bluuebunny/crossref_metadata_2025 huggingface dataset:
Aberrations of growth factors as biomarkers of cancer progression
Authors: Ivanovic Vesna
Published: March 2006

Cell proliferation and growth are regulated by a complex network of growth factor and growth inhibitorinitiated signal transduction pathways. The disruption of these signaling pathways through genetic, epigenetic, or somatic alterations is a major area of cancer research. Increasing evidence indicates that oncogenic activation of growth factors and their receptor proteins occur through mutations (oncoproteins) that lead to constitutive activation of the signaling pathways, thus providing the grounds for putative prognostic marker(s) and potential target(s) for treatment of various cancers. Over the past few years, the study of genomics has revealed the gene expression signatures for many malignancies. Present communication outlines literature survey on genomic molecular markers of breast, lung, and prostate cancers. Reassuringly, the dominant genomic markers of these malignancies include oncoproteins and provide a support for their clinical validity as cancer targets. More specifically, this article reviews recent advances in clinical targeting of these malignancies by two types of growth factor/receptors, namely transforming growth factor-? (TGF-?), and EGFR subfamily of tyrosine kinase receptors including ErbB2. Overexpression of these proteins has been demonstrated in patients with cancer progression and correlated with poor prognosis, increased frequency of metastasis and death. In addition, EGFR and ErbB2 inhibitors have been used in targeted therapy of lung and breast cancer, respectively. Recent investigations of lung cancer have uncovered that EGFR inhibitors have their greatest effect in patients with EGFR somatic mutations thus raising a possibility that EGFR mutations may be a molecular predictors of sensitivity to EGFR inhibitors.
Molecular mimicry of HIV gp120: Possible implications on prevention and therapy of AIDS
Authors: Veljkovic Nevena
Published: March 2006

A broad range of similarities between HIV-1 gp120 and human proteins-especially those participating in immune responses-highlight gp120 as a pleiotropic protein which can influence many important functions of the human immune system. The molecular mimicry that serves to the human immunodeficiency virus as potent destructive arms against immune system could be the weak point we are in search of over decades. Examples involving sequence and informational similarities of HIV-1 gp120 and immunerelated host cell proteins important for prevention and treatment of HIV infection are presented. .
Tissue microarray: A valuable method in diagnosis and prognosis of hematological malignances
Authors: Marjanovic Goran , Dojcinov Stefan
Published: March 2006

BACKGROUND: The novel technology of tissue microarray (TMA) allows rapid and cost-effective analysis of hundreds of markers on the same set of specimens. Limited amount of tissue that could be analyzed and problem of tissue heterogeneity, are the major drawbacks of TMA technique for immunohistochemical characterization of lymphomas. METHODS: In this paper 65 cases of lymphomas were analyzed using TMA with following panel of antibodies: BOB1, Oct2, Bcl2, Bcl6, CD20, CD21, CD23, CD3, CD5, CD10, CD43, CD79a, CD138, Cyclin D1, Ki67, MUM1, Pax5, p53. RESULTS: In 14 patients with diffuse large B-cell lymphoma (DLBCL), 5 were classified as germinative center and 3 as non-germinative center cases according to the Bcl6, CD10, and MUM1 positivity. Other 2 patients were identified as T cell rich B cell lymphoma based on morphology and Oct2 and BOB1 positivity of pleomorphic B lymphocytes. DLBCL with Bcl6+ immunophenotype had better overall survival than Bcl6- cases. All cases of classic mantle cell lymphoma had significantly lower Ki-67 proliferation index than blastoid subtypes. There were 14 cases of chronic lymphocytic leukemia/small cell lymphocytic lymphoma, 6 cases with follicular lymphoma, 5 cases of marginal zone lymphoma, and 7 cases of lymphoplazmacitoid lymphoma. In the indolent lymphoma group, survival of patients with p53+/- was poorer comparing to p53- group. CONCLUSION: We conclude that TMA technique is a valuable method in diagnosis and prognosis of lymphomas, which are considered very heterogeneous group of hematological neoplasms.
Alkali Metals: Organometallic ChemistryBased in part on the article Alkali Metals: Organometallic Chemistry by Charles M. Lukehart which appeared in the
Encyclopedia of Inorganic Chemistry, First Edition
.
Authors: Harvey Melanie J.
Published: March 2006

Organolithium complexes, like the organomagnesium Grignard Reagents, are important reactants in organic synthesis. The similarity in structure, bonding, and reactivity of organolithium and ‐magnesium compounds exemplifies the common chemistry exhibited by representative elements that appear in the same diagonal in the periodic table. Although much debate exists over the degree of covalency within lithium – carbon‐bonding interactions, the presence of some covalent character in LiC bonds of alkyllithium compounds is widely accepted. The bonding interactions within organoalkali metal complexes of the heavier alkali metals are generally considered to be strongly electrostatic or ionic in nature. This is supported by a large collection of evidence, consisting primarily of solution NMR data, single‐crystal X‐ray analyses, and gas‐phase computational studies. Many of the organolithium compounds are soluble in hydrocarbons, but organometallic compounds of the heavier group 1 metals generally require more polar solvents. In general, the reactivity of the alkali metals and the reactivity of the organometallic compounds of these metals increase as we go down the group or column. Organoalkali metal compounds are similar to, but more reactive than Grignard reagents. Organoalkali metal compounds are both air‐ and moisture‐sensitive and are sometimes pyrophoric. In addition, organoalkali metal compounds will react as Brønsted bases with protic reagents. Specific details regarding the synthesis, reactivity, and structures of various types of organoalkali metal compounds will be discussed.
Beryllium & Magnesium: Organometallic ChemistryBased in part on the article Beryllium & Magnesium: Organometallic Chemistry by E. Alexander Hill which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.
Authors: Saulys Dovas A. , Hill E. Alexander
Published: March 2006

