Bioinorganic Chemistry: A Survey

Bioinorganic Chemistry: A Survey

Bioinorganic Chemistry: A Survey Eiichiro Ochiai AMSTERDAM BOSTON HEIDELBERG LONDON OXFORD NEW YORK PARIS SAN DIEGO SAN FRANCISCO SINGAPORE SYDNEY TOKYO Academic Press is an imprint of Elsevier

Cover Design: Joanne Blank Cover Image Ei-Ichiro Ochiai Academic Press is an imprint of Elsevier 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald s Road, London WC1X 8RR, UK Copyright 2008, Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier s Science & Technology Rights Department in Oxford, UK: phone: ( 44) 1865 843830, fax: ( 44) 1865 853333, E-mail: permissions@elsevier.com. You may also complete your request online via the Elsevier homepage ( http://elsevier.com ), by selecting Support & Contact then Copyright and Permission and then Obtaining Permissions. Library of Congress Cataloging-in-Publication Data Application Submitted British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. ISBN: 978-0-12-088756-9 For information on all Academic Press publications visit our Web site at www.books.elsevier.com Typeset by Charon Tec Ltd., A Macmillan Company (www.macmillansolutions.com) Printed in China 08 09 10 9 8 7 6 5 4 3 2 1

Contents Preface xiii Introduction: Basics of Bio/Ecosystems and Biochemistry, and Other Basic Concepts 1 Biosphere (Ecosystem) 1 Components of the Biosphere Living Organisms 1 Bodily Structures of Living Organisms 3 Cells, the Basic Functional Units of Living Organisms 3 Biochemical Compounds Essential to Life 4 Carbohydrates 5 Monosaccharides 5 Polysaccharides and Derivatives 7 Lipids 8 Fats and Phospholipids 9 Steroids 10 Proteins and Amino Acids 10 Structures 10 Reactions Formation and Hydrolysis of Protein 16 Vitamins (Coenzymes), Nucleotides, and Others 17 Coenzymes 17 Nucleotides 18 Other Vitamins 19 DNA/RNA (Polynucleotide) 19 Structures 19 Reactions 23 Types of Biochemical Reactions 24 Reactions of Acid-Base Type 24 Reactions of Oxidation-Reduction Type 25 The Idea of Oxidation State 26 The Oxidation State of C in Organic Compounds and Recognition of Oxidation-Reduction Reactions 26 Other Kinds of Oxidation-Reduction Reactions 29 Free Radical Reactions 30 Transition State Theory of Reaction, and Enzyme Kinetics 30 Energy Profile and Transition State Theory of Reaction 31 Enzyme Kinetics 32 Enzyme Reaction Mechanism 33 CHAPTER 1 The Distribution of Elements 37 1.1. The Distribution of Elements in the Earth s Crust, Seawater, and Organisms 37 1.2. The Engines That Drive the Biochemical Cycling of the Elements 41 v

vi Contents 1.3. Flow of the Elements Biogeochemical Cycling 42 1.4. Historical Change in the Biogeochemical Cycling of Elements 45 CHAPTER 2 Biological Needs for and the Behaviors of Inorganic Elements 53 2.1. Introduction 53 2.2. Inorganic Elements in the Biological Systems 54 2.2.1. Inorganic Elements Involved at the Molecular Level 54 2.2.2. Inorganic Elements Involved at the Cellular Level 55 2.2.3. Inorganic Elements Involved at the Physiological Level 55 2.2.4. Biological Systems Involved in the Metabolism of Inorganic Elements 56 2.3. Why Has a Specific Organism Chosen Specific Elements for Its Specific Needs? 58 2.4. Behaviors of Inorganic Elements-I: Fundamentals of Coordination Chemistry 58 2.4.1. Coordination Compounds or Metal Complexes 59 2.4.2. Ligand Field Theory How the Predominant Structure Is Determined 60 2.4.3. Thermodynamic Tendency to Form Coordination Compounds 64 2.4.4. Chelate Effect 66 2.4.5. Ligand Substitution Reactions Kinetic Factors 67 2.4.6. Oxidation Reduction and Reduction Potential 68 2.5. Behaviors of Inorganic Elements-II: Basics of Organometallic Chemistry 73 2.5.1. Metal Carbonyls and the 18-Electron (18 e ) Rule 73 2.5.2. Other Organometallic Compounds 75 2.5.3. Some Special Types of Reactions Involving Organometallic Compounds 76 CHAPTER 3 How Do Enzymes Work? 81 3.1. Enzymatic Enhancement of Reaction Rate: General Considerations 81 3.1.1. Transition State Theory 82 3.1.2. The Dynamic Effects 85 3.1.3. A Composite Theory 87 3.2. Metalloenzymes/Proteins and Metal-Activated Enzymes 89 CHAPTER 4 Reactions of Acid-Base Type and the Functions of Metal Cations 93 4.1. General Considerations 93 4.1.1. Different Types (Definitions) of Acid-Base 93 4.1.2. Reactions of Acid-Base Type Catalyzed by Enzymes 94 4.1.3. Acidity Scale and Acid Character of Metal Cations: Prominence of Zn(II) and Mg(II) 95 4.1.4. Kinetic Factors 98 4.1.5. Enhancement of Reaction by Protein Residues 99 4.2. Mg(II)-Dependent Enzymes 100 4.2.1. Rubisco (Ribulose 1,5-Bisphosphate Carboxylase/Oxygenase) 100 4.2.2. Pyruvate Kinase 101 4.3. Zn(II)-Dependent Enzymes 102 4.3.1. Carbonic Anhydrase 103

