to stimulate further work in this field of chemistry. A challenge is the preparation of even larger transition metal complexes featuring more than six different early-late metals and new functionalities. This chemistry opens the possibility for creating new materials with innovative electronic, catalytic, optical, and/or magnetic properties. ACKNOWLEDGMENT The very creative and fruitful contributions of Drs. S. Back, W. Frosch, T. Stein, K. Köhler, M. Al-Anber, and Dipl.-Chem. S. Köcher, M. Lohan, J. Kühnert, A. del Villar, and D. Friedrich and specially R. Packheiser are gratefully acknowledged. The financial support from the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and the VW-Foundation have been essentiell throughout. REFERENCES [1] For example: (a) Balzani, V.; Juris A.; Venturi, M.; Campagna, S., and Serroni, S.(1996). Luminescent and Redox-Active Polynuclear Transition Metal Complexes.Chem. Rev., 96, 759-833. (b) Balzani, V.; Campagna, S.; Denti, G.; Juris A.; Serroni, S., and Venturi, M. (1998). Designing Dedrimers Based on Transition- Metal Complexes. Light-Harvesting Properties and Predetermined Redox Patterns. Acc. Chem. Res., 31, 26-34. (c) Long, N. J. (1995). Organometallic Compounds for Nonlinear Optics - The Search for En-light-Enment! Angew. Chem., Int. Ed., 34, 21–38. (d) Wong, K. M. C.; Lam, S. C. F.; Ko, C. C.; Zhu, N.; Yam, V. W. W.; Roué S.; Lapinte, C.; Fathallah, S.; Costuas, K.; Kahlal, S., and Halet, J. F. (2003). Electroswitchable Photoluminescence Activity: Synthesis, Spectroscopy, Electrochemistry, Photophysics, and X-ray Crystal and Electronic Structures of [Re(bpy)(CO)3(C≡C-C6H4-C≡C)Fe(C5Me5)(dppe)][PF6]n (n = 0, 1). Inorg. Chem., 42, 7086–7097. (e) Powell C. E., and Humphrey M. G. (2004). Nonlinear Optical Properties of Transition Metal Acetylides and their Derivatives. Coord. Chem. Rev., 248, 725-756. (f) Cifuentes, M. P.; Humphrey, M. G; Morall J. P.; Samoc, M.; Paul, F.; Roisnel, T., and Lapinte C. (2005). Third-Order Nonlinear Optical Properties of Some Electron-Rich Iron Mono- and Trinuclear Alkynyl Complexes. Organometallics, 24, 4280-4288. (g) Low P. J. (2005). Metal Complexes in Molecular Electronics: Progress and Possibilities. Dalton Trans., 17, 2821-2824. (h) Long, N. J.; Angela, A. J.; de Biani, F. F., and Zanello, P. (1998). Synthetic and Electrochemical Studies of Some Metal Mixed Transition Metal Acetylides with Different Metals Connected … 425 Complexes of 1,3,5-Triethynylbenzene J. Chem. Soc., Dalton Trans., 2017-2022. (i) Koellner, C.; Pugin, B., and Togni, A. (1998). Dendrimers Containing Chiral Ferrocenyl Diphosphine Ligands for Asymmetric Catalysis. J. Am. Chem. Soc., 120, 10274-10275. (j) Devadoss, C.; Bharathi, P., and Moore, J. S. (1996). Energy Transfer in Dendritic Macromolecules: Molecular Size Effects and the Role of an Energy Gradient. J. Am. Chem. Soc., 118, 40, 9635-9644. (k) Hu, Q. S.; Pugh, V.; Sabat, M., and Pu, L. (1999). Structurally Rigid and Optically Active Dendrimers J. Org. Chem., 64, 20, 7528-7536. (l) Paul, F., and Lapinte, C. (1998). Organometallic Molecular Wires and other Nanoscale-sized Devices: An Approach Using the Organoiron (dppe)Cp*Fe Building Block. Coord. Chem. Rev., 178-180, 431-509. (m) Brunschwig, B. S.; Creutz, C., and Sutin, N. (2002). Optical Transitions of Symmetrical Mixed- Valence Systems in the Class II–III Transition Regime Chem. Soc. Rev., 31, 168-184. (n) Nelson S. F. (2001). In V. Balzani (Ed.) Electron Transfer in Chemistry (Vol. 1, Chapter 10). Weinheim, Germany; Wiley-VCH. (o) Kaim, W.; Klein, A., and Glöckle, M. (2002). Exploration of Mixed-Valence Chemistry: Inventing New Analogues of the Creutz-Taube Ion. Acc. Chem. Res., 33, 755-763. (p) Ceccon, A.; Santi, S.; Orian, L., and Bisello, A. (2004). Electronic Communication in Heterobinuclear Organometallic Complexes Through Unsaturated Hydrocarbon Bridges. Coord. Chem. Rev., 248, 683- 724. (q) Ward, M. D. (1995). Metal-Metal Interactions in Binuclear Complexes Exhibiting Mixed Valency; Molecular Wires and Switches. Chem. Soc. Rev., 121-134. (r) Astruc D. (1997). From Organotransition-Metal Chemistry toward Molecular Electronics: Electronic Communication between Ligand-Bridged Metals. Acc. Chem. Res., 30, 383-391. (s) Sarkar, B.; Kaim, W.; Fiedler, J., and Duboc, C. (2004). Molecule-Bridged Mixed-Valent Intermediates Involving the RuI Oxidation State. J. Am. Chem. Soc.; 126, 14706-14707. (t) Connelly, N. G., and Geiger, W. E. (1996). Chemical Redox Agents for Organometallic Chemistry. Chem. Rev., 96, 877-910. [2] (a) Michl, J., and Magnera F. (2002). Two-dimensional Supramolecular Chemistry with Molecular Tinkertoys. Proc. Natl. Acad. Sci. U.S.A., 99, 4788-4792. (b) Levin, M.; Kaszynski, P., and Michl, J. (2000). Bicyclo[1.1.1]pentanes, [n]Staffanes, [1.1.1]Propellanes, and Tricyclo[2.1.0.02,5]pentanes. Chem. Rev., 100, 169-234. (c) Kaszynski, P., and Michl, J. (1998). [n]Staffanes: A Molecular-Size "Tinkertoy" Construction Set for Nanotechnology. Preparation of End-Functionalized Telomers and a Polymer of [ l.l.l]Propellane. J. Am. Chem. Soc., 110, 5225-5226. [3] (a) Stoddart, J. F. (1992). Constructing a Molecular LEGO Set. Chem. Soc. Rev., 21, 215-225. (b) Raymo, F. M., and Stoddart, J. F. (1999). Interlocked Macromolecules. Chem. Rev., 99, 1643-1663; (c) Kessler, V. G. (2003). Molecular Structure Design and Synthetic Approaches to the Heterometallic Alkoxide Complexes (Soft Chemistry Approach to Inorganic Materials by the Eyes of a Crystallographer) Chem. Commun., 1213. [4] Long, N. J., and Williams, C. K. (2003). Metal Alkynyl Complexes: Synthesis and Materials. Angew. Chem., Int. Ed., 42, 2586-2617. (b) Yam V. W. W. (2004). Luminescent Metal Alkynyls – From Simple Molecules to Molecular Rods and Materials. J. Organomet. Chem., 689, 1393. (c) Bruce, M. I.; Low, P. J.; Frantisek, F.; Humphrey, P. A.; De Montigny, F.; Jevric, M.; Lapinte, C.; Perkins, G. J.; Roberts, R. L.; Skelton, B. W., and White, A. H. (2005). Syntheses, Structures, some Reactions, and Electrochemical Oxidation of Ferrocenylethynyl Complexes of Iron, Ruthenium, Heinrich Lang and Alexander Jakob 426 and Osmium. Organometallics, 24, 5241-5255. (d) Low, P. J.; Roberts, R. L.; Cordiner, R. L., and Hartl F. J. (2005). Electrochemical Studies of Bi- and Polymetallic Complexes Featuring Acetylide Based Bridging Ligands. Solid State Electrochem., 9, 717-731. (e) Szafert, S., and Gladysz, J. A. (2003). Carbon in One Dimension: Structural Analysis of the Higher Conjugated Polyynes. Chem. Rev., 103, 4175-4205. (f) Bruce, M. I.; Low, P. J.; Costuas, K.; Halet, J. F.; Best, S. P., and Heath G. A. (2000). Oxidation Chemistry of Metal-Bonded C4 Chains: A Combined Chemical, Spectroelectrochemical, and Computational Study: J. Am. Chem. Soc., 122, 1949-1962. (g) Narvor, N. L.; Toupet, L., and Lapinte, C. (1995). Elemental Carbon Chain Bridging Two Iron Centers: Syntheses and Spectroscopic Properties of [Cp*(dppe)Fe- C4-FeCp*(dppe)]n+·n[PF6]-. X-ray Crystal Structure of the Mixed Valence Complex (n= 1). J. Am. Chem. Soc., 117, 7129-7138; (h) Baumgartner, T., and Reau, R. (2006). Organophosphorus π-Conjugated Materials. Chem. Rev., 106, 4681-4727. (i) Yam, V. W. W.; Lo, K. K. W., and Wong K. M. C. (1999). Luminescent Polynuclear Metal Acetylides. J. Organomet. Chem., 578, 3-30. [5] Chawdhury, N.; Long, N. J.; Mahon, M. F.; Ooi, L.; Raithby, P. R.; Rooke, S.; White, A. J. P.; Williams, D. J., and Younus, M. (2004). Synthesis, Characterisation and Optical Spectroscopy of Platinum(II) Di-ynes and Poly-ynes Incorporating Condensed Aromatic Spacers in the Backbone. J. Organomet. Chem., 689, 840-847. (b) de Montigny, F.; Argouarch, G.; Costuas, K.; Halet, J. F.; Roisnel, T.; Toupet, L., and Lapinte, C. (2005). Electron Transfer and Electron Exchange Between [Cp*(dppe)Fe]n+(n = 0, 1) Building Blocks Mediated by the 9,10- Bis(ethynyl)anthracene Bridge Organometallics, 24, 4558-4572. (c) Callejas-Gaspar, B.; Laubender, M., and Werner, H. (2003). Synthesis and Reactivity of Dinuclear Rhodium Complexes with Rh=C=CHR and Rh=C=C=CRR′ Units as Building Blocks. J. Organomet. Chem., 684, 144-152. (d) Klein, A.; Lavastre, O., and Fiedler, J. (2006). Role of the Bridging Arylethynyl Ligand in Bi- and Trinuclear Ruthenium and Iron Complexes Organometallics, 25, 635-643. (e) Hurst, S. K.; Cifuentes, M. P.; McDonagh, A. M.; Humphrey, M. G.; Samoc, M.; Luther-Davies, B.; Asselberghs, I., and Persoons, A. (2002). Organometallic Complexes for Nonlinear Optics. Part 25. Quadratic and Cubic Hyperpolarizabilities of some Dipolar and Quadrupolar Gold and Ruthenium Complexes. J. Organomet. Chem., 642, 259-262. (f) Hurst, S. K., and Ren, T. (2002). Synthesis, Characterization and Electrochemistry of Diruthenium Complexes Linked by Aryl Acetylide Bridges. J. Organomet. Chem., 660, 1-5. (g) Fraysse, S.; Coudret, S., and Launay, J. P. (2003). Molecular Wires Built from Binuclear Cyclometalated Complexes. J. Am. Chem. Soc., 125, 5880-5888. (h) Back, S.; Lutz, M.; Spek, A. L.; Lang, H., and van Koten, G. (2001). Preparation and Electrochemical Behaviour of Dinuclear Platinum Complexes Containing NCN Ligands (NCN=[C6H3(Me2NCH2)2-2,6]−). The Crystal Structure of [C6H3(Me2NCH2)2-1,3- (C≡C)-5]2. J. Organomet. Chem., 620, 227-234. (i) Weyland, T.; Ledoux, I.; Brasselet, S.; Zyss, J., and Lapinte, C. (2000). Nonlinear Optical Properties of Redox-Active Mono-, Bi-, and Trimetallic σ-Acetylide Complexes Connected Through a Phenyl Ring in the Cp*(dppe)Fe Series. An Example of Electro-Switchable NLO Response Organometallics, 19, 5235-5237. (j) Colbert, M. C. B.; Lewis, J.; Long, N. J.; Raithby, P. R.; Younus, M.; White, A. J. P.; Williams, D. J.; Payne, N. N.; Yellowlees, L.; Mixed Transition Metal Acetylides with Different Metals Connected … 427 Beljonne, D.; Chawdhury, N., and Friend, R. H. (1998). Synthesis and Characterization of Dinuclear Metal σ-Acetylides and Mononuclear Metal σ-Allenylidenes. Organometallics, 17, 3034-3043. (k) Bruce, M. I.; Hall, B. C.; Kelly, B. D.; Low, P. J.; Skelton, B. W., and White, A. H. J. (1999). An Efficient Synthesis of Polyynyl and Polyynediyl Complexes of Ruthenium(II). J. Chem. Soc., Dalton Trans., 19, 3719- 3728. (l) Lavastre, O.; Even, M.; Dixneuf, P. H.; Pacreau, A., and Vairon, J. (1996). Novel Ruthenium- or Iron-Containing Tetraynes as Precursors of Mixed-Metal Oligomers. Organometallics, 15, 1530-1531. [6] (a) Lam, S. C. F.; Yam, V. W. W.; Wong, K. M. C.; Cheng, E. C. C., and Zhu, N. (2005). Synthesis and Characterization of Luminescent Rhenium(I)-Platinum(II) Polypyridine Bichromophoric Alkynyl-Bridged Molecular Rods Organometallics, 24, 4298-4305. (b) Younus, M.; Long, N. J.; Raithby, P. R., and Lewis, J. (1998). Synthetic, Spectroscopic and Electrochemical Characterisation of Mixed-Metal Acetylide Complexes. J. Organomet. Chem., 570, 55-62. (c) Lavastre, O.; Plass, J.; Bachmann, P.; Guesmi, S.; Moinet, C., and Dixneuf, P. H. (1997). Ruthenium or Ferrocenyl Homobimetallic and RuPdRu and FePdFe Heterotrimetallic Complexes Connected by Unsaturated, Carbon-Rich -C≡CC6H4C≡C- Bridges. Organometallics, 16, 184-189. [7] (a) Fink, H.; Long, N. J.; Martin, A. J.; Opromolla, G.; White, A. J. P.; Williams, D. J., and Zanello, P. (1997). Ethynylferrocene Compounds of 1,3,5-Tribromobenzene. Organometallics, 16, 2646-2650. (b) Weyland, T.; Costuas, K.; Mari, A.; Halet, J. F., and Lapinte, C. (1998). [(Cp*)(dppe)Fe(III)]+ Units Bridged Through 1,3- Diethynylbenzene and 1,3,5-Triethynylbenzene Spacers: Ferromagnetic Metal-Metal Exchange Interaction. Organometallics, 17, 5569-5579. (c) Tykwinski, R. R., and Stang, P. J. (1994). Preparation of Rigid-Rod, Di- and Trimetallic, σ-Acetylide Complexes of Iridium(III) and Rhodium(III) via Alkynyl(pheny1)iodonium Chemistry Organometallics, 13, 3203-3208. (d) Müller, T. J. J., and Lindner, H. J. (1996). Palladium-Copper-Catalyzed Coupling of Tricarbonylchromium-Complexed Phenylacetylene with Iodoarenes. A Facile Access to Alkynyl-Bridged Cr(CO)3- Complexed Benzenes. Chem. Ber., 129, 607-613. (e) Irwin, M. J.; Manojlovic-Muir, L.; Muir, K. W.; Puddephatt, R. J., and Yufit, D. S. (1997). Trigold Triacetylides: Polymerization Through Gold···Gold Bonding or Bridging Ligands. Chem. Commun., 219-220. (f) Leininger, S.; Stang, P. J., and Huang S. (1998). Synthesis and Characterization of Organoplatinum Dendrimers with 1,3,5-Triethynylbenzene Building Blocks. Organometallics, 17, 3981-3987. [8] (a) Vicente, J.; Chicote, M. T., and Alvarez-Falcon, M. M. (2005). Platinum(II) and Mixed Platinum(II)/Gold(I) σ-Alkynyl Complexes. The First Anionic σ-Alkynyl Metal Polymers. Organometallics, 24, 2764-2772. (b) Chong, S. H. F.; Lam, S. C. F.; Yam, V. W. W.; Zhu, N.; Cheung, K. K.; Fathallah, S.; Costuas, K., and Halet, J. F. (2004). Luminescent Heterometallic Branched Alkynyl Complexes of Rhenium(I)- Palladium(II): Potential Building Blocks for Heterometallic Metallodendrimers. Organometallics, 23, 4924-4933. (c) Long, N. J.; Martin, A. J.; White, A. J. P.; Williams, D. J.; Fontani, M.; Laschi, F., and Zanello, P. (2000). Synthesis and Characterisation of Unsymmetrical Metal (RuII, OsII) and Ferrocenyl Complexes of 1,3,5-Triethynylbenzene. J. Chem. Soc., Dalton Trans., 3387-3392. (d) Long, N. J.; Heinrich Lang and Alexander Jakob 428 Martin, A. J.; De Biani, F. F., and Zanello, P. (1998). Synthetic and Electrochemical Studies of some Metal Complexes of 1,3,5-Triethynylbenzene. J. Chem. Soc., Dalton Trans., 2017-2022. [9] Lucas, N. T.; Cifuentes, M. P.; Nguyen, L. T., and Humphrey, M. G. (2001). Ruthenium Cluster Chemistry with Ph2PC6H4-4-C≡CH. J. Cluster Science, 12, 201- 221. [10] (a) Barbieri, A.; Ventura, B.; Flamigni, L.; Barigelletti, F.; Fuhrmann, G.; Baeuerle, P.; Goeb, S., and Ziessel, R. (2005). Binuclear Wirelike Dimers Based on Ruthenium(II)- Bipyridine Units Linked by Ethynylene-Oligothiophene-Ethynylene Bridges. Inorg. Chem., 44, 8033-8043. (b) Newkome, G. R.; Patri, A. K.; Holder, E., and Schubert, U. S. (2004). Synthesis of 2,2´-Bipyridines: Versatile Building Blocks for Sexy Architectures and Functional Nanomaterials. Eur. J. Org. Chem., 2, 235-254. (c) Hissler, M.; Harriman, A.; Khatyr, A., and Ziessel, R. (1999). Intramolecular Triplet Energy Transfer in Pyrene-Metal Polypyridine Dyads: A Strategy for Extending the Triplet Lifetime of the Metal Complex. Chem. Eur. J., 5, 3366-3381. (d) Constable, E. C. (1989). Homoleptic Complexes of 2,2'-Bipyridine. Advan. Inorg. Chem., 1989, 34, 1-63. (e) McWhinnie, W. R., and Miller, J. D. (1969). Chemistry of Complexes Containing 2,2'-Bipyridyl, 1,10-Phenanthroline, or 2,2',6',2"-Terpyridyl as Ligands. Advan. Inorg. Chem., Radiochem., 12, 135-215. [11] Le Stang, S.; Paul, F., and Lapinte, C. (2000). Molecular Wires: Synthesis and Properties of the New Mixed-Valence Complex [Cp*(dppe)Fe-C≡C-X- C≡CFe(dppe)Cp*][PF6] (X = 2,5 -C4H2S) and Comparison of its Properties with those of the Related All-Carbon-Bridged Complex (X = -C4-). Organometallics, 19, 1035- 1043. [12] Wong, W. Y.; Lu, G. L.; Ng, K. F.; Choi, K. H., and Lin, Z. (2001). Synthesis, Structures and Properties of Platinum(II) Complexes of Oligothiophene-Functionalized Ferrocenylacetylene. J. Chem. Soc., Dalton Trans., 22, 3250-3260. (b) Viola, E.; Lo Sterzo, C., and Trezzi, F. (1996). Formation of a Molybdenum-Iron Heterobimetallic Bis(acetylide) Derivative of 2,5-Diethynylthiophene via Palladium-Catalyzed Metal- Carbon Coupling. Organometallics, 15, 4352-4354. [13] Lang, H.; Packheiser, R., and Walfort, B. (2006). Organometallic π-Tweezers, NCN Pincers, and Ferrocenes as Molecular “Tinkertoys” in the Synthesis of Multiheterometallic Transition-Metal Complexes. Organometallics, 25, 1836-1851. [14] (a) Packheiser, R.; Walfort, B., and Lang, H. (2006). Heterobi- and Heterotrimetallic Transition Metal Complexes with Carbon-Rich Bridging Units. Organometallics, 25, 4579-4587. (b) Al-Anber, M.; Stein, T., and . Lang, H. (2005). Organometallic π- Tweezers Incorporating Pyrazine- and Pyridine-Based Bridging Units. Inorg. Chim. Acta, 358, 50-56. (c) Bruce, M. I.; Zaitseva, N. N.; Skelton, B. W.; Somers, N., and White, A. H. (2003). Crystal and Molecular Structures of Some Alkynyl-Group 9/Group 11 Complexes [M2m4(C2R)8(PPh3)2] (M = Rh, Ir; m = Cu, Ag; R = Ph, Fc (Ir/Cu only)). Aust. J. Chem., 56, 509-516. (d) Lang, H.; Stein, T.; Back, S., and Rheinwald, G. (2004). Titanocene-Based Group-11 Metal Ions; Solid-State Structure of [(η5-C5H4SiMe3)2Ti(C≡CPh)2]2AgNO3. J. Organomet. Chem., 689, 2690-2696. (e) Al- Anber, M.; Walfort, B.; Stein, T., and Lang, H. (2004). {[Ti](C≡CSiMe3)2}Ag(OClO3) π-Tweezer Units Bridged by Pyrazine. Inorg. Chim. Acta, 357, 1675-1681. (f) Lang, H.; Meichel, E.; Stein, Th.; Weber, C.; Kralik, J.; Rheinwald, G., and Pritzkow, H. (2002). Mixed Transition Metal Acetylides with Different Metals Connected … 429 Stabilisierung niedervalenter Ni(CO)-Bausteine durch [Ti](C≡CR)2; Reaktionsverhalten von {[Ti](C≡CR)2}Ni(CO) gegenüber Triphenylphosphan und Phosphiten. J. Organomet. Chem., 664, 150-160. (g) Stein, T., and Lang, H. (2002). Monomere Kupfer(I)-Alkyle mit β-Wasserstoffatomen und Kupfer(I)-Aryle mit kondensierten Aromaten; die Festkörperstruktur von [(η5-C5H4SiMe3)2Ti(C≡CSiMe3)2]CunC4H9. J. Organomet. Chem., 664, 142-149. (h) Stein, T.; Lang, H., and Holze, R. (2002).Intramolecular Intermetallic Interactions in Bi- and Tetrametallic Organometallic Complexes as Demonstrated with Cyclic Voltammetry, J. Electro. Chem., 520, 163-167. (i) Back, S.; Stein, T.; Frosch, W.; Wu, I.-Y.; Kralik, J.; Büchner, M.; Huttner, G.; Rheinwald, G., and Lang, H. (2001). Heterometallic Early–Late π- Tweezer Complexes: Their Synthesis, Electrochemical Behaviour and the Solid-State Structures of (η5- C5H4SiMe3)2Ti(C≡CPh)2 and [(η5-C5H4SiMe3)2Ti(C≡CPh)2]Pd(PPh3). Inorg. Chim. Acta., 325, 94-102. (j) Frosch, W.; Back, S.; Müller, H.; Köhler, K.; Driess, A.; Schiemenz, B.; Huttner, G., and Lang, H. (2001). Donor-funktionalisierte Alkinyle von Titan(IV), Kupfer(I) und Silber(I); Festkörperstrukturen von [Ti](C≡CCH2NMe2)2 und {[Ti](C≡CtBu)2}CuC≡CC≡CC2H5. J. Organomet. Chem., 619, 99-109. (k) Lang, H.; Mansilla, N., and Rheinwald, G. (2001). First Example of Zinc(II) Monomeric Species Stabilized by η2-Bonded Alkynes. Organometallics, 20, 1592-1596. (m) Frosch, W.; Back, S.; Rheinwald, G.; Köhler, K.; Zsolnai, L.; Huttner, G., and Lang, H. (2000). Mono-, Di-, and Tricarboxylic Acids: Central Building Blocks for the Formation of Multinuclear Transition Metal Complexes. Organometallics, 19, 5769-5779. (n) Lang, H.; George, D., and Rheinwald, G. (2000). Bis(alkynyl) Transition Metal Complexes, R1C≡C-[M]-C≡CR2, as Organometallic Chelating Ligands; Formation of μ,η1(2)- Alkynyl-Bridged Binuclear and Oligonuclear Complexes. Coord. Chem. Rev., 206-207, 101-197, and references cited therein. (o) Frosch, W.; Back, S.; Rheinwald, G.; Köhler, K.; Pritzkow, H., and Lang, H. (2000). (η2-Alkyne)2CuMe as a Synthetic Tool in the Preparation of Numerous Inorganic and Organic Copper(I) Species. Organometallics, 19, 4016-4024. (p) Rupp, R.; Huttner, G.; Lang, H.; Heinze, K.; Büchner, M., and Robert, E. (2000). Synthesis and π-Tweezer Properties of Tripod Cobalt-Bisalkynyl Compounds [CH3C(CH2PPh2)3Co(C≡CR)2] - Application to the Oxidative Coupling of Alkynyl Groups. Eup. J. Inorg. Chem., 9, 1953-1959. (q) Frosch, W.; del Vilar, A., and Lang, H. (2000). Heterobimetallische Komplexe von Titan(IV)-Quecksilber(II) und Platin(II)-Quecksilber(II). J. Organomet. Chem., 602, 91-96. (r) Frosch, W.; Back, S.; Köhler, K., and Lang, H. (2000). Zur Umsetzung von Bis(alkinyl)-Titanocenen mit Übergangsmetall-Verbindungen von Cu(II), Pd(II), Pt(II), Fe(III) und Au(III). J. Organomet. Chem., 601, 226-232. (s) Back, S.; Rheinwald, G., and Lang, H. (2000). Synthesis, Electrochemistry and Electronic Spectra of Tetranuclear Bis(η2-alkynyl) Transition-Metal Complexes. The Molecular Structure of [(η5-C5H4SiMe3)2Ti(C≡CFc)2]CuBr. J. Organomet. Chem., 601, 93-99. (t) Lang, H.; Weinmann, S.; Wu, I. Y.; Stein, T.; Jacobi, A., and Huttner, G. (1999). (η5- C5H4SiMe3)2Ti(C≡C–SiMe2–C≡CSiMe3)2: a Unique Entry to Monomeric and Oligomeric Alkyne–Copper(I) and Alkyne–Silver(I) Halides. J. Organomet. Chem., 575, 133-140. (u) Lang, H., and Rheinwald, G. (1999). Kupfer, Silber, Gold; fixiert in metallorganischen π-Pinzetten. J. Prakt. Chem., 341, 1-19. (v) Back, S.; Pritzkow, H., and Lang, H. (1998). C2-Bridged Titanocene-Ferrocenyl Complexes: Synthesis, Reaction Chemistry, and Electrochemical Behavior. Organometallics, 17, 41-44. (w) Heinrich Lang and Alexander Jakob 430 Hayashi, Y.; Osawa, M.; Kobayashi, K.; Sato, T.; Sato, M., and Wakatsuki, Y. (1998). The Reaction of Titanocene Bis(ferrocenylacetylide) and Bis(ruthenocenylacetylide) with Silver Cation: Formation of Bis(Ti-Tweezers) Silver Complexes. J. Organomet. Chem., 569, 169-175. (x) Back, S.; Rheinwald, G.; Zsolnai, L.; Huttner, G., and Lang H. (1998). Synthesis, Reaction Chemistry and Electrochemical Behaviour of (η5- C5H4SiMe3)2Hf(C≡CFc)2. J. Organomet. Chem., 563, 73-79. (y) Koehler, K.; Silverio, S.; Hyla-Kryspin, I.; Gleiter, R.; Zsolnai, L.; Driess, A.; Huttner, G., and Lang, H. (1997). Trigonal-Planar-Coordinated Organogold(I) Complexes Stabilized by Organometallic 1,4-Diynes: Reaction Behavior, Structure, and Bonding. Organometallics, 16, 4970-4979. (z) Lang, H., and Weinmann, M. (1996). Bis(alkynyl) Titanocenes as Organometallic Chelating Ligands for the Stabilization of Monomeric Organo Copper(I) Compounds. Synlett, 1, 1-10. (aa) Hayashi, Y.; Osawa, M.; Kobayashi, K., and Wakatsuki, Y. (1996). Reductive Elimination by Remote Electron Transfer Activation in C4-Bridged Titanocene-Ferrocenyl Complexes. Chem. Commun., 1617-1618. (bb) Janssen, M. D.; Herres, M.; Zsolnai L.; Grove, D. M.; Spek, A. L., and Lang, H. (1995). A Stable Bimetallic Copper(I) Titanium Acetylide. Organometallics, 14, 1098-1100. (cc) Janssen, M. D.; Smeets, W. J. J.; Spek, A. L.; Grove, D.M.; Lang, H., and van Koten, G. (1995). Intramolecular Addition of Monomeric Arylcopper Entities Across an Alkyne Grouping in a Complex of Type [(η5-C5H4SiMe3)2- Ti(C≡CSiMe3)2]CuR; X-ray Structure of [(η5-C5H4SiMe3)2Ti(C≡CSiMe3)(μ- C=C(SiMe3)(C6H3(CH2NMe2)2-2,6))Cu]. J. Organomet. Chem., 505, 123-126. (dd) Janssen, M. D.; Herres, M.; Spek, A. L.; Grove, D. M.; Lang, H., and van Koten, G. (1995). Monomeric Bis(η2-Alkyne) Complexes of (η1-Mesityl)Copper(I) and (η1- mesityl)Silver(I) Obtained from a Bis(Alkynyl)Titanocene; X-ray Structure of [(η5- C5H4SiMe3)2Ti(C≡CSiMe3)2]Cu(η1-Mes) (Mes = C6H2Me3-2,4,6). J. Chem. Soc., Chem. Commun., 925-926. (ee) Janssen, M. D.; Herres, M.; Zsolnai, L.; Spek, A. L.; Grove, D. M.; Lang, H., and van Koten, G. (1996). Monomeric Bis(η2- Alkyne)Copper(I) and -Silver(I) Halides, Pseudohalides, and Arenethiolates. Inorg. Chem., 35, 2476-2483. (ff) Back, S.; Rheinwald, G., and Lang, H. (1999). Synthesis and Electrochemistry of a Bis- η2-Coordinated Tetrametallic Transition-Metal Complex. Crystal Structure of [(η5-C5H4SiMe3)2Ti(C≡CFc)2]Pd(PPh3). Organo- metallics, 18, 4119-4122. (gg) Lang, H., and Leschke, M. (2002). From Heterobimetallic Transition Metal Complexes to Linear Coordination Polymers Based on cis- and trans-L2Pt(C≡CPh)2. Heteroat. Chem., 13, 521-533. [15] (a) Gosiewska, S.; Martinez, S. H.; Lutz, M.; Spek, A. L.; van Koten, G., and Klein Gebbink, R. J. M. (2006). Diastereopure Cationic NCN-Pincer Palladium Complexes with Square Planar η4-N,C,N,O Coordination. Eup. J. Inorg. Chem., 22, 4600-4607. (b) Köcher, S.; Lutz, M.; Spek, A. L.; Prasad, R.; van Klink, G. P.M.; van Koten, G., and Lang, H. (2006). Heterobimetallic Fe–Pd and Fe–Pt NCN Pincer Complexes (NCN = [C6H2(CH2NMe2)2-2,6]−). Inorg. Chim. Acta, 359, 4454-4462. (c) Szabo, K. J. (2006). Palladium-Pincer-Complex-Catalyzed Transformations Involving Organometallic Species. Synlett, 6, 811-824. (d) Slagt, M. Q.; van Zwieten, D. A.P.; 144 Heinrich Lang and Alexander Jakob Moerkerk, A. J. C. M; Klein Gebbink, R. J. M., and van Koten, G. (2004). NCN–Pincer Palladium Complexes with Multiple Anchoring Points for Functional Groups. Coord. Chem. Rev., 248, 2275-2282. (e) van der Boom, M., and Milstein, D. (2003). Cyclometalated Phosphine-Based Pincer Complexes: Mechanistic Mixed Transition Metal Acetylides with Different Metals Connected … 431 Insight in Catalysis, Coordination, and Bond Activation. Chem. Rev., 103, 1759-1792. (f) Singleton, J. T. (2003). The Uses of Pincer Complexes in Organic Synthesis. Tetrahedron, 59, 1837-1857. (g) Martin, A., and van Koten, G. (2001). Platinum Group Organometallics Based on „Pincer” Complexes: Sensors, Switches, and Catalysts. Angew. Chem. Int. Ed., 40, 3750-3781. (h) Gossage, R.; van de Kuil, L. A., and van Koten, G. (1998). Diaminoarylnickel(II) "Pincer" Complexes: Mechanistic Considerations in the Kharasch Addition Reaction, Controlled Polymerization, and Dendrimeric Transition Metal Catalysts. Acc. Chem. Res., 31, 423-431. (i) Rietveld, M. H. P.; Grove, D. M., and van Koten, G. (1997). Recent Advances in the Organometallic Chemistry of Aryldiamine Anions that Can Function as N,C,N'- and C,N,N'- Chelating Terdentate "Pincer" Ligands: an Overview. New J. Chem., 21, 751-771. [16] Sutcliffe, O. B., and Bryce, M. R. (2003). Planar Chiral 2-Ferrocenyloxazolines and 1,1′-Bis(oxazolinyl)ferrocenes: Syntheses and Applications in Asymmetric Catalysis. Tetrahedron: Asymmetry, 14, 2297-2325. (b) Dai, L.