Medicinal Applications of Coordination Chemistry

Chapter I Introduction 01 I l Metals in Medicine - A Historical Perspective 01 1.2 Metals and Human Biochemistry 03 1.3 Metallopharmaceuticals 06 1.3 . General Requirements 06 1.3.2 Structure-Activity Relationships 09 l.3, Clinical Trials 11 1 4 The Special Properties of Metals 11 1.4.1 Comparison with Organic and Biologicai Compounds 1 1.4.2 Coordination Chemistry 14 Chapter 2 The Chemistry of Metals in a Nutshell 15 2.1 The Structure of Materials 15 2.. 1 States of Matter 15 2.1.2 Chemical Elements 16 2.1 13 Chemical Compounds 20 2. The Structures and Properties of Atoms 24 12.1 Electron Configurations 24 2.2.2 The Spacial Distribution of Electrons in Atoms 26 2.23 The Electronic Properties of Atoms and Ions 35 .2.4 The Radii of Atoms and Ions 37 2.3 The Formation of Compounds 38 23.1 Chemical Bonds 38 2.3,2 The Ionic Bond 39 2.3.3 The Covalent Bond 40 2.3.4 The Coordinate Bond 42 2.35 Polarity in Bonding 44 2.4 The Chemistry of Metals - An Overview 49 2..1 The Oxidation Numbers and Electron Configurations of Metal lons 49 2.4.2 The Structures of Metal Compounds 54 2.5 Bonding in Metal Complexes 60 2.5.1 The Crystal Field Theory and Octahedral Complexes 60 .152 he MO Theory and Octahedrai Complexes 70 2 5.3 The Eighteen- Electron Rule 74 2.5.4 The Crystal Field Theory and Complexes of CN 4 75 ' 6 The Magnetism and Spectroscopy of Metal Complexes 78 2,6.1 I he Electronic Spectra of Metal Complexes 78 2, 6.2 Lanthlnide Luminescence 80 2.6.3 The Magnetic Properties of Transitional Element Complexes 81 2 7 The Energetics of Metat Complex F ormation 8 2. Equilibriun or Stability Constants 83 2. .2 Hard and oft Donors or Acceptors 88 17 3 The Chelate and Macrocyclic Effects 89 2.8 Reactions at Metal Centres 90 28.,1 Thermodynamic and Kinetic Stability 90 2.8.2 Substitution Reactions at Metal Centres 92 2.8.3 Mechanisms of Substitution at Metal Centres 93 2.9 Redox Potentials 96 2.10 Conclusions 99 hapter 3 Diagnostic Medicine 101. 3. Introduction 101 3.2 Anatomical Imaging 103 3.2.1 Magnetic Resonance Imaging Contrast Agents 103 3.2.2 X-ray Contrast Agents 130 33 Functional Imaging 13 "3. 1 Radiopha rmaceuticals for Functional Imaging. 133 3, 2? Nuclear Medicine 134 3 ... 3 Radiopharmaceuticas 1 39 3.3 4 Aspects of Technetium Chemistry 141 "3.3.5 Blood-pool Imaging and Labelled Blood Cells 152 3.6 ""'Tc SPECT Imaging Agents for Bone 153 3.3.7 Kidney maging 56 3,3.8 Liver and Hepatobiliary System 159 3 ."9 Heart SPECT and PET Inaging 161 3.3.10 Brain Imaging 169 33.11 Turors Abscesses and Hypoxia 176 "3.3,12 Synt htic Approaches to Bifunctional "'Tc Radiopharmaceuticals 85 3.4 n vitro Applications 199 Chapter 4 Therapeutic Medicine 201 41 The Use of Metal Compounds in Therapy 201 4.2 Clhelation Therapy 2 02 4.2.1 Metal Sequestration 202 42.2 Macrocyclic Antibiotics 203 4 .23 Metal Intoxication 205 4.2.4 Thalassaemnia -Iron 212 4,2.5 W oion Diseasc-Copper 216 4.3 Cancer Therapy .2 18 4 Metal Complexes in Cancer Therapy 218 4.3.2 Platinum and Palladium Anticancer Agents 219 4.3.3 Non-Platinum Anticancer Agents 257 4A4 Rheumatoid Arthritis 283 44.41 Introduction 283 4.4.2 Gold Chemistry 284 4.4.3 Gold Compounds for the Treatment of Rheumatoid Arthritis 285 4 5 Diabetes 292 4.5 1 Va nadium and Diabetes 2 92 45.2 Vanadium Chemistryv 292 4.5.3 Vanadium Salts as Insulin Mimics 293 4.5.4 Vanadium Coordination Compounds as Insulin Mimics 294 4.5.5 Mechanism of Action of Vanadium Compounds 297 4.6 Cardiovascular System 298 4,6.1 In vivo Management of Gaseous Compounds 298 4.6.2 Superoxide Dismutase Mimics 299 4.6.3 Nitric Oxide Management 306 4.7 Therapeutic Radiopharmaceutica s 309 4.7.1 Radiation Therapy 309 4.7.2 -Emirtters 309 4.7.3 3-Emitter 311t 4 7,4 Radiosensitisers 321 Chapter 5 Metallopharmaceuticals Design 324 5.1 Introduction 324 5 2 Structure Activity Relationships 3 24 5.2. Organic Molecules 325 5 ... 2 Metallopharmaceuticals 327 5. Future Directions 335.