an intRoduCtion and guide
seCond edition
BIOINORGANIC CHEMISTRY: INORGANIC ELEMENTS IN THE CHEMISTRY OF LIFE
Wolfgang KaiMbRigitte sCHWedeRsKiaxel Klein
inoRganiC CHeMistRy a Wiley textbooK seRies
Bioinorganic Chemistry: Inorganic Elements inthe Chemistry of Life
Inorganic Chemistry
A Wiley Series of Advanced TextbooksISSN: 1939-5175
Editorial Board
David Atwood, University of Kentucky, USABob Crabtree, Yale University, USAGerd Meyer, University of Cologne, GermanyDerek Woollins, University of St. Andrews, UK
Previously Published Books in this Series
Structural Methods in Molecular Inorganic ChemistryDavid W. H. Rankin, Norbert W. Mitzel & Carole A. Morrison; ISBN: 978-0-470-97278-6
Introduction to Coordination ChemistryGeoffrey Alan Lawrance; ISBN: 978-0-470-51931-8
Chirality in Transition Metal ChemistryHani Amouri & Michel Gruselle; ISBN: 978-0-470-06054-4
Bioinorganic Vanadium ChemistryDieter Rehder; ISBN: 978-0-470-06516-7
Inorganic Structural Chemistry 2nd EditionUlrich Muller; ISBN: 978-0-470-01865-1
Lanthanide and Actinide ChemistrySimon Cotton; ISBN: 978-0-470-01006-8
Mass Spectrometry of Inorganic and Organometallic Compounds: Tools-Techniques-TipsWilliam Henderson & J. Scott McIndoe; ISBN: 978-0-470-85016-9
Main Group Chemistry, Second EditionA.G. Massey; ISBN: 978-0-471-19039-5
Synthesis of Organometallic Compounds: A Practical GuideSanshiro Komiya; ISBN: 978-0-471-97195-5
Chemical Bonds: A DialogJeremy Burdett; ISBN: 978-0-471-97130-6
The Molecular Chemistry of the Transition Elements: An Introductory CourseFrancois Mathey & Alain Sevin; ISBN: 978-0-471-95687-7
Stereochemistry of Coordination CompoundsAlexander von Zelewsky; ISBN: 978-0-471-95599-3
For more information on this series see: www.wiley.com/go/inorganic
Bioinorganic Chemistry:Inorganic Elements in theChemistry of LifeAn Introduction and Guide
Second Edition
Written and Translated by
Wolfgang KaimUniversity of Stuttgart, Institute of Inorganic Chemistry,Stuttgart, Germany
Brigitte SchwederskiUniversity of Stuttgart, Institute of Inorganic Chemistry,Stuttgart, Germany
Axel KleinUniversity of Cologne, Institute of Inorganic Chemistry,Cologne, Germany
Originally published in the German language by Vieweg+Teubner, 65189 Wiesbaden, Germany, as “Wolfgang Kaim and Brigitte Schwederski:Bioanorganische Chemie. 4. Auflage (4th Edition)”.© Vieweg+Teubner/Springer Fachmedien Wiesbaden GmbH 2005.Springer Fachmedien is part of Springer Science+Business Media
This edition first published 2013© 2013 John Wiley & Sons, Ltd
First English language edition published 1994
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Library of Congress Cataloging-in-Publication Data
Kaim, Wolfgang, 1951–[Bioanorganische Chemie. English]Bioinorganic chemistry : inorganic elements in the chemistry of life : an introduction and guide /
written and translated by Wolfgang Kaim, Brigitte Schwederski, Axel Klein. – Second edition.pages cm
Translation of: Bioanorganische Chemie.Includes bibliographical references and index.
ISBN 978-0-470-97524-4 (cloth) – ISBN 978-0-470-97523-7 (paper) 1. Bioinorganic chemistry.I. Schwederski, Brigitte, 1959– II. Klein, Axel, 1964– III. Title.
QP531.K3513 2013572′.51–dc23 2013011894
A catalogue record for this book is available from the British Library.