Victor Grignard found in 1900 that solutions of organomagnesium halides form easily in the reaction of an organic halide with magnesium metal in diethyl ether. These Grignard reagents undergo useful reactions with many kinds of substrates. This discovery ushered in a new era in organometallic chemistry and provided chemists with a powerful and versatile reagent for synthesis of a wide variety of organic and organometallic compounds. This article discusses Grignard reagents in the broader context of organomagnesium chemistry. Preparatory methods surveyed include direct reaction of organic halides with the metal, exchange reactions with other organometallic compounds, as well as carbo‐ and hydrometalations. The current level of understanding of the mechanism of Grignard formation is summarized. The formation and reactivity of unusual species such as cluster Grignard reagents, for example, RMg4X (R = organic group, and X = halide) and polymagnesium compounds, for example, Ru[C5(MgCl)5]2are also discussed. The bonding and structure of organomagnesium compounds (as well as that of beryllium analogues) as described by diffraction methods, thermochemical data, colligative properties, spectroscopic (vibrational, nuclear magnetic, and electronic) measurements, kinetic studies, mass spectrometry, and theoretical methods are outlined.

The most prominent chemical property of organomagnesium compounds is their ability to deliver an effectively ‘anionic’ organic group with nucleophilic properties. As alkylating reagents, their important reactions include nucleophilic displacement of less basic leaving groups from saturated carbon atoms or other elements, addition to carbonyl groups and other unsaturated functions, and nucleophilic substitution at the acyl group of carboxylic acid derivatives. This broad array of substrates is surveyed, as are the effects of solvents and catalysts on reactivity. Less conspicuous reactions with wholly or predominantly inorganic substrates are also considered. Electron transfer reactions where organomagnesium compounds act as reductants are discussed.

Organoberyllium compounds are more difficult to prepare and are less nucleophilic than their magnesium counterparts. These features, together with their high toxicity, have limited their utility. Methods of preparation, as well as descriptions of bonding, structure, and reactivity patterns are presented. Of special note are recent advances in cyclopentadienyl beryllium chemistry, as well as the advent of beryllium–silicon chemistry.
Bismuth: Organometallic Chemistry
Authors: Whitmire Kenton H.
Published: March 2006

Bismuth readily forms a variety of tri‐ and pentavalent organic derivatives by the reactions of bismuth halides with Grignard, organolithium, organozinc, or organoaluminum reagents. Bismuth(III) triaryl compounds are readily oxidized by chlorine and bromine to triaryl dihalides, while iodine reacts to produce aryl bismuth iodides. Some organobismuth compounds are Lewis acidic, showing the ready formation of higher coordination number adducts with traditional ligands. A variety of organobismuth compounds with bismuth–bismuth and bismuth–transition metal bonds are described. Organobismuth(V) have found uses as selective oxidants and aryl transfer reagents.
Boron: Polyhedral CarboranesBased in part on the article Boron: Polyhedral Carboranes by Robert E. Williams which appeared in the
Encyclopedia of Inorganic Chemistry, First Edition
.
Authors: Hosmane Narayan S. , Maguire John A.
Published: March 2006

Carboranes are compounds in which carbon, boron, and hydrogen atoms are present in polyhedral cages. The cages are stabilized by multi‐centered bonds, which gives the carboranes unique chemical and structural properties. Many of these compounds are chemically and thermally stable enough to allow their use as boron delivery agent for boron neutron capture therapy (BNCT) in cancer treatment and as molecular assemblies.
Carbon: Fullerenes
Authors: Crane Jonathan D. , Kroto Harold W.
Published: March 2006

The discovery of the fullerenes has revolutionalized the chemistry of carbon. For the first time a molecular form of the element carbon is available that can be manipulated and functionalized by the wide range of techniques available to molecular and materials scientists. In a very short space of time the fullerenes and their derivatives have been found to display many fascinating physical and chemical properties, and the astonishing pace of development in fullerene research is ample testimony to their great potential.
Carbon: Inorganic ChemistryBased in part on the article Carbon: Inorganic Chemistry by R. Bruce King which appeared in the
Encyclopedia of Inorganic Chemistry, First Edition
.
Authors: Friščić Tomislav , MacGillivray Leonard R.
Published: March 2006

The article provides a brief and general overview of the chemical and physical properties of carbon, as it relates to inorganic chemistry. Several allotropic forms of carbon are described, with general properties discussed. The characteristics and synthetic methods for the preparation of simple compounds involving carbon or carbon and hydrogen with halogens, oxygen, sulfur, as well as nitrogen, are provided. In addition, recent developments in supramolecular chemistry to construct ladder‐like carbon frameworks are outlined.
Chalcogenides: Solid‐State ChemistryBased in part on the article Chalcogenides: Solid State Chemistry by Patricia M. Keane which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.
Authors: Kanatzidis Mercouri G.
Published: March 2006