-X.; Tu, T.; You, S.-L.; Deng, W.- P., and Hou, X.-L. (2003). Asymmetric Catalysis with Chiral Ferrocene Ligands. Acc. Chem. Res., 36, 659-667. (c) Herberhold, M. (2002). 1,1´-Ferrocenedi(amido) Chelate Ligands in Titanium and Zirconium Complexes. Angew. Chem. Int. Ed., 41, 956-958. (d) Colacot, T. J. (2001). Ferrocenyl Phosphine Complexes of the Platinum Metals in Non-Chiral Catalysis. Platinum Metals Rev., 45, 22-30. (e) Bandoli, G., and Dolmella, A. (2000). Ligating Ability of 1,1′-Bis(diphenylphosphino)ferrocene: a Structural Survey (1994-1998). Coord. Chem. Rev., 209, 161-196. (f) Vogler, A., and Kunkely, H. Photochemistry (2000). Induced by Metal-to-Ligand Charge Transfer Excitation. Coord. Chem. Rev., 208, 321-329. (g) Thomas, J. M.; Maschmeyer, T.; Johnson, B. F. G. (1999). Shephard, D. S. Constrained Chiral Catalysts. J. Mol. Catalysis A: Chemical, 141, 139-144. (h) Beyer, L.; Richter, R., and Seidelmann, O. (1999). Ferrocensubstituierte 1,3-bidentate Liganden und ihre heteronuklearen Übergangsmetallchelate. J. Prakt. Chem., 341, 704-726. (i) Fong, A. S.-W., and Hor, A. T. S. (1998). Clusters and Aggregates of 1,1′-Bis(diphenylphosphino)ferrocene (dppf). J. Cluster Sci., 9, 351-392. [17] Haussler, M.; Sun, Q.; Xu, K.; Lam, J. W. Y.; Dong, H., and Tang, B. Z. (2005). Hyperbranched Poly(ferrocenylene)s Containing Groups 14 and 15 Elements: Syntheses, Optical and Thermal Properties, and Pyrolytic Transformations into Nanostructured Magnetoceramics. J. Inorg. Organomet. Poly. Mat., 15, 67-81. (b) Fery-Forgues, S., and Delavaux-Nicot, B. (2000). Ferrocene and Ferrocenyl Derivatives in Luminescent Systems. J. Photochem. Photobio., 132, 137-159. (c) Yuan, Z.; Collings, J.; Taylor, N. J.; Marder, T. B.; Jardin, C., and Halet, J.-F. (2000). Linear and Nonlinear Optical Properties of Three-Coordinate Organoboron Compounds. J. Solid State Chem., 154, 5-12. (d) Delville, M.-H. (1999). Organometallic Electron Reservoir Sandwich Iron Complexes as Potential Agents for Redox and Electron Transfer Chain Catalysis. Inorg. Chim. Acta, 291, 1-19. (e) Bethell, D.; Schiffrin, D. J., and Brust, M. (1996). Method of Synthesizing Materials Having Controlled Electronic, Magnetic, and/or Optical Properties. PCT Int. Appl., 56 pp. PIXXD2 WO 9607487 A1 19960314 Can 125:24123 AN 1996:365688. (f) Sokolov, V. I. (1995). Optically Active Organometallic Compounds (a Personal Account from the Inside). J. Organomet. Chem., 500, 299-306. (g) Astruc, D.; Desbois, M. -H.; Lacoste M., Moulines, F.; Heinrich Lang and Alexander Jakob 432 Hamon, J. -R., and Varret, F. (1990). Iron Sandwiches as Molecular Reservoir Materials: Design, Electronic Properties and Prospects. Polyhedron, 2727-2732. [18] Special issue, “50th Anniversary of the Discovery of Ferrocene”. (2001). J. Organomet. Chem., 637-639 (Adams, R. D., Ed.), and references cited therein. [19] For example: (a) Rüffer, T.; Ohashi, M., Shima, A.; Mizomoto, H.; Kaneda, Y., and Mashima, K. (2004). Unique Oxidative Metal-Metal Bond Formation of Linearly Aligned Tetranuclear Rh-Mo-Mo-Rh Clusters. J. Am. Chem. Soc., 126, 12244-12245 and references cited therein. (b) Sterenberg, B. T.; Scoles, L., and Carty, A. J. (2002). Synthesis, Structure, Bonding and Reactivity in Clusters of the Lower Phosphorus Oxides. Coord. Chem. Rev., 231, 183-197. (c) Adams R. D., and Qu, B. (2001). Mixed Metal Cluster Complexes Containing the Bis-Ferrocenylbutadiyne Ligand: Their Structures and Electrochemical Responses. J. Organomet. Chem., 620, 303-307. (d) Bruce, M. I.; Low, P. J.; Ke, M.; Kelly, B. D.; Skelton, B. W.; Smith, M. E.; White, A. H., and Witton, N. B. (2001). Some Chemistry of Diynyl-Tungsten Complexes. Aust. J. Chem., 54, 453-460. (e) Bruce, M. I., and Humphrey, M. G. (2000). Organo-Transition Metal Cluster Compounds. Organomet. Chem., 28, 275-366. (f) Blenkiron, P.; Enright, G. D., and Carty, A. J. (1997). Polycarbon Ligand Chemistry. Novel Behaviour of μ- η1,η2__-Butadiynyls towards Metal Fragment Additions. Chem. Commun., 5, 483-484. (g) Doherty, S.; Corrigan, J. F.; Carty, A. J., and Sappa, E. (1995). Homometallic and Heterometallic Transition Metal Allenyl Complexes: Synthesis, Structure, and Reactivity. Adv. Organomet. Chem., 37, 39-130. (h) Bantel, H.; Powell, A. K., and Vahrenkamp, H. (1990). Alkyne-Bridged Tetranuclear Clusters by Expansion of Trinuclear Clusters. Chem. Ber., 123, 677-684. (i) Huttner, G., and Knoll, K. (1987). RP-Bridged Carbonyl Metal Clusters: Synthesis, Properties and Reactions. Angew. Chem., 99, 765-783. [20] (a) Taher, D., Walfort, B., and Lang, H. (2004). A New Approach to Novel Homobimetallic Palladium Complexes. Inorg. Chem. Commun., 7, 1006-1009. (b) Taher, D.; Walfort, B.; van Koten, G., and Lang, H. (2006). Thiol End-Capped One- Dimensional Platinum and Palladium Complexes. Inorg. Chem. Commun., 9, 955-958. (c) Lang, H.; Taher, D.; Walfort, B., and Pritzkow, H. (2006). Linear Homobimetallic Palladium Complexes. J. Organomet. Chem., 691, 3834-3845. (d) Jung, D. R., and Czanderna, A. W. (1994). Chemical and Physical Interactions at Metal/Self-Assembled Organic Monolayer Interfaces. Crit. Rev. Solid State Mater. Sci., 19, 1-54. (e) Herdt, G. C.; Jung, D. R., and Czanderna, A. W. (1995). Weak Interactions between Deposited Metal Overlayers and Organic Functional Groups of Self-Assembled Monolayers. Prog. Surf. Sci., 50, 103-129. (f) Tarlov, M. J. (1992). Silver Metalization of Octadecanethiol Monolayers Self -Assembled on Gold. Langmuir, 8, 80-89. (g) Ohgi, T.; Sheng, H. Y.; Dong, Z. C., and Nejoh, H. (1999). Observation of Au Deposited Self-Assembled Monolayers of Octanethiol by Scanning Tunneling Microscopy. Surf. Sci., 442, 277-282. (h) Ohgi, T.; Fujita, D.; Dong, Z. C., and Nejoh, H. (2001). Scanning Tunneling Microscopy and X-Ray Photoelectron Spectroscopy of Silver Deposited Octanethiol Self-Assembled Monolayers. Surf. Sci., 493, 453-459. (i) Fisher, G. L.; Hooper, A. E.; Opila, R. L.; Allara, D. L., and Winograd, N. (2000). he 146 Heinrich Lang and Alexander Jakob Interaction of Vapor-Deposited al Atoms with CO2H Groups at the Surface of a Self- Assembled Alkanethiolate Monolayer on Gold. J. Phys. Chem. B, 104, 3267-3273. (j) Konstadinidis, K.; Zhang, P.; Opila, R. L., and Mixed Transition Metal Acetylides with Different Metals Connected … 433 Allara, D. L. (1995). An In-Situ X-Ray Photoelectron Study of the Interaction between Vapor-Deposited Ti Atoms and Functional Groups at the Surfaces of Self-Assembled Monolayers. Surf. Sci., 338, 300- 312. (k) Hooper, A. E.; Fisher, G. L.; Konstadinidis, K.; Jung, D.; Nguyen, H.; Opila, R. L.; Collins, R. W.; Winograd, N., and Allara, D. L. (1999). Chemical Effects of Methyl and Methyl Ester Groups on the Nucleation and Growth of Vapor-Deposited Aluminum Films. J. Am. Chem. Soc., 121, 8052-8064. (l) Fisher, G. L.; Walker, A. V.; Hooper, A. E.; Tighe, T. B.; Bahnck, K. B.; Skriba, H. T.; Reinard, M. D.; Haynie, B. C.; Opila, R. L.; Winograd, N., and Allara, D. L. (2002). Bond Insertion, Complexation, and Penetration Pathways of Vapor-Deposited Aluminum Atoms with HO- and CH3OTerminated Organic Monolayers. J. Am. Chem. Soc., 124, 5528-5541. (m) Carlo, S. R.; Wagner, A. J., and Fairbrother, D. H. (2000). Iron Metalization of Fluorinated Organic Films: A Combined X-ray Photoelectron Spectroscopy and Atomic Force Microscopy Study. J. Phys. Chem. B, 104, 6633-6641. (n) Nuzzo, R. G., and Allara, D. L. (1983). Adsorption of Bifunctional Organic Disulfides on Gold Surfaces. J. Am. Chem. Soc., 105, 4481-4483. (o) Lehn, J. M. (1995). Supramolecular Chemistry-Concepts and Perspectives. Weinheim, Germany: VCH. (p) Mayor, M.; von Hänisch, C.; Weber, H. B.; Reichert, J., and Beckmann, D. (2002). A trans-Platinum(II) Complex as a Single-Molecule Insulator. Angew. Chem., Int. Ed., 41, 1183-1186. (q) Mayor, M., and Weber, H. B. (2004). Statistical Analysis of Single-Molecule Junctions. Angew. Chem., 43, 2942-2884. (r) van Ryswyk, H.; Moore, E. E.; Joshi, N. S.; Zeni, R. J.; Eberspacher, A. T., and Collman, J. P. (2004). Surface- Confined Metalloporphyrin Oligomers. Angew. Chem., 43, 5827-5830. [21] (a) Creutz, C., and Taube, H. (1969). A Direct Approach to Measuring the Franck- Condon Barrier to Electron Transfer between Metal Ions. J. Am. Chem. Soc., 91, 3988- 3989. (b) C. Creutz, C. (1983). Mixed Valence Complexes of d5-d6 Metal Centers. Prog. Inorg. Chem., 30, 1-73. (c) Creutz, C.; Newton, M. D., and Sutin, N. (1994).Metal-Ligand and Metal-Metal Coupling Elements. J. Photochem. Photobiol. A: Chem.,82, 47-59. [22] For further literature see: (a) Ward, M. D. (1995). Metal-Metal Interactions in Binuclear Complexes Exhibiting Mixed Valency; Molecular Wires and Switches. Chem. Soc. Rev., 24, 121-134. (b) Barlow, S., and O´ Hare, D. (1997). Metal-Metal Interactions in Linked Metallocenes. Chem. Rev., 97, 637-669. (c) Whittall, I. R., McDonagh, A. M., Humphrey and M. G.; Samoc, M. (1998). Organometallic Complexes in Nonlinear Optics II: Third-Order Nonlinearities and Optical Limiting Studies. Adv. Organomet. Chem., 43, 349-405. (d) Astruc, D. (1997). From Organotransition-Metal Chemistry Toward Molecular Electronics: Electronic Communication Between Ligand-Bridged Metals. Acc. Chem. Res., 30, 383-391. (e) Skibar, W., Kopacka, H., Wurst, K., Salzmann, C., Ongania, K. H., de Biani, F. F., Zanello, P., and Bildstein, B. (2004). α,ω-Diferrocenyl Cumulene Molecular Wires. Synthesis, Spectroscopy, Structure, and Electrochemistry. Organometallics, 23, 1024-1041. (f) Chung, M. C.; Gu, X.; Etzenhouser, R. A.; Spuches, A. M.; Rye, P. T.; Seetharaman, S. K.; Rose, D. J., Zubieta, J., and Sponsler, M. B. (2003). Intermetal Coupling in [(η5-C5R5)Fe(dppe)]2(μ- CH=CHCH=CH) and in Their Dicationic and Monocationic Mixed-Valence Forms. Organometallics, 22, 3485-3494. (g) Zheng, Q.; Hampel, F., and Gladysz, J. A. (2004). Longitudinally Extended Molecular Wires Based upon PtC≡CC≡CC≡CC≡C Repeat Heinrich Lang and Alexander Jakob 434 Units: Iterative Syntheses of Functionalized Linear PtC8Pt, PtC8PtC8Pt, and PtC8PtC8PtC8Pt Assemblies. Organometallics, 23, 5896-5899. (h) Chanda, N.; Sarkar, B.; Fiedler, J.; Kaim, W., and Lahiri, C. K. (2003). Synthesis and Mixed Valence Aspects of [{(L)ClRu}2(μ-tppz)]n+ incorporating 2,2´-Dipyridylamine (L) as Ancillary and 2,3,5,6-Tetrakis(2-pyridyl)pyrazine (tppz) as Bridging Ligand. Dalton Trans., 18, 3550-3555. (i) Venkatesan, K.; Blacque, O., and Berke, H. (2006). Metallacumulenes as Potential Electron Reservoir Devices. Organometallics, 25, 5190-5200. (j) Akita, M.; Sakurai, A.; Chung, M.-C., and Moro-oka, Y. (2003). Cluster Compounds Containing a Linear Carbon Chain Derived From Polyynediyl and Polyynyl Complexes, Fp*- (C≡C)n-X [X = Fp*, H; Fp*=Fe(η5-C5Me5)(CO)2]. J. Organomet. Chem., 670, 2-10 and references cited therein. (k) Nguyen, P.; Gomez-Elipe, P., and Manners, I. (1999). Organometallic Polymers with Transition Metals in the Main Chain. Chem. Rev., 99, 1515-1548. (l) Paul, F., and Lapinte C. (1998). Organometallic Molecular Wires and other Nanoscale-Sized Devices. An Approach Using the Organoiron (dppe)Cp*Fe Building Block. Coord. Chem. Rev., 178-180, 431-509. (m) Sauvage, J. P.; Collin, J. P.; Chambron, J. C.; Guillerez, S.; Coudret, C.; Balzani, V.; Barigelletti, F.; De Cola, L., and Flamigni, L. (1994). Ruthenium(II) and Osmium(II) Bis(terpyridine) Complexes in Covalently-Linked Multicomponent Systems: Synthesis, Electrochemical Behavior, Absorption Spectra, and Photochemical and Photophysical Properties. Chem. Rev., 94, 993-1019. (n) Low, P. J., and Bruce, M. I. (2001). Transition Metal Chemistry of 1,3- Diynes, Polyynes, and Related Compounds. Adv. Organomet. Chem., 48, 71-286. (o) Rigaut, S.; Massue, J.; Touchard, D.; Fillaut, J. L.; Golhen, S., and Dixneuf, P. H. (2002). Unprecedented Coupling of Allenylidene and Diynyl Metal Complexes: A Bimetallic Ruthenium System with a C7 Conjugated Bridge. Angew. Chem., Int. Ed., 41(23), 4513-4517. (p) Schwab, P. F. H.; Levin, M. D., and Michl, J. (1999). Molecular Rods. 1. Simple Axial Rods. Chem. Rev., 99, 1863-1933. (q) Weyland, T.; Costuas, K.; Toupet, L.; Halet, J. F., and Lapinte, C. (2000). Organometallic Mixed-Valence Systems. Two-Center and Three-Center Compounds with meta Connections around a Central Phenylene Ring. Organometallics, 19, 4228-4239. (r) Ceccon, A.; Santi, S.; Orian, L., and Bisello, A. (2004). Electronic Communication in Heterobinuclear Organometallic Complexes through Unsaturated Hydrocarbon Bridges. Coord. Chem. Rev., 248, 683-724. (s) Mantovani, N.; Brugnati, M.; Gonsalvi, L.; Grigiotti, E.; Laschi, F.; Marvelli, L.; Peruzzini, M.; Reginato, G.; Rossi, R., and Zanello, P. (2005). Synthesis, Characterization, and Electrochemical Behavior of Mono- and Bimetallic Ruthenium and Rhenium Allenylidenes Bearing Multiconjugated Organic Spacers. Organometallics, 24, 405-418. (t) Le Narvor, N., and Lapinte, C. (1993). First C4 Bridged Mixed-Valence Iron(II)–Iron(III) Complex Delocalized on the Infrared TimeScale. J. Chem. Soc., Chem. Commun., 4, 357-359. (u) Dewhurst, R. D.; Hill, A. F., and Willis, A. C. (2005). Stoichiometric and Catalytic Demercuration of is(tricarbido) mercurials: The First Dimetallaoctatetraynes. Organometallics, 24, 3043- 3046. (v) Roue, S.; Lapinte, C., and Bataille, T. (2005). Organometallic Mixed-Valence Systems. Electronic Coupling through an Alkyndiyl Bridge Incorporating Methylene Groups. Organometallics, 23, 2558-2567. (w) Coat, F.; Paul, F.; Lapinte, C.; Toupet, L.; Costuas, K., and Halet, J. F. (2003). Chemistry of the 1,3,5,7-Octatetraynediyl Carbon Rod End-Capped by Two Electron-Rich (η5-C5Me5)(η2-dppe)Fe Groups. J. Organomet. Chem., 683, 368-378. (x) Roue, S.; Le Stang, S.; Toupet, L., and Lapinte, Mixed Transition Metal Acetylides with Different Metals Connected … 435 C. (2003). Magnetic Communication Between two [(η5-C5Me5)(η2-dppe)Fe(III)] Units Mediated by the 2,5-Bis(ethynyl)thiophene Spacer. C. R. Chim., 6, 353-366. (y) Jiao, H.; Costuas, K.; Gladysz, J. A.; Halet, J. F.; Guillemot, M.; Toupet, L.; Paul, F., and Lapinte, C. (2003). Bonding and Electronic Structure in Consanguineous and Conjugal Iron and Rhenium sp Carbon Chain Complexes [MC4M']n+: Computational Analyses of the Effect of the Metal. J. Am. Chem. Soc., 125, 9511-9522. (z) Bruce, M. I.; Ellis, B. G.; Skelton, B. W., and White, A. H. (2005). Further Reactions of some Bis(vinylidene)diruthenium Complexes. J. Organomet. Chem., 690, 792-801. (aa) Bruce, M. I.; Buntine, M. A.; Costuas, K.; Ellis, B. G.; Halet, J. F.; Low, P. J.; Skelton, B. W., and White, A. H. (2004). Some Ruthenium Complexes Containing Cyanocarbon Ligands: Syntheses, Structures and Extent of Electronic Communication in Binuclear Systems. J. Organomet. Chem., 689, 3308-3326. (bb) Liu, S. H.; Xia, H.; Wan, K. L.; Yeung, R. C. Y.; Hu, Q. Y., and Jia, G. (2003). Synthesis of [TpRu(CO)(PPh3)]2(μ- CH=CH-CH=CH-C6H4-CH=CH-CH=CH) from Wittig Reactions. J. Organomet. Chem., 683, 331-336. (cc) Cifuentes, M. P., and Humphrey, M. G. (2004). Alkynyl Compounds and Nonlinear Optics. J. Organomet. Chem., 689, 3968-3981. (dd) Novikova, L. N.; Peterleitner, M. G.; Sevumyan, K. A.; Semeikin, O. V.; Valyaev, D. A.; Ustynyuk, N. A.; Khrustalev, V. N.; Kuleshova, L. N., and Antipin, M. Y. (2001). Oxidative Dehydrodimerization of Manganese Phenylvinylidene Complex (η5- C5H5)(CO)2Mn=C=C(H)Ph. X-ray Structure of Phenyl(trityl)vinylidene Complex (η5- C5H5)(CO)2Mn=C=C(CPh3)Ph. J. Organomet. Chem., 631, 47-53. (ee) Vicente, J.; Chicote, M. T.; Alvarez-Falcon, M. M., and Bautista, D. (2004). The First Metal Complexes Derived from 3,5-Diethynylpyridine. X-ray Crystal Structure of [(AuPTo3)2{μ-(C≡C)2Py}] (Py = Pyridine-3,5-diyl; To = p-Tolyl). Organometallics, 23, 5707-5712. (ff) Weyland, T.; Ledoux, I.; Brasselet, S.; Zyss, J., and Lapinte, C. (2000). Nonlinear Optical Properties of Redox-Active Mono-, Bi-, and Trimetallic σ-Acetylide Complexes Connected through a Phenyl Ring in the Cp*(dppe)Fe Series. An Example of Electro-Switchable NLO Response. Organometallics, 19, 5235-5237. (gg) Yam, V. W. W.; Tao, C. H.; Zhang, L.; Wong, K. M. C., and Cheung, K. K. (2001). Synthesis, Structural Characterization, and Luminescence Properties of Branched Palladium(II) and Platinum(II) Acetylide Complexes. Organometallics, 20, 453-459. (hh) Russo, M. V.; LoSterzo, C.; Franceschini, P.; Biagini, G., and Furlani, A. (2001). Synthesis of Highly Ethynylated Mono and Dinuclear Pt(II) Tethers Bearing the 4,4′- Bis(ethynyl)biphenyl (debp) Unit as Central Core. J. Organomet. Chem., 619, 49-61. (ii) Hoshino, Y. (2001). Molecular Design for Long-Range Electronic Communication between Metals Polyyne and Ethynylated Aromatic Systems as Molecular Wires in Binuclear Ruthenium β-Diketone Complexes. Platinum Met. Rev., 45, (1), 2-11. (jj) Meyer, W. E.; Amoroso, A. J.; Horn, C. R.; Jaeger, M., and Gladysz, J. A. (2001). Synthesis and Oxidation of Dirhenium C4, C6, and C8 Complexes of the Formula (η5- C5Me5)Re(NO)(PR3)(C≡C)n(R3P)(ON)Re(η5-C5Me5) (R = 4-C6H4R', c-C6H11): In Search of Dications and Radical Cations with Enhanced Stabilities. Organometallics, 20, 1115-1127. (kk) Doppiu, A.; Minghetti, G.; Cinellu, M. A.; Stoccoro, S.; Zucca, A., and Manassero, M. (2001). Unprecedented Behavior of 2,2':6',2' '-Terpyridine: Dinuclear Platinum(II) Derivatives with a New N,C^C,N Bridging Ligand. Organometallics, 20, 1148-1152. (ll) Matsuzaka, H.; Okimura, H.; Sato, Y.; Ishii, T.; Heinrich Lang and Alexander Jakob 436 Yamashita, M.; Kondo, M.; Kitagawa, S., and Shiro, M.; Yamasaki, M. (2001). Synthesis, Structure and Reactivities of the Dinuclear μ-η1:η6-Arylethynyl Ruthenium Complexes [Cp(PR3)2Ru(μ-η1:η6-C≡CC6H4Me-p)RuCp*]·Cl (R = Ph, Me; Cp = η5- C5H5, Cp* = η5-C5Me5). The Molecular Structure of [Cp(PPh3)2Ru(μ-η1:η6- C≡CC6H4Me-p)RuCp*]·PF6. J. Organomet. Chem., 625, 133-139. (mm) Ara, I.; Berenguer, J. R.; Eguizabal, E.; Fornies, J.; Gomez, J.; Lalinde, E., and Saez-Rocher, J. M. (2000). Synthesis, Photophysical Properties, and Theoretical Studies of Hydride- Alkynyl Platinum(II) Complexes. Molecular Structures of [trans-PtH(C≡CC5H4N- 2)(PPh3)2] and [Pt(η2-HC≡CCPh2OH)(PPh3)2]. Organometallics, 19, 4385-4397. (nn) Hartmann, H.; Scheiring, T.; Fiedler, J., and Kaim, W. (2000). Structures and Spectroelectrochemistry (UV–vis, IR, EPR) of Complexes [(OC)3ClRe]n(abpy), n = 1, 2; abpy = 2,2′-Azobispyridine. J. Organomet. Chem., 604, 267-272. (oo) Hartbaum, C.; Mauz, E.; Roth, G.; Weissenbach, K., and Fischer, H. (1999). Bimetallic Complexes with Conjugated C4, C6, C10, and C14 Bridges: Synthetic Routes to Alkynediyl-Bridged Bis(carbene) Complexes. Organometallics, 18, 2619-2627. (pp) Peters, T. B.; Bohling, J. C.; Arif, A. M., and Gladysz, J. A. (1999). C8 and C12 sp Carbon Chains That Span Two Platinum Atoms: The First Structurally Characterized 1,3,5,7,9,11-Hexayne. Organometallics, 18, 3261-3263. (qq) Xia, H. P.; Ng, W. S.; Ye, J. S.; Li, X. Y.; Wong, W. T.; Lin, Z.; Yang, C., and Jia, G. (1999). Synthesis and Electrochemical Properties of C5H-Bridged Bimetallic Iron, Ruthenium, and Osmium Complexes. Organometallics, 18, 4552-4557. (rr) Kheradmandan, S.; Heinze, K.; Schmalle, H. W., and Berke, H. (1999). Electronic Communication in C4-Bridged Binuclear Complexes with Paramagnetic Bisphosphane Manganese End Groups. Angew. Chem. Int. Ed., 38, 2270-2273. (ss) Sato, M.; Iwai, A., and Watanabe, M. (1999). Synthesis and Redox Behavior of Ruthenium(II) 2,3,4,5-Tetramethylruthenocenylacetylide and Related Complexes. Formation of μ-η6:η1-[(Cyclopentadienylidene)ethylidene]diruthenium Complexes Containing a Strong Metal-Metal Interaction. Organometallics, 18, 3208- 3219. (tt) Sakurai, A.; Akita, M., and Moro-oka, Y. (1999). Synthesis and Characterization of the Dodecahexaynediyldiiron Complex, Fp*-(C≡C)6-Fp* [Fp* =Fe(η5-C5Me5)(CO)2], the Longest Structurally Characterized Polyynediyl Complex. Organometallics, 18, 3241-3244. (uu) Glöckle, M., and Kaim, W. (1999). An Exceedingly Stable Diiron(II,III) Complex Ion [(tz){Fe(CN)5}2]5- with Comproportionation Constants between 108 (in H2O) and 1019 (in CH3CN). Angew. Chem. Int. Ed., 38, 3072-3074. (vv) Coat, F.; Guillemot, M.; Paul, F., and Lapinte, C. (1999). First Synthesis and Spectroscopic Characterization of Isolated Butatrienylidene Complexes of Transition Metals. J. Organomet. Chem., 578, 76-84. (ww) Akita, M.;Chung, M. C.; Sakurai, A.; Sugimoto, S.; Terada, M.; Tanaka, M., and Moro-oka, Y. (1997). Synthesis and Structure Determination of the Linear Conjugated Polyynyl and Polyynediyl Iron Complexes Fp*-(C≡C)n-X (X = H (n = 1, 2); X = Fp* (n = 1, 2, 4); Fp* = (η5-C5Me5)Fe(CO)2). Organometallics, 16, 4882-4888. (xx) Steenwinkel, P.; Grove, D. M.; Veldman, N.; Spek, A. L., and van Koten, G. (1998). Ionic 4,4'- Biphenylene-Bridged Bis-ruthenium Complexes [Ru2(4,4'-{C6H2(CH2NMe2)2- 2,6}2)(terpy)2]n+ (n = 2 and 4) and their Reversible Redox Interconversion: A Molecular Switch. Organometallics, 17, 5647-5655. Mixed Transition Metal Acetylides with Different Metals Connected … 437 [23] (a) Marcus, R. A., and Sutin, N. (1985). Electron Transfers in Chemistry and Biology. Biochim. Biophys. Acta, 811, 233-322. (b) Hush, N. S. (1985). Distance Dependence of Electron Transfer Rates. Coord. Chem. Rev., 64, 135-157. (c) Coe, B. J. (1999). Molecular Materials Possessing Switchable Quadratic Nonlinear Optical Properties. Chem. Eur. J., 5, 2464-2471. (d) Bruce, M. I.; de Montigny, F.; Jevric, M.; Lapinte, C.; Skelton, B. W.; Smith, M. E., and White, A. H. (2004). Molecular Materials Possessing Switchable Quadratic Nonlinear Optical Properties. J. Organomet. Chem., 689, 2860- 2871. (e) Weng, W.; Ramsden, J. A.; Arif, A. M., and Gladysz, J. A. (1993). A New Form of Coordinated Carbon: An Unsupported C3 Chain Spanning Two Different Transition Metals. J. Am. Chem. Soc., 115, 3824-3825. (f) Bullock, R. M.; Femke, F.R., and Szalda, D. J. (1990). Complexes Containing a C2 Bridge between an Electron-Rich Metal and an Electron-Deficient Metal. An Agostic Interaction in a RuCH2CH2Zr Moiety. J. Am. Chem. Soc., 112, 3244-3245. (g) Bürger, H., and Kluess, (1973). C. Titan-Stickstoff-Verbindungen XVII. σ-(Ferrocenyl)-Titan-Dialkylamide. J. Organomet. Chem., 56, 269-277. (h) Razuvaev, G. A.; Domrachev, G. A.; Sharutin, V. V., and Suvorova, O. N. (1977). Ferrocenyl Derivatives of Dicyclopentadienyl- Titanium, -Zirconium and -Hafnium. J. Organomet. Chem., 141, 313-317. (i) Zakharov, L. N.; Struchkov, V. T., Sharutin, V. V., and Suvorova, O. N. (1979). Crystal Structure of Diferrocenyltitanocene, C30H28Fe2Ti. Cryst. Struct. Commun., 8, 439-444. (j) Dias, A. R.; Salema, M. S., and Simoes, J. A. M. (1982). Enthalpies of Formation of Bis(η5- cyclopentadienyl)diphenyltitanium and Bis(η5-cyclopentadienyl) Diferrocenyltitanium. Organometallics, 1, 971-973. (k) Wedler, M.; Roesky, H. W., and Edelmann, F. T. (1988). Ferrocenyl Complexes of the Early Transition Metals - Synthesis and Structure. Z. Naturforsch., B43, 1461-1467. (l) Lemke, F. R.; Szalda, D. J.; Bullock, R. M. (1991). Ruthenium/Zirconium Complexes Containing C2 Bridges with Bond Orders of 3, 2, and 1. Synthesis and Structures of Cp(PMe3)2RuCHnCHnZrClCp2 (n = 0, 1, 2). J. Am. Chem. Soc., 113, 8466-8477. (m) Gu, X., and Sponsler, M. B. (1998). Synthesis of Fe-C≡C-M Complexes through Condensation of Fe-C≡C-H with M-H or M-NMe2. Organometallics, 17, 5920-5923. (n) Mitani, M.; Hayakawa, M.; Yamada, T., and Mukaiyama, T. (1996). Novel Zirconium-Iron Multinuclear Complex Catalysts for Olefin Polymerizations. Bull. Chem. Soc. Jpn., 69, 2967-2976. (o) Qian, C.; Guo, J.; Sun, J.; Chen, J.; Zheng, P. (1997). Heterobimetallic Complexes with Phenylcyclopentadienyl Ligand: Syntheses and Structures of Tricarbonylchromium- η6,η5-Phenylcyclopentadienyl-Transition Metal Complexes. Inorg. Chem., 36, 1286- 1295. (p) Weng, W.; Bartik, T., and Gladysz, J. A. (1994). On the Way to Coupling of Single Metals to One-Dimensional Carbon Wires: Charge Transfer between Terminal Rhenium and Manganese Centers in C5-Cumulene. Angew. Chem., Int. Ed. Engl., 33, 2199-2202. (q) Stepnicka, P.; Podlaka, J.; Horacek, M.; Hanus, V., and Mach, K. (1999). A Directly Ring-to-Ring Linked Ferrocene–Pseudotitanocene Complex. J. Organomet. Chem., 580, 210-213. (r) Wong, W. Y.; Ho, K. Y.; Ho, S. L., and Lin, Z.