Contents vii 4.3.2. Thermolysin, Carboxypeptidase A, and Others 105 4.3.3. Leucine Aminopeptidase 106 4.3.4. Alkaline Phosphatase and Purple Acid Phosphatase 106 4.3.5. Alcohol Dehydrogenase 107 4.4. Other Metal Cation-Dependent Acid-Base Enzymes 108 4.4.1. Aconitase, an Iron-Sulfur Enzyme, and Others 108 4.4.2. Arginase: Mn Enzyme 109 4.4.3. Urease and Other Ni Enzymes 109 4.5. Structural Effects of Metal Ions 111 4.6. Metal Ions and Polynucleic Acids (DNA and RNA) 112 4.6.1. General Characteristics of Interactions of Metal Ions with Polynucleotides 113 4.6.1.1. Effects on Structures 113 4.6.1.2. Catalytic Metal Ions in DNA Polymerases and Nucleases 114 4.6.2. Gene Regulation and Metal Ions 116 4.6.3. Ribozymes 117 CHAPTER 5 Reactions of Oxidation Reduction Type Including Electron Transfer Processes 123 5.1. General Consideration 123 5.1.1. Reduction Potential 124 5.1.1.1. Heme Proteins and Enzymes 124 5.1.1.2. Iron-Sulfur Proteins 127 5.1.1.3. Copper Proteins 130 5.1.1.4. Molybdenum and Tungsten Proteins 131 5.1.2. Kinetic Factors Electron Transfer between and in Protein(s) 132 5.2. Iron Enzymes and Proteins 133 5.2.1. Cytochromes and Iron-Sulfur Electron Transfer Proteins 134 5.2.2. Nitrite Reductase and Nitric Oxide Reductase 134 5.2.3. Horseradish Peroxidase (HRP), Catalase, and Cytochrome C Peroxidase 135 5.2.4. Hydrogenase 136 5.3. Copper Enzymes and Proteins 137 5.3.1. Blue Copper Proteins 138 5.3.2. Blue Copper Oxidases 139 5.3.3. Cytochrome C Oxidase 140 5.3.4. Nitrite Reductase and Nitrous Oxide Reductase 140 5.3.5. Amine Oxidases 142 5.3.6. Superoxide Dismutase (SOD) 144 5.4. Molybdenum Enzymes and Tungsten Enzymes 145 5.4.1. Xanthine Oxidase and Aldehyde Oxidase 145 5.4.2. Sulfite Oxidase and Nitrate Reductase (Assimilatory) 147 5.4.3. DMSO Reductase and Nitrate Reductase (Respiratory or Dissimilatory) 148 5.4.4. Tungsten Enzymes 150 5.5. Manganese Oxidoreductases 150