HB ISBN: 9780470975244PB ISBN: 9780470975237
Typeset in 10/12pt Times by Aptara Inc., New Delhi, India
1 2013
Contents
Preface to the Second Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Preface to the First Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
1 Historical Background, Current Relevance and Perspectives . . . . . . . . . . . . . . . 1References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
2 Some General Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72.1 Occurrence and Availability of Inorganic Elements in Organisms . . . . . . . . . . . 7
Insertion: The Chelate Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14Insertion: “Hard” and “Soft” Coordination Centers . . . . . . . . . . . . . . . . . . 14
2.2 Biological Functions of Inorganic Elements . . . . . . . . . . . . . . . . . . . . . 142.3 Biological Ligands for Metal Ions . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.3.1 Coordination by Proteins-Comments on Enzymatic Catalysis . . . . . . . . 17Insertion: The “Entatic State” in Enzymatic Catalysis . . . . . . . . . . . . . . . . 202.3.2 Tetrapyrrole Ligands and Other Macrocycles . . . . . . . . . . . . . . . . 22Insertion: Electron Spin States in Transition Metal Ions . . . . . . . . . . . . . . . . 282.3.3 Nucleobases, Nucleotides and Nucleic Acids (RNA, DNA) as Ligands . . . . 31Insertion: Secondary Bonding . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.4 Relevance of Model Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 34References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3 Cobalamins, Including Vitamin and Coenzyme B12 . . . . . . . . . . . . . . . . . . . 373.1 History and Structural Characterization . . . . . . . . . . . . . . . . . . . . . . . 37
Insertion: Bioorganometallics I . . . . . . . . . . . . . . . . . . . . . . . . . . . 383.2 General Reactions of Alkylcobalamins . . . . . . . . . . . . . . . . . . . . . . . 41
3.2.1 One-electron Reduction and Oxidation . . . . . . . . . . . . . . . . . . . 413.2.2 Co–C Bond Cleavage . . . . . . . . . . . . . . . . . . . . . . . . . . . 42Insertion: Electron Paramagnetic Resonance I . . . . . . . . . . . . . . . . . . . . 43
3.3 Enzyme Functions of Cobalamins . . . . . . . . . . . . . . . . . . . . . . . . . . 453.3.1 Adenosylcobalamin (AdoCbl)-dependent Isomerases . . . . . . . . . . . . 45Insertion: Organic Redox Coenzymes . . . . . . . . . . . . . . . . . . . . . . . . 483.3.2 Alkylation Reactions of Methylcobalamin (MeCbl)-dependent Alkyl
Transferases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513.4 Model Systems and the Enzymatic Activation of the Co–C Bond . . . . . . . . . . . 52
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
4 Metals at the Center of Photosynthesis: Magnesium and Manganese . . . . . . . . . . . 574.1 Volume and Efficiency of Photosynthesis . . . . . . . . . . . . . . . . . . . . . . 574.2 Primary Processes in Photosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . 59
vi Contents
4.2.1 Light Absorption (Energy Acquisition) . . . . . . . . . . . . . . . . . . . 594.2.2 Exciton Transport (Directed Energy Transfer) . . . . . . . . . . . . . . . . 594.2.3 Charge Separation and Electron Transport . . . . . . . . . . . . . . . . . . 62Insertion: Structure Determination by X-ray Diffraction . . . . . . . . . . . . . . . 65
4.3 Manganese-catalyzed Oxidation of Water to O2 . . . . . . . . . . . . . . . . . . . 67Insertion: Spin–Spin Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . 73References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
5 The Dioxygen Molecule, O2: Uptake, Transport and Storage of an InorganicNatural Product . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775.1 Molecular and Chemical Properties of Dioxygen, O2 . . . . . . . . . . . . . . . . . 775.2 Oxygen Transport and Storage through Hemoglobin and Myoglobin . . . . . . . . . 825.3 Alternative Oxygen Transport in Some Lower Animals: Hemerythrin and Hemocyanin 92
5.3.1 Magnetism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 925.3.2 Light Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 935.3.3 Vibrational Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . 93Insertion: Resonance Raman Spectroscopy . . . . . . . . . . . . . . . . . . . . . . 935.3.4 Mossbauer Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . 94Insertion: Mossbauer Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . 945.3.5 Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