This article deals with the solid‐state chemistry of chalcogenides and describes mainly the developments during the past decade. The article is not exhaustive but is meant to give a broad set of examples of interesting compounds and solid‐state chemistry of these compounds so that the reader can obtain a reasonable and rounded view of the recent activities in this area. Further depth and additional information can be obtained from the available references.
Chlorine, Bromine, Iodine, & Astatine: Inorganic ChemistryBased in part on the article Chlorine, Bromine, Iodine, & Astatine: Inorganic Chemistry by Jacob Shamir which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.
Authors: Lang Jian‐Ping
Published: March 2006

This chapter summarizes the occurrences, atomic structures, and molecular properties of the elements of group 17, chlorine, bromine, iodine, and astatine. The charge‐transfer complexes of halogens with different inorganic or organic compounds are outlined. The interhalogen compounds, especially those of polyiodides, are discussed with respect to their preparation and their structure varieties. The halogen oxides such as halogen oxide cations, halogen oxide fluorides, oxoacids and oxoacid salts, and halogen derivatives of oxoacids are discussed. Finally, organic polyvalent halogen derivatives, mainly including those of iodine (I), iodine (III), and iodine (V), are mentioned.
Cobalt: Organometallic ChemistryBased in part on the article Cobalt: Organometallic Chemistry by Ulrich Koelle which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.
Authors: Quisenberry Keith T. , Hanusa Timothy P.
Published: March 2006

Among the longest known families of organometallic compounds, those of cobalt display great diversity in their structures and oxidation states. The ligands accommodated in organocobalt compounds range from strong σ‐donors such as hydrides and alkyls, to π‐acid ligands such as carbonyls and phosphines. The carbonyl cluster compounds of cobalt are numerous and they play a major role in catalytic reactions of enormous industrial importance such as hydroformylation reactions (conversion of alkenes to aldehydes) and Pauson–Khand cycloaddition (production of cyclic ketones). Cobalt is an electron‐rich late transition metal, a property reflected throughout its organometallic chemistry. Thus, the carbonyl ‘hydride’ HCo(CO)4is actually a strong acid and does not have ‘hydridic’ (H−) properties. Similarly, cobalt does not complex to any group 15 or 16 heterocycles such as pyridine or thiophene. In contrast, boracycles are good ligands for cobalt in a sandwich complex because an electropositive atom such as boron incorporated in a π‐cyclic ring stabilizes the electron‐rich central metal. The cyclopentadienyl ligand is found extensively throughout organocobalt chemistry – not only in cobaltocenes, but also in half‐sandwich complexes of the type (C5H5)CoL2, where L is CO, alkene, alkyne, or phosphine. The (C5H5)CoL2complexes are useful in alkyne dimerization and trimerization. Cobaltocene itself ((C5H5)2Co) is easily oxidized to the extraordinarily stable 18‐electron cobaltocenium cation, [(C5H5)2Co]+. Cobalt can be incorporated into carborane cages, which have been found to be efficient extractors of radioactive metal ions such as90Sr and137Cs in water at low pH. Cobalamins, which consist of a cobalt central atom in a substituted corrin ring, are examples of naturally occurring organometallic compounds, and coenzyme B12was the first recognized example of a biological organometallic compound. Methylcobalamins play a role in biology, where they are found in microorganisms and can methylate mercury in the environment.
Coordination Chemistry: History
Authors: Kauffman George B.
Published: March 2006

This article discusses a chronological history of the major discoveries, both theoretical and experimental, of coordination chemistry from antiquity through 2003. In view of Alfred Werner's central role in the field, considerable space is allotted to his achievements, but contributions of lesser‐known pioneers are also included. Some of the most historically significant coordination compounds are first discussed, along with several pre‐Werner theories of their formation, constitution, and configuration, followed by Werner's theory and his most important discoveries.
Coordination Numbers & Geometries
Authors: Clare Brian W. , Kepert David L.
Published: March 2006

The principles governing the adoption of specific coordination geometries by transition metal complexes is discussed with emphasis on monodentate and bidentate ligands. Geometric parameters describing the structures are noted as well as polyhedral rearrangements of such structures.
Copper Proteins with Type 1 SitesBased in part on the article Copper Proteins with Type 1 Sites by Edward N. Baker which appeared in the
Encyclopedia of Inorganic Chemistry, First Edition
.
Authors: Hart P. John , Nersissian Aram. M. , George Serena DeBeer
Published: March 2006

Copper Proteins with Type 1
Sites is a general review that focuses on single‐domain proteins that bind ‘blue’ or ‘type 1’ copper. Larger, multidomain proteins that contain type 1 copper in addition to other types of copper centers are not discussed at any length in this article. Blue copper proteins are so named because in solution they are a brilliant blue/azure color when the copper ion is in its Cu(II) oxidation state. The bright blue color comes from a charge transfer (CT) between Cu(II) and the sulfur (thiolate) of a ligating cysteine residue. Because of this intense color, type 1 copper proteins were among the first to be isolated because they could be tracked easily during purification processes. This, together with their unique spectroscopic properties that have no parallel in small‐molecule copper complexes, has made them the subject of intense study over the last 35 years. This article focuses on three main aspects of type 1 copper proteins: (1) their occurrence, distribution, and classification based on analyses of genomic and expressed sequence tag data; (2) their three‐dimensional structures as determined by the well‐established tools of single‐crystal X‐ray diffraction and nuclear magnetic resonance (NMR); and (3) their electronic, spectroscopic, and electron‐transfer properties.
Decarbonylation Catalysis
Authors: Jardine Fred H.
Published: March 2006