viii Contents 5.5.1. Manganese Catalase 151 5.5.2. Water Oxidase 151 5.6. Ni-Containing Redox Enzymes 153 5.6.1. Ni-Fe (Se) Hydrogenase 154 5.6.2. Carbon Monoxide Dehydrogenase (CODH) 155 5.6.3. Acetyl CoA Synthase (ACS) 156 5.6.4. Methyl-Coenzyme M Reductase 156 CHAPTER 6 Oxygen Carrying Processes and Oxygenation Reactions 161 6.1. The Chemistry of Oxygen, Dioxygen, and Related Entities 161 6.1.1. Electronic Structures 161 6.1.2. Basic Reactions of O and O 2 162 6.1.3. Reactions of Ground State O and O 2 163 6.1.4. Interactions of Ground State O 2 with Compounds of Transition Metals 164 6.1.5. Reactions of Oxygen Derivatives 167 6.2. Reversible O 2 Binding: Oxygen Carriers 168 6.3. Monooxygenases 169 6.3.1. Monooxygenases Dependent on Cytochrome P-450 170 6.3.2. Nonheme Mononuclear Iron Monooxygenases 173 6.3.3. Nonheme Dinuclear Iron Monooxygenases 176 6.3.4. Copper Monooxygenases 177 6.4. Dioxygenases 178 6.5. Prostaglandin Endoperoxide Synthase 181 CHAPTER 7 Metal-Involving Free Radical Reactions 185 7.1. A Survey of Biologically Relevant Free Radicals 185 7.2. Why Radicals? 187 7.3. Reactivities of Free Radicals 188 7.4. B 12 -Coenzyme (Adenosylcobalamin)-Dependent Enzymes 192 7.4.1. Mutases, Diol Dehydratase, and Ethanolamine Ammonia Lyase 192 7.4.1.1. Homolytic Cleavage of the Cobalt-to-Carbon Bond upon Binding a Substrate 193 7.4.1.2. Hydrogen Abstraction from Substrates 195 7.4.1.3. 1,2-Shift or Other Reactions of Substrate Free Radicals 195 7.4.2. Ribonucleotide Reductases (Cobalamin-Dependent) 198 7.5. S-Adenosyl Methionine (SAM)-Dependent Enzymes 199 7.6. Iron-Dependent Ribonucleotide Reductases 200 7.7. Galactose Oxidase 202 7.8. Other Examples 203 CHAPTER 8 Nitrogen Fixation 205 8.1. Nitrogen Metabolism 205 8.2. Chemistry of N 2 Reduction 206

Contents ix 8.3. Mo-Dependent Nitrogenase 208 8.4. Other Nitrogenases 214 CHAPTER 9 Other Essential Elements 217 9.1. Introduction 217 9.2. Biochemistry of Nitrogen Compounds 218 9.3. Biochemistry of Phosphorus 219 9.4. Biochemistry of Sulfur Compounds 219 9.4.1. Cellular Processes 219 9.4.2. Marine Biogeochemical Cycling 221 9.5. Selenium 222 9.5.1. Chemistry of Selenium as Compared to That of Sulfur 222 9.5.2. Glutathione and Selenium: Glutathione Peroxidase 222 9.5.3. Thioredoxin Reductase 224 9.5.4. Other Selenium-Containing Proteins and Enzymes 225 9.6. Boron 225 9.7. Silicon 227 9.7.1. Chemistry of Silicon 228 9.7.2. Frustules of Diatoms 229 9.7.3. Spicules in Sponge 230 9.7.4. Other Biological Functions of Silicon 231 9.8. Vanadium 232 9.8.1. Vanabins 232 9.8.2. Amavadin 233 9.8.3. Haloperoxidases 233 9.9. Chromium 235 9.10. Halogens and the Like 235 9.10.1. Formation of Volatile Halocarbons in Macroalgae 236 9.10.2. HOX Formation in Mammals and Others 236 9.10.2.1. Formation of HOX by a Fungal Chloroperoxidase 236 9.10.2.2. Formation of HOX by Mammalian Peroxidases 237 CHAPTER 10 Metal-Related Physiology 243 10.1. Metabolism of Metallic Elements 244 10.1.1. Iron Metabolism (in Mammals) 244 10.1.1.1. Ferric Reductase 245 10.1.1.2. Divalent Metal Transporter (DMT1) 246 10.1.1.3. Ferroxidase 246 10.1.1.4. Transferrin (Tf) and Transferrin Receptor (TfR) 246 10.1.1.5. Ferritin 248 10.1.1.6. Ferroportin (Fpn)/Hepcidin 249 10.1.1.7. Regulation of Ferritin and Transferrin 249