5.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
6 Catalysis through Hemoproteins: Electron Transfer, Oxygen Activation and Metabolismof Inorganic Intermediates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 996.1 Cytochromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1016.2 Cytochrome P-450: Oxygen Transfer from O2 to Nonactivated Substrates . . . . . . . 1036.3 Peroxidases: Detoxification and Utilization of Doubly Reduced Dioxygen . . . . . . . 1086.4 Controlling the Reaction Mechanism of the Oxyheme Group: Generation
and Function of Organic Free Radicals . . . . . . . . . . . . . . . . . . . . . . . 1106.5 Hemoproteins in the Catalytic Transformation of Partially Reduced Nitrogen
and Sulfur Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112Insertion: Gasotransmitters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
7 Iron–Sulfur and Other Non-heme Iron Proteins . . . . . . . . . . . . . . . . . . . . . 1177.1 Biological Relevance of the Element Combination Iron–Sulfur . . . . . . . . . . . . 117
Insertion: Extremophiles and Bioinorganic Chemistry . . . . . . . . . . . . . . . . 1187.2 Rubredoxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1227.3 [2Fe-2S] Centers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1227.4 Polynuclear Fe/S Clusters: Relevance of the Protein Environment and Catalytic Activity 1237.5 Model Systems for Fe/S Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . 1287.6 Iron-containing Enzymes without Porphyrin or Sulfide Ligands . . . . . . . . . . . . 130
7.6.1 Iron-containing Ribonucleotide Reductase . . . . . . . . . . . . . . . . . 1307.6.2 Soluble Methane Monooxygenase . . . . . . . . . . . . . . . . . . . . . 1327.6.3 Purple Acid Phosphatases (Fe/Fe and Fe/Zn) . . . . . . . . . . . . . . . . 1337.6.4 Mononuclear Non-heme Iron Enzymes . . . . . . . . . . . . . . . . . . . 133References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Contents vii
8 Uptake, Transport and Storage of an Essential Element, as Exemplified by Iron . . . . . 139Insertion: Metallome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
8.1 The Problem of Iron Mobilization: Oxidation States, Solubility and Medical Relevance 1408.2 Siderophores: Iron Uptake by Microorganisms . . . . . . . . . . . . . . . . . . . . 141
Insertion: Optical Isomerism in Octahedral Complexes . . . . . . . . . . . . . . . . 1448.3 Phytosiderophores: Iron Uptake by Plants . . . . . . . . . . . . . . . . . . . . . . 1498.4 Transport and Storage of Iron . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
8.4.1 Transferrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1528.4.2 Ferritin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1558.4.3 Hemosiderin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
9 Nickel-containing Enzymes: The Remarkable Career of a Long-overlooked Biometal . . 1639.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1639.2 Urease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1649.3 Hydrogenases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1669.4 CO Dehydrogenase = CO Oxidoreductase = Acetyl-CoA Synthase . . . . . . . . . . 1699.5 Methyl-coenzyme M Reductase (Including the F430 Cofactor) . . . . . . . . . . . . 172
Insertion: Natural and Artificial (Industrial) C1 Chemistry . . . . . . . . . . . . . . 174Insertion: Bioorganometallics II: The Organometallic Chemistry of Cobalt and Nickel . 176
9.6 Superoxide Dismutase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1779.7 Model Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
10 Copper-containing Proteins: An Alternative to Biological Iron . . . . . . . . . . . . . . 18310.1 Type 1: “Blue” Copper Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
Insertion: Electron Paramagnetic Resonance II . . . . . . . . . . . . . . . . . . . . 18710.2 Type 2 and Type 3 Copper Centers in O2-activating Proteins: Oxygen Transport
and Oxygenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19110.3 Copper Proteins as Oxidases/Reductases . . . . . . . . . . . . . . . . . . . . . . . 19510.4 Cytochrome c Oxidase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20010.5 Cu,Zn- and Other Superoxide Dismutases: Substrate-specific Antioxidants . . . . . . 203
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
11 Biological Functions of the “Early” Transition Metals: Molybdenum, Tungsten,Vanadium and Chromium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21111.1 Oxygen Transfer through Tungsten- and Molybdenum-containing Enzymes . . . . . . 211
11.1.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21111.1.2 Oxotransferase Enzymes Containing the Molybdopterin or
Tungstopterin Cofactor . . . . . . . . . . . . . . . . . . . . . . . . . . . 213Insertion: “Oxidation” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
11.2 Metalloenzymes in the Biological Nitrogen Cycle: Molybdenum-dependentNitrogen Fixation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
11.3 Alternative Nitrogenases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22611.4 Biological Vanadium Outside of Nitrogenases . . . . . . . . . . . . . . . . . . . . 22911.5 Chromium(III) in the Metabolism? . . . . . . . . . . . . . . . . . . . . . . . . . 231
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
viii Contents
12 Zinc: Structural and Gene-regulatory Functions and the Enzymatic Catalysis ofHydrolysis and Condensation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . 23512.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23512.2 Carboanhydrase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23812.3 Carboxypeptidase A and Other Hydrolases . . . . . . . . . . . . . . . . . . . . . 24312.4 Catalysis of Condensation Reactions by Zinc-containing Enzymes . . . . . . . . . . 24812.5 Alcohol Dehydrogenase and Related Enzymes . . . . . . . . . . . . . . . . . . . . 24912.6 The “Zinc Finger” and Other Gene-regulatory Zinc Proteins . . . . . . . . . . . . . 25112.7 Insulin, hGH, Metallothionein and DNA Repair Systems as Zinc-containing Proteins . 253
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
13 Unequally Distributed Electrolytes: Function and Transport of Alkali and Alkaline EarthMetal Cations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25713.1 Characterization and Biological Roles of K+, Na+, Ca2+ and Mg2+ . . . . . . . . . . 257
Insertion: Heteroatom Nuclear Magnetic Resonance . . . . . . . . . . . . . . . . . 26213.2 Complexes of Alkali and Alkaline Earth Metal Ions with Macrocycles . . . . . . . . 26413.3 Ion Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26713.4 Ion Pumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
14 Catalysis and Regulation of Bioenergetic Processes by the Alkaline Earth Metal IonsMg2+ and Ca2+ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27714.1 Magnesium: Catalysis of Phosphate Transfer by Divalent Ions . . . . . . . . . . . . 27714.2 The Ubiquitous Regulatory Role of Ca2+ . . . . . . . . . . . . . . . . . . . . . . 283
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
15 Biomineralization: The Controlled Assembly of “Advanced Materials” in Biology . . . . 29515.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29515.2 Nucleation and Crystal Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
Insertion: Dimensions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30015.3 Examples of Biominerals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
15.3.1 Calcium Phosphate in the Bones of Vertebrates and the Global P Cycle . . . . 301Insertion: The Global P Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30515.3.2 Calcium Carbonate and the Global Inorganic C Cycle . . . . . . . . . . . . 306Insertion: The Global C Cycle and the Marine Inorganic C Cycle . . . . . . . . . . . 30715.3.3 Amorphous Silica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30815.3.4 Iron Biominerals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30915.3.5 Strontium and Barium Sulfates . . . . . . . . . . . . . . . . . . . . . . . 310
15.4 Biomimetic Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
16 Biological Functions of the Nonmetallic Inorganic Elements . . . . . . . . . . . . . . . 31516.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31516.2 Boron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31516.3 Silicon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Contents ix