Aldehydes or acid chlorides can be decarbonylated to alkanes or alkenes respectively by rhodium complexes. However, α,ω‐alkenals frequently isomerize to cyclic ketones. Palladium complexes decarbonylate aroyl cyanides. Stoichiometric reactions occur with many carbonyl compounds at low temperatures. Above 150°C, several of the reactions are catalytic. Aldehyde tautomers such as allylic alcohols or carbohydrates are also decarbonylated.
Dinuclear Organometallic Cluster Complexes
Authors: Kiss Gabor , McDonough James Eric , Weir John J. , Hoff Carl D.
Published: March 2006

Metal–metal bonding in dinuclear complexes plays a key role in inorganic and organometallic chemistry. It is the basis for development of polymers and clusters derived from this simple unit. Its chemistry now approaches the ‘functional group’ status, typically used in organic chemistry for classes of compounds. However, owing to the array of metals and oxidation states involved, a wide range of structures, reactions, and properties are observed for this important class of compounds. This article introduces the topic of metal–metal bonded complexes and attempts to outline the synthetic strategies used to prepare metal–metal bonded complexes, some of their characteristic properties and reactions, as well as to provide a brief introduction to historical development and emerging directions of this central area of inorganic chemistry.
Electron Transfer Reactions: TheoryBased in part on the article Electron Transfer Reactions: Theory by Roderick D. Cannon which appeared in the
Encyclopedia of Inorganic Chemistry, First Edition
.
Authors: Matyushov Dmitry
Published: March 2006

This article discusses the progress in the field of electron‐transfer theory over the period of about 50 years since early 50s marked by the development of theories of radiationless transitions in molecules in the gas phase and the Marcus theory of electronic transitions between ions in solution. The article starts with the classification of electron‐transfer reactions in terms of reaction mechanisms and the extent of electronic delocalization. This is followed by the outline of the picture of intersecting parabolas due to Marcus, which defines the activation barrier for nonadiabatic electron transfer. The rate of nonadiabatic electron transfer strongly depends on electronic coupling between the donor and acceptor states. The Mulliken‐Hush theory, along with its recent generalizations, provides coupling from spectroscopic observables. The success of electron‐transfer theories has largely been supported by the connection between thermal rates and optical spectroscopy. The activation barrier can be obtained from optical spectra by using the band‐shape analysis discussed next. This is followed by the overview of the inverted region of electron transfer and the consequences of introducing nonparabolic free energy surfaces of electron transfer in polarizable systems. The advent of ultrafast spectroscopic techniques opened up a new avenue in electron‐transfer research related to the effects of polarization dynamics on the reaction rate. Measurements at varying pressure allow one to introduce an additional thermodynamic variable probing the activation barrier. The article concludes with a brief account of magnetic effects in electron transfer.
Electronic Structure of Clusters
Authors: Wales David J.
Published: March 2006

The electronic structure of main group and transition metal clusters is reviewed in the context of electron‐counting rules. A consistent framework for rationalising and extending these rules is presented in terms of Stone's tensor surface harmonic theory. Several applications are described to show how the theory works, along with predictions for cluster rearrangement mechanisms.
Electronic Structure of Main‐Group CompoundsBased in part on the article Electronic Structure of Main Group Compounds by Jeremy K. Burdett which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.
Authors: Frenking Gernot , Lein Matthias
Published: March 2006

Quantum chemical research has made significant progress in the understanding of the electronic structure and the nature of the interatomic interactions yielding chemical bonds in molecules. Ad hoc models of chemical bonding have been complemented or replaced by more sophisticated approaches for analyzing the bonding situation in molecules. The new methods build a well‐defined bridge between the heuristic bonding models using pictorial approaches and the physical mechanism of a chemical bond. Bonding models can be examined with quantum chemical methods, which show that chemical intuition and physics do not exclude each other. The paper describes important methods using charge and energy partitioning approaches, which are helpful and widely used in modern theoretical inorganic chemistry for understanding the electronic structure and bonding situation of main‐group compounds. The application of the methods to representative main‐group compounds is described and the results are critically discussed.
Germanium: Inorganic ChemistryBased in part on the article Germanium: Inorganic Chemistry by Frank Glockling which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.
Authors: Qin Chao , Gao Lei , Wang Enbo
Published: March 2006

In this article, the basic physical and chemical properties, preparation, and applications of germanium and its related compounds are all described in detail. The whole chapter is divided into 12 sections, namely, introduction, analysis, the element, hydrides, boron derivatives, nitrogen compounds, phosphorus and arsenic compounds, oxygen‐bonded compounds, sulfides, selenides and tellurides, halides, metalloid‐ and metal‐bonded compounds, and polyoxometalates of germanium. In each section, some new development in the synthesis and applications of new compounds are included following the fundamental information.

In the introduction section, the discovery, distribution, effect on organisms, basic chemistry, and application of germanium are given briefly.

The analysis section gives a concise description of the main analysis processes.

The preparation, basic physical and chemical properties of metal germanium, and anionic germanium clusters are included in the element section.