x Contents 10.1.1.8. Iron Metabolism in Bacteria, Fungi, and Plants 250 10.1.2. Copper Metabolism 252 10.1.2.1. Outline of Copper Metabolism in Mammals 252 10.1.2.2. Copper Metabolism in Bacteria and Plants 253 10.1.3. Zinc Metabolism 254 10.1.3.1. In Mammals 254 10.1.3.2. In E. coli 255 10.1.4. A Mg(II) Transporter 256 10.2. Physiological Roles Played by Metallic Elements 256 10.2.1. Na/K-ATPase and Ca-ATPase 256 10.2.1.1. Mechanism 256 10.2.1.2. Ion Selectivity in Metal Ion Transporters and Channels A General Discussion 257 10.2.2. Ca(II) Second Messenger and Other Functions 259 10.2.2.1. Control of Cytoplasmic Ca(II) Concentration 260 10.2.2.2. Basic Mechanisms of Ca(II) Physiology 261 10.2.2.3. Synaptotagmin, an Example of Physiology Mediated by Ca(II) 262 10.2.2.4. Why Calcium(II)? 263 10.2.3. Zinc-Enriched Neuron (ZEN) 266 10.2.4. Sensors for Small Molecules 266 10.2.4.1. Oxygen Sensors 267 10.2.4.2. CO-Sensors 268 10.2.4.3. NO-Sensors 269 10.2.4.4. H 2 -Sensors 270 10.2.4.5. Redox Sensors 270 10.2.5. Plant Hormone Ethylene and Copper 271 10.2.6. Magnetic Navigation 271 10.2.7. Radiation Shields 272 10.3. Biological Skeletons (Biominerals) 272 10.3.1. Calcium Carbonate 273 10.3.2. Calcium Oxalate 275 10.3.3. Calcium Phosphate 275 CHAPTER 11 Environmental Bioinorganic Chemistry 279 11.1. General Considerations 279 11.2. Toxicity of Inorganic Compounds 281 11.2.1. Abundance and Toxicity 281 11.2.2. Toxicity of Reactive Oxygen Species, and Defense Mechanisms Against Them 282 11.3. Molecular Mechanisms of Toxicity of Inorganic Compounds 284 11.3.1. Discrimination of Elements by Organisms General Considerations 284 11.3.2. Oxidative Stress and Metals and As General Effects 288 11.3.3. Individual Element s (Acute) Toxicity 290 11.3.3.1. Cd(II) and Hg(II) 290

Contents xi 11.3.3.2. Pb(II) 290 11.3.3.3. Organometallic Compounds 291 11.3.3.4. Organotin Compounds 292 11.3.3.5. Be(II), Al(III) 292 11.3.3.6. Tl(I) 293 11.3.3.7. Cr 293 11.3.3.8. Ni(II) 293 11.3.3.9. Anions 294 11.3.4. Alzheimer s Disease and Metals 294 11.4. Biological Defenses against Toxicity 295 11.4.1. Biological Defense against Mercury 296 11.4.2. Metallothioneins and Phytochelatins 298 11.4.2.1. Metallothioneins 298 11.4.2.2. Copper-Thionein (Cu-MT) 299 11.4.2.3. Phytochelatins 300 11.4.2.4. Use of Sulfide 301 11.4.3. Defense against Lead 301 11.4.4. Biotransformation of Arsenic 302 11.5. Bioremediaion of Metals 303 11.5.1. Biosorption by Brown Algae and by Microbial Surfactants 303 11.5.2. Phytoremediation (Phytoextraction of Metals from Soil) 305 11.5.3. Phytoextraction by Microalgae (Remediation of Polluted Water) 308 11.5.4. Other Types of Bioremediation 308 CHAPTER 12 Medical Applications of Inorganic Compounds: Medicinal Inorganic Chemistry 311 12.1. Introduction 311 12.2. Cancer Therapy 312 12.2.1. Platinum Compounds 313 12.2.2. Bleomycin 316 12.2.3. Radioactive Pharmaceuticals 319 12.3. Gold Compounds for Rheumatoid Arthritis 319 12.4. Vanadium Compounds for Diabetes 320 12.5. Lithium Compounds for Psychiatric Disorders 322 12.6. Other Potential Drugs Containing Inorganic Compounds 323 12.7. Diagnostic (Imaging) Agents 323 12.7.1. Gd(III)-Contrasting Agents for MRI 323 99m 12.7.2. Tc-Radioactive Diagnostic Pharmaceuticals 324 Appendix 327 References 329 Index 351