(2003). Carbon-Rich Organometallic Materials Derived from 4- Ethynylphenylferrocene. J. Organomet. Chem., 683, 341-353. (s) Yam, V. W. W.; Wong, K. M. C.;Chong, S. H. F.; Lau, V. C. Y.; Lam, S. C. F.; Zhang, L., and Cheung, K. K. (2003). Synthesis, Electrochemistry and Structural Characterization of Luminescent Rhenium(I) Monoynyl Complexes and their Homo- and Hetero-Metallic Binuclear Complexes. J. Organomet. Chem., 670, 205-220. (t) Launay, J. P. (2001). Heinrich Lang and Alexander Jakob 438 LongDistance Intervalence Electron Transfer. Chem. Soc. Rev., 30, 386-397. (u) Brunschwig, B. S., and Sutin, N. (1999). Energy Surfaces, Reorganization Energies, and Coupling Elements in Electron Transfer. Coord. Chem. Rev., 187, 233-254. (v) Wong, K. M. C.; Lam, S. C. F.; Ko, C. C.; Zhu, N.; Yam, V. W. W.; Roue, S.; Lapinte, C.; Fathallah, S.; Costuas, K.; Kahlal, S., and Halet, J. F. (2003). Electroswitchable Photoluminescence Activity: Synthesis, Spectroscopy, Electrochemistry, Photophysics, and X-ray Crystal and Electronic Structures of [Re(bpy)(CO)3(C≡C-C6H4-C≡C)- Fe(C5Me5)(dppe)][PF6]n (n = 0, 1). Inorg. Chem., 42, 7086-7097. (w) Paul, F.; Meyer, W. E.; Toupet, L.; Jiao, H.; Gladysz, J. A., and Lapinte, C. (2000). A "Conjugal" Consanguineous Family of Butadiynediyl-Derived Complexes: Synthesis and Electronic Ground States of Neutral, Radical Cationic, and Dicationic Iron/Rhenium C4 Species. J. Am. Chem. Soc., 122, 9405-9414. (x) Wheatley, N., and Kalck, P. (1999). Structure and Reactivity of Early-Late Heterobimetallic Complexes. Chem. Rev., 99, 3379-3419. (y) Guo, J. H., and Qian, C. T. (1996). Synthesis and Reactivity of Heterobimetallic Complexes. Youji Huaxue, 16, 301-309. (z) Kuwabara, J.; Takeuchi, D., and Osakada, K. (2004). Preparation and Properties of Cp2Zr(μ- N=CAr2)2PdCl(Me), New Zr/Pd Heterobimetallic Complexes with Bridging Alkylideneamido Ligands. Organometallics, 23, 5092-5095. (aa) Berenguer, J. R.; Bernechea, M.; Fornie´s, J.; Garcia, A., and Lalinde, E. (2004). (p-Cymene)- Ruthenium(II)(diphenylphosphino)alkyne Complexes: Preparation of (μ-Cl)(μ - PPh2C≡CR)-Bridged Ru/Pt Heterobimetallic Complexes. Organometallics, 23, 4288- 4300. (bb) Gauthier, S.; Quebatte, L.; Scopelliti, R., and Severin, K. (2004). Syntheses and Structures of Homo- and Heterobimetallic, Chloro-Bridged Complexes Containing the RuCl3(AsPh3)n Fragment (n = 1, 2). Inorg. Chem. Commun., 7, 708-712. (cc) Thurston, J. H.; Tang, C. G. Z.; Trahan, D. W., and Whitmire, K. H. (2004). Toward Rational Control of Metal Stoichiometry in Heterobimetallic Coordination Complexes: Synthesis and Characterization of Pb(Hsal)2(Cu(salen*))2, [Pb(NO3)(Cu(salen*))2]- (NO3), Pb(OAc)2(Cu(salen*)), and [Pb(OAc)(Ni(salen*))2](OAc). Inorg. Chem., 43, 2708-2713. (dd) Yang, Y.; Abboud, K. A., and McElwee-White, L. (2003). Heterobimetallic Complexes with dppm-Bridged Ru/Pd, Ru/Pt, Ru/Au and Ru/Cu Centers. Dalton Trans., 22, 4288-4296. (ee) Berenguer, J. R.; Fornie s, J.; Lalinde, E., and Martinez, F. (1996). Reactions of (σ-Alkynyl)platinum Complexes with [Pd(η3- C3H5)Cl]2. Synthesis of Bis(η2-alkyne)(η3-allyl)palladium(II) Complexes. Crystal and Molecular Structure of [cis-(PPh3)2Pt(μ-η1:η2-C≡CtBu)2Pd(η3-C3H5)](ClO4). Organometallics, 15, 4537-4546. (ff) Dennett, J. N. L.; Knox, S. A. R.; Anderson, K. M.; Charmant, J. P. H., and Orpen, A. G. (2005). The Synthesis of [FeRu(CO)2(μ- CO)2(η-C5H5)(η-C5Me5)] and Convenient Entries to its Organometallic Chemistry. Dalton Trans., 1, 63-73. (gg) Friedrich, H. B.; Howie, R. A.; Laing, M., and Onani, M. O. (2004). Transition Metal-Substituted Paraffins: Synthesis and Properties of some μ- Saturated Heterobimetallic Complexes Containing Mo and W or Fe and the Crystal Structures of [(η5-C5H5)(CO)3W(CH2)3Mo(CO)2(PPh3)(η5-C5H5)] and [(η5- C5H5)(CO)2(PPh3)Mo(CH2)3Fe(CO)2(η5-C5H5)]. J. Organomet. Chem., 689, 181-193. (hh) Li, Q. S.; Xu, F. B.; Cui, D. J.; Yu, K.; Zeng, X. S.; Leng, X. B.; Song, H. B., and Zhang, Z. Z. (2003). Heterobimetallic Pt(II)–M(I) (M = Cu, Ag) Eight-Membered Macrocyclic Complexes with Large-Bite P,N-Ligand Bridges. Dalton Trans., 8, 1551- Mixed Transition Metal Acetylides with Different Metals Connected … 439 1557. (ii) Fornie s-Camer, J.; Claver, C.; Masdeu-Bulto, A. M., and Cardin, C. J. (2002). New Half-Sandwich Heterobimetallic CpMPt (M = Rh, Ir) Dithiolato Bridged Complexes. X-Ray Structure of [(PPh3)2Pt(μ-S(CH2)2S)RhCl(η5-C5H5)]BF4. J. Organomet. Chem., 662, 188-191. (jj) Meichel, E.; Stein, T.; Kralik, J.; Rheinwald, G., and Lang, H. (2002). Synthese von [(η5-C5H5)2Ti(Cl)(C≡CSiMe3)]Ni(CO) und dessen Reaktionsverhalten gegenüber Phosphiten: die Festkörperstruktur von (CO)2Ni- [P(OC6H4CH3-2)3]2. J. Organomet. Chem., 649, 191-198. (kk) Le Gendre, P.; Picquet, M.; Richard, P., and Moise, C. (2002). Ti–Ru Bimetallic Complexes: Catalysts for Ring-Closing Metathesis. J. Organomet. Chem., 643-644, 231-236. (ll) Burgos, F.; Chavez, I.; Manriquez, J. M.; Valderrama, M.; Lago, E.; Molins, E.; Delpech, F.; Castel, A., and Rivie´re, P. (2001). A New Heterobimetallic Ru, Rh Complex with a Dianionic Pentalene as Bridging Ligand. Synthesis, Crystal Structure, and Catalytic Activity of [Cp*Ru(μ-η5,η3-C8H6)Rh(η4-COD)]. Organometallics, 20, 1287-1291. (mm) Bruce, M. I.; De Montigny, F.; Jevric, M.; Lapinte, C.; Skelton, B. W.; Smith, M. E., and White, A. H. (2004). Synthesis, Structures and some Reactions of Ru(C≡CC≡CFc)(PP)Cp (PP = dppm, dppe) and Related Compounds. J. Organomet. Chem., 689, 2860-2871. (nn) Bruce, M. I., and Low, P. J. (2004). Transition Metal Complexes Containing All-Carbon Ligands. Adv. Organomet. Chem., 50, 179-444. (oo) Antonova, A. B.; Bruce, M. I.; Ellis, B. G.; Gaudio, M.; Humphrey, P. A.; Je vric, M.; Melino, G.; Nicholson, B. K.; Perkins, G. J.; Skelton, B. W.; Stapleton, B.; White, A. H., and Zaitseva, N. N. (2004). A Novel Methodology for the Synthesis of Complexes Containing Long Carbon Chains Linking Metal Centres: Molecular Structures of {Ru(dppe)Cp*}2(μ-C14) and {Co3(μ-dppm)(CO)7}2(μ3:μ3-C16). Chem. Commun., 8, 960-961. (pp) Bruce, M. I.; Skelton, B. W.; White, A. H., and Zaitseva, N. N. (2003). Preparation and Molecular Structures of some Complexes Containing C5 Chains. J. Organomet. Chem., 683, 398-405. (qq) Low, P. J., and Bruce, M. I. (2001). Transition Metal Chemistry of 1,3-Diynes, Poly-ynes, and Related Compounds. Adv. Organomet. Chem., 48, 71-286. (rr) Bruce, M. I.; Ellis, B. G.; Gaudio, M.; Lapinte, C.; Melino, G.; Paul, F.; Skelton, B. W.; Smith, M. E.; Toupet, L., and White, A. H. (2004). Preparation, Structures and some Reactions of Novel Diynyl Complexes of Iron and Ruthenium. Dalton Trans., 10, 1601-1609. (ss) Bruce, M. I.; Hall, B. C.; Low, P. J.; Smith, M. E.; Skelton, B. W., and White, A. H. (2000). Heterometallic Complexes Containing C4 Chains. X-Ray Structures of {Cp(OC)3W}C≡C-C≡C{Ir(CO)(PPh3)2- (O2)} and cis-Pt{C≡CC≡C[W(CO)3Cp]}2(PEt3)2. Inorg. Chim. Acta, 300-302, 633-644. (tt) Cheung, K. L.; Yip, S. K., and Yam, V. W. W. (2004). Synthesis, Characterization, Electrochemistry and Luminescence Studies of Heterometallic Gold(I)–Rhenium(I) Alkynyl Complexes. J. Organomet. Chem., 689, 4451-4462. (uu) Enders, M.; Kohl, G., and Pritzkow, H. (2002). Novel Heterobimetallic Compounds with Metal-Metal Bonds: The Use of Quinolyl-Substituted Metallocenes as Tridentate Ligands. Organometallics, 21, 1111-1117. (vv) Dewhurst, R. D.; Hill, A. F., and Smith, M. K. (2004). Heterobimetallic C3 Complexes through Silylpropargylidyne Desilylation. Angew. Chem. Int. Ed., 43, 476-478. (ww) Pizzotti, M.; Ugo, R.; Roberto, D.; Bruni, S.; Fantucci, P., and Rovizzi, C. (2002). Organometallic Counterparts of Push-Pull Aromatic Chromophores for Nonlinear Optics: Push-Pull Heteronuclear Bimetallic Complexes with Pyrazine and trans-1,2-Bis(4-pyridyl)ethylene as Linkers. Organometallics, 21, 5830-5840. (xx) Zhang, L. Y.; Chen, J. L.; Shi, L. X., and Chen, Heinrich Lang and Alexander Jakob 440 Z. N. (2002). Utilizing Diruthenium Components for the Design of Cyanide-Linked Tri- and Tetranuclear Organometallic Complexes with Multistep One-Electron Redox Processes. Organometallics, 21, 5919-5925. (yy) Adams, C. J., and Raithby, P. R. (1999). Novel Mixed-Metal–Alkynyl Complexes Stabilised by Di-Imine Ligands: Synthesis, Characterisation and Electrochemistry of [(tBu2bipy)Pt(C≡CR)2M(SCN)] (R = C6H4Me, SiMe3; M = Cu, Ag). J. Organomet. Chem., 578, 178-185. (zz) Thomas, K. R. J.; Lin, J. T.; Lin, H. M.; Chang, C. P., and Chuen, C. H. (2001). Ruthenium and Rhenium Complexes of Fluorene-Based Bipyridine Ligands: Synthesis, Spectra, and Electrochemistry. Organometallics, 20, 557-563. (aaa) Prim, D.; Auffrant, A.; Plyta, Z. F.; Tranchier, J. P.; Rose-Munch, F., and Rose, E. (2001). Bimetallic π-Conjugated Complexes Modulated by a Carbonyl Spacer: Synthesis of Arenetricarbonylchromium– Ferrocene Derivatives. J. Organomet. Chem., 624, 124-130. (bbb) Richardson, G. N., and Vahrenkamp, H. (2000). Cyanide Bridged Trinuclear Complexes with Fe-CN- MCl2-NC-Fe Backbones (M = Ni, Cu, Zn). J. Organomet. Chem., 593-594, 44-48. (ccc) Low, P. J.; Rousseau, R.; Lam, P.; Udachin, K. A.; Enright, G. D.; Tse, J. S.; Wayner, D. D. M., and Carty, A. J. (1999). Polycarbon Ligand Chemistry: Electronic Interactions between a Mononuclear Ruthenium Fragment and a Cobalt-Carbon Cluster Core. Organometallics, 18, 3885- 3897. (ddd) Bruce, M. I.; Hall, B. C.; Low, P. J.; Skelton, B. W., and White, A. H. (1999). Some Ruthenium Complexes Derived from 1,4-Diethynylbenzene: Molecular Structure of Ru{η3-C[=C(CN)2]C(C6H4C≡CH- 4)=C(CN)2}(PPh3)Cp. J. Organomet. Chem., 592, 74-83. (eee) Briel, O.; Fehn, A., and Beck, W. (1999). Hydrocarbon Bridged Metal Complexes XLV. Dinuclear Polyene- Bridged Fischer Carbene Complexes and a Star-Shaped Benzene-Bridged Tris(ferrocenyldecapentaenyl) Compound. J. Organomet. Chem., 578, 247-251. (fff) Colbert, M. C. B.; Lewis, J.; Long, N. J.; Raithby, P. R.; White, A. J. P., and Williams, D. J. (1997). Synthetic, Structural, Electrochemical and Electronic Characterisation of Heterobimetallic Bis(acetylide) Ferrocene Complexes. J. Chem. Soc., Dalton Trans., 99-104. (ggg) Lin, J. T.; Wu, J. J.; Li, C. S.; Wen, Y. S., and Lin, K. J. (1996). Conjugated Pyridines with an End-Capping Ferrocene. Organometallics, 15, 5028- 5034. (hhh) Le Stang, S. L.; Lenz, D.; Paul, F., and Lapinte, C. (1999). New Pyridyl- Functionalized Organoiron Alkynyl Complexes. Easy Access to Polymetallic Architectures Featuring an Electroactive Site by Simple Coordination Reactions. J. Organomet. Chem., 572, 189-192. (iii) Stepnicka, P.; Gyepes, R., and Cisarova, I. (1999). Synthesis and Structure of Titanocene Complexes with η2-Coordinated Internal Ferrocenylacetylenes. Organometallics, 18, 627-633. [24] (a) Laus, G.; Strasser, C. E.; Holzer, M.; Wurst, K.; Pürstinger, G.; Ongania, K.-H.; Rauch, M.; Bonn, G., and Schottenberger, H. (2005). The (E)-2- Ferrocenylethenylcobaltocenium Cation. A Missing Link in Heteronuclear Bimetallocene-Based Donor-Acceptor Conjugate Chemistry Exhibiting Irregular Solvatochromism. Organometallics, 24, 6085-6093 (b) Obendorf, D.; Reichart, E; Rieker, C., and Schottenberger, H. (1994) Voltammetric Study of some Metallocene- Substituted (η4-1,3-Cyclopentadiene-5-exo-yl) Cobalt Complexes; ([CpCo(η4-C5H5R)], R = −C≡C-(η5−C5H4)FeCp; -(η5−C5H4)FeCp; -(η5C5H4)NiCp). Electrochimica Acta, 39, 2367-2375. (c) Wildschek, M.; Rieker, C.; Jaitner, P; Schottenberger, H., and Schwarzhans, K. E. (1990). Ethynylcobaltocenium Compounds as Precursors for Bridged, Heteronuclear Oligometallocenes: Preparation and Reactions of Ethynyl- Mixed Transition Metal Acetylides with Different Metals Connected … 441 ,trimethylsilylethynyl- and Ferrocenylethynylcobaltocenium Salts. J. Organomet. Chem., 396, 355-361. [25] Bartik, T.; Weng, W.; Ramsden, J. A.; Szafert, S.; Falloon, S. B.; Arif, A. M., and Gladysz, J. A. (1998). New Forms of Coordinated Carbon: Wirelike Cumulenic C3 and C5 sp Carbon Chains that Span Two Different Transition Metals and Mediate Charge Transfer. J. Am. Chem. Soc., 120, 11071-11081. [26] (a) Venkatesan, K.; Fox, T.; Schmalle, H. W., and Berke, H. (2005). Synthesis and Characterization of Redox-Active C4-Bridged Rigid-Rod Complexes with Acetylide- Substituted Manganese End Groups. Organometallics, 24, 2834-2847. (b) Venkatesan, K.; Blacque, O.; Fox, T.; Alfonso, M.; Schmalle, H. W., and Berke, H. (2004). Synthetic Access to Half-Sandwich Manganese C4 Cumulenic Complexes. Organometallics, 23, 4646-4671. (c) Fernández, F. J.; Venkatesan, K.; Blacque, O.; Alfonso, M.; Schmalle, H. W., and Berke, H. (2003). Generation and Coupling of [Mn(dmpe)2(C≡CR)(C≡C)]. Radicals Producing Redox-Active C4-Bridged Rigid-Rod Complexes. Chem. Eur. J., 9, 6192-6206. (d) Venkatesan, K.; Fox, T.; Schmalle, H. W., and Berke, H. (2005). New Access to Homodinuclear Half-Sandwich Vinylidenemanganese Complexes. Eur. J. Inorg. Chem., 901-909. (e)Venkatesan, K.; Blacque, O.;Fox, T.; Alfonso, M.; Schmalle, H. W.; Kheradmandan, S., and Berke, H. (2005). μ-Carbon-Carbon Bonds of Dinuclear Manganese Half-Sandwich Complexes as Electron Reservoirs. Organometallics, 24, 920-932. [27] Kheradmandan, S.; Venkatesan, K.; Blacque, O.; Schmalle, H. W., and Berke, H. (2004). Facile Access to Redox-Active C2-Bridged Complexes with Half-Sandwich Manganese End Groups. Chem. Eur. J., 10, 4872-4885. [28] (a) Herrmann, C.; Neugebauer, J.; Gladysz, J. A., and Reiher, M. (2005). Theoretical Study on the Spin-State Energy Splittings and Local Spin in Cationic [Re]-Cn-[Re] Complexes. Inorg. Chem., 44, 6174-6182. (b) Neugebauer, J., and Reiher, M. Mode (2004). Tracking of Preselected Vibrations of One-Dimensional Molecular Wires. J. Phys. Chem. A, 108, 2053-2061. (c) Horn, C. R., and Gladysz, J. A. (2003). Syntheses of Dimetallamacrocycles by Intramolecular Oxidative Couplings of Dinuclear Bis(1,3- butadiynyl) Complexes: A New Approach to Steric Shielding in (sp-Carbon chain)dirhenium Complexes [(η5-C5Me5)Re(NO)(PR3)(C≡CC≡CC≡CC≡C)(R3P)(ON)- Re(η5-C5Me5)]. Eur. J. Inorg. Chem., 2211-2218. [29] Smith, M. E.; Cordiner, R. L.; Albesa-Jové, D.; Yufit, D. S.; Hartl, F.; Howard, J. A. K., and Low, P. J. (2006). The Synthesis, Structure, and Electrochemical Properties of Fe(C≡CC≡N)(dppe)Cp and Related Compounds. Can J. Chem., 84, 154-163. (b) Low, P. L.; Roberts, R. L.; Cordiner, R. L., and Hartl, F. (2005). Electrochemical Studies of Bi- and Polymetallic Complexes Featuring Acetylide Based Bridging Ligands. J. Solid State Electrochem., 9, 717-731 (c) Cordiner, R. L. Corcoran, D.; Yufit, D. S.; Goeta, A. E.; Howard, J. A. K., and Low, P. J. (2003). Cyanoacetylenes and Cyanoacetylides: Versatile Ligands in Organometallic Chemistry. Dalton Trans., 3541-3549. [30] LeVanda, C.; Cowan, D. O.; Leitch, C., and Bechgaard, K. (1974). Mixed-Valance Diferrocenylacetylene Cation. J. Am. Chem. Soc., 96, 6788-6789. [31] (a) Y. Masuda, Y., and Shimizu, C. (2006). Solvent Effect on Intramolecular Electron Transfer Rates of Mixed-Valence Biferrocene Monocation Derivatives. J. Phys. Chem., 110, 7019-7027. (b) Jiao, J.; Long, G. J.; Rebbouh, L.; Grandjean, F.; Beatty, A. M., and Fehlner, T. P. (2005). Properties of a Mixed-Valence (FeII)2(FeIII)2 Square Cell for Heinrich Lang and Alexander Jakob 442 Utilization in the Quantum Cellular Automata Paradigm for Molecular Electronics. J. Am. Chem. Soc., 127, 17819-17831. (c) Kramer, J. A., and Hendrickson, D. N. (1980). Electron Transfer in Mixed-Valent Diferrocenylacetylene and [2.2]-Ferrocenophane- 1,13-diyne. Inorg. Chem., 19, 3330-3337. (d) Brady, M.; Weng, W.; Zhou, Y.; Seyler, J. W.; Amoroso; A. J.; Arif, A. M. Böhme, M.; Frenking, G., and Gladysz, J. A. (1997). Consanguineous Families of Coordinated Carbon: A ReC4Re Assembly That is Isolable in Three Oxidation States, Including Crystallographically Characterized ReC≡CC≡CRe and +Re=C=C=C=C=Re+ Adducts and a Radical Cation in which Charge is Delocalized between Rhenium Termini. J. Am. Chem. Soc., 119, 775-788. [32] (a) Mochida, T., and Yamazaki, S. (2002). Mono- and Diferrocenyl Complexes with Electron-Accepting Moieties Formed by the Reaction of Ferrocenylalkynes with Tetracyanoethylene. J. Chem. Soc., Dalton Trans., 3559-3564. (b) Levanda, C. Bechgaard, K., and Cowan D. O. (1976). Mixed Valence Cations. Chemistry of n- Bridged Analogues of Biferrocene and Biferrocenylene. J. Org. Chem., 41, 2700-2704. (c) Adams, R. D.; Qu, B.; Smith, M. D., and Albright, T. A. (2002). Syntheses, Structures, Bonding, and Redox Behavior of 1,4-Bis(ferrocenyl)butadiyne Coordinated Osmium Clusters. Organometallics, 21, 2970-2978. (d) McAdam, C. J.; Brunton, J. J.; Robinson, B. H., and Simpson, J. (1999). Ferrocenylethynylnaphthalenes and Acenaphthylenes; Communication Between Ferrocenyl and Cluster Redox Centres. J. Chem. Soc. Dalton Trans., 2487-2496. (e) Jutzi, P., and Kleinebekel, B. (1997). Octamethylferrocenylethynyl Units as Peripheral Groups in Rigid, π-Conjugated Molecular Architectures. J. Organomet. Chem., 545-546, 573. (f) Levanda, C.; Cowan, D. O.; Leitch, C., and Bechgaard, K. (1974). Mixed-Valence Diferrocenylacetylene Cation. J. Am. Chem. Soc., 96, 6788-6789. (g) McManis, G. E.; Gochev, A.; Nielson, R. M., and Weaver, M. J. (1989). Solvent Effects on Intervalence Electron-Transfer Energies for Biferrocene Cations: Comparisons with Molecular Models of Solvent Reorganization. J. Phys. Chem., 93, 7733-7739. (h) Delgado-Pena, F.; Talham, D. R., and Cowan, D. O. (1983). Near-IR Spectroscopic Studies of Mixed-Valence Di-, Tri-, and Tetraferrocene Derivatives. J. Organomet. Chem., 253, C43-C46. (i) Powers, M. J. Meyer, T. J. (1978). Intervalence Transfer in Mixed-Valence Biferrocene Ions. J Am. Chem. Soc., 100, 4393-4398. [33] Schimanke, H., and Gleiter, R. (1998). Synthesis and Electrochemical Properties of Butadiyne-Bridged Cyclopentadienylcobalt-Cyclobutadiene Complexes. Organometallics, 17, 275-277. [34] (a) Hore, L.-A.; John McAdam, C.; Kerr, J. L.; Duffy, N. W.; Robinson, B. H., and Simpson, J. (2000). Communication between Co2(CO)4dppm Units via Polyferrocenylalkyne Linkages. Organometallics, 19, 5039-5048. (b) Richardson, D. E., and Taube, H. (1981). Determination of E20-E10 in Multistep Charge Transfer by Stationary-Electrode Pulse and Cyclic Voltammetry: Application to Binuclear Ruthenium Ammines. Inorg. Chem., 20, 1278-1285. (c) Cotton, F. A.; Donohue, J. P., and Murillo, C. A. (2003). Polyunsaturated Dicarboxylate Tethers Connecting Dimolybdenum Redox and Chromophoric Centers: Syntheses, Structures, and Electrochemistry. J. Am. Chem. Soc., 125, 5436-5450. (d) Berry, J. F.; Cotton, F. A., and Murillo, C. A. (2004). A Trinuclear EMAC-Type Molecular Wire with Redox- Active Ferrocenylacetylide "Alligator Clips" Attached. Organometallics, 23, 2503- 2506. (e) Sheng, T.; Appelt, R.; Comte, V., and Vahrenkamp, H. (2003). Chain-Like Mixed Transition Metal Acetylides with Different Metals Connected … 443 Tetra-, Penta- and Heptanuclear Cyanide-Bridged Complexes by Attachment of Organometallic Cyanides to M2, M3 and M5 Units. Eur. J. Inorg. Chem., 3731-3737. [35] Köcher, S. (2000). Mehrkernige Übergangsmetallkomplexe: Synthese, Reaktionsverhalten und elektronische Eigenschaften. Diploma Thesis, TU Chemnitz. [36] Hayashi, Y.; Osawa, M., and Wakatsuki, Y. (1997). Reductive Coupling Reaction Induced by Remote-Site Oxidation in Titanocene Bis(metallocenylacetylide), where Metallocenyl = Ferrocenyl or Ruthenocenyl: a Novel Route to Cn (n = 4, 6, and 8) Wire with the Metallocenyl Groups at Both Terminals. J. Organomet. Chem., 542, 241-246. [37] Wetzold, N. (2003). Sythese Lewis-Basen-stabilisierter Bis(alkinyl)-Platin-Komplexe und deren Reaktionsverhalten. Diploma Thesis, TU Chemnitz. [38] (a) Osella, D.; Milone, L.; Nervi, C., and Ravera, M. (1995). Electronic Interactions in Organometallic Dimers. An Electrochemical Approach. J. Organomet. Chem., 488, 1-7. (b) Osella, D.; Gobetto, R.; Nervi, C.; Ravera, M.; D’Amato, R., and Russo, M. V. (1998). Synthesis and Characterisation of Bis(ferrocenylethynyl) Complexes of Platinum (II) a Re-Investigation of their Electrochemical Behaviour. Inorg. Chem. Commun., 1, 239-245. (c) Russo, M. V., and Furlani, A. (1994). Synthesis of some Bis(triphenylphosphine)(ethynylferrocenyl) Platinum(II) Complexes; Molecular Structure of [PtH(C≡C-C5H4FeC5H5)(PPh3)2]. J. Organomet. Chem., 469, 245-252. [39] Müller, T. J. J., and Lindner, H. J. (1996). Palladium-Copper-Catalyzed Coupling of Tricarbonylchromium-Complexed Phenylacetylene with Iodoarenes. A Facile Access to Alkynyl-Bridged Cr(CO)3-Complexed Benzenes. Chem. Ber., 129, 607-613. (b) Müller, T. J. J.; Ansorge, M., and Lindner, H. J. (1996). Synthesis and Substituent Interactions of Tricarbonylchromium-Complexed (Arylalkynyl)benzenes. Novel Organometallic Push-Pull Chromophores. Chem. Ber., 129, 1433-1440. (c) Müller, T. J. J. (1999). Redox Active Alkenyl-Bridged Bi- and Trinuclear Arene–Cr(CO)3-Complexes by Horner–Emmons–Wadsworth Olefinations. J. Organomet. Chem., 578, 95. (d) Müller, T. J. J.; Netz, A.; Ansorge, M.; Schmälzlin, E.; Bräuchle, C., and Meerholz, K. (1999). Syntheses and NLO Properties of Chromium Carbonyl Arene Complexes with Conjugated Side Chains: The Amphoteric Nature of Chromium Carbonyl Complexation in Push-Pull Chromophores. Organometallics, 18, 5066. [40] Friedrich, D. (2006). Alkinyl-Übergangsmetallkomplexe: Synthese und Reaktionverhalten. Diploma Thesis, TU Chemnitz. [41] Sato, M., and Emiko, M. (1995). Unprecedented Promoting Effect of a Ferrocenyl Group for the Oxidatively Induced Reductive Elimination in cis-Aryl(ferrocenyl acetylide)platinum(II) Complexes. Organometallics, 14, 3157-3159. [42] Kirchbauer, F. G.; Pellny, P.-M.; Sun, H.; Burlakov, V. V.; Arndt, P.; Baumann, W.; Spannenberg, A., and Rosenthal, U. (2001). Synthesis and Reactions with Carbon Dioxide of Mono(σ-alkynyl) Titanocene(III) Complexes Cp*2Ti(C≡CR) (R = Me, t- Bu) and the Corresponding "Ate" Complexes [Cp*2Ti(C≡CR)2Li(THF)n] (R = SiMe3, t- Bu, Ph). Organometallics, 20, 5289-5296. [43] Erker, G.; Frömberg, W.; Benn, R.; Mynott, R.; Angermund, K., and Krüger, C. (1989). π-Conjugation and Dynamic Behavior in Doubly Acetylide-Bridged Binuclear Group 4 Bent Metallocene Complexes. Organometallics, 8, 911-920 [44] Back, S.; Gossage, R. A.; Rheinwald, G.; Lang, H., and van Koten, G. (1999). Titanium σ-Acetylides as Building Blocks for Heterobimetallic Transition Metal Complexes: Heinrich Lang and Alexander Jakob 444 Synthesis and Redox Behaviour of π-Conjugated Organometallic Systems. J. Organomet. Chem., 582, 126. [45] Lang, H., and Stein, T. (2001). Bis(alkynyl)-Titanium and -Platinum Complexes in the Synthesis of Oligo- and Polynuclear Early-Late and/or Late-Late Transition Metal Species: An Overview. Abhath Al-Yarmouk: Basic Sci. Eng., 10, 155; Chem. Abstr.(2001), 142, 38297. [46] Lemket, F. R., and Bullock, R. M. (1992). Insertion and Beta-Hydride Elimination Reactions of Ruthenium/Zirconium Complexes Containing C2 Bridges with Bond Orders of 1, 2, and 3. Organometallics, 11, 4261-4267. [47] Back, S.; Gossage, R. A.; Lutz, M.; del Rio, I.; Spek, A. L.; Lang, H., and van Koten, G. (2000). Bis-ortho-chelated Diaminoaryl Platinum Compounds with _-Acetylene Substituents. Investigations into Their Stability and Subsequent Construction of Multimetallic Systems. The Crystal Structure of [(μ2-[(η2-NCN)Pt(η1-CO)C≡CSiMe3]) Co2(CO)6] (NCN = 2,6-Bis[(dimethylamino)methyl]phenyl). Organometallics, 19, 3296-3304. [48] Packheiser, R. (2003). Multimetallische Übergangsmetallkomplexe mit π-konjungierten organischen Bausteinen. Diploma Thesis, TU Chemnitz. [49] Köcher, S. (2007). Ph.D. Thesis, TU Chemnitz. [50] Köcher, S.; Walfort, B.; Lutz, M.; Spek, L. A.; Prasad, R.; van Koten, G., and Lang, H. Submitted for publication in J. Organomet. Chem. [51] Frosch, W.; Back, S.; del Río, I.; van Koten, G., and Lang, H. (1999). An Easy Entry to Novel Early–Late Oligonuclear Transition Metal Complexes Containing π-Conjugated Systems. Inorg. Chem. Commun., 2, 584-586. [52] Back, S., and Lang, H. (2000). Heterometallic Assemblies with Bridging Cyano Ligands. Organometallics, 19, 749-751. [53] (a) Wilson, A. J. C. (1995). In International Tables of Crystallography; Kluwer Academic: London, Vol. C. (b) Lang, H. Köhler, K., and Schiemenz B. (1995). Lewisbasen Addukte monomerer bis(η2-alkin) AgIX-Verbindungen (X = BF4 oder OSO2CF3). J. Organomet. Chem., 495, 135-140. [54] Ara, I.; Berenguer, J. R.; Forniés, J.; Lalinde, E., and Moreno, M. T. (1996). Synthesis and Characterization of Cationic Heteronuclear Complexes of Platinum(II) and Silver(I) Bridged by Alkynyl Ligands. J. Organomet. Chem., 510, 63-70. [55] del Villar, A.; Rheinwald, G., and Lang, H. Unpublished results. [56] Lang, H., and del Villar, A. (2003). Heterobimetallic Platinum–Copper and Platinum– Silver Transition Metal Complexes Based on cis-[Pt](C≡CPh)2: An Overview. J Organomet.Chem., 670, 45-55. [57] Lang, H.; del Villar, A.; Walfort, B., and Rheinwald, G. (2007) in press J. Organomet. Chem. [58] Wong, W.-Y.; Lu, G.-L., and Choi, K.-H. (2002). Synthesis, Characterization and Structural Studies of New Heterometallic Alkynyl Complexes of Platinum and Group 11 Metals with Chelating Bis(diphenylphosphino)ferrocene Ligand. J. Organomet. Chem., 659, 107-116. [59] del Villar, A.; Rheinwald, G.; Walfort, B., and Lang, H. Unpublished. [60] (a) Bassetti, M. Floris, B., and Illuminati G. (1985). Reaction of Ethynylferrocene with Mercuric Acetate. Organometallics, 4, 617-623. (b) Cook, D. J.; Hill, A. F., and Wilson, D. J. (1998). Convenient Synthesis of Alkynyl Aryl Seleno- and Telluro Ethers. Mixed Transition Metal Acetylides with Different Metals Connected … 445 J. Chem. Soc. Dalton Trans., 7, 1171-1173. (c) Dewhurst, R. D.; Hill, A. F., and Smith, M. K. (2006). Hazards Associated with Bis(alkynyl)mercurials. Organometallics, 25, 2388-2389. [61] Wetzold, N. (2007). Bis(alkinyl)-Komplexe und Ferrocene als modulare Bausteine für den Aufbau mehrkerniger Übergangsmetallkomplexe. PhD Thesis, TU Chemnitz. [62] Köcher, S., and Lang, H. (2001). 