In the following sections, different germanium compounds are described mainly according to the different valence germanium exhibits. Their fundamental synthetic routes, discovery and synthesis of new compounds, and the new development in the related fields are emphasized. In particular, contents concerning the construction of framework materials, the synthesis of polyoxometalates, which represent the tendency of development in inorganic chemistry, are presented comprehensively.

More than seventy equations are used to illustrate certain reactions, and detailed information of some important compounds and their synthetic routes are also given in the form of structures, schemes, and figures. Certain data, properties and structure information of germanium, and its compounds are listed in some tables.

Related articles are also given following the main content with the details explained in the text.

This article containing extensive contents about germanium should provide a basic resource for reference of the related studies. An explanation of the development of the recent germanium chemistry may provide insight into the exploration of new fields.
Gold: Inorganic & Coordination Chemistry
Authors: Vittal Jagadese J. , Puddephatt Richard J.
Published: March 2006

Gold compounds are finding new applications in catalysis, medicine, and molecular materials, based on their reactivity and unusual physical and chemical properties. The theoretical basis of the unique properties of gold compounds continues to develop rapidly and provides a constant challenge for synthesis of new types of gold compounds. This chapter gives an overview of these exciting developments while giving an overview of the modern inorganic chemistry of gold.
Hydroboration CatalysisBased in part on the article Hydroboration Catalysis by Kevin Burgess & Wilfred A. van der Donk which appeared in the
Encyclopedia of Inorganic Chemistry, First Edition
.
Authors: Vogels Christopher M. , Westcott Stephen A.
Published: March 2006

Among the most significant advances in organic synthesis over the past few decades are those associated with the development of transition metal complexes for their use as catalysts in organic reactions. The discovery that transition metals can also be used to catalyze the addition of BH bonds to unsaturated substrates has provided the synthetic chemist with another valuable tool. This review examines recent advances in the field of catalyzed hydroborations and their applications in organic synthesis.
Indium: Organometallic Chemistry
Authors: Kumar Banger Kulbinder
Published: March 2006

An overview of the chemistry of organoindium compounds containing at least one InC bond over the last ten years is reported in detail. In particular, the synthesis, characterization, properties of homoleptic and heteroleptic organoindium derivatives, organoindium(0), (I), and (II) compounds, and in addition anionic compounds are also reported. Furthermore, the use of organoindium compounds for thin film, nanotechnology, and organic synthesis is discussed.
Ionic Conductors
Authors: Greenblatt Martha
Published: March 2006

The fundamental structural and physical properties of ionic conductors in the solid state are briefly discussed. Recent developments in ionically conducting solids are reviewed. Materials discussed include: crystalline cation conductors with Na+, Li+, and H+ion motion; crystalline anion conductors, primarily with the fluorite‐type structure and with oxide‐ and fluoride ion mobilities; mixed ionic/electronic conductors; amorphous glass electrolytes and polymer solid electrolytes. Applications of some of these solid‐state ionic conductors in electrochemical devices such as sodium and lithium rechargeable batteries, sensors, fuel cells and electrochromic smart windows are presented.
Iridium: Organometallic Chemistry
Authors: Merola Joseph S.
Published: March 2006

The organometallic chemistry of iridium is reviewed. The general classes of complexes of iridium containing iridium to carbon bonds are surveyed. The preparations of iridium olefin complexes, iridium arene complexes, iridium carbonyl complexes, iridium cyclopentadienyl complexes, and other types of complexes are covered along with the use of those classes of compounds in preparing other organometallic iridium species. In addition, three areas in which organoiridium compounds find particular application are specifically reviewed: catalysis utilizing organometallic compounds of iridium, carbon–hydrogen (CH) bond activation chemistry with iridium, and hydrodesulfurization (HDS) studies using iridium. References to other reviews, to monographs, and to the primary literature are provided in all cases.
Iron: Heme Proteins & Dioxygen Transport & StorageBased in part on the article Iron: Heme Proteins & Dioxygen Transport by Harold M. Goff which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.
Authors: Hayashi Takashi
Published: March 2006

Most organisms require dioxygen (O2) to survive; however, simple O2diffusion in blood does not supply a sufficient amount of oxygen for respiration. Thus, in all mammals, O2is carried and stored by O2‐binding heme proteins, myoglobin, and hemoglobin. Myoglobin is a single‐chain globular protein with heme as a prosthetic group, while hemoglobin consists of four heme‐containing subunits. O2binds to ferrous pentacoordinated heme‐iron and is stabilized by distal and proximal amino acid residues in the heme pocket. The O2pathway in the protein matrix and the binding mechanisms are discussed in detail by O2‐binding kinetic data for a series of myoglobin and hemoglobin mutants. Particularly, several residues, B10, E7, E10, E11, F7, and F8, mainly regulate the O2binding in the vertebrate heme proteins. In contrast, invertebrate and plant hemoglobins with unusually high O2affinities have been found in nature. InAscarishemoglobin, O2dissociation is very slow, whereas leghemoglobin shows a large O2association rate constant. In the case of trematode hemoglobin fromParamphistonum epiclitum, both kinetic parameters are improved. Artificial molecular design to modify O2affinity is another way to understand the O2binding mechanisms of the heme proteins. The strategy of heme protein modification can be divided into at least two approaches: One is a point mutation at distal or proximal amino acid residues, and the other is reconstitution by replacement of the native heme with an artificial heme. The physiological function of vertebrate hemoglobins is O2transport from the lungs or gills to the tissues; thus, they are required to exhibit cooperative interactions in binding O2to heme‐iron in the protein matrix. Although it is well known that a Hill coefficient of approximately 3.0 has been observed for tetrameric human hemoglobin, the mechanism of allosteric interaction is still discussed based on theoretical and experimental data. At present, an a two‐state (MWC) model proposed by Monod, Wyman, and Changeux for cooperative ligand binding is preferred to a sequential model. In addition, a study on the allosteric effectors for hemoglobins seems to be attractive from physiological aspects. The conventional effectors such as organic polyphosphate for human hemoglobin reduce the O2affinity of the T‐state, while it has been found that bezafibrate (BZF) or inositol hexaphosphate (IHP) can regulate O2binding not only for the T‐state but also for the R‐state. Finally, the interaction of NO with the heme proteins and modification of myoglobin for conversion into a new oxidase are briefly described.
Iron: Heme Proteins & Electron Transport
Authors: Durham Bill , Millett Francis S.
Published: March 2006