16.4 Arsenic and Trivalent Phosphorus . . . . . . . . . . . . . . . . . . . . . . . . . . 31616.5 Bromine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31716.6 Fluorine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31716.7 Iodine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31816.8 Selenium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
17 The Bioinorganic Chemistry of the Quintessentially Toxic Metals . . . . . . . . . . . . 32717.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32717.2 Lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32917.3 Cadmium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33217.4 Thallium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33417.5 Mercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33517.6 Aluminum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34017.7 Beryllium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34217.8 Chromium and Tungsten . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34317.9 Toxicity of Nanomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
18 Biochemical Behavior of Radionuclides and Medical Imaging Using InorganicCompounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34918.1 Radiation Risks and Medical Benefits from Natural and Synthetic Radionuclides . . . 349
18.1.1 The Biochemical Impact of Ionizing Radiation from Radioactive Isotopes . . 34918.1.2 Natural and Synthetic Radioisotopes . . . . . . . . . . . . . . . . . . . . 35018.1.3 Bioinorganic Chemistry of Radionuclides . . . . . . . . . . . . . . . . . . 351Insertion: Fukushima Daiichi, Chernobyl, Hiroshima and Nuclear Weapons Testing . . 35318.1.4 Radiopharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . 35618.1.5 Technetium: A “Synthetic Bioinorganic Element” . . . . . . . . . . . . . . 35918.1.6 Radiotracers for the Investigation of the Metallome . . . . . . . . . . . . . 363
18.2 Medical Imaging Based on Nonradioactive Inorganic Compounds . . . . . . . . . . 36318.2.1 Magnetic Resonance Imaging . . . . . . . . . . . . . . . . . . . . . . . 36318.2.2 X-ray Contrast Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . 364Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
19 Chemotherapy Involving Nonessential Elements . . . . . . . . . . . . . . . . . . . . . 36919.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36919.2 Platinum Complexes in Cancer Therapy . . . . . . . . . . . . . . . . . . . . . . . 369
19.2.1 Discovery, Application and Structure–Effect Relationships . . . . . . . . . . 36919.2.2 Cisplatin: Mode of Action . . . . . . . . . . . . . . . . . . . . . . . . . 372
19.3 New Anticancer Drugs Based on Transition Metal Complexes . . . . . . . . . . . . 37819.3.1 Overview and Aims for Drug Development . . . . . . . . . . . . . . . . . 37819.3.2 Nonplatinum Anticancer Drugs . . . . . . . . . . . . . . . . . . . . . . . 379
19.4 Further Inorganic Compounds in (Noncancer) Chemotherapy . . . . . . . . . . . . . 38319.4.1 Gold-containing Drugs Used in the Therapy of Rheumatoid Arthritis . . . . . 38319.4.2 Lithium in Psychopharmacologic Drugs . . . . . . . . . . . . . . . . . . . 38419.4.3 Bismuth Compounds against Ulcers . . . . . . . . . . . . . . . . . . . . . 385
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19.4.4 Vanadium-containing Insulin Mimetics and V-containing Anti-HIV Drugs . . 38619.4.5 Sodium Nitroprusside . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
19.5 Bioorganometallic Chemistry of Nonessential Elements . . . . . . . . . . . . . . . 387Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
Preface to the Second Edition
The predictably enormous growth of bioinorganic chemistry has made a second edition ofthis text both necessary and difficult. While there are several extensive and often specializedreviews, major texts and handbooks on this subject, our experience in teaching it has sug-gested the provision of an updated overview of the classical, novel and applied sections of thefield, which has not only become one of the major subdisciplines of inorganic chemistry but,due to its highly interdisciplinary nature, has also pervaded other areas of the life sciences.
