Bioinorganic Chemistry -- Inorganic Elements in the Chemistry of Life

Professor Dr Wolfgang Kaim, Institute of Inorganic Chemistry, University of Stuttgart, Germany Wolfgang Kaim was born in 1951 near Frankfurt am Main, Germany, and studied chemistry at the universities of Frankfurt and Konstanz. After obtaining his PhD with H. Bock in 1978 he spent a postdoctoral year with F.A. Cotton at the University of Texas A&M University. In 1987 he moved from the University of Frankfurt to a Full Professorship at the University of Stuttgart. His main research interests focus on the charge and electron transfer reactivity of molecular compounds and various aspects of coordination chemistry. Dr Brigitte Schwederski, Institute of Inorganic Chemistry, University of Stuttgart, Germany Brigitte Schwederski was born in 1959 in Recklinghausen, Germany. From 1977 to 1983 she studied chemistry and biology at the University of Bochum and in 1988 completed her PhD in the research group of Dale W. Margerum at Purdue University, Indiana. Since 1988 she has been a Research Assistant at the University of Stuttgart. Her main research interests include inorganic model complexes of bioinorganic systems, their characteristics and reactivity. Professor Dr. Axel Klein, Universitaet zu Koeln, Institut fuer Anorganische Chemie, Germany Axel Klein is a Professor of Inorganic Chemistry at the University of Cologne, Germany. His research interests lie in the preparation and investigation of novel coordination compounds including organometallic derivatives, aiming at the rational design, preparation and use of coordination units with specific properties in mononuclear or oligonuclear complexes or as part of materials.