This chapter discusses the structure and function of cytochromes, which are a class of iron‐containing heme proteins primarily involved in biological electron‐transfer reactions. Subcellular organelles called mitochondria are responsible for carrying out oxidative phosphorylation, the major energy‐transduction process in eukaryotic cells. Enormous progress has been made in our understanding of the molecular mechanism of the mitochondrial electron‐transport chain over the past decade. X‐ray crystal structures have been determined for three of the four electron‐transfer complexes: succinate–ubiquinone reductase, cytochromebc1, and cytochromecoxidase (CcO). Cytochromec(Cc) is a small heme protein with a molecular weight of 12 500 Da that transports electrons from cytochromebc1to CcO. It is a very positively charged protein, and is known to bind to both cytochromebc1and CcO by means of electrostatic interactions. Extensive chemical modification studies have demonstrated that the binding domain on Cc for both proteins involves lysines immediately surrounding the heme crevice, and Cc functions as a mobile shuttle during electron transport. The reactions of Cc with its redox partners are too fast to resolve by conventional techniques such as stopped‐flow spectroscopy. A new method to study biological electron transfer has been introduced that utilizes a photoactive tris(bipyridine)ruthenium complex, Ru(II), which is covalently attached to a protein such as Cc. Photoexcitation of Ru(II) to the metal‐to‐ligand charge‐transfer state, Ru(II*), a strong reductant, leads to rapid electron transfer to the ferric heme group in Cc. Subsequent electron transfer from photoreduced heme c to redox center(s) in another protein can be measured on a timescale as short as 50 ns. This technique has been used to measure intracomplex electron transfer between Cc and its physiological partners, CcO, cytochromebc1, cytochromecperoxidase (CcP), and cytochromeb5. The ruthenium technique was used to characterize sequential electron transfer in cytochromebc1from ubiquinol to the Rieske iron–sulfur protein (2Fe2S), cytochromec1, and finally to Cc. Cytochrome oxidase contains four redox centers, CuA, heme a, heme a3, and CuB. A ruthenium Cc derivative was used to demonstrate that the initial site of electron entry into CcO is CuA, followed by electron transfer to heme a, and then heme a3.
Iron: Inorganic & Coordination ChemistryBased in part on the article Iron: Inorganic & Coordination Chemistry by Pelham N. Hawker & Martyn V. Twigg which appeared in the
Encyclopedia of Inorganic Chemistry, First Edition
.
Authors: Burgess John , Twigg Martyn V.
Published: March 2006

Iron, the most abundant transition element in the biosphere, is essential in higher forms of life and its compounds have numerous industrial applications. The element has catalytic properties. Several simple iron compounds are industrially important, for example, large amounts of iron oxides are produced for pigment and magnetic recording media applications. Oxidation states ranging from −2 to +6 are known, the most familiar are +2 (ferrous iron) and +3 (ferric iron). Most common complexes are octahedral, although examples of higher (e.g. seven coordinate) and lower (e.g. tetrahedral and square planar) geometries are well known, as are a variety of mixed oxidation state compounds. Depending on ligands involved high‐ and low‐spin complexes can be formed, and temperature‐dependent spin‐state crossover complexes are well documented. The thermodynamics and kinetics of reactions of low‐spin iron(II) complexes with ligands such as 1,4‐diimines and CN
−
have been extensively studied. While low‐spin iron(II) is present in biological systems such as oxygenated heme centered oxygen carriers and thiolate clusters, iron(III) is more common. Thiolate‐containing iron clusters form readily, and here mixed oxidation states are a prominent feature that is exploited in some important electron transfer proteins. Microorganism iron uptake is facilitated by tris‐catecholate and tris‐hydroxamate ligands like enterobactin that have an extraordinarily high affinity for iron(III) that results in a dramatic enhancement of the 3+ relative to the 2+ state in terms of redox potential.
Iron: Organometallic ChemistryBased in part on the article Iron: Organometallic Chemistry by James R. Green which appeared in the
Encyclopedia of Inorganic Chemistry, First Edition
.
Authors: Paley Robert S.
Published: March 2006