The second edition contains updates of many kinds. New structure information on someintricate metalloproteins, such as water oxidase and the molybdopterin-based enzymes,has been included, replacing the earlier speculative models. Emerging developments arereferred to at various points, covering such topics as bioorganometallic chemistry, nucleicacid ligation, gasotransmitters, nanoparticles and global cycles of the elements C, P and N.The vastly increased focus on the medical applications of inorganic compounds has requiredthat more space be devoted to this particular aspect. Nonetheless, we have tried to keep theamount of material at a constant, manageable level suitable for an introductory overview,rather than the typical condensed fragments presented in general textbooks of inorganicchemistry or biochemistry. To achieve this, we have tried to concentrate on the facts and ondescriptions of function, rather than on model compounds or mechanistic hypotheses (whichmay vary with time); excellent treatments of the reaction mechanisms of bioinorganicsystems are available in T. D. H. Bugg’s Introduction to Enzyme and Coenzyme Chemistry,third edition (John Wiley & Sons, 2012) and D. Gamenara, G. Seoane, P. Saenz Mendezand P. Dominguez de Maria’s Redox Biocatalysis: Fundamentals and Applications (JohnWiley & Sons, 2012). A basic knowledge of inorganic, organic, physical and biologicalchemistry remains necessary to make optimal use of this text.
Throughout this book, we have made reference to the RCSB Protein Data Bank forbiological macromolecules. Each structure deposited therein is given a unique PDB code(e.g. 1SOD), and all information pertaining to that structure can be found using its code.For easy reference, we have included this code with all the structures in this book, so thatthe reader can refer to the original data online.
For comments and encouragement during the planning and completion of this edition,we thank many of our colleagues. We thank the publishers for their support and patienceand Martina Bubrin for help in retrieving crystal structure files and drawing the structures.Most special thanks are due to Angela Winkelmann for her continued contributions to thepreparation of the manuscript.
Wolfgang KaimBrigitte Schwederski
Axel KleinStuttgart and Cologne, January 2013
Instructors can access PowerPoint files of the illustrations presented within this text, forteaching, at: http://booksupport.wiley.com.
Preface to the First Edition
This book originated from a two-semester course offered at the Universities of Frankfurtand Stuttgart (W.K). Its successful use requires a basic knowledge of the modern sciences,especially of chemistry and biochemistry, at a level that might be expected after one yearof study at a university or its equivalent. Despite these requirements we have decidedto explain some special terms in a glossary and, furthermore, several less conventionalphysical methods are briefly described and evaluated with regard to their practical relevanceat appropriate positions in the text.
A particular problem in the introduction to this highly interdisciplinary and not yet fullymature or definitively circumscribed field lies in the choice of material and the depth oftreatment. Although priority has been given to the presentation of metalloproteins andthe electrolyte elements, we have extended the scope to therapeutically, toxicologicallyand environmentally relevant issues because of the emphasis on functionality and becauseseveral of these topics have become a matter of public discussion.
With regard to details, we can frequently only offer hypotheses. In view of the explosivegrowth of this field there is implicit in many of the statements regarding structure and mech-anisms the qualification that they are “likely” or “probable”. We have tried to incorporaterelevant literature citations up to the year 1993.
Another difficult aspect when writing an introductory and, at the same time, fairly inclu-sive text is that of the organization of the material. For didactic reasons we follow partlyan organizational principle focused on the elements of the periodic table. However, livingorganisms are opportunistic and could not care less about such systematics; to successfullycope with a problem is all that matters. Accordingly, we have had to be “nonsystematic” invarious sections, for example, treating the hemerythrin protein in connection with the sim-ilarly O2-transporting hemoglobin (Chapter 5) and not under ‘diiron centers’ (Section 7.6).Several sections are similarly devoted to biological-functional problems such as biomin-eralization or antioxidant activity and may thus include several different elements or evenorganic compounds. The simplified version of the P-450 monooxygenase catalytic cyclewhich we chose for the cover picture illustrates the priority given to function and reactivityas opposed to static-structural aspects.
We regret that the increasingly available color-coded structural representations of com-plex proteins and protein aggregates cannot be reproduced here. General references tothe relevant literature are given in the bibliography at the end of the book while specificreferences are listed at the end of each chapter in the sequence of appearance.
For helpful comments and encouragement during the writing and correction ofmanuscripts we thank many of our colleagues. Recent results have become available tous through participation in the special program “Bioanorganische Chemie” of the Deutsche