Preface to the Second Edition xi

Preface to the First Edition xiii

1 Historical Background, Current Relevance and Perspectives 1

References 6

2 Some General Principles 7

2.1 Occurrence and Availability of Inorganic Elements in Organisms 7

Insertion: The Chelate Effect 14

Insertion: “Hard” and “Soft” Coordination Centers 14

2.2 Biological Functions of Inorganic Elements 14

2.3 Biological Ligands for Metal Ions 16

2.3.1 Coordination by Proteins: Comments on Enzymatic Catalysis 17

Insertion: The “Entatic State” in Enzymatic Catalysis 20

2.3.2 Tetrapyrrole Ligands and Other Macrocycles 22

Insertion: Electron Spin States in Transition Metal Ions  28

2.3.3 Nucleobases, Nucleotides and Nucleic Acids (RNA, DNA) as Ligands 31

Insertion: Secondary Bonding 32

2.4 Relevance of Model Compounds 34

References 34

3 Cobalamins, Including Vitamin and Coenzyme B12 37

3.1 History and Structural Characterization 37

Insertion: Bioorganometallics I [1] 38

3.2 General Reactions of Alkylcobalamins 41

3.2.1 One-electron Reduction and Oxidation 41

3.2.2 Co–C Bond Cleavage 42

Insertion: Electron Paramagnetic Resonance I 43

3.3 Enzyme Functions of Cobalamins 45

3.3.1 Adenosylcobalamin (AdoCbl)-dependent Isomerases 45

Insertion: Organic Redox Coenzymes 48

3.3.2 Alkylation Reactions of Methylcobalamin (MeCbl)-dependent Alkyl Transferases 51

3.4 Model Systems and the Enzymatic Activation of the Co–C Bond 52

References 53

4 Metals at the Center of Photosynthesis: Magnesium and Manganese 57

4.1 Volume and Efficiency of Photosynthesis 57

4.2 Primary Processes in Photosynthesis 59

4.2.1 Light Absorption (Energy Acquisition) 59

4.2.2 Exciton Transport (Directed Energy Transfer) 59

4.2.3 Charge Separation and Electron Transport 62

Insertion: Structure Determination by X-ray Diffraction 62

4.3 Manganese-catalyzed Oxidation of Water to O2 68

Insertion: Spin–Spin Coupling 73

References 75

5 The Dioxygen Molecule, O2: Uptake, Transport and Storage of an Inorganic Natural Product 77

5.1 Molecular and Chemical Properties of Dioxygen, O2 77

5.2 Oxygen Transport and Storage through Hemoglobin and Myoglobin 82

5.3 Alternative Oxygen Transport in Some Lower Animals: Hemerythrin and Hemocyanin 92

5.3.1 Magnetism 92

5.3.2 Light Absorption 93

5.3.3 Vibrational Spectroscopy 93

Insertion: Resonance Raman Spectroscopy 93

5.3.4 M¨ossbauer Spectroscopy 94

Insertion: M¨ossbauer Spectroscopy 94

5.3.5 Structure 95

5.4 Conclusion 96

References 96

6 Catalysis through Hemoproteins: Electron Transfer, Oxygen Activation and Metabolism of Inorganic Intermediates  99

6.1 Cytochromes 101

6.2 Cytochrome P-450: Oxygen Transfer from O2 to Nonactivated Substrates 103

6.3 Peroxidases: Detoxification and Utilization of Doubly Reduced Dioxygen 108

6.4 Controlling the Reaction Mechanism of the Oxyheme Group: Generation and Function of Organic Free Radicals  110

6.5 Hemoproteins in the Catalytic Transformation of Partially Reduced Nitrogen and Sulfur Compounds 112

Insertion: Gasotransmitters 113

References 114

7 Iron–Sulfur and Other Non-heme Iron Proteins 117

7.1 Biological Relevance of the Element Combination Iron–Sulfur 117

Insertion: Extremophiles and Bioinorganic Chemistry 118

7.2 Rubredoxins 122

7.3 [2Fe-2S] Centers 122

7.4 Polynuclear Fe/S Clusters: Relevance of the Protein Environment and Catalytic Activity 123

7.5 Model Systems for Fe/S Proteins 128

7.6 Iron-containing Enzymes without Porphyrin or Sulfide Ligands 130

7.6.1 Iron-containing Ribonucleotide Reductase 130

7.6.2 Soluble Methane Monooxygenase 132

7.6.3 Purple Acid Phosphatases (Fe/Fe and Fe/Zn) 133

7.6.4 Mononuclear Non-heme Iron Enzymes 133

References 135

8 Uptake, Transport and Storage of an Essential Element, as Exemplified by Iron 139

Insertion: Metallome 139

8.1 The Problem of Iron Mobilization: Oxidation States, Solubility and Medical Relevance 140

8.2 Siderophores: Iron Uptake by Microorganisms 141

Insertion: Optical Isomerism in Octahedral Complexes 144

8.3 Phytosiderophores: Iron Uptake by Plants 149

8.4 Transport and Storage of Iron 150

8.4.1 Transferrin 152

8.4.2 Ferritin 155

8.4.3 Hemosiderin 159

References  160

9 Nickel-containing Enzymes: The Remarkable Career of a Long-overlooked Biometal 163

9.1 Overview 163

9.2 Urease 164

9.3 Hydrogenases 166

9.4 CO Dehydrogenase = CO Oxidoreductase = Acetyl-CoA Synthase 169

9.5 Methyl-coenzyme M Reductase (Including the F430 Cofactor) 172

Insertion: Natural and Artificial (Industrial) C1 Chemistry 174

Insertion: Bioorganometallics II: The Organometallic Chemistry of Cobalt and Nickel 176

9.6 Superoxide Dismutase 177

9.7 Model Compounds 178

Further Reading 178

References 179

10 Copper-containing Proteins: An Alternative to Biological Iron 183

10.1 Type 1: “Blue” Copper Centers 186

Insertion: Electron Paramagnetic Resonance II 187

10.2 Type 2 and Type 3 Copper Centers in O2-activating Proteins: Oxygen Transport and Oxygenation 191

10.3 Copper Proteins as Oxidases/Reductases 195

10.4 Cytochrome c Oxidase 200

10.5 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  211

11.1 Oxygen Transfer through Tungsten- and Molybdenum-containing Enzymes 211

11.1.1 Overview 211

11.1.2 Oxotransferase Enzymes Containing the Molybdopterin or Tungstopterin Cofactor  213

Insertion: “Oxidation” 214

11.2 Metalloenzymes in the Biological Nitrogen Cycle: Molybdenum-dependent Nitrogen Fixation  219

11.3 Alternative Nitrogenases 226

11.4 Biological Vanadium Outside of Nitrogenases 229

11.5 Chromium(III) in the Metabolism? 231

References 232

12 Zinc: Structural and Gene-regulatory Functions and the Enzymatic Catalysis of Hydrolysis and Condensation Reactions 235