Studies involving the preparation, reactivity, and properties of the organometallic complexes of iron (compounds possessing a FeC bond) have played a central role in the growth of organometallics as a major subdiscipline with chemistry. From the discovery of ferrocene in the 1950s to the present day, interest and research activity remain high. This entry provides a survey of this large and diverse area of organometallic chemistry, and is arranged by increasing hapticity of the organic ligand of interest that is bound to iron. Included are discussions of the chemistry of iron σ‐alkyl, acyl, alkynyl, and vinyl complexes, iron carbenes, η1‐ and η3‐allyl iron complexes, η2‐alkene and η4‐diene iron complexes, trimethylenemethane and cyclobutadiene complexes of iron, cationic iron pentadienyl, cyclohexadienyl, and arene complexes, and ferrocenes and heteroferrocenes.
Iron Porphyrin Chemistry
Authors: Walker F. Ann , Simonis Ursula
Published: March 2006

This article reviews most aspects of the chemistry of iron porphyrins, from Fe(0) to Fe(V), including occurrence and roles of natural iron porphyrins (hemes) and their synthetic analogs, structures and electron configurations of iron porphyrins of all oxidation and spin states, π electron configuration of the porphyrin ring, synthesis of metal‐free porphyrins and other related macrocycles, insertion of iron into free‐base porphyrins and related macrocycles, the properties, reactions, uses and biological relevance of iron(0), ‐(I), ‐(II) porphyrins (the latter withS = 0, 1, and 2 spin state possibilities), of iron(II) porphyrin π‐cation radicals, of iron(III) porphyrins (withS = 1/2, 3/2, and 5/2 spin state possibilities), of iron(III) porphyrin and corrole π‐cation radicals, of iron(IV) porphyrins (including five‐ and six‐coordinate ferryl (FeO)2+, iron(IV) phenyl, carbene and hydrazine complexes, and the bis‐methoxide complex) and a comparison of iron(IV) porphyrins to iron(III) porphyrin π‐cation radicals, of iron(IV) porphyrin π‐cation radicals, and of the possible existence of iron(V) porphyrins. Included in the Fe(II) part are sections on addition of ligands to four‐coordinate iron(II) porphyrins, including equilibrium binding constants, photodissociation of ligands from PFeL2complexes, binding of small molecules (O2, CO, NO, HNO) to 5‐coordinate iron(II) porphyrins and design of porphyrin ligands that will mimic the active sites of heme proteins such as myoglobin and hemoglobin, the cytochromes P450 and nitric oxide synthases, and the nitrophorins and guanylyl cyclases. Included in the iron(III) part are sections on both 5‐ and 6‐coordinate high‐spin complexes and their similarities and differences, bridged or through‐space magnetically coupled complexes of high‐spin iron(III) porphyrins with other metal complexes as possible models for cytochrome oxidase and the assimilatory sulfite reductases, coupled oxidation of hemes by hydrogen peroxide or its equivalent, and the relationship of this reactivity to the reactions of heme oxygenase, iron(III) porphyrins as reduction catalysts, and photochemistry of iron(III) porphyrins, possible electron configurations of low‐spin iron(III) porphyrins, the phenomenon and possible electronic consequences of ruffling of the porphinato core in iron(III) porphyrins, the preferred orientation of planar axial ligands bound to low‐spin iron(III) porphyrins, NO complexes of iron(III) porphyrins, reduction potentials, equilibrium constants and rates of axial‐ligand addition and exchange, kinetics of axial‐ligand rotation and porphyrin ring inversion, kinetics of reduction and autoreduction of iron(III) porphyrins, electron self‐exchange between low‐spin iron(III) and iron(II) porphyrins, synthetic ferriheme proteins, and synthesis of five‐coordinate low‐spin iron(III) porphyrins having σ‐alkyl or σ‐aryl groups as axial ligands. The iron(IV) and iron(IV) cation radical sections discuss the high‐valent states of cytochromes P450 and related enzymes.
Iron Proteins with Dinuclear Active Sites
Authors: Kurtz Donald M.
Published: March 2006

Iron proteins with dinuclear active sites include those containing stable nonheme, non‐sulfur diiron sites. Though still dwarfed by the numbers of heme or iron‐sulfur proteins, the list of proteins known to contain nonheme, non‐sulfur diiron sites has steadily expanded over the past thirty years. These proteins share the following active site properties: (1) two iron atoms separated by 4 Å or less; (2) stable high spin ferrous and ferric oxidation states; (3) terminal histidinyl imidazole, carboxylate and solvent ligands; (4) at least one ligand that bridges the two irons; and (5) magnetic superexchange coupling of the unpaired spins on the two irons mediated by the bridging ligand atom(s). With one possible exception, the bridging ligands are either known or are strongly suspected to include one or two carboxylates. Two distinct subclasses, the purple acid phosphatases and the flavo‐diiron enzymes, seem to have no structural or functional relationships to each other or to any of the other diiron enzymes. The oxygen‐carrying protein, hemerythrin, for many years served as the prototype for nonheme, non‐sulfur diiron proteins. However, its structure and function have turned out to be distinct from those of the O2‐activating enzymes, which now form the largest subclass of these diiron‐containing proteins, with at least seven distinct types known; the most numerous of these are the alkane (including methane) monooxygenases and fatty acyl desaturases. Evidence for catalytically competent high‐valent diiron intermediates resulting from reaction of the diferrous sites with dioxygen have been obtained for at least two of the O2‐activating enzymes. Among the most intriguing and mysterious of the O2‐activating enzymes are the membrane‐bound ‘eight‐His’ diiron desaturases and monooxygenases.
Iron Proteins with Mononuclear Active Sites
Authors: Emerson Joseph P. , Mehn Mark P. , Que Lawrence
Published: March 2006