Preface Bioinorganic chemistry as a discipline is now two and a half decades old, if we consider its birth to be the first International Conference on Bioinorganic Chemistry (ICBIC) held in Florence, Italy in 1983. I wrote one of the earliest books on the subject, Bioinorganic Chemistry, an Introduction (Allyn and Bacon) in 1977. The emphasis there was on physicochemical data and their interpretations. Since then the scope of research on bioinorganic chemistry has greatly expanded, diversified, and deepened, and the quantity of the literature has exploded. This book does not attempt to summarize the current status of research in all the various areas of the field. It also omits discussion of the methods of research, and hardly deals with biophysical data. For experimental methods, readers are referred to works such as L. Que s Physical Methods in Bioinorganic Chemistry (2000) and an ACS publication, Spectroscopic Methods in Bioinorganic Chemistry (2003); and some textbooks including the ones by J. Cowan, Inorganic Biochemistry, 3 rd ed., Wiley-VCH (2007) and R. M. Roat- Malone, Bioinorganic Chemistry, Wiley-Interscience (2002). Instead of research details, this book aims to provide general readers as well as specialists with an understanding of the basic chemistry of interactions of inorganic substances with biological systems at the molecular level (as much as possible), and also a perspective on the subject, as the subtitle A Survey implies. Since living organisms and the biosphere they constitute are both open systems, they are in contact with and constantly exchanging energy and material with their environments. The environments experienced by a single organism include all the other organisms and the physical environment, which is composed of inorganic substances. This fundamental situation inevitably entails the inclusion of almost all inorganic elements in living organisms. Hence bioinorganic chemistry, or rather what it implies, is not a novelty but a necessity, and should be universal. Indeed we are increasingly being made aware of the fact that inorganic compounds are intimately associated with all biological phenomena. My second book ( The General Principles of Biochemistry of the Elements, Plenum Press, 1987) attempted to lay down several basic principles in order to answer some fundamental questions such as why iron is used for this purpose, and not copper. The present work is to try to extend these ideas while incorporating some of the more recent discoveries. xiii

xiv Preface This book looks at the entire picture of the existence of organisms on Earth in terms of chemistry molecules/compounds, their interactions and reactions, and the roles that inorganic elements play and why. The Introduction and the first two chapters give fundamentals of interactions between the biosphere and inorganic compounds from the molecular level to the geochemical level. The Introduction is a brief review of basic concepts of biochemistry, and can be skipped or can be used as a Glossary. Chapter 1 is an overview of biogeochemical aspects of bioinorganic chemistry, and Chapter 2 gives a brief introduction to relevant inorganic chemistry. Chapter 3 is a discussion of the basic issue of why enzymes are so efficient. The information discussed here is not indispensable for understanding the rest of the book, so it can be skipped if circumstances require. Chapters 4 through 9 are concerned mainly with the chemical bases of functions of inorganic elements associated with enzymes and proteins. Chapter 10 deals with workings of inorganic compounds at physiological levels, and Chapter 11 treats the environmental issues including toxicity associated with inorganic elements. The last chapter deals with the medicinal applications of inorganic elements. Two different kinds of exercises are provided at the end of each chapter review questions and problems to explore. Both types of exercises are in line with the spirit of this book; they concern chemical principles of the interactions of inorganic chemicals with the biological systems at a molecular level, without discussing experimental data. Therefore, no question is provided regarding experimental data such as kinetic and spectroscopic data. Such questions, if necessary and appropriate, need to be provided by the instructors. As the volume of relevant literature has become enormous and more details have become available, a single author surely has the difficulty of being sufficiently versed in each and every area of current research. No single book would be able to cover every aspect of the bioinorganic chemistry of even a single element such as calcium in full detail, let alone that of all the significant elements. However, that is in essence what I have tried to do, but not in full detail. In writing this book, I have relied heavily on some excellent summaries in the form of review articles written by experts in each field. I am much indebted to them, and would like to express my gratitude to all those researchers who have contributed to a better understanding of these fascinating aspects of chemical biology.

Preface xv One of the results of technical advances made in recent decades is an increase in the structural data on proteins (and nucleic acids), and their accessibility through the PDB (Protein Data Bank). Individual researchers and students alike can now explore protein structures in detail. The availability of the PDB has been of enormous help in writing this book. In addition, several other Internet sites have proven very useful; in particular, the general literature search engines called Scopus and ScienceDirect have been indispensable in writing a book of this nature. I would like to express my gratitude to those individuals and organizations that are responsible for providing such readily accessible databases. This book concludes my efforts over the last three decades to survey the fascinating subject of bioinorganic chemistry. I gratefully acknowledge the comments and suggestions by reviewers: R. J. P. Williams of Oxford University, C. Frank Shaw, III. of Illinois State University, and Murray S. Davies of James Cook Univeristy, Australia. Their comments have improved the manuscript. I also acknowledge gratefully the assistance of J. Woodling of Juniata College Library in finding literature.