4-Ethinyl-benzonitrile-ferrocenes Bridged by a Pd(PPh3)2 Unit; the Solid-State Structure of (η5-C5H5)Fe(η5-C5H4C≡CC6H4C≡N-1,4). J. Organomet. Chem., 637-639, 198-203. [63] Köcher, S.; Walfort, B.; van Klink, G. P. M.; van Koten, G., and Lang, H. (2006). Trimetallic FePd2 and FePt2 4-Ferrocenyl-NCN Pincer Complexes. J. Organomet. Chem., 691, 3955-3961. [64] Packheiser, R. (2007). PhD Thesis, TU Chemnitz. [65] (a) Ohs, A. C.; Rheingold, A. L.; Shaw, M. J., and Nataro, C. (2004). Electrochemistry of Group VI Metal Carbonyl Compounds Containing 1,1'-Bis(diphenylphosphino)- ferrocene. Organometallics, 23, 4655-4660. (b) Koo, L. K.; Phang, L. T.; Hor, T. S. A., and Lee, H. K. (1991). High-Performance Liquid Chromatographic Separation of Metal Carbonyl Complexes Substituted with Bridging and Chelating 1,1'- Bis(diphenylphosphino) ferrocene. J. Liquid Chromatography, 14, 2079-2087. (c) Chan, H. S. O.; Hor, T. S. A.; Phang, L. T., and Tan, K. L. (1991). XVI. X-ray Photoelectron Spectroscopic Differentiation of Chemically Distinct Phosphorus Environments in Unidentate Complexes of 1,1′-Bis(diphenylphosphino)ferrocene. J. Organomet. Chem., 407, 353-357. (d) Hor, T. S. A.; Phang, L.-T.; Liu, L.-K., and Wen, Y. S. (1991). Substituted Metal Carbonyls XV. Crystal and Molecular Structures of Two Isomorphous Singly Diphosphine-Bridged Complexes (OC)5M(μ- dppf)M(CO)5·CH2Cl2(M = Cr, Mo; dppf = (Ph2PC5H4)2Fe). J. Organomet. Chem., 397, 29-39. (e) Hor, T. S. A., and Phang, L.-T. (1989). Substituted Metal Carbonyls XI. 1,1′- Bis(diphenylphosphino)ferrocene — a Bridging, Chelating and Unidentate Ligand in the Synthesis of M2(CO)10(μ-P-P), M(CO)4(η2-P-P) and M(CO)5(η1-P-P) (where M = Cr, Mo, W and P-P = Fe(C5H4PPh2)2). J. Organomet. Chem., 373, 319-324. (f) Estevan, F.; Lahuerta, P.; Latorre, J.; Sanchez, A., and Sieiro, C. (1987). Electrochemical Study of Dinuclear Ruthenium(II)-Arene Compounds: Electrogeneration of Ru(II)-Ru(I) Species. Polyhedron, 6, 473-478. (g) Houlton, A.; Roberts, R. M. G., and Silver, J. (1991). Studies on Gold(I) Complexes of 1,1′-Bis(diphenylphosphino)ferrocene. J. Organomet. Chem., 418, 269-275. (h) Mai, J.-F., and Yamamoto, Y. (1998). Preparations and Structures of (η6-Arene)ruthenium(II) Complexes Bearing 1,1′- Bis(diphenylphosphinomethyl)ferrocene or 1,1′-Bis(diphenylphosphino)ferrocene. J. Organomet. Chem., 560, 223-232. (i) Delgado, E.; Hernandez, E.; Mansilla, N.; Moreno, M. T., and Sabat, M. (1999). Co-ordinative Ability of the New Compounds [Ti(η5-C5H4R)2(C≡CBut)2] (R = PPh2, Ph2P=O or Ph2P=S) as Precursors in the Synthesis of Heterodi- and Heterotri-Nuclear Species. Crystal Structure of [ClCu(μ- η5:σ P-C5H4PPh2)2Ti(μ-η2-C≡CtBu)2CuCl] J. Chem. Soc., Dalton Trans., 4, 533-538. (j) Ara, I.; Berenguer, J. R.; Fornie´s, J., and Lalinde, E. (1997). Synthesis, Characterisation and NMR Study of Paramagnetic Heteropolynuclear Anionic Pt-Co Species. Crystal Structures of [NBu4]2[cis-Pt(C6F5)2(C≡CSiMe3)2CoCl3)2·0.5(CH3)2CO and NBu4]2[Pt(C≡CtBu)42]·1.5(CH3)2CO. Inorg. Chim. Acta, 264, 199-210. Heinrich Lang and Alexander Jakob 446 [66] Charmant, J. P. H.; Gomez, J.; Orpen, A. G.; Falvello, L. R.; Fornie´s, J.; Rueda, A.; Gomez, J.; Lalinde, E., and Moreno, M. T. (1999). Synthesis, Structural Characterisation and Luminescence Studies of the First Alkynyl Stabilised Platinum– Cadmium Complexes. Chem. Commun., 20, 2045-2046. [67] Zhang, D.; McConville, D. B.; Tessier, C. A., and Youngs, W. J. (1997). Synthesis and Crystallographic Characterization of the Planar Tetraethynylplatinum Complex (NBu4)2[Pt(OBET)2] and its Double-Tweezer Mercury Dichloride Complex (NBu4)2[Pt(OBET)2](HgCl2)2. Organometallics, 16, 824-825. [68] Zhu, Y.; Olivier Clot, O.; Wolf, M. O., and Yap, G. P. A. (1998). Effect of Ancillary Ligands on Ru(II) on Electronic Delocalization in Ruthenium(II) Bisferrocenylacetylide Complexes. J. Am. Chem. Soc., 120, 1812-1821. [69] (a) Lebreton, C.; Touchard, D.; Pichon, L. L.; Daridor, A.; Toupet, L., and Dixneuf, P. H. (1998). Mono- and Bis-Alkynyl Ruthenium(II) Complexes Containing the Ferrocenyl Moiety; Crystal Structure of trans-[Ru(C≡CC5H4FeC5H5)2(Ph2PCH2CH2- PPh2)2] and Electrochemical Studies. Inorg. Chim. Acta, 272, 188-196. (b) Jones, N. D., and Wolf, M. O. (1997). Synthesis of a Ferrocenyl-Capped Ruthenium(II) Bis- (acetylide) Complex: A Model for Organometallic Molecular Wires. Organometallics, 16, 1352-1354. [70] (a) Vives, G.; Carella, A.; Sistach, S.; Launay, J.-P., and Rapenne, G. (2006). Synthesis of Triester-Functionalized Molecular Motors Incorporating Bis-Acetylide trans- Platinum Insulating Fragments. New J. Chem., 30, 1429-1438. (b) D'Amato, R.; Furlani, A.; Colapietro, M.;, G. Portalone, G.; Casalboni, M.; Falconieri, M., and Russo, M. V. (2001). Synthesis, Characterisation and Optical Properties of Symmetrical and Unsymmetrical Pt(II) and Pd(II) Bis-Acetylides. Crystal Structure of trans- [Pt(PPh3)2(C≡C–C6H5)(C≡C–C6H4NO2)]. J. Organomet. Chem., 627, 13-22. (c) Osella, D.; Gambino, O.; Nervi, C.; Ravera, M.; Russo, M. V., and Infante, G. (1994). Electron Transfer in trans-[Pt(PPh3)2(C≡CFc)2] and Related Compounds. Inorg. Chim. Acta,225, 35-40. [71] Jakob, A., and Lang, H. Unpublished. [72] (a) Ferrocene/ferrocenium redox couple: Gritzner, G., and Kuta, J. (1984). Recommendations on Reporting Electrode Potentials in Nonaqueous Solvents. Pure Appl. Chem., 56, 461. (b) Strehlow, H.; Knoche, W.; Schneider, H. (1973). A Conversion of Given Electrode Potentials to the Standard Normal Hydrogen Electrode is Possible. Ber. Bunsen-Ges. Phys. Chem., 77, 760-717. [73] Al-Anber, M.; Vatsadze, S.; Holze, R.; Thiel, W. R., and Lang, H. (2005). π- Conjugated N-heterocyclic Compounds: Correlation of Computational and ElectroChemical Data. J. Chem. Soc., Dalton Trans., 3632. (b) Vatsadze, S.; Al-Anber, M.; Thiel, W. R.; Lang, H., and Holze, R. (2005). Electrochemical Studies and Semiempirical Calculations on p-Conjugated Dienones and Heterocyclic Nitrogen Containing Donor Ligand Molecules. J. Solid State Electrochem., 9, 764. [74] For example: (a) Puddephatt, R. J. (1987). In Comprehensive Coordination Chemistry; G. Wilkinson, R. D. Gillard, J. A. McCleverty (Eds.); (Vol. 5, p 861) Oxford, U.K.: Pergamon. (b) Grohmann, A.; Schmidbaur, H. (1995). In Comprehensive Organometallic Chemistry II; E. W. Abel, F. G. A. Stone, G. Wilkinson, (Eds.); (Vol. 3, p 1). Oxford, U.K.: Pergamon. (c) Jia, G.; Puddephatt, R. J.; Scott, J. D., and Vittal, J. J. (1993). Organometallic Polymers with Gold(I) Centers Bridged by Diphosphines Mixed Transition Metal Acetylides with Different Metals Connected … 447 and Diacetylides. Organometallics, 12, 3565-3574. (d) Mingos, D. M. P.; Yau, J.; Menzer,S., and Williams, D. J. (1995). A Gold(I) [2]-Catene. Angew. Chem., Int. Ed. Engl., 34, 1894-1895. (e) Puddephatt, R. J. (1998). Precious Metal Polymers: Platinum or Gold Atoms in the Backbone. Chem. Commun., 1055-1062. (f) Irwin, M. J.; Jia, G.; Payne, N. C., and Puddephatt, R. J. (1996). Rigid-Rod Polymers and Model Compounds with Gold(I) Centers Bridged by Diisocyanides and Diacetylides. Organometallics, 15, 51-57. (g) Irwin, M. J.; Vittal, J. J., and Puddephatt, R. J. (1997). Luminescent Gold(I) Acetylides: From Model Compounds to Polymers. Organometallics, 16, 3541-3547. (h) Yam, V. W. W.; Choi, S. W. K., and Cheung, K. K. (1996). Synthesis and Design of Novel Tetranuclear and Dinuclear Gold(I) Phosphine Acetylide Complexes. First X-ray Crystal Structures of a Tetranuclear ([Au4(tppb)(C≡CPh)4]) and a Related Dinuclear ([Au2(dppb)(C≡CPh)2]) Complex. Organometallics, 15, 1734-1739. (i) Irwin, M. J.; Manojlovic-Muir, L.; Muir, K. W.; Puddephatt, R. J., and Yufit, D. S. (1997). Trigold Triacetylides: Polymerization through Gold···Gold Bonding or Bridging ligands. Chem. Commun., 219-220. (j) Lang, H.; Köcher, S.; Back, S.; Rheinwald, G., and van Koten, G. (2001). Synthesis and Coordination Chemistry of Gold(I) Acetylides. The Solid-State Structure of {[η2- (Ph3P)AuC≡CFc]Cu(μ-Cl)}2. Organometallics, 20, 1968-1972. (k) Back, S.; Gossage, R. A.; Lang, H., and van Koten, G. (2000). Mixed Metal Acetylides: The Pt(II) Aryl Acetylide"[PtC6H2(CH2NMe2)2-2,6-(C≡C)-4]"as a Connective Fragment Eur. J. Inorg. Chem., 1457-1464. (l) Yam, V. W. W. (2002). Molecular Design of Transition Metal Alkynyl Complexes as Building Blocks for Luminescent Metal-Based Materials: Structural and Photophysical Aspects. Acc. Chem. Res., 35, 555-563. (m) Whittall, I. R.; Humphrey, M. G.; Houbrechts, S.; Persoons, A., and Hockless, D. C. R. (1996). Organometallic Complexes for Nonlinear Optics. 8. Syntheses and Molecular Quadratic Hyperpolarizabilities of Systematically Varied (Triphenylphosphine)gold σ- Arylacetylides: X-ray Crystal Structures of Au(C≡CR)-(PPh3) (R = 4-C6H4NO2, 4,4'- C6H4C6H4NO2). Organometallics, 15, 5738-5745. (n) Naulty, R. H.; Cifuentes, M. P.; Humphrey, M. G.; Houbrechts, S.; Boutton, C.; Persoons, A.; Heath, G. A.; Hockless, D. C. R.; Luther-Davies, B., and Samoc, M. (1997). Syntheses and Quadratic Hyperpolarizabilities of some (Pyridylalkynyl)metal Complexes: Crystal Structures of [Ni{2-(C≡C)C5H3NNO2-5}(PPh3)(η5-C5H5)], [Au{2-(C≡C)C5H3NNO2-5}(PPh3)] and [Au{2-(C≡C)C5H4N}(PPh3)] . J. Chem. Soc., Dalton Trans., 4167-4174. (o) Whittall, I. R.; Humphrey, M. G.; Samoc, M.; Luther-Davies, B., and Hockless, D. C. R. (1997). Organometallic Complexes for Non-Linear Optics XII Syntheses and Second-Order Susceptibilities of (Neomenthyldiphenylphosphine) Gold σ-Arylacetylides: X-ray Crystal Structures of Au(C≡CPh) (nmdpp) and Au((E)-4,4′- C≡CC6H4CH=CHC6H4NO2)(nmdpp). J. Organomet. Chem., 544, 189-196. (p) Whittall, I. R.; Humphrey, M. G.; Samoc, M., and Luther-Davies, B. (1997). Molecular Cubic Hyperpolarizabilities of Systematically Varied (Triphenylphosphane)-Gold-σ- Arylalkynyl Complexes. Angew. Chem., Int. Ed. Engl., 36, 370-371. (q) Yamamoto, Y.; Shiotsuka, M., and Onaka, S. (2004). Luminescent Rhenium(I)–Gold(I) Hetero Organometallics Linked by Ethynylphenanthrolines. J. Organomet. Chem., 689, 2905- 2911. (r) Ferrer, M.; Rodriguez, L.; Rossell, O.; Lima, J. C.; Gomez-Sal, P., and Martin, A. (2004). Unexpected Alkyne Transfer between Gold and Rhenium Atoms and its Heinrich Lang and Alexander Jakob 448 Application to the Synthesis of Alkynyl Rhenium(I) Compounds. Organometallics, 23, 5096-5099. (s) Lu, X. X.; Li, C. K.; Cheng, E. C. C.; Zhu, N., and Yam, V. W. W. (2004). Syntheses, Structural Characterization, and Host-Guest Chemistry of Ethynylcrown Ether Containing Polynuclear Gold(I) Complexes. Inorg. Chem., 43, 2225-2227. [75] (a) Bruce, M. I.; Cole, M. L.; Gaudio, M.; Skelton, B. W., and White, A. H. (2006). Some Complexes Containing Carbon Chains End-Capped by M(CO)2Tp′ [M = Mo, W; Tp′ = HB(pz)3, HB(dmpz)3] Groups. J. Organomet. Chem., 691, 4601-4614. (b) Fillaut, J. L.; Dua, N. N.; Geneste, F.; Toupet, L., and Sinbandhit, S. (2006). Nitrile Ligands for Controlled Synthesis of Alkynyl-Ruthenium based homo and Hetero Bimetallic Systems. J. Organomet. Chem., 691, 5010-5018. (c) Onitsuka, K.; Ohara, N.; Takei, F., and Takahashi, S. (2006). Synthesis and Redox Properties of Trinuclear Ruthenium– Acetylide Complexes with Tri(ethynylphenyl)amine Bridge. Dalton Trans., 3693-3698. (d) Sato, M.; Kubota, Y.; Kawata, Y.; Fujihara, T.; Unoura, K., and Oyama, A. (2006). Synthesis and Some Properties of Binuclear Ruthenocenes Bridged by Oligoynes: Formation of Bis(cyclopentadienylidene)cumulene Diruthenium Complexes in the Two-Electron Oxidation. Chem. Eup. J., 12, 2282-2292. (e) Paul, F.; Ellis, B. G.; Bruce, M. I.; Toupet, L.; Roisnel, T.; Costuas, K.; Halet, J. F., and Lapinte, C. (2006). Bonding and Substituent Effects in Electron-Rich Mononuclear Ruthenium σ- Arylacetylides of the Formula [(η2-dppe)(η5-C5Me5)Ru(C≡C)-1,4-(C6H4)X][PF6]n (n =0, 1; X = NO2, CN, F, H, OMe, NH2). Organometallics, 25, 649-665. (f) Kuo, C.-K.; Chang, J.-C.; Yeh, C.-Y.; Lee, G.-H.; Wang, C. C., and Peng, S. M. (2005). Synthesis, Structures, Magnetism and Electrochemical Properties of Triruthenium–Acetylide Complexes. Dalton Trans., 3696-3701. (g) Xu, G.-L.; Crutchley, R. J.; DeRosa, M. C.; Pan, Q.-J.; Zhang, H.-X.; Wang, X., and Ren, T. (2005). Strong Electronic Couplings between Ferrocenyl Centers Mediated by Bis-Ethynyl/Butadiynyl Diruthenium Bridges. J. Am. Chem. Soc., 127, 13354-13363. (h) Hu, Q. Y.; Lu, W. X.; Tang, H. D.; Sung, H. H. Y.; Wen, T. B.; Williams, I. D.; Wong, G. K. L.; Lin, Z., and Jia, G. (2005). Synthesis and Photophysical Properties of Trimetallic Acetylide Complexes with a 1,3,5-Triazine Core. Organometallics, 24, 3966-3973. (i) Wilton-Ely, J. D. E. T.; Honarkhah, S. J.; Wang, M.; Tocher D. A., and Slawin, A. M. Z. (2005). σ-Organyl Complexes of Ruthenium and Osmium Supported by a Mixed-Donor Ligand. Dalton Trans., 1930-1939. [76] Ara, I.; Berenguer, J. R.; Eguizabal, E.; Fornies, J., and Lalinde, E. (2001). Formation of an Unsymmetrical Pt-Ir Tetraalkynyl Complex and Investigation into Subsequent Construction of Multimetallic Systems. Organometallics, 20, 2686-2696. [77] Wu, I. Y.; Lin, J. T.; Luo, J.; Sun, S. S.; Li, C. S.; Lin, K. J.; Tsai, C.; Hsu, C. C., and Lin, J. L. (1997). Syntheses and Reactivity of Ruthenium σ-Pyridylacetylides. Organometallics, 16, 2038-2048. [78] (a) Vicente, J.; Chicote, M.-T.; Alvarez-Falcón, M. M., and Jones, P. G. (2005). Platinum(II) and Mixed Platinum(II)/Gold(I) σ-Alkynyl Complexes. The First Anionic σ-Alkynyl Metal Polymers. Organometallics, 24, 2764-2772. (b) Chin, C. S.; Kim, M.; Won, G.; Jung, H., and Lee, H. (2003). Diastereocontrolled Synthesis of cis-Olefins by Selective C–C Bond Formation Between Alkyl and Alkynyl Groups Coordinated to „Ir(CH=CHPPh3)(CO)(PPh3)2“. Dalton Trans., 2325-2328. (c) Albinati, A.; Leoni, P.; Mixed Transition Metal Acetylides with Different Metals Connected … 449 Marchetti, L., and Rizzato, S. (2003). Assembling Metal Clusters with Covalent Linkers: Synthesis and Structure of a Quasi-Planar Pt18 Dendrimer Containing Five Clusters Connected by σ-Alkynyl Spacers. Angew. Chem. Int. Ed., 42, 5990-5993. (d) Chin, C. S.; Kim, M.; Lee, H.; Noh, S., and Ok, K. M. (2002). Regio- and Stereoselective C-C Bond Formation between Alkynes: Synthesis of Linear Dienynes from Alkynes. Organometallics, 21, 4785-4793. (e) Bruce, M. I.; Davy, J.; Hall, B. C.; van Galen, Y.; Skelton, B. W., and White, A. H. (2002). Some Platinum(II) Complexes Derived from Aromatic Alkynes. Appl. Organomet. Chem., 16, 559-568. [79] Weyland, T.; Lapinte, C.; Frapper, G.; Calhorda, M. J.; Halet, J.-F., and Toupet, L. (1997). Bi- and Trimetallic σ-Acetylide Complexes Connected Through a Phenyl Ring in the Fe(Cp*)(dppe) Series. Organometallics, 16, 2024-2031. [80] (a) Cifuentes, M. P.; Powell, C. E.; Morrall, J. P.; McDonagh, A. M.; Lucas, N. T.; Humphrey, M. G.; Samoc, M.; Houbrechts, S.; Asselberghs, I.; Clays, K.; Persoons, A., and Isoshima, T. (2006). Electrochemical, Spectroelectrochemical, and Molecular Quadratic and Cubic Nonlinear Optical Properties of Alkynylruthenium Dendrimers. J. Am. Chem. Soc.; 128, 10819-10832. (b) McDonagh, A. M.; Powell, C. E.; Morrall, J. P.; Cifuentes, M. P., and Humphrey, M. G. (2003). Convergent Synthesis of Alkynylbis(bidentate phosphine)ruthenium Dendrimers. Organometallics, 22, 1402- 1413. (c) Long, N. J.; Martin, A. J.; White, A. J. P.; Williams, D. J.; Fontani, M.; Laschi, F., and Zanello, P. (2000). Synthesis and Characterisation of Unsymmetrical Metal (RuII, OsII) and Ferrocenyl Complexes of 1,3,5-Triethynylbenzene. J. Chem. Soc., Dalton Trans., 3387-3392. [81] (a) Hearshaw, M. A., and Moss, J. R. (1999). Organometallic and Related Metal- Containing Dendrimers. Chem. Commun. 1-8. (b) Stoddart, F. J., and Welton, T. (1999). Metal-Containing Dendritic Polymers. Polyhedron, 18, 3575-3591. (c) Cuadrado, I.; Mora´n, M.; Casado, C. M.; Alonso, B., and Losada, J. (1999). Organometallic Dendrimers with Transition Metals. Coord. Chem. Rev., 193-5, 395- 445. (d) Astruc, D.; Blais, J.-C.; Cloutet, E.; Djakovitch, L.; Rigaut, S.; Ruiz, J.; Sartor, V., and Vale´rio, C. (2000). The First Organometallic Dendrimers: Design and Redox Functions. In F. Vögtle, (Ed.), Topics in Current Chemistry (Vol. 210, p 229-259). Berlin, Germany: Springer. (e) Juris, A.; Venturi, M.; Ceroni, P.; Balzani, V.; Campagna, S., and Serroni, S. (2001). Dendrimers Based on Electroactive Metal Complexes. A Review of Recent Advances. Collect. Czech. Chem. Commun., 66, 1-32. (f) van Manen, H.-J.; van Veggel, F. C. J. M.; Reinhoudt, D. N. (2001). Non-Covalent Synthesis of Metallodendrimers. In F. Vögtle and C. A. Schalley, (Eds.) Topics in Current Chemistry; (Vol. 217, p 121-161). Berlin, Germany: Springer. (g) Kreiter, R.; Kleij, A. W.; Klein Gebbink, R. J. M.; van Koten, G. (2001). Dendritic Catalysts. In F. Vögtle, and C. A. Schalley, (Eds.) Topics in Current Chemistry (Vol. 217, p 163-199). Berlin, Germany: Springer. (h) Astruc, D. (2003). Organometallic Chemistry at the Nanoscale. Dendrimers for Redox Processes and Catalysis. Pure Appl. Chem., 75, 461481. (i) Sengupta, S. (2003). A Ferrocene Dendrimer Based on a Cyclotriphosphazene core. Tetrahedron Lett., 44, 7281-7284. (j) Poniatowska, E., and Salamon´czyk, G. M. (2003). Phosphite Dendrimers and their Organometallic Derivatives. Tetrahedron Lett., 44, 4315-4317. (k) Angurell, I.; Muller, G.; Rocamora, M.; Rossell, O., and Seco, M. (2003). Synthesis and Catalytic Properties of Neutral and Heinrich Lang and Alexander Jakob 450 Cationic Rhodium- and Iridium-Containing Carbosilane Dendrimers. Dalton Trans., 3 1194-1200. (l) Angurell, I.; Muller, G.; Rocamora, M.; Rossell, O., and Seco, M. (2004). Single and Double Metallic Layer-Containing Ruthenium Dendrimers. Synthesis and Catalytic Properties. Dalton Trans., 2450-2457. (n) Astruc, D. (2004). Organoiron Activation Combined with Electron- and Proton Transfer: Implications in Biology, Organic Synthesis, Catalysis and Nanosciences. J. Organomet. Chem., 689, 4332-4344. (o) Busetto, L.; Cassani, M. C.; van Leeuwen, P. W. N. M.; Mazzoni, R. (2004). Synthesis of New Poly(propylenimine) Dendrimers DAB-dendr- [NH(O)COCH2CH2OC(O)C5H4Rh(NBD)]n {n = 4, 8, 16, 32, 64} Functionalized with Alkoxycarbonylcyclopentadienyl Complexes of Rhodium(I). Dalton Trans., 2767- 2770. (p) Onitsuka, K.; Fujimoto, M.; Kitajima, H.; Ohshiro, N.; Takei, F., and Takahashi, S. (2004). Convergent Synthesis of Platinum-Acetylide Dendrimers. Chem. Eur. J., 10, 6433-6446. (q) Caminade, A.-M., and Majoral, J.-P. (2005). Phosphorus Dendrimers Possessing Metallic Groups in their Internal Structure (Core or Branches): Syntheses and Properties. Coord. Chem. Rev., 249, 1917-1926. (r) Turrin, C.-O.; Donnadieu, B.; Caminade, A.-M., and Majoral, J.-P. (2005). Organometallic Derivatives at the Core of Phosphorus-Containing Dendrimers. Z. Anorg. Allg. Chem., 631, 2881-2887. (s) Angurell, I.; Rossell, O.; Seco, M., and Ruiz, E. (2005). Dendrimers Containing Two Metallic Layers. Chloride Migration from Peripheral Gold, Palladium, or Rhodium Metals to Internal Ruthenium Atoms. Organometallics, 24, 6365-6373. (t) Ornelas, C.; Vertlib, V.; Rodrigues, J., and Rissanen, K. (2006). Ruthenium Metallodendrimers Based on Nitrile-Functionalized Poly(alkylidene imine)s. Eur. J. Inorg. Chem., 1, 47-50. [82] Mongin, O.; Papamicaël, C.; Hoyler, H., and Gossauer, A. (1998). Modular Synthesis of Benzene-Centered Porphyrin Trimers and a Dendritic Porphyrin Hexamer. J. Org. Chem., 63, 5568-5580. [83] Chong, S. H-F.; Lam, S. C.-F.; Yam, V. W.-W.; Zhu, N., and Cheung, K.-K. (2004). Luminescent Heterometallic Branched Alkynyl Complexes of Rhenium(I)- Palladium(II): Potential Building Blocks for Heterometallic Metallodendrimers. Organometallics, 23, 4924-4933. [84] Jakob, A. (2007). PhD Thesis, TU Chemnitz. [85] Baumgartner, T.; Fiege, M.; Pontzen, F., and Arteaga-Müller, R. (2006). Redox-Active, Multinuclear (Ferrocenylethynyl)phosphanes and Their Palladium and Platinum Complexes. Organometallics, 25, 5657-5664. [86] Milde, B. (2007). Diploma Thesis, TU Chemnitz. [87] Stein, T. (2001). Bi- und oligonukleare Komplexe basierend auf Metallorganischen π- Pinzetten. PhD Thesis, TU Chemnitz. [88] Köcher, S.; van Klink, G. P. M.; van Koten, G., and Lang, H. (2006). Biferrocene NCN Pincer Metal-d8 Complexes: Synthesis, Reaction Chemistry and Cyclovoltammetric Studies. J. Organomet. Chem., 691, 3319-3324. [89] (a) Horikoshi, R.; Mochida, T.; Torigoe, R., and Yamamoto, Y. (2002). Preparation and Electrochemical Properties of Polynuclear Organometallic Complexes Derived from Ferrocene-Containing Bidentate Ligands. Eur. J. Inorg. Chem., 3197-3203. (b) Lohan, M. (2005). Biferrocene in der metallorganischen Synthese. Diploma Thesis, TU Chemnitz. [90] Lohan, M. PhD Thesis, TU Chemnitz. Mixed Transition Metal Acetylides with Different Metals Connected … 451 [91] Dong, T.-Y.; Lin, M.; Chiang, M. Y.-N., and Wu, J.-Y. (2004). Development of Polynuclear Molecular Wires Containing Ruthenium(II) Terpyridine Complexes. Organometallics, 23, 3921-3930. [92] Packheiser, R.; Walfort, B., and Lang, H. (2007). Synthesis and Characterization of a Heterometallic Fe-Au-Ti-Cu Transition Metall Complex. Jord. J. Chem., in press. [93] Kühnert, J. (2008). PhD Thesis, TU Chemnitz. [94] Frosch, W.; Back, S., and Lang, H. (1999). 1,1'-Ferrocenyldicarboxylic Acid as Starting Material for the Formation of Trimetallic Ti(IV)-Fe(II)-Cu(I) and Pentametallic Ti2(IV)-Fe(II)-Cu2(I) Complexes. Organometallics, 18, 5725-5728. [95] Stein, T., and Lang, H. (2001). A Cross-Shaped Ag5Ti4 Molecule Based on a [Ag(C≡N)4]3– Core. Chem. Commun., 1502-1503. [96] Al-Anber, M. (2003). Organic and/or Inorganic π-Conjugated Units in the Synthesis of Multinuclear Transition Metal Complexes. PhD Thesis, TU Chemnitz. [97] Al-Anber, M.; Taher, D.; Walfort, B., and Lang, H. (2007). Novel Heterotetrametallic Fe-Au-Ti-Cu Transition Metal Complexes. Jordan J. Chem., 1, 121-127 . [98] (a) Müller, T. E.; Green, J. C.; Mingos, D. M. P.; McPartlin, C. M.; Whittingham, C.; Williams, D. J., and Woodroffe, T. M. (1998). Complexes of Gold(I) and Platinum(II) with Polyaromatic Phosphine Ligands. J. Organomet. Chem., 551, 313-330. (b) Müller, T. E.; Choi, S. W.-K.; Mingos, D. M. P.; Murphy, D.; Williams, D. J., and Yam, V. W.- W. (1994). Synthesis, Structural Characterization and Photophysical Properties of Ethyne-Gold(I) Complexes. J. Organomet. Chem., 484, 209-224. [99] Garrison, J. C.; Panzner, M. J.; Custer, P. D.; Reddy, D. V.; Rinaldi, P. L.; Tessier, C. A., and Youngs, W. J. (2006). Synthesis and Characterization of a Trigonal Bipyramidal Supramolecular Cage Based upon Rhodium and Platinum Metal Centers. Chem. Commun., 4644-4646. [100] Vives, G.; Carella, A.; Launay, J.-P., and Rapenne, G. (2006). A Star-Shaped Ruthenium Complex with Five Ferrocenyl-Terminated Arms Bridged by trans- Platinum Fragments. Chem. Commun., 2283-2285. [101] Packheiser, R., and Lang, H. (2007). A First Mixed Heteropentametallic Transition Metall Complex: Synthesis and Charcterisation. Inorg. Chem. Commun., 10, 580-582. In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0 Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc. Chapter 12 REACTIVITY OF UNSTABLE CHEMICALS IN THE PRESENCE OF TRANSITION METALS * Mieko Kumasaki National Institute of Occupational Safety and Health, Tokyo, Japan ABSTRACT Some hazardous materials show characteristic features in their reaction with transition metals; they are unstabilized, and sometimes decompose when in contact with transition metals. Their chemical structure indicates that they have a high tendency to interact with transition metals since they include electronegative atoms. Transition metal atoms attract lone pairs of electronegative atoms. This tendency leads to the formation of a complex of transition metals and the molecules. However, some complexes, especially those with unstable molecules, can dissociate immediately along with decomposition of unstable chemicals, or they can be unstabilized by heat, friction and other stimulation because bond strength is affected and weakened by electronic condition change through complex formation. The effect sometimes results in a reaction beyond control and explosion. This article provides an overview of current research on the reactivity of transition metals and unstable chemicals, and the decomposition behavior of unstable chemicals interacting with metals. The subject is related through three viewpoints: the stability change caused by the interactions, the reaction features from the viewpoint of heat release, and the interaction features of oxygen and nitrogen with Fe 3+ . 