Metals in Medicine

Metals in Medicine......Page 2
Contents......Page 10
Feature Boxes......Page 16
Preface......Page 18
Acknowledgments......Page 20
1.1 Crystal field theory......Page 22
1.1.1 Octahedral crystal field......Page 23
1.1.2 Other crystal fields......Page 26
1.1.3 Factors affecting the crystal field splitting parameter, Δ......Page 28
1.1.4 High- and low-spin complexes......Page 30
1.2.1 MO diagram of molecular hydrogen......Page 32
1.2.2 MO diagram for [Co(NH3)6]3+......Page 34
1.3 Absorption spectra of metal complexes......Page 37
1.3.1 Band intensity/selection rules......Page 40
1.3.2 Spectroscopic and crystal field terms......Page 41
1.3.3 Band assignments and Δ......Page 45
1.4 Magnetic properties of metal complexes......Page 49
1.5.1 Forward and reverse rates and equilibrium......Page 50
1.5.2 Water exchange rates for metal ions......Page 52
1.5.3 Transition State Theory, the kinetic rate constant and equilibrium......Page 54
1.5.4 Trans effect and substitution reactions......Page 58
1.5.5 Stability of metal complexes......Page 61
1.5.6 Chelate effect......Page 62
1.5.7 Macrocyclic effect......Page 63
1.5.8 Hard–soft acids–bases......Page 65
Problems......Page 66
Further reading......Page 68
2.2 Proteins as targets for metallo-drugs......Page 70
2.2.1 Protein structure......Page 71
2.2.2 Metal binding sites on proteins......Page 72
2.3.1 Structure of DNA and RNA......Page 79
2.3.2 Metal binding sites on DNA......Page 83
2.4.1 Reactions with chloride......Page 84
2.4.3 Reactions with carbonate......Page 85
2.5.1 Measuring the cytotoxicity of a drug......Page 86
2.5.2 Measuring drug uptake......Page 87
2.6.1 Drug approval process......Page 88
Problems......Page 90
References......Page 91
Further reading......Page 92
3 Cisplatin......Page 94
3.1 Physical and chemical properties of cisplatin......Page 96
3.2 Formulation, administration and pharmacokinetics......Page 101
3.3 Reaction of cisplatin in biological media......Page 102
3.4.1 Influx and efflux of cisplatin......Page 104
3.4.2 Modification by glutathione and metallothionein......Page 110
3.4.3 DNA repair......Page 111
3.5.1 DNA as a target......Page 112
3.5.2 Non-DNA targets......Page 119
Problems......Page 122
References......Page 123
Further reading......Page 128
4.1.1 Synthesis and properties of carboplatin......Page 130
4.1.2 Formulation, administration and pharmacokinetics of carboplatin......Page 134
4.1.3 Reactions of carboplatin in the biological milieu......Page 135
4.1.4 Cytotoxicity and uptake of carboplatin......Page 138
4.1.5 Interaction of carboplatin with cellular targets......Page 140
4.2.1 Stereochemistry of oxaliplatin......Page 143
4.2.2 Synthesis and properties of oxaliplatin......Page 147
4.2.3 Formulation, administration and pharmacokinetics of oxaliplatin......Page 148
4.2.4 Reaction of oxaliplatin in the biological milieu......Page 149
4.2.6 Interaction of oxaliplatin with cellular targets......Page 151
4.3 New platinum agents......Page 155
4.3.1 Nedaplatin......Page 156
4.3.4 Satraplatin (JM216)......Page 157
4.3.5 Picoplatin (AMD473, ZD473)......Page 160
4.3.6 BBR3464......Page 161
Problems......Page 162
References......Page 164
Further reading......Page 168
5.1.1 Chemistry of ruthenium in the biological milieu......Page 170
5.1.2 Structure, synthesis and properties of ruthenium antitumor agents......Page 171
5.1.3 Synthesis and biological properties of NAMI-A......Page 174
5.1.4 Control of tumor growth by NAMI-A......Page 177
5.1.6 Interaction of NAMI-A with potential biological targets......Page 178
5.1.8 Biological activity of KP1019......Page 179
5.1.10 Interaction of KP1019 with potential biological targets......Page 180
5.1.11 Synthesis and properties of ruthenium arene compounds......Page 182
