Metals in Medicine

SECOND EDITION
Metals in Medicine

Working from basic chemical principles, Metals in Medicine, Second Edition describes a wide range of metal–based agents for treating and diagnosing disease. Thoroughly revised and restructured to reflect significant research activity and advances, this new edition contains extensive updates and new pedagogical features while retaining the popular feature boxes and end–of–chapter problems of the first edition.

Topics include:

Metallo–drugs and their action Platinum drugs for treating cancer Anticancer agents beyond cisplatin including ruthenium, gold, titanium and gallium Responsive metal complexes Treating arthritis and diabetes with metal complexes Metal complexes for killing bacteria, parasites and viruses Metal ion imbalance and its links to diseases including Alzheimer′s, Wilson′s and Menkes disease Metal complexes for detecting disease Nanotechnology in medicine

Now in full colour, Metals in Medicine, Second Edition employs real–life applications and chapter–end summaries alongside feature boxes and problems. It provides a complete and methodical examination of the use of metal complexes in medicine for advanced undergraduate and postgraduate students in medicinal inorganic chemistry, bioinorganic chemistry, biochemistry, pharmacology, biophysics, biology and bioengineering. It is also an invaluable resource for academic researchers and industrial scientists in inorganic chemistry, medicinal chemistry and drug development.

Feature Boxes xv

Preface to the Second Edition xvii

Preface to the First Edition xix

Acknowledgments xxi

About the Companion Website xxiii

1 Inorganic Chemistry Basics 1

1.1 Introduction 1

1.2 Crystal Field Theory 1

1.3 Molecular Orbital Theory 12

1.4 Absorption Spectra of Metal Complexes 22

1.5 Magnetic Properties of Metal Complexes 33

1.6 Structure and Reactivity of Metal Complexes 35

2 Metallo–Drugs and Their Action 59

2.1 Introduction 59

2.2 Proteins asTargets forMetallo–Drugs 59

2.3 DNAas aTarget forMetallo–Drugs 71

2.4 Reaction of Metal Complexes in the Biological Milieu 76

2.5 Evaluating the Pharmacological Effects of Agents 79

2.6 FromDiscoverytotheClinic 82

3 Platinum Drugs for Treating Cancer 91

3.1 Introduction 91

3.2 Cisplatin 91

3.3 Carboplatin 115

3.4 Oxaliplatin 126

3.5 RegionallyUsedPlatinumDrugs 133

3.6 Platinum Agents in Preclinical Development 135

4 Anticancer Agents Beyond Cisplatin 157

4.1 Introduction 157

4.2 Ruthenium Anticancer Agents 157

4.3 Gold Anticancer Agents 173

4.4 Titanium Compounds for Treating Cancer 181

4.5 Gallium for Treating Cancer 187

4.6 Other Anticancer Active Metal Complexes 194

5 Responsive Metal Complexes 217

5.1 Introduction 217

5.2 Prodrug Activation by Redox 217

5.3 ProdrugActivationbypH 225

5.4 Prodrug Activation by Enzymes 227

5.5 ProdrugActivationbyLight 229

5.6 Photodynamic Therapy 233

6 Metal Complexes for Treating Arthritis and Diabetes 245

6.1 Introduction 245

6.2 ChemistryofGoldinBiologicalMedia 245

6.3 Gold Compounds for Treating Arthritis 247

6.4 Vanadium Compounds for Treating Diabetes 263

7 Metal Complexes for Killing Parasites, Bacteria and Viruses 285

7.1 Introduction 285

7.2 Malaria 285

7.3 Leishmaniasis 293

7.4 American Trypanosomiasis (Chagas Disease) 298

7.5 Human African Trypanosomiasis 301

7.6 Tuberculosis 301

7.7 PepticUlcerDisease 306

7.8 Syphilis 311

7.9 Bacterial Infections 312

7.10 Acquired Immunodeficiency Syndrome (AIDS) 314

8 Metal Ion Imbalance in the Body 329

8.1 Introduction 329

8.2 Alzheimer s Disease 329

8.3 LithiumandtheBrain 337

8.4 Wilson s Disease: Copper Overload 338

8.5 Menkes Disease: Copper Deficiency 340

8.6 Beta–Thalassemia: IronOverload 342

8.7 Iron–Deficiency Anemia 344

8.8 Calcium Imbalance 344

8.9 ChelationTherapy 346

9 Metal Complexes for Detecting Disease 357

9.1 Introduction 357

9.2 Technetium in Diagnostic Nuclear Medicine 358

9.3 Metal Compounds as Contrast Agents for MRI 371

9.4 Radiotherapy 382

10 Nanomedicine 395

10.1 Introduction 395

10.2 Circulation, Uptake, and Elimination of Nanoparticles 396

10.3 Nanoscience for Treating Cancer 407

10.4 Nanoparticles for Detecting Disease 419

10.5 Theranostic Nanoparticles 426

10.6 Cytotoxicity of Nanoparticles 428

Index 441

James C. Dabrowiak
Department of Chemistry, Syracuse University, USA