1. INTRODUCTION Hazardous materials are those materials which represent characteristic features or have potential to pose damages: physical damages by explosion and runaway reaction, or biological damage such as mutation or acute toxicity [1,2]. The damages impact basic * A version of this chapter also appears in Research Progress in Materials Science, edited by William Olsson and Filip Lindberg, published by Nova Science Publishers, Inc. It was submitted for appropriate modifications in an effort to encourage wider dissemination of research. Mieko Kumasaki 454 reliance on chemical industries even though they have provided demanded chemicals, and contributed to an affluent society. The physical damage, in particular, can produce widespread as well as long-term consequences. It sometimes triggers biological damage, also. In terms of wide-spread consequence, the chemical plant explosion occurring in 1991 in Japan is taken for example. The explosion killed and injured personnel working inside the premises, even far from the explosion center. The deadly fragments flew about 100m to break through iron bars on the window. Other fragments flew more than 250m to crash through a ceiling. As for a long-term consequence, destruction of facility allowed chemicals on site to spill into rivers, ocean, soil, and air. The chemicals can remain long term in the environment and may cause a biological impact. For this reason, knowledge of the reactivity of hazardous materials is essential to retain them under control, and to prevent any disaster for the sustainable development of modern society. One of the characteristic reactions of some hazardous materials is found in their reaction with transition metals [1]. Considering the chemical structures of hazardous materials, most of them include electronegative atoms, especially for unstable and reactive molecules. Electronegative atoms can easily interact with transition metals by donating lone pairs to vacant atomic orbit of transition metals. The interaction results in the formation of a complex: species of a central metal atom or ion surrounded by a set of ligands [3]. A complex consists of coordination linkage whose bond electrons are donated by ligands. Various kinds of complexes are found in nature such as hemoglobin, Vitamin B12, and so on. These complexes are stabile to serve in a body or natural environment when ligands are stable enough. On the contrary, complex formation has an intensified impact on unstable molecules as ligands. Transition metals provide perturbation to the electronic condition of a molecule, and this can change molecular form and bond strength. Strength of bond affects molecular stability since chemicals generally start decomposition with a break in weak bonds. Therefore unstable molecules can change bond strength and be unstabilized through complex formation. Furthermore, some complexes dissociate immediately after complex formation, along with rearrangement within ligands or decomposition of ligands. While this kind of function is utilized as catalysts to generate valuable chemicals [4], it sometimes leads a reaction beyond control (runaway reaction) and explosion. Unstable chemicals as ligands decompose easily, and have the potential to lead to explosion because of their fragility. This article provides an overview of current research on the interaction between transition metals and unstable chemicals. It can be divided into three parts: the stability change caused by interactions, the reaction features from the viewpoint of heat release, and the interaction features of oxygen and nitrogen with Fe 3+ . The first part describes cases where the kind of interaction changes sensitivity to heat, friction, electronic spark, and mechanical impact. Tetrazole and triazole (azoles) are subjected to investigation. The chemicals are utilized in pyrotechnic devices as energetic materials: that means they are categorized in reactive materials. By formation of complexes, they change sensitivity as well as energy release behavior. The second part focuses on heat release behavior of hydrogen peroxide (H 2 O 2 ), hydrazine (NH 2 NH 2 ), and hydroxylamine (NH 2 OH) which are the simplest molecules containing electronegative atoms. Simple chemical structure enables us to eliminate structural hindrance to metal-electronegative atom interaction which frequently occurs in a large molecule. Reactivity of Unstable Chemicals in the Presence of Transition Metals 455 Additionally, tracking heat release behavior provides information about reactions since heat generation directly corresponds to the enthalpy difference between reactant and stable products. The results can provide some insight into reactivity difference between nitrogen and oxygen, as well as their individual reactivity. Contrary to the second part, the third part relates the reaction between NH 2 OH and Fe 3+ affected by steric hindrance. This part focuses on the reaction of substituted NH 2 OH by the methyl group. The Steric hindrance by the methyl group can restrict the reaction center in NH 2 OH. This part also relates the protected iron ion by ligands, acidity of solutions, and charge distribution on NH 2 OH by way of ab initio molecular orbital calculation. 2. THE STABILITY CHANGE CAUSED BY INTERACTIONS: THE STABILITY CHANGE OF TETRAZOLE AND TRIAZOLE THROUGH THE INTERACTION WITH TRANSITION METAL [5] This section provides an overview of the effect of the interaction on the sensitivity to azoles by way of synthesized azole-metal complexes. Azoles are energetic materials which are frequently used as an ingredient of pyrotechnic devices. In the field of energetic materials, azole complexes with transition metals, however, had less attraction compared to a mixture of azoles and transition metal compounds. For instance, transition metal oxides have been added to propellants and other energetic devices so as to enhance reactivity by releasing oxygen [7,8]. Some oxides achieved better heat conduction and promotion of the electron-transfer process as well as improvement of burning rate. In that sense, the evaluation of azole-metal complexes started originally from the attempt to enhance the reactivity of azoles by means of effective interaction between azoles and transition metal as catalysts [5]. Since the distance between transition metal and azole becomes shorter in complex, the interaction was expected to be stronger. Through the experiments and analysis, the interaction has been recognized as perturbation on azole’s stability. This section describes the evaluation of 1H-tetrazole-metal complex and 1H-1,2,4- triazole-metal complex in terms of sensitivity (Figure 1). 1H-tetrazole (abbreviated as 1HT) and 1H-1,2,4-triazole (abbreviated as 1HTRI) are basic azoles which can easily coordinate to transition metals through nitrogen atoms. Previous studies reported that azoles exist as bidentate ligands in many azole-metal complexes [8, 9]. Many transition metals are able to form complexes with azoles. This section is concerned only with complexes including copper, apart from other reports which have assessed their sensitivity and reactivity [10-13]. Figure 1. The chemical structures of 1H-tetrazole(a) and 1H-1,2,4-triazole(b). Mieko Kumasaki 456 2.1. Synthesis On of the sample was prepared by mixing aqueous solutions of 1HT and Cu(NO 3 ) 2 ･3H 2 O. Pale blue precipitate immediately generated. The precipitate was subsequently washed with water, methanol, ether, and dried under reduced pressure. Their molecular formula were determined to be [Cu(CN 4 H) 2 ]H 2 O (abbreviated 1HTCu) based on an elemental analysis. One proton was liberated from 1HT since the parent molecule has a pKa value of about 4.8, which is similar to that of acetic acid [14]. All attempts to dissolve the complexes in common solvents failed because of poor solubility. The other complex of 1HTRI was synthesized in the aqueous solution as well as one of 1HT. Purple precipitate was determined as [Cu(C 2 N 3 H 3 ) 2 ](NO 3 ) 2 (abbreviated 1HTRICu) based on elemental analysis. All attempts to dissolve the complexes in common solvents failed because of poor solubility, either. The poor solubility precluded recrystalization. 2.2. Sensitivity Tests to Friction, Mechanical Impact, and Electronic Spark The drop Hammer Test is a popular method of assessing the sensitivity of explosives to mechanical impact [15]. There exist a few kinds of the tests for mechanical impact developed at Swiss Chemicals Industry, Bundesanstalt für Materialforschung und prüfung (Federal Institute for Materials Research and Testing in English, BAM), the U.S. Bureau of Mines, and Japan Industrial Standards (JIS). In this study, experiments carried out in the manner of JIS. The test sample is sandwiched between two cylinders and placed on anvil in a tester so that 5kg of a dropping hammer free-fall onto it. The experimental results provide sensitivity to mechanical impact as a function of energies calculated from dropping heights. Based on the up-and-down method, the 50% explosion height and the corresponding energy were determined as is presented in Table 1 [16]. For the complexes, the test was carried out 6 times with a hammer height setting of 50cm. Both complexes did not explode in this test and were categorized as grade 8 according to JIS. The test revealed that complex is more stable to mechanical impact than azoles. Although this test is strongly influenced by physical properties such as grain size and humidity, the interaction between azole and transition metal appear to stabilize azole to mechanical impact. Friction sensitivity test was carried out in accordance with JIS K 4810 by using of BAM friction test apparatus [17]. Substance is spread onto a porcelain plate, and the ceramic place is dragged under weighed porcelain stick. Sensitivity of substance to friction is evaluated from an amount of load at which one explosion occurs at least out of 6 trials. The load is utilized as indexes for 1/6 explosion point. From the friction sensitivity test, the 1/6 explosion point was equal to be 25.2kgf for 1HT and 24.2-25.2kgf for 1HTRI. On the other hand, 1HTCu and 1HTRI did not explode at the highest load of 36.0kgf. Therefore, they are too insensitive to measure using the BAM friction sensitivity test. These results are summarized in Table 2. This test is strongly influenced by physical properties such as grain size and humidity as well as drop hammer test. However, the azole-metal complexes can be considered to be more stable to friction than azoles. Reactivity of Unstable Chemicals in the Presence of Transition Metals 457 Table 1. Summary of the results of Drop Hammer Test Samples H 50 [cm] E 50 [J] 1HT 12 5.9 1HTRI 3.4 1.7 1HTCu >50 >24.5 1HTRICu >50 >24.5 Table 2. Summary of the results of BAM friction sensitivity test Samples M 1/6 [kgf] 1HT 25.2 1HTRI 24.2-25.2 1HTCu >36.0 1HTRICu >36.0 Meanwhile, they showed different tendency of the sensitivity to electronic spark from other stimulation. Sensitivity to electronic spark was evaluated according to Electrostatic Sensitivity Test in Japan Explosives Society Standard (IV) [18]. The sample was sandwiched between two electrodes connected to condensers and the electrical spark applied by discharge. The sensitivity was estimated by the 50% explosion point using an up-and-down method. The results of the electric spark ignition are shown in Table 3. The test revealed that the complexes were sensitive compared to the pure azoles. The sensitivity of 1HTCu was close to the mixture of Al and KClO 4 (logE 50 is -0.76) which is utilized as spark source in fireworks [19, 20]. As for 1HTRICu, the sensitivity was close to the mixture of B and KClO 3 which is utilized as igniter for propellants and airbag inflator (0.06). Sakata reported that the sodium and potassium salts of 1HT were more insensitive to impact, friction and electric spark than 1HT [21]. The copper complex showed the same trend except for the sensitivity to static electricity. 2.3. Thermal Analysis for Sensitivity to Heat Sealed Cell-Differential Scanning Calorimetry (SC-DSC) was used for surveying behavior under heating conditions. In the analysis, the calorimeter heats sample and reference under the programmed temperature control. The heat release or absorption data as a function of temperature enable to estimate sensitivity of the sample to heat. The sample weight for the investigation was about 1.0mg. The heating rate was 10K/min. Table 3. Summary of the results of sensitivity test to static electricity Samples LogE 50 E 50 [mJ] 1HT 0.52 3.29 1HTRI 0.04 1.10 1HTCu -0.88 0.13 1HTRICu -0.08 0.84 Mieko Kumasaki 458 Figures 2 and 3 show the SC-DSC charts of the azoles, azole-metal complexes and tetrazole-metal nitrate mixtures. Horizontal axis indicates temperature. Upward peaks indicate heat release (exothermic) while downwards do heat absorption (endothermic). The exothermic peaks of the complex stretched sharply compared with the pure azole and azole- metal nitrate mixture. The 1HT in complexes decompose faster than as pure azole. These results confirmed that an azole definitely interacts with a metal and coordination to the metal effects on the decomposition velocity. Figure 2. Figure 3. Reactivity of Unstable Chemicals in the Presence of Transition Metals 459 In figures 2 and 3, the azoles exhibit endothermic behavior corresponding to melting below their decomposition temperatures at which heat release starts. For the complexes, however, the endothermic peaks disappeared. This disappearance is considered to be due to a change in their electronic properties. Neutral molecules link together via a Van der Waals force in the pure azole crystal. In 1HTCu, however, tetrazole negatively charged because of proton liberation. In this way, 1HT molecules and copper link via a Coulombic force in the complex solid because copper positively charged. Contrary to 1HT in complex, 1HTRI can be considered to slightly charge positively in complex because 1HTRI donate electrons to metal to form coordination linkage. The electron-donation also generates Coulombic force. Since the Coulombic force is stronger than the Van der Waals force, 1HTCu and 1HTRICu as ionic crystal are difficult to melt compared molecular crystals of 1HT and 1HTRI. The values of T DSC and Q DSC are summarized in Table 4. T DSC is an onset temperature of exothermic peak which indicates the temperature explosion or decomposition starts. Q DSC is the heat of reaction per unit mass calculated based on peak integral. Since there are heavy copper atoms (and nitrate anion for 1HTRICu) in the complex, the Q DSC of the complexes should decrease. As for 1HTCu, the heat of reaction per unit mass was naturally smaller than 1HT. However, the heat of reaction per azole molecule calculated based on the elemental analysis results is almost the same as 1HT, but larger than the potassium and sodium salts. Meanwhile, Q DSC of 1HTRICu was larger than that of the 1H-1,2,4-triazole. This is considered to be due to fragmentation easily progresses in 1HTRICu. Williams et al. reported that triazoles are able to form polymers [22]. As a result of complex formation, a high reactivity achieved fragmentation during decomposition and a more exothermic reaction along with generation of small stable molecules. As for T DSC , the thermal stability of 1HTCu was higher compared to 1HT. In the study on substituted tetrazoles, Ohno concluded that tetrazoles were thermally stabilized by electron donating substituents because of an increase of aromaticity [23]. In 1HTCu, the tetrazole valence was –1 and the electronic state of triazole ring is similar to one in the tetrazole with electron-donating groups which make tetrazole ring slightly anionic. Figure 4 indicates the optimized structures of the anionic and neutral 1H-tetrazoles by using a molecular orbital calculation at the HF/6-31G* level of theory with GAUSSIAN94 [24]. In the optimized structures, the uniformity of the bond lengths and an increase in the aromaticity were found in the anionic 1H-tetrazole. The calculation results indicate the anionic character of 1H-tetrazole influences the thermal stabilities. Furthermore, the N1-C5 and N3-N4 bonds are shorter in the anionic state than in the neutral state. Considering that the decomposition of 1H-tetrazole starts from breaking these bonds under the stated condition [25], it can be said that the anionic state is more stable than the neutral state. For 1HTRICu, the triazole ring has a slight cationic character due to electron donation. The cationic state of the molecule was optimized and is shown in Figure 5. In this calculation, triazole valence was +1 so as to simulate slightly charged condition. Consequently, the standard deviation of the average bond length became greater in the cationic state than in the neutral state. This might indicate a decrease in aromaticity. That can explain the stability of 1HTRI decreased. Mieko Kumasaki 460 Figure 4. Optimized structures of neutral and negatively charged 1HT. Figure 5. Optimized structures of Neutral and positively charged 1HTRI. The concept of aromaticity can explain well the change in thermal stability for copper complex. However, some complex of 1HT and 1HTRI behave differently. For instance, complex of nickel and 1HTRI exhibited the similar thermal stability to 1HTRI [10]. To reveal principle for stability of the complexes, analysis will be required for structural information and coordination manner. Table 4. Summary of the results under the heating condition Sample T DSC [ o C] Q DSC [J/g] Q DSC [kJ/mol] Q DSC [kJ/azole] 1HT 204 4257 298 1HTCu 264 2516 552 276 1HTNa[21] 324 1700 157 1HTK[21] 311 1620 175 1HTRI 342 1506 104 1HTRICu 312 1987 647 324 Reactivity of Unstable Chemicals in the Presence of Transition Metals 461 3. THE REACTION FEATURES FROM THE VIEWPOINT OF HEAT RELEASE: THE REACTION BETWEEN TRANSITION METAL AND SIMPLE MOLECULES WITH ELECTRONEGATIVE ATOMS [26-29] In chemical structures of reactive hazardous materials, nitrogen and oxygen atoms appear most frequently. Both of them have a capability to interact with transition metals by donating electrons used in coordination bond formation. Their affinity for transition metals must be one of the subjects of research to reveal the nature of the reactivity. Starting research from simpler molecule is common line of reasoning for research on chemistry. This section describes the research on three chemicals with simple molecular structures: hydrazine (NH 2 NH 2 ), hydroxylamine (NH 2 OH), and hydrogen peroxide(H 2 O 2 ). They have similar chemical structure composed of two electronegative atoms and hydrogen atoms. All of them exhibit high solubility into water. Furthermore, they have triggered several explosion accidents due to high reactivity. As for NH 2 NH 2 , it is easy to understand to explode since this compound is utilized in a rocket propellant ingredient. NH 2 OH and its salts are widely available commercially and frequently used industrially in chemical synthesis and the manufacturing of semiconductors. NH 2 OH, however, killed five people in the state of Pennsylvania in the U.S.A. in 1999, and four people in Japan, in 2000. The accidents occurred by H 2 O 2 is too numerous to enumerate. The numerous number of the accident of H 2 O 2 reflects its utility in chemical industry, as environmentally-friendly breaching agent and bactericide. Besides, similar properties are found in some regards: redox behavior. They are available as both of reducing agent and oxidizing agent. In general, H 2 O 2 , NH 2 OH and NH 2 NH 2 act as reducing agent in acidic solutions and as oxidizing agents in neutral or alkaline media. Based on the potential of half-reactions, H 2 O 2 serves as oxidizing agent, NH 2 NH 2 does as reducing agent, and NH 2 OH is considered as the intermediate compound. However, by varying the conditions, H 2 O 2 has a capacity as reducing agent in contact with stronger oxidizers [30, 31] In acid solution: 2H 2 OH 2 O 2 + 2H + +2e - E=1.77V as oxidizer (1) H 2 O 2 O 2 + 2H + +2e - E=0.68 as reducer (2) N 2 H 5 + N 2 + 5H + + 4e - E=-1.16 as reducer [31] (3) NH 4 + +H 2 O HONH 3 + +2H + + 2e - E=1.35 as oxidizer (4) HONH 3 + 0.5N 2 + 2H + + H 2 O + e- E=-1.87 as reducer (5) 2HONH 3 + N 2 O + 6H + + H 2 O + 4e - E=-0.05 as reducer (6) 2HONH 3 + H 2 N 2 O 2 + 6H + + 4e - E=-0.44 as reducer (7) Mieko Kumasaki 462 In basic solution: 3OH - HO 2 - + H 2 O + 2e - E=0.87 as oxidizer (8) N 2 H 4 +4OH - N 2 +4H 2 O+4e - E=-1.16 as reducer [31] (9) 2NH 2 OH + 2OH - N 2 + 4H 2 O + 2e - E=-3.04 as reducer (10) 2NH 2 OH + 4OH - N 2 O + 5H 2 O + 4e - E=-1.05 as reducer (11) 2NH 2 OH + 6OH - N 2 O 2 2- + 6H 2 O + 4e- E=-0.73 as reducer (12) Meanwhile, transition metal generally works as oxidizer. They can have several oxidation states and transition easily from higher oxidation state to lower oxidation state companied with oxidizing neighboring reducer. Furthermore, some transition metals are able to reverse the direction of the transition, and be oxidized under some conditions. For example, Fe 2+ is easily oxidized into Fe 3+ in a basic solution. This kind of metal functions as catalysts through the process of exchange electrons between metal and substrates as is shown below. In the process, the metal can supply chain reaction carrier such as radicals and lead hazardous materials to react and decompose even in a small amount existence. In particular, it can trigger a severe accident if a substance behaves as both of oxidizer and reducer. P (oxidizer) + M n+ P･ + M (n+1)+ R･ (reducer) + M (n+1)+ R + M n+ Through this section, the difference in reactivity of three compounds is observed in terms of heat release behavior. 3.1. An Experimental Apparatus for Tracking Heat Release Behavior: SuperCRC Figure 6 shows the schematic view of the Super-CRC. Super-CRC is one of the reaction calorimeters. Among several reaction calorimeters on the market, Super-CRC is characterized by small-scaled (16ml at a maximum), differential system and built-in magnetic stirrer. In this study, all experiments were carried out in an isothermal mode. A glass vial containing 1ml of substrates (aqueous solution of H 2 O 2 , NH 2 OH and NH 2 NH 2 ) was placed in the heat sink. An amount of 1ml of water was used as a reference. After the baseline got stabilized, 0.1g of the metal aqueous solutions(prepared to give 0.2mmol/g) were injected respectively to vials at once through Teflon tubes instead of needle so as to prevent metal contamination and completely dose a small amount of solutions. Since the Super-CRC is a differential calorimeter, the temperature difference between substrates and iron solution can be canceled as long as the same amount of solution is injected into both reactors. Therefore Reactivity of Unstable Chemicals in the Presence of Transition Metals 463 the heat flow curve is supposed to be independent of the differences. The data collection carried out under the continuous stirring. A heat-flow datum point was obtained every 3 seconds during the course of the reaction. The limitation of a maximum of 15,000 data points defined the maximum test duration as 12.5 hours. If the reactions were complete within 12.5h, the measurements were stopped after the heat flow curves reached their baseline levels. When the chemicals slowly reacted and continuously generated heat, the measurement continued until the maximum test duration. Three trials were carried out for each sample, and average values of the peak and overall heat of the reaction were calculated. Figure 6. Schematic view of the Super-CRC. Mieko Kumasaki 464 3.2. Reactivity of H 2 O 2 and NH 2 NH 2 with Fe 3+ Figures 7, 8, and 9 show the reaction at 35 o C with three Fe 3+ compounds, Fe(NO 3 ) 3 , Fe 2 (SO 4 ) 3 and FeCl 3 . The concentration of H 2 O 2 and NH 2 NH 2 is 30wt.%. The mixing with Fe 3+ aqueous solution showed moderate heat release for NH 2 NH 2 and completed to give dark precipitate regardless of the different anions. It remained unconfirmed whether any reduced iron species generated such as oxides of Fe 2+ , complex like [Fe(NH 2 NH 2 ) 2 Cl 2 ]･2H 2 O, [Fe(NH 2 NH 2 ) 2 SO 4 ]･H 2 O, [Fe(NH 2 NH 2 ) 2 (NO 3 ) 2 ]･H 2 O reported in previous study [32], and so forth. The precipitation, however, appeared Fe(OH) 3 due to the basicity of the NH 2 NH 2 aqueous solution. Even under the reductive condition due to NH 2 NH 2 , it is possible that Fe persist in Fe(OH) 3 since basic condition lets reduction of Fe 3+ more difficult rather than acidic one [33]. Meanwhile, the reactivity of H 2 O 2 exhibited quite different feature. H 2 O 2 released heat immediately after injection and gives transparent solution without precipitation. Considering the concentration of H 2 O 2 (8.8x10 -3 mol in a vial) and Fe(III)(2x10 -5 mol), Fe(III) species works as catalyst for H 2 O 2 . Figure 7. Heat release behavior in the reaction of H202 (circle) and NH2NH2 (square) with FeCI3. inset: the behavior of NH2NH2. Reactivity of Unstable Chemicals in the Presence of Transition Metals 465 Figure 8. Heat release behavior in the reaction of H202 (circle) and NH2NH2 (square) with Fe(NO3)3. inset: the behavior of NH2NH2. Figure 9. Heat release behavior in the reaction of H202(cicrle) and NH2NH (square) with Fe2(SO4)3/ inset: the behavior of NH2NH2. Mieko Kumasaki 466 The mechanism of the reaction between Fe(III) and H 2 O 2 has not been focused intensively in spite of numerous researches on the reaction H 2 O 2 and Fe(II) referred as the “Fenton reaction” [34, 35]. Among the research on Fe(III), Kremer mentioned the reaction of Fe 3+ associated with oxidation of Fe 2+ in a report. The idea that Fe 2+ ions participate in the Fe 3+ ion reaction, however, has not been proved [36] while the main process of the reaction considered as the fission of the O-O bond within complex with Fe 3+ ion. 3.3. Reactivity of NH 2 OH with Transition Metals NH 2 OH is intermediate compounds of H 2 O 2 and NH 2 NH 2 . It has capability to oxidize or reduce depending on counterpart compounds. Reactivity with various kind of transition metal is overviewed both in basic and acidic conditions by way of calorimetric measurements [26,27]. An aqueous solution of NH 2 OH (abbreviated as HA, basic solution), NH 2 OH･HCl (abbreviated as HACl, acidic solution), were used, and carefully prepared to give 2mol/l (about 6.4w.t.