12.1 Overview 235

12.2 Carboanhydrase 238

12.3 Carboxypeptidase A and Other Hydrolases 243

12.4 Catalysis of Condensation Reactions by Zinc-containing Enzymes 248

12.5 Alcohol Dehydrogenase and Related Enzymes  249

12.6 The “Zinc Finger” and Other Gene-regulatory Zinc Proteins 251

12.7 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 Earth Metal Cations 257

13.1 Characterization and Biological Roles of K+, Na+, Ca2+ and Mg2+ 257

Insertion: Heteroatom Nuclear Magnetic Resonance 262

13.2 Complexes of Alkali and Alkaline Earth Metal Ions with Macrocycles 264

13.3 Ion Channels 267

13.4 Ion Pumps 270

Further Reading 273

References 273

14 Catalysis and Regulation of Bioenergetic Processes by the Alkaline Earth Metal Ions Mg2+ and Ca2+ 277

14.1 Magnesium: Catalysis of Phosphate Transfer by Divalent Ions 277

14.2 The Ubiquitous Regulatory Role of Ca2+ 283

Further Reading 291

References 291

15 Biomineralization: The Controlled Assembly of “Advanced Materials” in Biology 295

15.1 Overview 295

15.2 Nucleation and Crystal Growth 299

Insertion: Dimensions 300

15.3 Examples of Biominerals 301

15.3.1 Calcium Phosphate in the Bones of Vertebrates and the Global P Cycle 301

Insertion: The Global P Cycle 305

15.3.2 Calcium Carbonate and the Global Inorganic C Cycle  306

Insertion: The Global C Cycle and the Marine Inorganic C Cycle 307

15.3.3 Amorphous Silica 308

15.3.4 Iron Biominerals 309

15.3.5 Strontium and Barium Sulfates 310

15.4 Biomimetic Materials 310

Further Reading 311

References 311

16 Biological Functions of the Nonmetallic Inorganic Elements 315

16.1 Overview 315

16.2 Boron 315

16.3 Silicon 315

16.4 Arsenic and Trivalent Phosphorus 316

16.5 Bromine 317

16.6 Fluorine 317

16.7 Iodine 318

16.8 Selenium 320

References 324

17 The Bioinorganic Chemistry of the Quintessentially Toxic Metals 327

17.1 Overview 327

17.2 Lead 329

17.3 Cadmium 332

17.4 Thallium 334

17.5 Mercury 335

17.6 Aluminum 340

17.7 Beryllium 342

17.8 Chromium and Tungsten 343

17.9 Toxicity of Nanomaterials 344

Further Reading 345

References 345

18 Biochemical Behavior of Radionuclides and Medical Imaging Using Inorganic Compounds 349

18.1 Radiation Risks and Medical Benefits from Natural and Synthetic Radionuclides 349

18.1.1 The Biochemical Impact of Ionizing Radiation from Radioactive Isotopes 349

18.1.2 Natural and Synthetic Radioisotopes 350

18.1.3 Bioinorganic Chemistry of Radionuclides 351

Insertion: Fukushima Daiichi, Chernobyl, Hiroshima and Nuclear Weapons Testing 353

18.1.4 Radiopharmaceuticals 356

18.1.5 Technetium: A “Synthetic Bioinorganic Element” 359

18.1.6 Radiotracers for the Investigation of the Metallome 362

18.2 Medical Imaging Based on Nonradioactive Inorganic Compounds 362

18.2.1 Magnetic Resonance Imaging 362

18.2.2 X-ray Contrast Agents 364

Further Reading 364

References 365

19 Chemotherapy Involving Nonessential Elements 369

19.1 Overview 369

19.2 Platinum Complexes in Cancer Therapy 369

19.2.1 Discovery, Application and Structure–Effect Relationships 369

19.2.2 Cisplatin: Mode of Action 372

19.3 New Anticancer Drugs Based on Transition Metal Complexes 378

19.3.1 Overview and Aims for Drug Development 378

19.3.2 Nonplatinum Anticancer Drugs 379

19.4 Further Inorganic Compounds in (Noncancer) Chemotherapy 383

19.4.1 Gold-containing Drugs Used in the Therapy of Rheumatoid Arthritis 383

19.4.2 Lithium in Psychopharmacologic Drugs 384

19.4.3 Bismuth Compounds against Ulcers 385

19.4.4 Vanadium-containing Insulin Mimetics and V-containing Anti-HIV Drugs 386

19.4.5 Sodium Nitroprusside 386

19.5 Bioorganometallic Chemistry of Nonessential Elements 387

Further Reading 389

References 389

Index