Metalloenzymes containing a mononuclear nonheme iron center are often involved in dioxygen metabolism. We have divided this superfamily of enzymes into seven subcategories: iron superoxide dismutase and superoxide reductase, lipoxygenase, catechol dioxygenases, α‐keto acid‐dependent enzymes, isopenicillinNsynthase, pterin‐dependent hydroxylases, and Rieske dioxygenases. The degree of catalytic versatility and coordination flexibility encompassed by these enzymes is unsurpassed by any other known metalloenzyme superfamily. Herein we discuss the present state of knowledge regarding their active site structures and the critical role the metal center plays in their respective catalytic mechanisms.
Iron Proteins for Storage & Transport & Their Synthetic Analogs
Authors: Lewin Allison , Le Brun Nick E. , Moore Geoffrey R.
Published: March 2006

This article reviews proteins involved in iron metabolism. Brief descriptions are given of the biological contexts for the proteins discussed but the main emphasis is on chemical and structural aspects of them.

Iron is essential to almost all forms of life, but its low bioavailability and toxicity mean that they require sophisticated mechanisms to transport it. Mammals acquire heme and nonheme iron via proteins in the gut wall, and transport it around the body using serum transferrin, for ferric iron, and hemopexin, for heme. Microbes have an active iron uptake mechanism involving small iron chelators called siderophores, for example, ferrichrome inEscherichia coli. Ferrichrome enters the cell via FhuA, a β‐barrel in the outer membrane. The periplasmic protein FhuD then transfers it to the FhuBC complex in the cytoplasmic membrane. FhuB forms a channel through which the ferric siderophore passes using energy supplied by FhuC. Once inside the cytoplasm the iron is removed from the ligand, possibly via reduction by FhuF. Some pathogenic bacteria have a similar system for heme uptake, secreting hemophores such as HasA, which can remove heme from hemoglobin. Other pathogens have outer membrane receptors that remove ferric iron from transferrin and transport it into the periplasm, where it is bound by ferric binding proteins that closely resemble a single lobe of transferrin.

Following its acquisition, iron needs to be stored safely. The most widespread form of iron storage is the ferritin superfamily, which includes ferritin, bacterioferritin, and Dps. Ferritin is found in bacteria, plants, and animals and is a large shell made up of 24 subunits within which up to 4,500 ferric ions can be stored as a ferrihydrite mineral core. Bacterioferritin is found in bacteria and is closely related to ferritin, but contains up to 12 heme groups bound between pairs of subunits, which may play a role in iron release or electron storage. The bacterial protein Dps is smaller than ferritin, with 12 subunits forming the protein shell, and can hold up to 500 ferric ions. All of these proteins contain dinuclear iron sites that catalyze the oxidation of ferrous iron. An alternative form of iron storage is frataxin, found in mitochondria. Although not related to ferritin, this protein has the ability to form large aggregates that can store up to 50 ferric ions per monomer in a mineral core resembling those of ferritins.
Iron–Sulfur Models of Protein Active SitesBased in part on the article Iron–Sulfur Models of Protein Active Sites by Akira Nakamura & Norikazu Ueyama which appeared in the
Encyclopedia of Inorganic Chemistry, First Edition
.
Authors: Collins David J. , Zhou Hong‐Cai
Published: March 2006

In pervasiveness of occurrence and multiplicity of function, iron–sulfur clusters rival biological prosthetic groups such as hemes and flavins. The development of iron–sulfur cluster chemistry paralleled the founding and maturation of the field of bioinorganic chemistry. Starting from the first spontaneous self‐assembly of the [Fe
4
S
4
(SR)
4
]
2−
cluster in 1972, and the identification of the protein‐bound Fe
4
S
4
in the same year, the study of iron–sulfur models of protein active sites has evolved into a unique field in which synthetic inorganic chemistry now resembles the total synthesis of natural products in organic chemistry. Some of the models had been built before the crystal structure of the protein was determined. Almost all the models successfully replicated the topology and the electronic properties of the protein active sites. In this article, the models will be discussed in the order of their complexity, from single iron rubredoxin models to Fe
2
S
2
, Fe
3
S
4
, Fe
4
S
4
, and Fe
8
S
7
model compounds. In each section, the chemical synthesis of the model compound will be discussed first, followed by structure comparison and contrast, electrochemical properties, and biochemical activities. Since the major function of iron–sulfur proteins is electron transfer, and the oxidation state of the iron atom determines its reactivity, electrochemical and Mössbauer data will be tabulated in detail. Some of the recent developments in site‐differentiated, peptide, and all‐ferrous Fe
4
S
4
clusters will be reviewed. Recent studies in modeling the topology of the P‐cluster of nitrogenase will also be covered. The challenge posed by iron–sulfur proteins has inspired new iron–sulfur cluster chemistry. No other metal–nonmetal combination has produced more structural types than the iron–sulfur system; the majority of them have yet to be found in biological systems. However, the modeling of the P‐cluster and the FeMoco center of nitrogenase have posed a daunting challenge to the analog chemists.