%). Solutions of the transition metals were prepared to give 0.2mmol/g of solutions by dissolving Fe(NH 4 )(SO 4 ) 2 ･12H 2 O(Fe 3+ ), Cr(NH 4 )(SO 4 ) 2 ･12H 2 O(Cr 3+ ), K 2 Cr 2 O 7 (Cr 6+ ), KMnO 7 (Mn 7+ ), Co(NH 4 ) 2 (SO 4 ) 2 ･6H 2 O(Co 2+ ), [Co(NH 4 ) 6 ]Cl 3 (Co 3+ ), and Cu(NH 4 ) 2 (SO 4 )･6H 2 O(Cu 2+ ). UV-Vis absorption spectra were collected before and after the reactions in order to follow the redox reaction from the aspect of the valence of metals. In case of precipitation, fine precipitate leads Tyndall phenomenon and light scattering. That inhibited collection of UV- Vis absorption spectra. 3.3.1. Reactivity of NH 2 OH with Fe 3+ Figure 10 shows a view of the exothermic behavior of HA and HACl caused by Fe 3+ . The average overall heat of the reaction was 3.39J for HACl, and one for HA was more than 237.82J. The reaction did not allow to calculate exact overall heat of the reaction since the reaction released heat to the maximum test duration. HA was consumed during the reaction despite the HA/Fe 3+ molar ratio of 100/1. Therefore, Fe 3+ was supposed to act as a catalyst in the decomposition of HA. After the injection of Fe 3+ , HA released heat immediately. In the reaction mixture, red- blown precipitate considered as Fe(OH) 3 and the evolution of gas was observed. The gas was recognized as NH 3 from its odor and the results of a previous study [37]. The following reaction schemes have been suggested in previous studies under basic condition [30]: NH 2 OH 1/3NH 3 + 1/3N 2 + H 2 O In contrast, the reaction of HACl was complete within one hour. The addition of free Fe 3+ to HACl provided a colorless mixture and no precipitation. The disappearance of the orange color in the Fe 3+ meant that HACl had turned Fe 3+ into Fe 2+ . No further reaction due to Fe 2+ was supposed to occur in an acidic condition. Reactivity of Unstable Chemicals in the Presence of Transition Metals 467 Figure 10. Heat release behavior in the reaction of HA (white triangle) and HACI (black circle) with Fe(Nh4)(SO4). Figure 11. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with Cr3+. Mieko Kumasaki 468 3.3.2. Reactions with Cr 3+ and Cr 6+ Cr 6+ has the highest oxidation state of any chromium, and is a strong oxidizing reagent. On the other hand, Cr 3+ has a lower oxidation state and is less oxidizing. The redox behavior of HA can be investigated by comparing these two oxidative states of chromium. The heat flow profiles of the reactions with Cr 3+ are shown in Figure 11. No heat release was observed for HACl in the reaction with Cr 3+ . The UV - Vis spectra exhibited no absorption change, either. The mixture suggested that Cr 3+ existed as [Cr(H 2 O) 6 ] 3+ and no redox reaction occurred by the reductive HACl. Meanwhile HA exothermically reacted with Cr 3+ . The reaction produced a sage-green precipitate, and the precipitation changed color to violet in a few hours. The green sage precipitation was Cr(OH) 3 , which is generated from Cr 3+ in an alkaline solution. However, the generation mechanism of the violet precipitate has not been currently understood. The precipitation suggested Cr 3+ is enough to stable to HA species, in other words, HA worked as neither oxidizing nor reducing agent for Cr 3+ despite acidity of solution. Figure 12 shows the exothermic behavior caused by Cr 6+ . In contact with CrO 4 2- , HACl bubbles and the yellow CrO 4 2- changed to a champagne color; the reactions of HACl completed within 30 minutes. The UV-Vis absorptions of CrO 4 2- disappeared (at 257 and 351nm), and new peaks suggesting the presence of [Cr(H 2 O) 6 ] 3+ appeared at 562nm. Figure 12. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with Mn7+. As far as the reaction with Cr 6+ , the acidic HACl exhibited a higher reactivity than HA. These results can be explained by the well-known fact that the oxidative ability of Cr 6+ is Reactivity of Unstable Chemicals in the Presence of Transition Metals 469 higher in an acidic solution than it is in a basic solution. The HA continuously generated heat for more than the maximum test duration, and a violet precipitate was obtained in HA. The origin of the continuous heat generation was unclear, however, transition among several oxidation states of chromium along with HA redox reaction or catalytic ability of surface of the precipitates would be plausible as what was behind. 3.3.3. Reactions with Mn 7+ Figure 13 shows the heat flow curves of HA and HACl caused by MnO 4 - . During the mixing, Mn 7+ exhibited a strongly oxidizing character as well as Cr 6+ . When the MnO 4 - solutions were injected into the substrates, bubble evolved, and the deep violet color of MnO 4 - immediately disappeared. HA gradually produced a white precipitate. The precipitate was considered to be Mn(OH) 2 . HACl completed the reaction within 30 minutes, whereas HA continuously generated heat for longer than the maximum test durations. The UV-Vis absorptions of manganese in HACl were too weak to identify any products. However, [Mn(H 2 O) 6 ] 2+ was plausible because of its weak UV-Vis absorption and its lowest redox potential among the manganese ions. Figure 13. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with MN7+. Mieko Kumasaki 470 Figure 14. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with Co2+. 3.3.4. Reactions with Co 3+ and Co 2+ Both of Co 3+ and Co 2+ are intermediate oxidation states of cobalt. They can act as either an oxidizer or a reducing agent, depending on the circumstances. The heat flow curves of the substrates caused by Co 2+ are shown in Figure 14. The UV-Vis spectra showed no absorption change in HACl. No heat release was observed in the mixing, either. From these results, it can be deduced that no redox reaction occurred in the substance. However, Co 2+ continuously generated heat with HA and produced a brown precipitate. In the reaction of HACl and Co 3+ , neither peak in the heat flow curve nor evidence of a redox reaction was observed. The orange color of [Co(NH 3 ) 6 ] 3+ remained in HACl and UV- Vis spectra indicate the existence of the species. Upon mixing with HA, no reaction seemed to occur at the beginning of the monitoring. However, the heat flow curve started to gradually rise following the injection, and it exhibited a peak about 10 hours later (Figure 15). After the induction period, the mixture provided a brown precipitate although it exhibited no change in color during the early hours. 3.3.5. Reactions with Cu 2+ Copper has three major oxidation states: Cu 2+ , Cu + , and Cu 0 . Since Cu 2+ is the highest oxidation state, Cu 2+ is considered liable to undergo reduction despite its low oxidation number. Reactivity of Unstable Chemicals in the Presence of Transition Metals 471 Figure 15. Heat release behavior in the reaction of HA (triangle) with Co3+. The heat flow curve caused by Cu 2+ is shown in Figure 16. The blue color of [Cu(H 2 O) 6 ] 2+ , which originated from Cu(NH 4 ) 2 (SO 4 ) was too visually faint to be determine whether the reactions occurred in HACl. UV-Vis spectroscopy doesn’t cover the range in which the absorption peaks of [Cu(H 2 O) 6 ] 2+ appear [38]. As another plausible product, [Cu(NH 3 ) 4 ] 2+ , which has an absorption peak is at 590nm, was not detected, whereas the APTAC experiments showed the complex from 50%HA and copper [37]. In order to generate [Cu(NH 3 ) 4 ] 2+ , ammonia-rich conditions are required and the mild condition in this experiment did not allow this complex to be generated. In HA, a yellow green film was observed on the liquid surface, which changed to brown. The appearance of a brown precipitate suggested that Cu 2 O formed. Apart from the spectroscopic results, calorimetric experiments showed the exothermic behavior of HA and HACl. Both substrates continuously generated a heat flow. The maximum heat flow of HA was not high; however, a continuous release of heat resulted in a high overall heat of the reaction. 3.3.6. Comparing Reactivity among the Three Chemicals H 2 O 2 , NH 2 NH 2 , and NH 2 OH consist of two electronegative atoms and hydrogen atoms. Despite the similar chemical structure, they exhibited different behavior in contact with Fe 3+ . H 2 O 2 and NH 2 OH exhibited high reactivity compared to NH 2 NH 2 . Fe 3+ reacted as a catalyst in H 2 O 2 and NH 2 OH while NH 2 NH 2 released small heat along with precipitation. As for precipitation, NH 2 OH also generate precipitation. NH 2 OH, however, continuously released heat by the reaction on surface of precipitated gel, considered as Fe(OH) 3 . Mieko Kumasaki 472 Figure 16. Heat release behavior in the reaction of HA (triangle) and HACI (black circle) with Cu2+. Table 5 summarize the result of the reaction of NH 2 OH and transition metals. All mixture of NH 2 OH generate precipitate because of its basicity while its acidic chloride salt prevented precipitation and showed moderate redox reactions in contact with high oxidative metals. NH 2 OH seems to maximize the reactivity under the basic condition while hydrogen peroxide works in acidic condition. The chemicals structures and reactivity implies that oxygen serves important roll in terms of heat releasing reactions. In the reactions, transition metals works catalytic. On the other hand, NH 2 NH 2 has a tendency to work as ligand to remain in complex while the others decompose immediately after the contact with metals. Table 5. Summary of the reactivity of HA and HACl Metal HA HACl Fe 3+ Precipitation Fe 3+ Fe 2+ Cr 3+ Precipitation No reaction Cr 6+ Precipitation Cr 6+ Cr 3+ Mn 7+ Precipitation Mn 7+ Mn 2+ Co 2+ Precipitation No reaction Co 3+ Precipitation No reaction Cu 2+ Precipitation Not distinguishable Reactivity of Unstable Chemicals in the Presence of Transition Metals 473 4. THE INTERACTION FEATURES OF OXYGEN AND NITROGEN WITH FE 3+ : THE REACTION BETWEEN FE 3+ AND SUBSTITUTED NH 2 OH This section relates some investigation to deepen understanding of the nature of reactivity of NH 2 OH by using of structural change. The investigation can be divided into two parts: steric hindrance on Fe 3+ , and steric hindrance on NH 2 OH. Steric hindrance on Fe 3+ also contributes to hydrophilicity. The previous section related the manner that precipitation decelerated the heat release of NH 2 OH. Aqueous solution of NH 2 OH is basic and easy to precipitate metal hydroxide. By using suitable ligands for Fe 3+ , precipitation can be prevented and observed an interaction. Two complexes of iron are focused in this article: [Fe(CN) 6 ] 3- and Fe(EDTA) - . Additionally, intended steric crowding for NH 2 OH enables to restrict reaction center. For example, NH 2 OH is expected to reaction with metal on oxygen if methyl group attaches on nitrogen atom. By using of steric hindrance, the affinity of oxygen or nitrogen to transition metal was able to be investigated. At the same time, the acidic condition was controlled by using NaOH since the acidity has influence on the reactivity of NH 2 OH shown in the previous section. 4.1. Exothermic Behavior Caused by Coordinated Fe 3+ CN- is known as a ligand which strongly coordinates to metals. In the complex, six CN- species occupy coordination sites around Fe 3+ . The donating atom is C, and Fe 3+ , C, and N atoms form a line in the six directions [39] (Figure 17). EDTA is the common chelating reagent that exists in the complex as EDTA 4- and is associated with the liberation of four H + . The complex with Fe 3+ has the highest stability of all EDTA complexes, excluding that with V 3+ . The previous X-ray study of Fe(EDTA)- revealed that Fe was surrounded by six donating atoms of EDTA and an O atom of H 2 O which could easily substitute with substrate [40]; the geometry about Fe 3+ is pentagonal bipyramidal (Figure 18). Figure 17. The Structure of [Fe(CN)6]3-. Mieko Kumasaki 474 Figure 18. Figure 19. Heat release behavior in the reaction of HA and Fe(CN) 6 3-. Figures 19 and 20 show the expanded views of the exothermic behavior caused by Fe(CN) 6 3- and Fe(EDTA) - . NH 2 OH notably reacted with both Fe 3+ species. The heat flow of NH 2 OH provided by Fe(EDTA) - rose slowly, compared with that of free Fe 3+ from Fe(NH 4 )(SO 4 ). However, the maximum height of the curve was 489mW, which was larger than that of free Fe 3+ . Overall heat of reaction was 421.93J. The gas, including NH 3 , also evolved. The heat release caused by Fe(EDTA) - ended within 100 minutes. The difference to free Fe 3+ in the heat of the reaction was due to the EDTA 4- that dissolved Fe 3+ /Fe 2+ species in Reactivity of Unstable Chemicals in the Presence of Transition Metals 475 basic NH 2 OH and leads free contact with NH 2 OH homogeneously in solution, whereas Fe 3+ precipitated as the reaction proceeded and decreased the effective area for the reaction with NH 2 OH. Fe(CN) 6 3- also triggered an exothermic reaction of NH 2 OH, however, the maximum heat of reaction(99.11mW) and overall heat of reaction(6.26J) were low compared with that of the other Fe 3+ species. In the reaction mixture, Fe(CN) 6 4- was supposed to exist because the yellow color of Fe(CN) 6 3- disappeared and [Fe(CN) 6 ] 3- / [Fe(CN) 6 ] 4- remain stable under high pH condition. CN- ligand dissolve the Fe 3+ /Fe 2+ species even in basic conditions, and also prevent precipitation as well as EDTA 4- . In case of CN, no catalytic function appeared. Considering the stability, the redox reaction of [Fe(CN) 6 ] 3- can be described with outer sphere mechanism. The mechanism is an electron transfer in outer complex contact without ligand substitution, or with faster electron transfer than ligand substitution. The reaction manner implies [Fe(CN) 6 ] 3- has no site to contact directly with NH 2 OH. Six CN- occupy coordinate sites of Fe and prevent further intrusion of ligands onto inner sphere of Fe. Meanwhile, Fe(EDTA)- keep a coordination site open so as to interact with HA as shown in Figure 20. Not only electric effect but also steric effect has influence on the reaction with NH 2 OH 4.2. Exothermic Behavior of Substituted Hydroxylamine NH 2 OH includes oxygen and nitrogen atoms both of which can interact with transition metals. The chemical structure attracts the researchers’ interests and raises questions on how it interacts with metals and how the initiation process starts. Using steric hindrance is one of the ways to gain information about the reactivity. The steric crowding of ligands is expected to decrease associative process with metals. In case of blocking of position on nitrogen atom in NH 2 OH, a metal ion should prefer the interaction on oxygen atom, and vice versa. The difference in reactivity can imply the affinity of oxygen and nitrogen atoms to a metal atom. This section also reports reactivity depending on the acidic condition since acidity of aqueous solution appeared to have an effect on the reactivity in previous section. For the experiment, chemicals were chosen so as to include one or two adequate space- filling substituent groups: N-Methylhydroxylamine hydrochloride, NH(CH 3 )OH HCl (abbreviated as NHACl indicating methyl group attaching to a nitrogen atom), O- Methylhydroxylamine hydrochloride, NH 2 OCH 3 ･HCl (OHACl), N,N- Dimethylhydroxylamine hydrochloride, N(CH 3 ) 2 OH･HCl (NNHACl), N,O - Dimethylhydroxylamine hydrochloride NH(CH 3 )OCH 3 ･HCl (NOHACl). Corresponding basic substances were prepared by adding equivalent NaOH aqueous solution. They were NH(CH 3 )OH (NHA), NH 2 OCH 3 (OHA), N(CH 3 ) 2 OH (NNHA), NH(CH 3 )OCH 3 (NOHA). Aqueous solutions of substituted NH 2 OH were carefully prepared to give 2mol/l. The heat release behavior at mixing with iron species is obtained with SuperCRC, and summarized in Table 6. 2x10 -3 mol of substituted NH 2 OH and 2x10 -5 mol of Fe 3+ species were mixed. The result of NH 2 OH is added to the summary for reference. All the substituted chemicals exhibited lower reactivity than NH 2 OH. As a whole, acidic condition and steric hindrance on oxygen decelerate the interaction with metal. This phenomena is notable in the interaction with Fe(EDTA)-. Mieko Kumasaki 476 Figure 20. Heat release behavior in the reaction of HA and Fe (EDTA)-. Ab inito calculation provides some insight from the viewpoint of electronic structure on this matter. Figures 21 and 22 show the optimized structure of NHA and NNHA by ab initio molecular orbital calculations using density functional theory (DFT) in conjunction with B3LYP approach with Gaussian03 [41]. The 6-31G+(d,p) basis set was used. For acidic condition, the calculation indicated molecules protonated on nitrogen are more stable rather than on oxyegn. Figure 21. Optimized stable structure of NHA(A), and NNHA(b) under basic condition. Reactivity of Unstable Chemicals in the Presence of Transition Metals 477 Figure 22. Optimized stable structure of protonated NHA(A), and NNHA(b) under acidic condition. Mulliken charge analysis showed the difference on charge distribution in basic and acidic condition (Figure 23). Mulliken population analysis allocates charge onto atoms, and provides information about charge distribution in a molecule. The diameter of circles is proportional to amount of calculated charge. In basic condition, more charge lie on oxygen rather than nitrogen. On the contrary, optimized structures in basic condition shows more charge on nitrogen rather than oxygen. This result is consistent with the experimental result that substituted HA reacts more in basic condition with Fe 3+ since Fe 3+ prefers electrons in order to form coordination linkage. Figure 23. Charge distribution calculated by Muliken population analysis; (a)NHA, (b) protonated NHA, (c) NNHA, and (d) protonated NNHA. Mieko Kumasaki 478 Figure 24. Optimized structure of Fe(NH2OH): (a) interacting through 0, (b) interacting through N. The molecular orbital calculation also provided some insight of the interaction manner between Fe 3+ and NH 2 OH. Using Hartree Fock approach and 3-21G basis set, the optimized structures were calculated simulating the interaction (Figure 24). For Fe 3+ , only high-spin states were considered. Frequency calculations were performed to classify each stationary point. The structure was calculated assuming hydrated Fe 3+ with six H 2 O molecles. One of the H 2 O surrounding Fe 3+ is substituted with NH 2 OH. Based on the calculation results, interaction through the oxygen atom caused extend the N-O bond in NH 2 OH; the length of N- O is 1.4692A, and 1.4899A in the complex. The coordination bond between Fe 3+ and the oxygen atom is 2.0733A. In the optimized structure simulating interaction through the nitrogen, however, 2.2185A is the most stable distance between Fe 3+ and the nitrogen atom. Based on the N-O distance in the complex (1.4704A), N-Fe 3+ interaction may be difficult to represent the linkage formation. Table 6. Summary of overall heat of reaction Under acidic condition HACl NHACl OHACl NNHACl NOHACl Fe 3+ 3.39 4.53 0.26 0.28 0.20 [Fe(CN) 6 ] 3- 2.96 0.36 2.50 1.15 0.03 Fe(EDTA)- 2.02 0.74 1.01 0.07 0.18 Under basic condition HA NHAOH OHAOH NNHAOH NIHAOH Fe 3+ >238 20.6 0.71 1.70 2.45 [Fe(CN) 6 ] 3- 99.1 5.29 0.05 2.29 4.30 Fe(EDTA)- 489 165 0.22 133 3.47 Reactivity of Unstable Chemicals in the Presence of Transition Metals 479 CONCLUSION The nature of hazardous materials is their unstability, in other words, high reactivity. A molecule with high reactivity can interact with neighboring molecules and change their structure and itself. Hence, some hazardous materials have been utilized widely in chemical reaction in chemical and other industries. Some highly reactive materials, however, decompose by themselves if trigged by a slight stimulus such as heat, friction, impact, and so on. The decomposition generates sometimes stable gas molecules; the enthalpy difference between an unstable reactant and stable products turns into heat. Stable gas products expand by heat, and causes destruction. Alternatively, the heat ignites flammable gas product and causes fire. In order to prevent disasters caused by hazardous materials, knowledge of the reactivity is inevitably required so as to manage them safely and maximize their useful properties. This article overviewed current research on hazardous materials interacting with transition metals. The first part focused on sensitivity of a complex synthesized from copper and azole. The complex was stable enough to evaluate the change in sensitivity by complex formation. The interaction with transition metal has an influence on the sensitivity of azoles, especially to heat. Following this part, reaction behaviors of three simple unstable chemical, H 2 O 2 , NH 2 NH 2 , NH 2 OH were observed by way of mixing experiments. Despite their similar chemical structures, the three chemicals exhibited different properties respectively. Acidic H 2 O 2 shows high reactivity in contact with Fe 3+ , while basic NH 2 NH 2 released heat moderately, along with precipitation. Intermediate NH 2 OH demonstrated changed behavior depending on acidity. The acidic solution showed easy-to-understand redox reaction with high oxidated metals, while the basic solution generated precipitation and released heat continuously with some metals. The results proved the idea that oxygen plays a key role in the reaction. Based on the idea, the last section related the reaction manner of Fe 3+ and NH 2 OH by using of steric hindrance. The experimental result and ab initio molecular orbital calculation supported the idea. In the field of hazardous materials, most of the studies are case studies, or derivatives from accidents. In this way, researchers tend to focus on a quantitative study on released power, or resulting damage. There have been quite a few studies with this inductive approach. The research related in this article is trials to overview the properties of hazardous materials by way of chemical structure, and require further development. There are various kinds of questions remaining regarding the principle of hazardous materials’ properties. Further intensive research is expected to clarify the subject and contribute to safe handling of hazardous materials. REFERENCES [1] Urben, P.G.; Pitt, M.J.; Battle, L.A.; Ed; Bretherick’s Handbook of Reactive Chemical Hazards, fifth edition; Butterworth Heinemann: Oxford, 1995. [2] Recommendations of the Transportation of Dangerous Goods, Twelfth revised edition, United Nations, 2001. Mieko Kumasaki 480 [3] Shriver, D.F.; Atkins,P.W.; Langford,C.H. Inorganic Chemistry, second edition; Oxford University Press: Oxford, 1994; Chapter 6. [4] Martell,A.E.; Calvin, M.; Chemistry of Metal Chelate Compounds; Prentice-Hall: NewYork, 1952; p380. [5] Kumasaki, M.; Miyasaka, R.; Kiuchi, H.; Wada, Y.; Arai, M.; Tamura, M., J. Japan Explosives Soc. 2001, Vol.62, 109-116. [6] Krishnan, S.; Swami,R.D. J. Propul. Power 1998, Vol. 14, 295-300. [7] Kishore, K.; Sunitha,M.R. AIAAJ 1979, Vol. 17, 1119-1123. [8] Moore, D.S.; Robinson, S.D. Adv. Inorg. Chem. 1998, Vol.32, 171-239. [9] Haasnoot, J.G.Coord. Chem. Rev. 2000, Vol.200-202, 131-185. [10] Kowhakul,W.; Miyasaka,R.; Kumasaki,M.; Wada,Y.; Arai,M.; Tamura,M. J. Japan Explosives Soc. 2002, Vol.63, 362-366. [11] Kowhakul, W.; Kumasaki,M.; Wada,Y.; .Arai,M; Tamura,M. Sci. Tech. Energetic Materials 2005, Vol.66, 229-232. [12] Kowhakul,W.; Kumasaki, M.; Arai, M. Sci. Tech. Energetic Materials 2005, Vol.66 425-430. [13] Kowhakul, W.; Kumasaki, M.; Wada, Y.; Arai, M.; Tamura, M. Sci. Tech. Energetic Materials 2006, Vol.67, 87-90. [14] Mihina, J.S.; Herbst, R.M. J. Org. Chem. 1950, Vol.15, 1082. [15] Yoshida, T; Safety of Reactive Chemicals, Industrial Safety Series volume 1; Elsevier, 1987,250-265. [16] Dixon, W.J.; Masseg, F.J. Introduction to Statistical Analysis, second Edition, 1957, McGraw Hill , 318. [17] Japan Explosives Society, Japan Explosives Society Standard (IV) Sensitivity test method, 1996, 65-68. [18] Japan Explosives Society, Japan Explosives Society Standard (IV) Sensitivity test method, 1996, 76-80. [19] Yoshida,T.; Ding, D. Safety technique of chemical substances 1996, Tokyo Progress System , 108. [20] Aochi, T.; Miyake, A.; Ogawa, T.; Matsunaga, T.; Nakagawa, Y.; Iida, M. J. Japan Explosives. Soc. 1997, Vol.58, 202-210. [21] Sakata, K.; Materials of SG society for the study, third meeting at Tokyo, 1992. [22] Williams,J.K.; Palopoli,S.F.; Brill, T.B. Combust. Flame 1994, Vol.98, 197. [23] Ohno, Y.; Akutsu, Y.; Arai, M.; Tamura, M.; Matsunaga, M. J. Japan Explosives Soc. 1999, Vol. 60, 110-117. [24] Frish, M.J.; Trucks, G.W. Schlegel, H.B.; Gill, P.M.W.; Johnson, B.G; Robb, M.A.; Cheeseman, J.R.; Keith, T.; Petersson, G.A.; Montgomery, J.A.; Taghavachari, K.; Al- Laham, M.A.; Zakrzewski, V.G.; Ortiz, J.V.; Foresman, J.B.; Cislowski, J., Stefanov, B.B.; Nanayakkara, A.; Challacombe, M.; Peng, C.Y.; Ayala, P.Y.; Chen, W.; Wong, M.W.; Andres, J.L.; Replogle, E.S.; Gomperts, R.; Martin; R.L.; Fox, D.J.; Binkley, J.S.; Defrees, D.J.; Baker, J.; Stewart, J.P., Head-Gordon, M.; Gonzalez, C.; Pople, J.A. Gaussian 