5.1.12 Biological activity of the arene complexes......Page 184
5.1.13 Targets of the ruthenium arene compounds......Page 185
5.2 Titanium compounds for treating cancer......Page 188
5.2.1 Structure, synthesis and properties of titanocene dichloride......Page 189
5.2.3 Structure, synthesis and properties of budotitane......Page 191
5.2.4 Antitumor activity and clinical trials with budotitane......Page 195
5.2.6 Titanium anticancer drugs in development......Page 196
5.3.1 Chemistry of gallium in biological media......Page 198
5.3.2 Structures, synthesis and properties of gallium anticancer agents......Page 200
5.3.3 Uptake, cytotoxicity and reactivity of gallium agents in the biological system......Page 201
5.3.4 Gallium anticancer agents in development......Page 202
Problems......Page 203
References......Page 205
Further reading......Page 210
6.1 Chemistry of gold in biological media......Page 212
6.2 Gold compounds for treating arthritis......Page 213
6.2.1 Structures, synthesis and properties of gold antiarthritic drugs......Page 214
6.2.2 Formulation, administration and pharmacokinetics of gold antiarthritic drugs......Page 216
6.2.3 Reactions in biological media, uptake and cytotoxicity of gold drugs......Page 217
6.2.4 Interactions with cellular targets......Page 220
6.3.1 Structures, synthesis and properties of gold anticancer agents......Page 226
6.3.2 Reactions in biological media, uptake and cytotoxicity of gold anticancer agents......Page 228
6.3.3 Reactions with cellular targets......Page 229
6.4 Gold complexes for treating AIDS and other diseases......Page 231
Problems......Page 233
References......Page 235
Further reading......Page 238
7.1 Vanadium for treating diabetes......Page 240
7.1.1 Diabetes mellitus (DM)......Page 241
7.1.2 Bis(ethylmaltolato)oxovanadium(IV), BEOV and bis(maltolate)oxovanadium(IV), BMOV......Page 242
7.1.3 Bis(acetylacetonato)oxovanadium(IV), VO(acac)2, bis(picolinato)oxovanadium(IV), VO(pic)2 and oxodiperoxo(1,10-phenanthroline)vanadium(V), [bpV(phen)]¯......Page 247
7.1.4 Anticancer effects of vanadium compounds......Page 249
7.2.1 Metal chelating agents for treating Alzheimer’s disease......Page 251
7.2.2 Complexes of the amyloid beta (Aβ) peptide......Page 253
7.2.3 Radical production in AD......Page 255
7.3 Copper in Wilson’s and Menkes diseases......Page 256
7.4 Zinc–bicyclam: a chemokine receptor antagonist......Page 259
Problems......Page 263
References......Page 265
Further reading......Page 270
8 Metal Complexes for Diagnosing Disease......Page 272
8.1 Technetium in diagnostic nuclear medicine......Page 273
8.1.1 Clinically used 99mTc imaging agents......Page 276
8.1.2 Technetium imaging agents for selective targeting......Page 281
8.1.3 Innovations in synthesis, the [Tc(CO)3]+ core......Page 283
8.2 Metal compounds as contrast agents for MRI......Page 284
8.2.1 Clinically used MRI contrast agents......Page 287
8.2.2 Contrast agents in development......Page 291
8.2.3 Iron oxide particles......Page 294
8.3 Radionuclides for palliative care and cancer treatment......Page 295
Problems......Page 298
References......Page 300
Further reading......Page 303
9.1.1 Single walled carbon nanotubes......Page 304
9.1.2 Metal–organic frameworks......Page 307
9.1.3 Mesoporous silica......Page 309
9.1.4 Encapsulation......Page 311
9.1.5 Gold nanoparticles......Page 314
9.2.1 Computed tomography......Page 316
9.2.2 Magnetic resonance imaging......Page 317
9.2.3 Quantum dots......Page 321
9.3.1 Cell culture assays and nanomaterials......Page 325
9.3.2 Cytotoxicity of nanoparticles......Page 326
Problems......Page 327
References......Page 328
Further reading......Page 331
Index......Page 332
The Periodic Table......Page 342