94, Revision D.3. Gaussian, Inc., Pittsburgh, 1995. [25] Kawaguchi, S.; Kumasaki, M.; Wada, Y.; Akutsu, Y.; Arai, M.; Tamura, M. J. Japan Explosives Soc. 2001, Vol.62, 16-22. [26] Kumasaki,M.; Fujimoto, Y.; Ando, T. J. Loss Prev. Ind. 2003, Vol.16, 507-512. [27] Kumasaki, M.; J. Haz. Mat. 2004, Vol.115, 57-62. Reactivity of Unstable Chemicals in the Presence of Transition Metals 481 [28] Kowhakul, W.; Kumasaki, M.; Arai, M.; Tamura, M.; J. Loss Prev. Ind. 2006, Vol.19, 452-458. [29] Kumasaki, M.; J. Loss Prev. Ind. 2006, Vol. 19, 307-311. [30] Bailar, JR J.C.; Emeleus, H.J.; Nyholm, R; Trotman-Dickenson, A.F. Comprehensive Inorganic Chemistry, Volume 2, Pergamon Press, 1973, 272-273. [31] Schmidt, E. W. Hydrazine and Its Derivatives, Preparation, Properties, Applications, second edition, Volume 1, John Wiley & Sons, 2001, 498. [32] Aliev, R. Y.; Kuliev, A.D.; Klyuchnikov, N.G.;Ingibitory Korroz. Met., Moscow 1974, 86, 135-138. [33] Bailar, JR J.C.; Emeleus, H.J.; Nyholm, R; Trotman-Dickenson, A.F. Comprehensive Inorganic Chemistry, Volume 3, Pergamon Press, 1973, 1006. [34] Fenton,H.J.H. J.Chem.Soc. 1894, 65, 899-910. [35] Wardman, P.; Candeias, L.P. Radiaton Research 1996, 145, 523-531. [36] Kremer, M.L. Trans. Faraday Soc.1963, 59, 2535-2542. [37] Cisneros, L.O.; Rogers, W. J.; Mannan, M. S. J. Hazard. Mat. 2002, A95, 13-25. [38] The Chemical Society of Japan, Handbook of Chemistry: Pure Chemistry II. Third edition, 1993, Maruzen: Tokyo. [39] Wilkinson, Sir G. FRS, Comprehensive Coordination Chemistry, The Synthesis, Reactions, Properties and Applications of Coordination Compounds, Volume4 Middle Transition Elements, Pergamon Books, 1987, 220-221. [40] Hoard,J. L.; Lind,M.; Silverton, J. V. J. Am. Chem. Soc. 1961, 83, 2770-2771. [41] Frisch, M. J.; Trucks, G. W.; Schlegel,H. B.; Scuseria,G. E.; Robb, M. A.; Cheeseman,J. R;. Montgomery, Jr.,; Vreven,J. A. T.; Kudin,K. N.; Burant,J. C.; Millam, J. M;. Iyengar,S. S.; Tomasi,J.; Barone,V.; Mennucci,B.; Cossi,M.; Scalmani,G..; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida,M.; Nakajima, T.; Honda, Y.; Kitao,O.; Nakai,H.; Klene,M.; Li,X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G..; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q. A.; Baboul, G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin,R. L.; Fox, D. J.; Keith, T.; Al- Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe,M.; Gill,P. M. W.; Johnson, B.; Chen, W.; Wong, M.W.; Gonzalez, C.; Pople, J.A. Gaussian 03, Revision D.01, Gaussian, Inc., Wallingford CT, 2004. INDEX A absorption spectra, 193, 196, 464 absorption spectroscopy, 175 abstraction, 28, 33 acetic acid, 4, 121, 257, 398, 454 acetone, 254, 391, 404 acetonitrile, 181, 409, 419 acetylcholine, 32 acidity, 261, 342, 453, 466, 471, 473, 477 acidosis, 57 activation energy, 118 active compound, vii, 2, 15, 297, 302 active oxygen, 274 active site, 6, 10, 14, 31, 36, 158, 165, 194, 195, 220, 221, 250, 262, 263, 273, 275, 280, 283, 353, 370 active transport, 12 acylation, 194 adaptations, 315 adenosine triphosphate, 265 adjustment, 185, 318 adsorption, 299, 305, 318, 319 aerosols, 12 aetiology, 7 aggregation, 23, 25, 26, 27, 28, 29, 31, 39, 53, 54, 55, 56, 59, 61, 89, 280, 361, 362 aggregation process, 30 alanine, 174 albumin, 8, 10, 12 alcohols, 196, 259, 298, 304, 306, 307, 308, 310 aldehydes, 15, 164, 168, 306, 308, 310, 355 alkaline earth metals, 176 alkaline media, 459 alkane, 181 alkenes, 300, 304, 306, 307 alopecia, 13 alpha-tocopherol, 50 alters, 32, 34, 65 aluminium, 332, 334, 338, 339, 345, 350 ambient air, 18, 19 amine, 164, 176, 181, 182, 268, 285, 286, 305, 308, 309, 310, 332, 400, 408, 446 amines, 163, 164, 176, 300, 303, 305, 307, 308, 310 ammonia, 12, 34, 35, 284, 304, 469 ammonium, 180, 326, 332, 406 amygdala, 24, 52 amyloid beta, 23, 53, 54, 55, 57 amyloid deposits, 52 amyloidosis, 25 amyotrophic lateral sclerosis, 44, 361, 363 anemia, 267, 270 angiogenesis, 11, 44, 270 anhydrase, 2, 13, 273, 291, 352 annealing, 97, 105, 118, 120, 122, 123, 124, 125, 126, 127, 128, 129, 130, 132, 133, 136, 142, 143, 144, 145, 146, 148, 149, 152, 153, 154, 155, 335 anorexia, 270, 273 antagonism, 268 antiarthritis, 2 anticancer drug, 45, 285, 292, 293 anticonvulsant, 266 antigen, 274 anti-inflammatory drugs, 266, 269 antioxidant, 7, 11, 22, 24, 29, 36, 58, 264, 265, 266, 268, 269, 274, 281, 282, 340, 359, 364, 368 antitumor, 2, 11, 274, 277, 292, 293 apoptosis, 21, 50, 271, 360, 362, 363, 364 aqueous solutions, 192, 370, 454, 460 aqueous suspension, 335 aromatic compounds, 304 aromatic hydrocarbons, 301, 306, 307, 308, 309, 310 aromatic rings, 245, 247, 301 arsenic, 1, 4, 5, 6, 19, 46, 331 ascorbic acid, 20, 29, 58, 60, 182, 290, 356 asparagines, 10 aspartate, 13, 55, 271, 272 aspartic acid, 26, 281 Index 484 astrocytes, 10, 12, 44, 55 atherosclerosis, 267, 270, 276 atmosphere, 30, 45, 120, 191 atomic force, 30 atrophy, 23, 24, 29 autosomal recessive, 9, 15, 21 B bacteria, 16, 18, 21, 280, 284, 340 band gap, 65, 206 barium, 328 basal ganglia, 13, 40, 60 base catalysis, 256 base pair, 18 basic research, 365 basicity, 231, 301, 302, 303, 462, 470 batteries, 19 benefits, 137, 353 benzene, 165, 193, 276, 301, 305, 381, 382, 388, 405, 406, 413 beryllium, 19 beta-carotene, 50 binding energy, 151, 371 376 bioavailability, 32, 57, 271 biochemical processes, 18 biochemistry, viii, 6, 46, 56, 291, 365 biological markers, 291 biological processes, viii, 220, 354 biological roles, 271 biological samples, 318 biological systems, vii, 8, 14, 39, 46, 173, 220, 264, 277, 278, 279, 348, 353, 357, 363 biologically active compounds, 301 biomaterials, 319 biomedical applications, vii, 292, 293 biomolecules, 10, 220, 264, 316, 348, 354 biosynthesis, 16, 270 biotechnology, 350 blood, 7, 8, 10, 12, 13, 17, 23, 43, 45, 47, 51, 267, 269, 270, 274, 276, 277, 347, 352, 358, 366 blood vessels, 267, 270 blood-brain barrier, 7, 12, 43, 45 bonding, vii, 6, 25, 173, 183, 230, 256, 258, 259, 262, 285, 286, 299, 303, 304, 311, 347, 349, 350, 390, 398 bonds, 184, 223, 246, 247, 248, 249, 267, 272, 276, 285, 286, 308, 315, 316, 318, 333, 386, 388, 452, 457 bone, 12, 13, 269, 274, 277, 279, 290, 352 bone form, 277 bone marrow, 290 bone mass, 13 boric acid, 190, 269 bounds, 362 brain, 6, 9, 10, 12, 13, 22, 24, 25, 26, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 42, 43, 44, 46, 52, 55, 56, 58, 60, 269, 270, 350, 358, 360, 362, 364, 365, 367, 368 brain damage, 350 brain functions, 364 brain stem, 37 brain structure, 38 brass, 349 breakdown, 85, 101, 348 breast cancer, 11, 19, 44, 45, 48 breathing, 268 building blocks, 381, 382, 390, 391, 394, 398, 405, 409, 412, 414, 420, 422 bulimia nervosa, 273 bulk materials, 64 C Ca 2+ , 2, 3, 4, 278, 315, 316, 367 cadmium, 5, 7, 8, 11, 18, 19, 22, 42, 253, 262, 304, 305, 308, 310, 348 calcination temperature, 335 calcium, 1, 2, 9, 14, 25, 65, 269, 277, 278, 279, 289, 346, 350 calorimetric measurements, 464 cancer, 11, 19, 21, 22, 48, 49, 50, 267, 269, 270, 276, 293, 341, 346, 350, 354, 361, 365 cancer cells, 22, 267, 270, 341 capillary, 9, 305, 308, 371 carbides, 139, 142, 143, 144, 146 carbohydrate, 3, 264, 288, 353 carbohydrate metabolism, 3, 353 carbohydrates, 262, 268 carbon, 2, 20, 120, 122, 123, 125, 126, 127, 128, 129, 130, 131, 132, 133, 135, 140, 194, 251, 271, 305, 349, 350, 355, 381, 384, 385, 386, 387, 388, 390, 391, 405, 412, 413, 421, 422 carbon atoms, 140, 387 carbon dioxide, 271, 350 carbon monoxide, 305 carbonyl groups, 285, 286, 359 carboxyl, 181, 182, 183, 262, 264, 317 carboxylic acid, 183, 194, 253, 286, 343 carcinogen, 19, 340, 341, 342, 363 carcinogenesis, 21, 22, 44, 47, 48, 49, 277, 340, 341, 363, 366 carcinogenicity, 19, 22, 48, 50, 289, 339, 340, 341 cardiovascular disease, 17, 47, 264, 268, 270, 289 cardiovascular system, 266, 269 Index 485 catalysis, vii, 6, 14, 29, 52, 163, 164, 173, 195, 200, 220, 255, 264, 282, 291, 314, 347, 348, 355, 367, 405 catalyst, vii, 7, 271, 272, 344, 350, 356, 369, 370, 371, 374, 375, 376, 378, 405, 462, 464, 469 catalytic activity, viii, 157, 158, 174, 262, 272, 350 catalytic properties, 30, 55, 157, 158, 273, 333, 349, 383 catecholamines, 36, 58, 59 cation, 11, 40, 200, 223, 283, 303, 333, 338, 344, 397 C-C, 386, 389, 390, 391, 393, 399, 405, 417, 422, 436, 441, 447 CCA, 331 cell biology, 261, 288 cell culture, 31, 340 cell cycle, 21, 341, 368 cell death, 21, 25, 29, 34, 36, 55, 61, 278, 279, 291, 294, 341, 360, 362, 363 cell division, 3, 285 cell line, 271, 276, 279, 294 cell membranes, 25, 265, 274 cell surface, 31, 262, 359 cellular immunity, 274 central nervous system, 12, 288, 360, 361 ceramic, vii, 334, 335, 336, 337, 339, 351, 407, 454 cerebellum, 362 cerebrospinal fluid, 24, 30, 52, 55 ceruloplasmin, 7, 9, 24, 31, 52, 264, 268, 269, 290 charge density, 39 chelates, 42, 188, 189, 193, 266, 304, 308, 309, 310, 311, 312, 316, 319 chemical industry, 459 chemical interaction, 117 chemical properties, 22, 173, 176, 184, 261, 297, 348 chemical reactions, 348 chemical reactivity, 354 chemical structures, 452, 453, 459, 477 chemiluminescence, 357, 359, 366 chemisorption, 305 chemotherapy, viii chitin, 320 chlorination, 344 chlorine, 1, 173 chloroform, 406 chlorophyll, 2, 3, 342, 346 CHO cells, 340, 341 cholesterol, 264, 267, 276 choline, 365, 366 chondrocyte, 294 choroid, 9 chromatid, 341, 346 chromatographic technique, 298, 316 chromatography, 167, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 308, 309, 310, 311, 312, 313, 314, 315, 316, 319, 320, 323, 324, 341 chromium supplementation, 17, 47 chromosome, 9, 20, 340, 341, 345, 346 chronic diseases, 289 cleavage, 23, 30, 41, 49, 180, 263, 356, 388 clinical application, 365 closed shell zinc element, 2 clusters, 10, 31, 37, 108, 110, 118, 119, 137, 140, 159, 177, 292, 384 C-N, 391, 404 CNS, 10, 60 CO2, 2 coatings, 327, 331, 332, 333 cobalamines, 16 cobalt, 1, 3, 4, 5, 6, 8, 16, 39, 48, 182, 183, 187, 194, 196, 283, 304, 312, 334, 344, 349, 351, 359, 365, 370, 375, 376, 378, 387, 427, 438, 468 coenzyme, 16, 194 cognitive function, 32, 52, 271 cognitive impairment, 24, 52 coke formation, 370 collagen, 10, 265, 269 colon cancer, 21 color, 325, 327, 328, 331, 332, 333, 335, 337, 338, 464, 466, 467, 468, 469, 473 colorectal cancer, 21, 50, 286, 354 combustion, 18, 19, 350 composites, 63, 64, 65, 66, 84, 87, 88, 89, 90, 91, 92, 93, 95, 96, 97, 99, 101, 103, 105, 106, 344 composition, 66, 120, 122, 124, 128, 129, 133, 135, 136, 137, 138, 141, 142, 145, 153, 155, 156, 158, 159, 263, 326, 327, 328, 329, 332, 335, 336, 338, 339, 345, 369, 370, 377, 398, 420, 421 compression, 119, 126, 153 condensation, 57, 164, 167, 172, 174, 176, 183, 186, 195, 200, 206, 417 conductance, 176, 186, 193, 205 conduction, 151, 156, 157, 453 conductivity, 196, 206, 349 conductors, vii, 347, 349 configuration, 2, 14, 172, 177, 185, 190, 196, 203, 308, 348, 351, 407 connective tissue, 265, 269, 352 construction, 136, 137, 332, 335, 349, 384 consumption, 12, 17, 30, 33, 330 control group, 19 COOH, 164, 181, 186, 206, 224 copolymerization, viii coronary heart disease, 266, 267 correlation, 21, 24, 39, 220, 230, 241, 244, 250, 342 correlation analysis, 250 Index 486 correlations, 57, 220, 221, 233, 244, 252, 255 corrosion, 137, 327, 329, 331, 332 cortex, 42, 367 cortical neurons, 28, 31, 56 cotton, 330 coupling constants, 247 covalent bond, 221, 262, 264, 283, 298, 299, 315 covalent bonding, 315 covering, 165, 326, 330 critical value, 121 crystal structure, 117, 161, 182, 183, 184, 186, 206, 219, 239, 240, 245, 246, 247, 248, 249, 251, 252, 253, 254, 255, 256, 258, 259, 275, 293, 334, 335, 344 crystalline, 106, 155, 159, 165, 187, 253, 332, 339 crystallization, 86 crystals, 63, 65, 333, 335, 338, 339, 457 CSF, 24, 30, 43 culture, 25, 29, 32, 37, 341 culture medium, 29, 341 cyanide, 393, 416 cycles, viii, 30 cycling, 6, 10, 17, 27, 29, 36, 348, 354, 355 cyclopentadiene, 418 cysteine, 8, 10, 18, 20, 36, 59, 265, 271, 274, 276, 277, 280, 292, 294, 341 cytochrome, 3, 6, 10, 30, 36, 56, 58, 195, 268, 270, 352, 356, 361 cytochromes, 6, 8, 16, 38, 352 cytokines, 274 cytoplasm, 4, 7, 10, 275 cytotoxic agents, 274 cytotoxicity, 20, 27, 37, 54, 276, 293, 340, 360 D decomposition, 20, 146, 150, 155, 200, 219, 278, 279, 282, 311, 332, 339, 348, 353, 356, 372, 411, 451, 452, 456, 457, 464, 477 decomposition temperature, 457 defects, 13, 85, 93, 106, 117, 118, 119, 121, 124, 126, 129, 133, 134, 135, 137, 141, 155, 160, 161, 273 deficiencies, 17, 274 deficiency, 2, 9, 12, 13, 15, 16, 32, 43, 46, 57, 266, 267, 268, 269, 270, 271, 273, 290, 292, 361, 364, 365 deficit, 298 deformation, 120, 122, 333 degenerate, 67, 96 degradation, 8, 15, 24, 224, 225, 255 dehydrate, 253 dementia, 32, 56, 58, 60, 367 dendritic simplification, 25, 53 dendritic spine loss, 25 density functional theory, 474 deoxyribose, 36 dephosphorylation, 224 depolarization, 294 deregulation, 22, 24, 52, 362 derivatives, 25, 58, 168, 192, 193, 206, 221, 222, 233, 260, 263, 286, 289, 293, 298, 305, 310, 311, 312, 326, 381, 400, 477 desorption, 298 destruction, 33, 118, 121, 271, 274, 276, 452, 477 detection, 29, 311, 391 detoxification, 265, 353 deviation, 338 diabetes, 17, 264, 266, 276, 277, 278, 289, 293, 367 diagnostic markers, 52 dialysis, 290 diamines, 163, 165, 185, 189, 195 diarrhea, 13, 354 dielectric constant, 84 dielectrics, 63, 65, 66, 107, 108 dienes, 303 diet, 13, 15, 17, 18, 47, 265, 270 dietary intake, 16, 18, 264 dietary supplementation, 17 diffraction, 53, 67, 87, 99, 143, 146, 155 diffuse reflectance, 338, 339 diffusion, 12, 100, 118, 119, 124, 136, 159 diffusion process, 136 dihydroxyphenylalanine, 36 dimethylsulfoxide, 410 diodes, 350 dipeptides, 258 discrimination, 311 disease progression, 361 diseases, 2, 15, 19, 22, 262, 266, 267, 268, 269, 271, 277, 361, 362 disequilibrium, 131, 136 dislocation, 118, 120, 122, 124, 125, 126, 127, 129, 130, 131, 133, 134, 135, 136, 137, 138, 139, 140, 141, 158, 160 disorder, 9, 12, 13, 23, 33, 38, 159, 161, 270 dispersion, 108, 283, 376 displacement, 6, 118, 135, 158, 159, 161, 189, 247, 284 distortions, 117, 118, 119, 126, 130, 131, 133, 140, 147, 148, 152, 156, 159 distribution, 4, 9, 58, 85, 86, 93, 123, 124, 125, 155, 277, 317, 333, 344, 366, 370, 453, 475 diversity, 220 DMF, 172, 180, 196 Index 487 DNA, 9, 10, 13, 14, 18, 19, 20, 21, 22, 23, 28, 29, 34, 40, 42, 48, 49, 50, 57, 58, 61, 263, 264, 265, 275, 281, 283, 284, 285, 286, 287, 288, 292, 340, 341, 345, 346, 354, 355, 363, 364, 367, 368 DNA damage, 20, 22, 40, 42, 48, 49, 61, 341, 346, 363, 367 DNA repair, 19, 21, 22, 48, 341, 363, 368 DNA strand breaks, 22 donors, 299, 300, 301, 302, 316, 382 dopamine, 10, 33, 34, 35, 36, 37, 38, 40, 41, 57, 58, 59, 61, 361, 367 dopaminergic, 33, 34, 37, 38, 39, 41, 59, 60, 61, 361 dopants, 335 doping, 118, 136 dose-response relationship, 21 double bonds, 257, 301 Drosophila, 29, 32, 55 drug delivery, viii, 45 drug design, 26 drugs, 2, 33, 58, 261, 263, 266, 269, 273, 274, 275, 278, 284, 293 drying, 369, 370, 372, 374, 376, 377 DSC, 455, 456 ductility, 347, 349 duodenum, 8 durability, 332 dusts, 11, 12, 18, 19, 44 dwarfism, 273 dyes, 19, 330 dysmenorrhea, 274 dystrophic neuritis, 23 E elastin, 10, 265 electric field, 66, 284 electrical conductivity, 206, 349 electrical properties, 349 electrical resistance, 149, 151 electricity, vii, 25, 347, 349, 455 electrochemical behavior, 381, 409 electrochemistry, 408 electrodes, 284, 386, 455 electroluminescence, 382 electrolysis, 325 electrolyte, 205, 325, 389, 401, 403 electromagnetic, 64, 84, 91 electromigration, 314 electron diffraction, 140, 141, 145, 146 electron microscopy, 60, 136, 143 electron pairs, 299, 300 electron paramagnetic resonance, 60, 258 Electron Paramagnetic Resonance, 39 electronic structure, 65, 220, 301, 474 electrons, vii, 6, 14, 38, 40, 110, 120, 151, 152, 156, 157, 161, 187, 228, 243, 247, 262, 270, 271, 298, 299, 300, 301, 302, 303, 304, 347, 349, 350, 351, 353, 354, 387, 393, 452, 457, 459, 460, 475 electroplating, 19 elementary particle, 119 elongation, 136, 141 elucidation, 150, 263 emission, 52, 189, 330, 357, 358, 359 enantiomers, 297, 298, 310, 314, 315, 320 encapsulation, 164, 282 endothelial cells, 9 endothermic, 456, 457 energetic materials, 452, 453 energy, vii, 5, 12, 13, 26, 63, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 85, 86, 87, 91, 92, 95, 96, 98, 100, 101, 102, 103, 104, 105, 106, 107, 117, 119, 136, 151, 157, 158, 159, 167, 187, 229, 265, 270, 271, 299, 300, 302, 330, 335, 362, 367, 382, 386, 410, 452, 454 environmental impact, 58 Environmental Protection Agency (EPA), 48, 289, 345 enzymatic activity, 272 epidemiology, 340 epilepsy, 266, 269, 362 EPR, 26, 28, 30, 39, 61, 174, 181, 251, 359, 434 equilibrium, 118, 121, 130, 135, 136, 145, 149, 155, 156, 159, 160, 168, 171, 172, 175, 277, 278, 280, 288, 303 erythrocytes, 8, 17 ESI, 420, 421 ESR, 20, 21, 167, 172, 186, 197, 387 ESR spectra, 167, 197 ester, 257, 307, 311 estrogen, 14, 270 ethanol, 176, 254 ethers, 300, 303, 304, 306, 307, 308, 309, 310 ethylene, 298, 302, 308, 309, 316, 437 ethylene glycol, 302 etiology, 58, 267 evacuation, 121, 153 evidence, 2, 17, 19, 21, 22, 23, 25, 33, 49, 54, 85, 155, 255, 266, 269, 270, 277, 341, 357, 360, 362, 364, 468 evolution, 157, 464 excitation, 64, 89, 92, 102, 106 exciton, 342 excretion, 9, 11, 12, 15 exothermic peaks, 456 experimental condition, 93, 107 Index 488 exposure, 5, 7, 11, 12, 15, 19, 20, 21, 33, 38, 41, 48, 49, 61, 86, 130, 133, 142, 148, 150, 267, 340, 341, 342, 345, 350, 363, 402, 412 F facilitators, 6 factories, 346 failure to thrive, 9 ferric ion, 22 ferric state, 267 ferritin, 7, 8, 21, 29, 31, 37, 38, 51, 60, 264, 352, 356 ferromagnetism, 229, 232, 258 ferrous ion, 12, 38 fertilizers, 3, 4 fibers, 27 fibrillation, 39, 61 fibroblasts, 56, 340 fibrosis, 23 field theory, 364 financial, 110, 208, 422 financial support, 110, 422 first generation, 387 first transition series, 2, 6 flow curves, 461, 467, 468 fluctuations, 85, 155, 159 fluorescence, 21, 189, 261, 283, 342, 346 fluorine, 1, 4, 6 formula, 120, 160, 194, 196, 219, 225, 228, 234, 235, 330, 333, 334, 336, 338, 339, 454 foundations, 331 four-wave mixing, 96 fragments, 39, 143, 155, 281, 282, 283, 285, 381, 382, 384, 386, 387, 389, 390, 392, 394, 406, 412, 418, 421, 452 free energy, 18, 151, 159 free GSH, 40 free radicals, 11, 21, 22, 33, 34, 35, 36, 37, 38, 43, 50, 268, 339, 348, 353, 354, 363, 364 friction, 451, 452, 454, 455, 477 frontal cortex, 361, 362, 364 fruits, 12, 13 FTIR, 333 functionalization, 262 fusion, 108 G gadolinium, 177, 196 gallium, 97 gastrointestinal tract, 7, 9, 12 gel, 175, 298, 315, 319, 469 gene expression, 14, 31, 48, 290, 350 genes, 22, 29, 46, 51 genetic defect, 15 genetic disease, 21 genetic information, 13 genetic predisposition, 22 genomic instability, 22, 341 genomic stability, 43 geometry, 6, 26, 27, 39, 54, 64, 164, 166, 171, 185, 190, 228, 230, 231, 237, 239, 243, 251, 271, 272, 282, 283, 300, 301, 394, 402, 405, 471 Germany, 63, 110, 322, 381, 423, 431, 447 gestation, 12 GG sequence, 285 Gibbs energy, 338 glasses, 63, 65, 85, 86, 88, 89, 90, 91, 93, 95, 107 glia, 35 glial cells, 24 gluconeogenesis, 12 glucose, 17, 264, 270, 276, 293, 353, 366 glue, 265 glutamate, 271, 362 glutamine, 12 glutathione, 2, 5, 6, 11, 17, 18, 19, 20, 22, 29, 34, 36, 38, 40, 48, 49, 55, 58, 60, 265, 275, 284, 340, 341, 348, 354, 360, 361, 364 glycerol, 121 glycol, 298, 302, 303 glycosaminoglycans, 12 gold and platinum complexes, 2 gold compound, 274, 276, 292 gold nanoparticles, 63, 66, 97, 103, 104, 106, 107 grain boundaries, 130, 138, 142, 143, 144, 145, 146, 153 grain size, 122, 454 growth factor, 31 growth hormone, 3 growth rate, 125 guanine, 49, 265, 284, 285 H Hamiltonian, 187, 229 haptoglobin, 8 hazardous materials, 451, 452, 459, 460, 477 hazardous waste, 20 H-bonding, 206, 285, 286 health problems, 350 heart disease, 267, 276 heat capacity, 106 heat release, 451, 452, 455, 456, 457, 460, 462, 466, 468, 471, 472, 473 heat transfer, 93, 106 Index 489 heating rate, 455 heavy metals, 34, 261, 327 heme, 8, 38, 43 hemochromatosis, 50, 51, 354 hemoglobin, 6, 8, 279, 280, 341, 352, 452 hepatocarcinogenesis, 363, 365 hepatocellular carcinoma, 11, 21, 44 hepatocytes, 9, 21 hepatotoxicity, 342, 348, 363 heterogeneity, 155, 319 heterogeneous catalysis, vii hexane, 305 hippocampus, 24, 32, 38, 51, 52, 361, 362, 364 histidine, 10, 25, 26, 27, 28, 30, 31, 54, 55, 271, 272, 279, 281 histogram, 125, 135 histone, 19, 48 history, 278 homeostasis, 9, 13, 30, 34, 43, 45, 56, 57, 278, 279, 288, 350, 362, 364, 366, 368 homogeneity, 305 homogeneous catalyst, 167 homolytic, 355 hormones, 3, 265, 271, 277 host, 22, 84, 92, 93, 106 human, 1, 2, 4, 5, 8, 9, 12, 14, 15, 17, 18, 19, 20, 21, 22, 30, 33, 36, 37, 38, 39, 42, 43, 44, 47, 48, 49, 50, 52, 55, 56, 59, 60, 61, 262, 265, 276, 277, 290, 291, 292, 294, 331, 340, 341, 345, 346, 350, 352, 353, 354, 356, 361, 363, 364, 365, 367 human aliments, 2 human body, 4, 5, 9, 265, 350, 352, 361 human brain, 36, 37, 38, 59, 354 human exposure, 345 human genome, 14 human health, 5, 6, 42, 47, 364 hydrazine, 183, 452, 459 hydrides, 45 hydrocarbons, 301, 303, 304, 305, 308, 309, 310 hydrogen, 2, 6, 16, 21, 25, 29, 33, 34, 48, 49, 50, 53, 55, 183, 184, 188, 220, 221, 223, 234, 245, 246, 247, 248, 249, 255, 256, 257, 258, 259, 260, 262, 264, 268, 270, 286, 300, 301, 302, 311, 348, 350, 352, 354, 355, 357, 371, 376, 402, 452, 459, 469, 470 hydrogen abstraction, 355, 357 hydrogen atoms, 402, 459, 469 hydrogen bonds, 220, 221, 234, 245, 246, 247, 248, 249, 260, 300, 302 hydrogen peroxide, 6, 21, 29, 34, 48, 49, 50, 53, 55, 262, 264, 268, 348, 352, 354, 355, 452, 459, 470 hydrogenase, 18 hydrogenation, 165, 350, 373, 374 hydrolysis, 192, 193, 195, 253, 255, 263, 285, 286, 288 hydrolytic stability, 262 hydroperoxides, 39, 282, 348, 353, 355, 356, 359, 363 hydrophilicity, 471 hydroxide, 14, 291, 335, 336, 338, 471 hydroxyl, 7, 10, 20, 21, 22, 29, 30, 31, 34, 35, 37, 38, 39, 49, 55, 56, 61, 188, 264, 268, 273, 298, 317, 340, 348, 354, 355, 366 hypothesis, 27, 38, 53, 151, 152, 266, 355, 359, 364 I immobilization, 175, 283, 298, 315, 317 immune function, 13, 270, 354 immune response, 269, 274, 291 immune system, 271 impact strength, 148, 149 impaired immune function, 264 implantation of silver ions, 100 impregnation, 369, 370, 371, 373, 375, 376, 377 improvements, 335 impurities, 127, 130, 134, 135, 136, 139, 140, 337 in transition, 7, 349 in vitro, 21, 25, 29, 31, 33, 49, 58, 59, 60, 208, 268, 270, 277, 282, 285, 292, 293, 341, 346, 354, 355, 364 In vitro precipitation, 25 in vivo, 7, 10, 12, 28, 29, 31, 37, 61, 261, 270, 271, 277, 278, 285, 289, 292, 293, 342, 355, 357, 359 incubation period, 30, 134, 135, 141, 158 Iindium, 67 individuals, 12, 21, 38 inducer, 27, 363 induction, 22, 120, 292, 362, 363, 468 infarction, 267 infection, 269, 270 inflammation, 20, 23, 25, 33, 49, 266, 268, 269, 270, 273, 274, 276, 290 inflammatory responses, 21, 341, 350 influenza virus, 289, 346 infrared spectroscopy, 59 inherited disorder, 46 inhibition, 19, 22, 26, 30, 56, 58, 59, 263, 274, 282, 283, 362, 363, 367 inhibitor, 30, 32, 58, 271, 291, 331 inhomogeneity, 124 initial state, 128, 129, 130, 131, 133, 134, 142, 149 initiation, 33, 268, 353, 355, 357, 473 inorganic micronutrients, 2 insertion, viii, 10, 336, 337 insulin, 17, 28, 47, 264, 277, 278, 279, 289, 293 Index 490 insulin resistance, 17, 47 insulin sensitivity, 17, 264, 289 insulin signaling, 17 integrated circuits, 350 integrated optics, 64 integrity, 13, 159, 268, 340, 364 interference, 22, 354, 363 intermolecular interactions, 245, 300 internalization, 8, 341 interstitial atom, 118, 121, 122, 123, 124, 131, 134, 135, 139, 140, 156, 159 intestinal tract, 9 intestine, 7, 9, 15, 42 intoxication, 56, 278, 279, 354, 368 iodine, 1, 4, 6, 46, 352 ion implantation, vii, 63, 64, 65, 66, 67, 84, 85, 86, 87, 92, 95, 96, 97, 99, 100, 101, 102, 103, 104, 105, 111 ion transport, 29, 42 ion-exchange, 338 ionizing radiation, 267 IR spectra, 164 iridium, 404, 405 iron transport, 268 irradiation, 89, 93, 95, 101, 103, 117, 118, 119, 120, 121, 122, 124, 126, 127, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 155, 156, 157, 158, 159, 160, 161 IR-spectra, 97 ischemia, 362 isobutane, 302 isolation, 298, 311, 315, 318, 319, 320 isoleucine, 174, 311 isomers, 219, 220, 228, 301, 302, 303, 305, 308, 309, 314 isotope, 15, 420 J jejunum, 8 joints, 267, 276 K K + , 3, 4 ketones, 300, 303, 304, 306, 307, 308, 310, 312 kidney(s), 10, 12, 342, 366 kinetics, 26, 46, 135, 143, 146, 261, 268, 300, 302 L lactic acid, 270 lactoferrin, 294, 352 landfills, 20 lanthanide, 186, 191, 196 laser radiation, 86, 87, 89, 90, 92, 93, 95, 97, 98, 100, 101, 102, 106, 107, 108 lasers, 84 lateral sclerosis, 368 lattice parameters, 142, 147, 148, 338 lattices, 283 LDL, 267 LEA, 61 leaching, 331 lead, 2, 5, 6, 8, 11, 18, 19, 20, 22, 25, 26, 28, 30, 34, 36, 38, 60, 63, 107, 118, 151, 164, 165, 230, 246, 262, 263, 272, 284, 325, 327, 328, 329, 335, 336, 339, 340, 341, 346, 350, 355, 360, 362, 452, 460 lean body mass, 17 learning, 288 lecithin, 267 lesions, 13, 20, 51, 269, 284, 340, 341 leukemia, 50, 267 liberation, 34, 192, 457, 471 lipid metabolism, 264, 288, 353 lipid oxidation, 39 lipid peroxidation, 7, 19, 21, 22, 23, 29, 55, 268, 278, 279, 282, 348, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 366 lipoproteins, 266, 268 liposomes, 357, 358, 359 liquid chromatography, 315 liquid phase, 282, 297, 299 liquids, vii, viii, 17, 116, 311 lithium, 65 liver, 8, 9, 12, 13, 21, 23, 38, 41, 50, 269, 339, 342, 354, 357, 358, 362, 363, 365, 367 liver cancer, 21 liver damage, 339, 342, 354 liver disease, 12, 13 localization, 51 locus, 37 lung cancer, 19, 21, 48, 342, 363 Luo, 49, 367, 446 lymphocytes, 49, 341 Index 491 M macromolecules, 245, 272, 283, 294, 318, 339, 348, 354, 363 macronutrients, 1, 2 magnesium, 1, 2, 14, 253, 304, 327, 334 magnetic field, 172, 349, 353 magnetic materials, 220, 221 magnetic moment, 166, 167, 173, 184, 186, 189, 193, 194, 197, 205 magnetic properties, 177, 187, 220, 221, 227, 230, 234, 240, 243, 249, 250, 252, 253, 254, 255, 256, 257, 258, 259, 383, 422 magnetic resonance imaging, 13 magnetism, 163, 195, 220, 250, 251, 252, 257 magnitude, 93, 95, 107, 135, 136, 137, 141, 200, 220, 229, 230, 231, 232, 234, 236, 237, 238, 241, 243, 244, 247, 349 major histocompatibility complex, 274 mammalian cells, 7, 21, 346, 348, 356, 360 mammals, 11, 16, 43, 45, 47, 347, 352 manganese, 1, 4, 5, 8, 11, 12, 14, 24, 33, 39, 40, 45, 46, 61, 182, 252, 253, 291, 292, 304, 305, 312, 325, 334, 335, 336, 337, 350, 364, 467 mass spectrometry, 167, 176 matrix, 32, 66, 84, 93, 95, 100, 106, 117, 122, 123, 124, 126, 127, 128, 129, 130, 140, 143, 145, 146, 147, 148, 152, 155, 156, 158, 159, 161, 317, 318 matrixes, 67 matter, iv, 37, 115, 261, 474 MCP, 342 MCP-1, 342 mechanical properties, 25, 118, 136, 137 mechanical stress, 117 mechanical testing, 120, 140 media, 63, 64, 89, 97 medicine, viii, 60, 261, 266, 288, 289, 292, 295, 299, 320 melanin, 10, 37, 59, 60, 265 mellitus, 367 melting, vii, 108, 120, 131, 347, 349, 350, 457 membrane permeability, 341 membranes, 35, 319, 348, 354 Mendeleev, 294 mental state, 24 mercury, 5, 7, 11, 13, 19, 262, 303, 305, 348, 398, 444 metabolic disturbances, 361 metabolic pathways, 353 metabolism, 3, 8, 9, 12, 13, 14, 15, 16, 23, 32, 33, 34, 35, 36, 42, 43, 261, 262, 277, 281, 288, 341, 348, 361, 365 metabolites, 6, 37, 58, 340 metabolizing, 280, 340 metal complexes, vii, viii, 163, 164, 165, 167, 168, 169, 174, 176, 195, 197, 202, 206, 254, 256, 258, 259, 261, 263, 297, 298, 299, 301, 304, 305, 314, 320, 383, 384, 390, 399, 405, 406, 422, 453, 454, 456 metal extraction, 175 metal nanoparticles, vii, 63, 64, 65, 67, 107, 111 metal oxides, 304, 333, 334, 337, 350, 453 metal phase (MNPs), 63, 64, 65, 66, 83, 84, 85, 87, 88, 89, 90, 91, 92, 93, 95, 97, 100, 101, 102, 103, 104, 106, 107, 110 metal salts, 168, 171, 172, 202, 206, 251, 415 metal-based photodynamically active compounds, 2 metal-free conditions, 17 metallo- therapeutics, 2 metalloenzymes, 10, 12, 13, 165, 194, 195, 221, 262, 263, 271, 291 metallo-therapy, 2 metallurgy, 345, 347, 348 metal-organic complexes, 2, 38 metal-oxide-semiconductor, 65 metastasis, 267 methanol, 168, 200, 260, 344, 406, 454 methodology, viii, 413 methyl group, 172, 197, 453, 471, 473 methyl groups, 172, 197 methylcobalamin (MeCbl), 16 Mexico, 364 Mg 2+ , 2, 4 MHC, 274 mice, 19, 21, 31, 32, 48, 50, 57, 289, 291, 346 microelectronics, 64, 65 micronutrients, 2, 3, 352 microorganisms, 1, 16 microphotographs, 140 microscope, 121, 335 microscopy, 26, 30, 51 microsomes, 348, 354 microstructure, 118, 121, 143, 155 midbrain, 33 migration, 118, 180, 314 milligrams, 12 mineralization, 12, 279 miniaturization, 64 mitochondria, 8, 10, 12, 30, 37, 41, 59, 61, 348, 352, 354, 360, 361, 362, 365, 367 mitogen, 363 mitosis, 285, 340 mitotic index, 20 mixing, 67, 118, 119, 155, 156, 157, 158, 159, 160, 161, 338, 374, 454, 462, 467, 468, 473, 477 MMP, 32 Index 492 MMP-3, 32 model system, 60, 221 modelling, 286 models, 7, 31, 51, 220, 221, 292, 367 modern science, 63 modern society, 452 modifications, 19, 97, 315 moisture, 197 molar ratios, 337, 338, 339 molar volume, 338 molecular mass, 25 molecular oxygen, 39, 262, 282, 339, 361 molecular structure, 199, 224, 227, 228, 247, 248, 251, 253, 256, 257, 258, 459 molecular weight, 8, 10, 20, 186, 205, 221, 262, 268 molybdenum, 1, 2, 3, 4, 5, 9, 14, 15, 17, 46, 47, 120, 132, 133, 171, 270, 325, 327, 352, 370, 376 monoclonal antibody, 50 monomers, viii, 25, 27 mononucleotides, 285 morphology, 26, 31, 118, 135, 333 mortality, 48, 50, 346 motif, 10, 14, 183, 401, 407 multiple factors, 33 multiplication, 22 muscle mass, 277 muscles, 277, 278 mutant, 10, 28, 31, 32 mutation, 363, 451 mutations, 9, 22 myelodysplasia, 267 myocardial infarction, 267 myoglobin, 6, 8, 280, 352 N Na + , 4, 305 Na2SO4, 304 NaCl, 35, 304 NAD, 352, 354 NADH, 16, 18, 49, 354, 361 nanomaterials, 64, 110, 119, 407 nanoparticles, 65, 84, 85, 86, 88, 89, 90, 92, 93, 95, 99, 100, 101, 102, 106, 107, 108, 110, 114, 119, 350 nanostructured materials, 63, 111, 405 nanostructures, 102, 162 nanotechnology, viii, 64, 111 NAS, 45 National Research Council, 45 NATO, 250 nausea, 354 NCS, 220, 254 Nd, 84, 85, 97, 196 necrosis, 360, 365 neocortex, 23 nerve, 31, 33, 34, 57, 352 nerve growth factor, 31, 57 nervous system, 288 neuritis, 23, 39 neuroblastoma, 58 neurodegeneration, 9, 30, 31, 51, 53, 59, 60, 268, 288, 354, 362, 365, 367 neurodegenerative diseases, 7, 23, 24, 53, 58, 288, 364, 367 neurodegenerative disorders, 2, 55, 56, 57, 271, 288, 361, 366 neurofibrillary tangles, 23, 24, 52, 361, 362 neurologic symptom, 13 neurological disease, 60 neuronal cells, 23, 41 neurons, 10, 23, 25, 29, 31, 32, 33, 35, 37, 38, 39, 44, 55, 59, 361, 362, 364 neuropathy, 290 neuropsychological tests, 24 neurotoxicity, 27, 29, 31, 40, 45, 53, 54, 57, 61, 348, 360, 361, 363 neurotransmission, 288 neurotransmitter, 33, 34, 38, 268, 362 neurotransmitters, 39, 367 neurotrophic factors, 31 neutral, 27, 28, 170, 172, 180, 223, 251, 263, 300, 359, 382, 384, 387, 401, 457, 458, 459 neutrons, 120, 122, 129, 133, 136, 137, 138, 139, 140, 141, 158 NH2, 39, 309, 446 nickel, 1, 4, 5, 6, 11, 18, 19, 27, 46, 47, 48, 49, 119, 120, 131, 135, 137, 138, 141, 142, 143, 145, 146, 147, 151, 152, 153, 154, 155, 157, 158, 159, 160, 161, 183, 194, 252, 253, 303, 305, 308, 312, 319, 333, 334, 339, 344, 348, 366, 458 nicotine, 32 nicotinic acid, 264 nigrostriatal, 33, 38 niobium, 120, 121, 122, 123, 126, 127, 128, 129, 130, 132, 133, 135 niobium carbonitrides, 120, 121, 122, 123, 126, 128, 129, 130, 132, 133 NIR, 386 nitrates, 4, 332, 339, 377 nitric oxide, 366, 367 nitric oxide synthase, 367 nitrogen, 2, 3, 6, 14, 27, 28, 39, 120, 122, 123, 125, 126, 127, 128, 129, 130, 131, 132, 133, 135, 164, 172, 180, 181, 191, 196, 197, 219, 223, 257, 258, Index 493 271, 279, 303, 304, 305, 316, 408, 451, 452, 453, 459, 471, 473, 474, 475, 476 nitrogen fixation, 3 nitrogenase, 3, 15 NMR, 39, 45, 54, 172, 174, 176, 186, 189, 190, 193, 205, 277, 278, 285, 417, 421, 443 N-N, 184 nonlinear optical response, 64, 66 nonlinear optics, 63, 116 non-steroidal anti-inflammatory drugs, 266 nucleation, 103, 118, 124, 130, 140, 145, 147, 150, 159 nuclei, 33, 159 nucleic acid, 3, 8, 13, 19, 48, 49, 262, 268, 285, 361 nucleophiles, 316 nucleotide sequence, 283 nucleus, 8, 265, 340, 352 nutrient(s), 2, 3, 4, 12, 16, 20, 47, 264, 277, 364 nutrition, 12, 13, 43, 47, 50, 365 nutritional status, 290 O occlusion, 221 olefins, viii, 302, 303, 304, 305, 306, 309 oleic acid, 282 oligodendrocytes, 9 oligomeric structures, 394, 406 oligomerization, 25, 27 oligomers, 25, 26, 30, 55, 57, 278, 279, 362 operations, 18, 330 optical limiters, 84, 89, 107 optical parameters, 88, 97, 107 optical properties, vii, 63, 64, 65, 66, 84, 89, 90, 93, 96, 102, 104, 107, 111, 115, 206 optoelectronics, 63 ores, 326, 351 organ, viii, 16, 169, 194, 269, 302, 304, 357, 359, 382, 383, 384, 385, 386, 388, 390, 392, 393, 394, 397, 400, 401, 403, 405, 406, 408, 411, 412, 414, 415, 416, 419, 420 organic compounds, 194, 266, 297, 299, 300, 303, 304, 305, 308, 309, 315 organic matter, 332 organic solvents, 339 organism, 262, 271 organometallics, viii, 2 organs, 269, 354, 358, 359, 363, 365 orthogonality, 200, 232, 234 oscillation, 155, 157 osmium, 406 osteoporosis, 267 overlap, 177, 200, 229, 231, 232, 244, 245, 303 oxalate, 19, 48, 286 oxidation, 3, 6, 14, 15, 16, 18, 19, 20, 22, 25, 27, 28, 29, 33, 34, 35, 36, 37, 40, 41, 54, 58, 59, 109, 164, 165, 174, 200, 202, 220, 262, 265, 274, 276, 277, 278, 281, 282, 283, 327, 342, 347, 353, 354, 355, 358, 361, 363, 386, 388, 389, 390, 400, 410, 418, 460,뫰464, 466, 467, 468 oxidative damage, 29, 45, 52, 264, 348, 350, 354, 359, 360, 361, 362, 364, 365, 367, 368 oxidative destruction, 282 oxidative reaction, 27 oxidative stress, 2, 5, 10, 22, 25, 29, 32, 33, 34, 35, 36, 37, 38, 40, 41, 42, 51, 55, 57, 58, 59, 61, 278, 279, 290, 348, 350, 354, 359, 360, 361, 362, 363, 365, 366, 367, 368 oxide nanoparticles, 364 oxygen consumption, 33, 279, 362 oxygen consumption rate, 33 oxyhemoglobin, 280 P palladium, 258, 303, 350, 391, 398, 406, 407, 436 pallor, 37 pancreas, 12 pathogenesis, 24, 29, 30, 35, 55, 58 pathology, 51, 291, 359, 365 pathophysiology, 23 pathways, 31, 34, 46, 58, 59, 250, 263, 279, 285, 294, 355, 360 PCT, 429 peptidase, 3 peptide(s), 18, 23, 25, 26, 27, 28, 29, 30, 53, 54, 55, 56, 57, 262, 264, 265, 268, 274, 276, 292, 297, 298, 299, 320, 361, 367 perchlorate, 251, 255, 257, 258 Periodic Table, 348, 351, 352 peripheral neuropathy, 264 permeability, 61, 362 pernicious anemia, 16 perovskite oxide, 200 peroxidation, 48, 266, 280, 282, 355, 356, 357, 359, 360, 362, 363 peroxide, 22, 29, 34, 56, 348, 355, 356 petroleum, 174, 278, 320 pH, 8, 13, 18, 27, 28, 34, 39, 57, 172, 180, 181, 185, 263, 264, 276, 277, 278, 279, 281, 284, 285, 298, 315, 318, 341, 359, 473 pharmaceutics, 281 pharmacology, 278, 279 phase decomposition, 143, 144 phase diagram, 118, 142, 145, 150 Index 494 phase transformation, 143 phase transitions, 146 phenol, 281, 282 phenolic compounds, 18 phenotype, 10, 15, 272 phenoxyl radicals, 281, 283 Philadelphia, 43 phosphate, 22, 49, 195, 265, 277, 278, 370 phosphates, 19, 48, 316, 353, 377 phosphoenolpyruvate, 12 phospholipids, 19, 48, 264, 348, 355, 356, 359, 360 phosphorous, 1, 2, 316, 370, 375 phosphorus, 9, 193, 369, 370, 371, 372, 373, 374, 375, 376 phosphorylation, 32, 57, 259, 264, 268, 361, 363 photonics, 64, 111 photons, 89, 92, 95, 155, 359 photosynthesis, 3 physical characteristics, 160, 161 physical mechanisms, 157 physical properties, 148, 152, 311, 386, 404, 454 physicochemical characteristics, 281 physicochemical properties, 49, 350 physics, 119, 220 physiology, 291, 353 PI3K, 32 pigmentation, 349 pituitary gland, 52 placebo, 32 plant growth, 42 plants, 1, 2, 3, 5, 11, 12, 18, 20, 47, 342 plaque, 26, 29, 54 plasma membrane, 9, 348, 354 plasticity, 39, 60, 220, 228, 230, 251 plastics, 327, 334, 335 platinum, 2, 274, 276, 283, 284, 285, 286, 287, 303, 350, 354, 386, 389, 390, 391, 397, 400, 404, 405, 406, 407, 408, 411, 417, 418, 424, 426, 429, 430, 433, 436, 441, 442, 444, 445, 446, 448, 449 point defects, 86, 117, 118, 126, 127, 130, 131, 132, 133, 135, 137, 140, 141, 155, 156, 157, 158, 159, 160 point mutation, 22 poison, 125 polarity, 300, 304 polarizability, 5, 316 polarization, 66, 84, 272 pollutants, 8, 298 polyamine, 283, 309 polyamines, 163, 165 polydimethylsiloxane, 304 polymer, viii, 37, 173, 174, 183, 251, 254, 298, 302, 304, 315, 337, 339 polymer synthesis, viii polymerase, 352 polymeric chains, 225, 227, 234 polymerization, viii, 257 polymers, 37, 66, 275, 305, 313, 330, 381, 399, 457 polynuclear complexes, 195, 220, 235, 257 polypeptide, 23 polypeptides, 263 polyphenols, 353 polystyrene, 173 polyunsaturated fat, 33 polyunsaturated fatty acids, 33 population, 11, 21, 38, 51, 52, 54, 340, 475 porosity, 135, 140, 317 porphyrins, 416 positrons, 155, 156 potassium, 1, 276, 326, 328, 336, 341, 349, 418, 455, 457 power lines, 349 power plants, 119 precipitation, 24, 25, 28, 34, 143, 144, 145, 146, 150, 153, 327, 335, 372, 462, 464, 466, 469, 470, 471, 473, 477 premature breast fed infants, 13 premature infant, 12 preparation, iv, 4, 64, 177, 181, 187, 202, 332, 333, 335, 369, 370, 375, 382, 383, 386, 390, 397, 399, 406, 408, 414, 420, 422 principles, 43, 98, 116, 263, 303, 313, 314, 318, 364 prions, 269 probability, 39, 140, 156, 402, 414 probe, 67, 278, 279 professionals, 47 progesterone, 292 progressive neurodegenerative disorder, 23 project, 33 proliferation, 22, 270, 332, 360, 363 promoter, 21, 268 propagation, 87, 107, 244, 245, 353, 355, 359 propane, 251 propylene, 309 protease inhibitors, 283 protective coating, 332 protective role, 37, 38 protein folding, 291 protein kinase C, 13, 61 protein kinases, 17, 363 protein misfolding, 53 protein oxidation, 23, 273, 361, 364 proteinase, 3 proteins, 2, 6, 7, 9, 13, 14, 18, 19, 23, 24, 29, 31, 36, 38, 43, 48, 51, 60, 250, 262, 264, 265, 268, 269, 270, 271, 272, 273, 274, 275, 278, 279, 291, 297, Index 495 299, 315, 316, 318, 319, 320, 330, 347, 352, 353, 354, 355, 357, 360, 364, 365, 367 proteolysis, 271 proteomics, 320 protons, 172, 263 psychiatric disorders, 23 publishing, 42 pumps, 353 purification, 123, 126, 291, 318, 319, 320 purines, 15 purity, 133, 298, 310 Q quantum well, 65 quantum yields, 261 quinolinic acid, 225 quinone(s), 34, 35, 36, 37, 58 R racemization, 311 radiation, 85, 88, 89, 91, 93, 94, 95, 97, 98, 99, 106, 107, 110, 117, 118, 119, 120, 121, 122, 124, 126, 127, 128, 129, 132, 135, 136, 137, 140, 141, 142, 152, 155, 157, 158, 159, 160, 161, 267, 289, 337, 346, 371 radiation damage, 119, 120, 126, 128, 132, 135, 136, 140, 141, 157, 160 radiation therapy, 267 radical formation, 29, 49, 61, 270, 355, 356 radical reactions, 50, 268, 288, 353, 366 radicals, 10, 20, 22, 29, 30, 34, 35, 37, 38, 41, 42, 49, 55, 56, 249, 264, 267, 268, 274, 348, 354, 355, 356, 357, 364, 365, 460 radius, 87, 93, 97, 99, 107, 132, 157, 280, 301, 333, 351 random media, 64, 110 raw materials, 327, 335, 337 reaction center, 6, 342, 453, 471 reaction mechanism, viii, 11, 355, 398 reaction medium, 172, 353 reaction rate, 350, 360 reaction temperature, 327 reaction time, 335, 394 reactive groups, 22, 193, 299, 382 reactive oxygen, 11, 21, 22, 24, 28, 29, 34, 36, 39, 44, 50, 281, 339, 354, 355, 359, 360, 362, 363, 367 reactivity, vii, viii, 6, 14, 22, 176, 250, 261, 264, 271, 285, 288, 316, 344, 353, 364, 451, 452, 453, 457, 459, 460, 462, 466, 469, 470, 471, 473, 477 reagents, 308 reasoning, 459 receptors, 11, 14, 29, 31, 42, 50, 56, 262, 288 recognition, 64, 195, 292, 314 recombination, 117, 118, 126, 127, 129, 130, 131, 132, 133, 134, 135, 137, 140, 141, 155, 156, 157, 158, 159, 160 recovery, 49, 267, 298, 311 recrystallization, 120, 122, 123, 124, 125, 126, 127, 128, 129, 130, 132, 133, 136 recycling, 9, 174, 175, 350 red blood cells, 13, 24, 341 redistribution, 104, 151, 362 redox groups, 399 refractive index, 64, 66, 91, 106, 107, 108 refractive indices, 64 regenerate, 30 regeneration, 318 relaxation process, 261 relaxation processes, 261 relevance, 55, 59, 61, 220, 278, 279, 366 repair, 18, 19, 22, 49, 265, 266, 267, 268, 284, 340, 341 replication, 21, 291, 341 requirements, 3, 42, 137, 187, 286, 335 researchers, 27, 28, 37, 174, 205, 208, 268, 270, 276, 473, 477 residues, 2, 10, 23, 26, 27, 30, 31, 36, 55, 274, 281, 282, 286, 292 resins, 334 resistance, 11, 43, 64, 117, 118, 119, 135, 137, 150, 152, 155, 157, 158, 159, 160, 161, 285, 330, 331, 332, 334, 341 resolution, 311, 314 respiration, 270, 347, 352, 361, 367 response, 19, 38, 49, 64, 91, 107, 172, 268, 281, 340, 341, 367, 386, 389, 399 restrictions, 39, 327 restructuring, 146 retardation, 270, 273 reticulum, 278, 279 reusability, 174 rhenium, 406, 418 rheumatoid arthritis, 274 rhodium, 253, 254, 304, 312, 313, 350, 404, 417 rings, 25, 26, 120, 121, 227, 240, 247, 405 risk, 15, 17, 19, 21, 22, 23, 24, 38, 46, 48, 50, 59, 60, 264, 266, 268, 350, 366 risk factors, 60, 264, 366 RNA, 11, 13, 28, 270, 281, 352, 354 rodents, 340 ROOH, 355, 356, 357 Index 496 room temperature, 122, 149, 167, 172, 187, 191, 197, 333, 336, 393, 409 roots, 13 rural areas, 38 ruthenium, 390, 403, 404, 410, 418, 434, 443, 447 rutile, 338 S salicylates, 269 salts, 4, 21, 172, 184, 196, 219, 224, 225, 256, 268, 274, 277, 304, 305, 330, 339, 349, 394, 417, 455, 457, 459 sapphire, 97, 106 saturated fat, 350 saturation, 21, 66, 95, 110, 133, 156 scandium, 347, 351 scattering, 89 scavengers, 10 Schiff base ligands, 163, 164, 165, 166, 185, 189, 193, 196 science, viii, 34, 64, 111, 119, 157, 220 secondary radiation, 117, 118, 129, 134, 137, 141, 160, 161 secretion, 32, 57 segregation, 135, 137 selectivity, 164, 175, 262, 263, 285, 293, 304, 305, 315, 317, 373, 374, 375, 376 selenium, 1, 4, 5, 6, 24, 352, 366 self-assembly, 26, 183 self-organization, 117, 119, 161 semiconductor, 64, 65, 66, 67, 89, 97, 349 semiconductors, 347, 349, 459 sensitivity, 17, 107, 340, 342, 452, 453, 454, 455, 477 sensors, 262 septum, 342 serotonin, 33, 37 serum, 8, 12, 17, 21, 24, 47, 52, 57, 268, 270, 289, 315, 319 serum ferritin, 21 shape, 101, 104, 121, 155, 220, 283 showing, 31, 35, 65, 140, 299, 300, 400, 405 sickle cell, 270 side chain, 26, 28, 197, 236, 259, 271, 272, 319 side effects, 276 sideroblastic anemia, 290 signal transduction, 13, 29, 270, 363 signaling pathway, 22, 341 silica, 66, 175, 298, 302, 304, 305, 308, 309, 315, 347 silicon, 1, 4, 5, 6, 46, 65, 130, 327, 350 silver, 63, 65, 84, 88, 89, 90, 95, 97, 99, 100, 101, 102, 104, 106, 107, 302, 303, 305, 348, 386, 390, 393, 394, 397, 401, 403, 408, 411, 412, 416 sinusitis, 270 SiO2, 67, 69, 70, 71, 72, 73, 74, 77, 78, 79, 80, 81, 82, 83, 85, 86, 87, 88, 89, 90, 91, 92, 93, 95, 96, 100, 107, 108, 109, 110, 328, 329 skeleton, 12, 23, 251, 387 skin, 13, 21, 265, 267, 269, 273, 339, 342 small intestine, 10, 273 SO42-, 3 society, 452, 478 sodium, 1, 34, 49, 65, 121, 276, 326, 327, 331, 335, 336, 349, 406, 455, 457 solar cells, 350 solid matrix, 104 solid solutions, 155, 333, 338, 339, 345 solid state, 163, 168, 172, 183, 197, 334, 335, 394, 398, 402, 404, 405, 411, 413, 421 solid tumors, 267 solubility, 14, 123, 124, 136, 261, 262, 265, 280, 328, 340, 341, 454, 459 solvation, 26, 263 solvent molecules, 196 solvents, viii, 183, 193, 398, 454 sorption, 315 spatial learning, 57 speciation, 42, 278, 279 specific adsorption, 317 specific surface, 350 specifications, 327, 328 spectroscopic techniques, 39 spectroscopy, viii, 28, 29, 30, 39, 54, 60, 61, 67, 110, 176, 189, 251, 252, 254, 257, 258, 277, 278, 285, 421, 469 spin, 21, 29, 39, 166, 167, 173, 184, 187, 195, 196, 197, 198, 202, 203, 229, 234, 239, 243, 245, 251, 261, 280, 281, 353, 359, 476 spine, 25, 53 spleen, 38 stability, 85, 117, 119, 137, 161, 261, 262, 272, 281, 283, 300, 301, 302, 303, 316, 318, 330, 336, 337, 338, 339, 382, 383, 451, 452, 453, 457, 458, 471, 473 stabilization, 131, 158, 258, 271, 272, 278, 279, 286, 335, 382, 390 stabilizers, 262, 353 stable complexes, 308, 330 standard deviation, 457 steel, 120, 122, 123, 124, 125, 126, 127, 129, 130, 133, 134, 135, 136, 141, 332, 349 stimulus, 477 stoichiometry, 26, 54, 200, 224, 344, 394, 416 Index 497 stomach, 269, 342 storage, 6, 7, 8, 264, 291, 352, 354, 360, 362, 382 stress, 10, 27, 29, 37, 40, 41, 51, 58, 271, 278, 279, 300, 305, 350, 359, 361, 362, 363, 365, 366 stretching, 177, 349 striatum, 33, 34, 61 stromal cells, 292 strong interaction, 244, 303 strontium, 328, 329 structural changes, 149, 150, 281, 302 structural characteristics, 27 structural transformations, 61, 149, 159 substitution, 118, 130, 133, 135, 176, 283, 301, 302, 333, 334, 338, 344, 405, 408, 473 substitution reaction, 176 substrate, 63, 90, 93, 94, 95, 97, 99, 262, 263, 273, 282, 283, 353, 471 substrates, 18, 93, 194, 196, 263, 460, 467, 468, 469 sulfate, 276, 277, 326, 327, 329 sulfonamides, 273 sulfur, 2, 5, 14, 15, 174, 271, 275, 280, 316, 330, 352, 356, 370, 376, 391 sulphur, 1, 2, 11, 16, 28, 168, 171, 173, 197, 257, 280, 307, 356 Sun, 45, 54, 253, 320, 324, 378, 429, 435, 441, 446 supplementation, 17, 24, 30, 47, 273 surface area, 63 surface energy, 157 surface layer, 121 surface properties, 97 surface structure, 357 survival rate, 267 susceptibility, 18, 33, 64, 66, 84, 93, 94, 95, 99, 107, 108, 132, 177, 183, 187, 258, 266, 268 sustainable development, 452 swelling, 41, 119, 126, 127, 138, 157, 318, 342 symmetry, 164, 181, 220, 229, 230, 239, 242, 243 synapse, 362 synergistic effect, 117, 283 synthesis, vii, viii, 3, 59, 63, 64, 65, 66, 111, 163, 164, 167, 173, 175, 176, 193, 195, 196, 200, 201, 219, 221, 255, 259, 261, 263, 265, 268, 269, 270, 276, 311, 330, 340, 344, 382, 383, 384, 390, 391, 398, 399, 400, 405, 407, 409, 413, 414, 415, 418, 419, 420, 421, 459 synthetic polymers, 330 T T cell, 292 target, 10, 23, 262, 265, 278, 279, 281, 285, 286, 318 target organs, 23, 265 tau, 23, 27, 32, 57, 362 techniques, vii, 63, 64, 297, 298, 299, 313, 314, 318, 320 tellurium, 366 temperature dependence, 26 temporal lobe, 24, 29 tension, 119, 126, 138, 139, 140 teratogen, 363 ternary oxides, 333 terpenes, 303 testing, 120, 140, 141, 276, 331, 332 testosterone, 14 tetrahydrofuran, 397, 401, 403, 404, 409, 419, 421 textiles, 327, 331 TFE, 28 therapeutic benefits, 31 therapeutic interventions, 261, 288 therapeutics, 2, 295 therapy, 2, 12, 28, 32, 44, 51, 262, 267, 270, 276, 283 thermal aging, 158 thermal analysis, 176 thermal decomposition, 200 thermal energy, 157 thermal resistance, 304, 305 thermal stability, 312, 457, 458 thermal treatment, 104 thermogravimetric analysis, 194 thermomechanical treatments, 121, 135 thymine, 284, 285 thymus, 49, 291 thyroid, 267, 271, 291 time resolution, 342 tin, 67, 193, 254, 330, 349 tissue, 9, 11, 19, 22, 23, 25, 29, 32, 33, 34, 37, 44, 45, 48, 50, 266, 267, 274, 276, 341, 342, 348, 352, 353, 354 titanium, 138, 139, 160, 193, 337, 349, 389, 393, 411, 416, 418 toluene, 407 tones, 332 topology, 233, 234, 243 total cholesterol, 264 toxic effect, 12, 269, 278, 342, 353, 355, 359, 361 toxic metals, 7, 363 toxicity, 6, 9, 12, 15, 17, 18, 21, 26, 27, 28, 29, 31, 32, 36, 37, 40, 42, 44, 45, 46, 53, 54, 55, 56, 58, 60, 261, 262, 265, 266, 268, 276, 277, 278, 279, 285, 288, 289, 290, 294, 339, 340, 348, 350, 353, 354, 355, 357, 358, 359, 360, 361, 362, 363, 364, 365, 451 toxicology, 48, 278, 279 toxin, 33 trace elements, 1, 4, 5, 44, 47, 52, 290, 352, 353, 364 Index 498 trafficking, 295 transactions, 345 transcription factors, 13, 14, 270, 291, 360, 365 transferrin, 2, 8, 11, 12, 17, 21, 45, 50, 264, 267, 281, 352, 361 transistor, 65 transition elements, vii, 2, 34, 158, 189, 351 transition metal ions, viii, 168, 176, 187, 195, 197, 262, 291, 299, 348, 354, 355, 357, 363, 364 transmittance spectra, 85, 95 transport, 6, 7, 8, 10, 12, 23, 38, 43, 44, 45, 46, 220, 264, 265, 267, 268, 269, 275, 284, 286, 342, 347, 352, 360, 362, 365, 366, 387 transportation, 25 transversion mutation, 22 treatment, 2, 11, 13, 26, 32, 60, 122, 128, 131, 168, 187, 262, 266, 267, 268, 269, 270, 273, 274, 277, 278, 293, 326, 331, 333, 340, 342, 354, 358, 361, 374, 393, 394, 397, 400, 404, 406, 408, 411, 413, 416 tricarboxylic acid, 414 triggers, 362, 367, 452 triglycerides, 264 triphenylphosphine, 276, 441 tryptophan, 38 tumor cells, 21, 269 tumor development, 11, 44 tumor growth, 21, 50, 267 tungsten, 47, 325, 349 turnover, 8, 34, 58, 271 type 2 diabetes, 17, 47 tyrosine, 28, 38, 258, 259 U ulcer, 266, 269, 339 ultrafast time response, 64 urea, 12 uric acid, 15 urine, 15, 17, 47 uterus, 274 uti, 50 UV, 42, 63, 86, 166, 174, 176, 186, 189, 193, 196, 205, 332, 335, 339, 434, 464, 466, 467, 468, 469 V valence, 151, 182, 301, 338, 382, 384, 387, 392, 393, 457, 464 valine, 311, 312 vanadium, 1, 2, 4, 5, 6, 17, 18, 19, 41, 46, 47, 48, 49, 160, 166, 200, 203, 276, 277, 278, 279, 293, 294, 304, 325, 334, 348 vapor, 325 vascular dementia, 367 vascular diseases, 366 velocity, 93, 359, 456 versatility, 165, 349 vibration, 344 vitamin A, 46 vitamin B1, 3, 16, 194, 353 vitamin B12, 3, 16, 194, 353 vitamin B3, 264 vitamin C, 9, 38, 268 vitamin D, 14 vitamin K, 46 vitamins, 47 VOCl3, 169 volatility, 305, 308 vomiting, 354 VSD, 67, 73, 81 W waste, 339 wastewater, 339, 345 water vapor, 350 wave vector, 87 wavelengths, 84 weak interaction, 241, 299 weakness, 267 weight gain, 264 weight loss, 264 weight ratio, 330, 337 welding, 49 WHO, 46, 47 wires, 102, 349 wood, 327, 331 wool, 330 workers, 19, 21, 48, 50, 165, 171, 173, 176, 187, 189, 311, 342, 346 workforce, 19 World Health Organization, 47 worldwide, 23, 33, 286 wound healing, 266, 273 X X-ray analysis, 223 X-ray diffraction (XRD), 333, 335, 338, 339, 397 X-ray photoelectron spectroscopy (XPS), 338, 369, 370, 371, 376, 377, 378 Index 499 Y yeast, 11, 45 yield, 22, 28, 84, 176, 199, 282, 335, 342, 357, 398, 404, 406, 408, 409, 410, 418, 419 Z zeolites, 305 zinc, 1, 2, 4, 5, 7, 8, 9, 13, 14, 17, 19, 23, 27, 29, 31, 32, 34, 37, 42, 43, 44, 46, 48, 50, 51, 52, 53, 54, 56, 57, 180, 181, 183, 253, 267, 268, 269, 270, 271, 272, 273, 274, 289, 290, 291, 292, 305, 308, 310, 315, 327, 328, 329, 332, 336, 337, 340, 343, 345, 348, 366 zinc deficiency disorder, 13 zinc oxide, 337 zirconium, 193, 390 ZnO, 75, 76, 329, 336, 337, 350 zwitterions, 223