Katja A Strohfeldt
Essentials of Inorganic Chemistry
For Students of Pharmacy, Pharmaceutical Sciences and Medicinal Chemistry
Katja A Strohfeldt
Essentials of Inorganic Chemistry
For Students of Pharmacy, Pharmaceutical Sciences and Medicinal Chemistry
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Medicinal inorganic chemistry is an area of numerous clinical developments and has become very prominent with the discovery of platinum-based anticancer drugs. Currently used clinical applications are not only limited to platinum-based drugs, but indeed encompass a majority of elements found in the periodic table of elements. Therefore, it is crucial that professionals in a variety of healthcare settings have a basic understanding of inorganic chemistry in order to handle the relevant metal-based therapeutics in the correct manner. Essentials of Inorganic Chemistry For Students of Pharmacy,…mehr
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Medicinal inorganic chemistry is an area of numerous clinical developments and has become very prominent with the discovery of platinum-based anticancer drugs. Currently used clinical applications are not only limited to platinum-based drugs, but indeed encompass a majority of elements found in the periodic table of elements. Therefore, it is crucial that professionals in a variety of healthcare settings have a basic understanding of inorganic chemistry in order to handle the relevant metal-based therapeutics in the correct manner. Essentials of Inorganic Chemistry For Students of Pharmacy, Pharmaceutical Sciences and Medicinal Chemistry, introduces the basic principles of inorganic chemistry and the science of metal-based drugs, using pharmacy-relevant examples. Each chapter deals with a group of elements, including the relevant chemical basics, and discusses clinically used examples. Within each chapter, the main inorganic principles or definitions are highlighted in feature boxes. Topics covered include: - Lithium based drugs - their role in the treatment of bipolar disorder - Organosilicon drugs - a modern alternative to traditional organic drugs - Salvarsan - the origin of chemotherapy - Platinum and other transition metal-based anticancer agents - Lanthanoids and their clinical use - Radiopharmacy - Chelation therapy Each chapter is complemented by a series of exercises and problem-based learning case studies to support self-directed studies, with additional materials available online at www.wiley.com/go/strohfeldt/essentials This textbook will provide students of pharmacy, pharmacology, pharmaceutical sciences, and medicinal chemistry with a detailed introduction to inorganic chemistry and the science of metal-based drugs.
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Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
Produktdetails
- Produktdetails
- Verlag: Wiley
- Seitenzahl: 288
- Erscheinungstermin: 9. Februar 2015
- Englisch
- Abmessung: 243mm x 198mm x 12mm
- Gewicht: 490g
- ISBN-13: 9780470665589
- ISBN-10: 0470665580
- Artikelnr.: 41094628
- Verlag: Wiley
- Seitenzahl: 288
- Erscheinungstermin: 9. Februar 2015
- Englisch
- Abmessung: 243mm x 198mm x 12mm
- Gewicht: 490g
- ISBN-13: 9780470665589
- ISBN-10: 0470665580
- Artikelnr.: 41094628
Katja A. Strohfeldt School of Pharmacy, University of Reading, UK
Preface xiii
About the Companion Website xv
1 Introduction 1
1.1 Medicinal inorganic chemistry 1
1.1.1 Why use metal-based drugs? 2
1.2 Basic inorganic principles 3
1.2.1 Electronic structures of atoms 3
1.2.2 Bonds 9
1.3 Exercises 17
References 18
Further Reading 18
2 Alkali Metals 19
2.1 Alkali metal ions 19
2.1.1 Extraction of alkali metals: an introduction to redox chemistry 20
2.1.2 Excursus: reduction - oxidation reactions 21
2.1.3 Chemical behaviour of alkali metals 27
2.2 Advantages and disadvantages using lithium-based drugs 29
2.2.1 Isotopes of lithium and their medicinal application 29
2.2.2 Historical developments in lithium-based drugs 29
2.2.3 The biology of lithium and its medicinal application 30
2.2.4 Excursus: diagonal relationship and periodicity 31
2.2.5 What are the pharmacological targets of lithium? 33
2.2.6 Adverse effects and toxicity 34
2.3 Sodium: an essential ion in the human body 34
2.3.1 Osmosis 35
2.3.2 Active transport of sodium ions 37
2.3.3 Drugs, diet and toxicity 38
2.4 Potassium and its clinical application 40
2.4.1 Biological importance of potassium ions in the human body - action
potential 40
2.4.2 Excursus: the Nernst equation 40
2.4.3 Potassium salts and their clinical application: hypokalaemia 42
2.4.4 Adverse effects and toxicity: hyperkalaemia 43
2.5 Exercises 45
2.6 Case studies 47
2.6.1 Lithium carbonate (Li2CO3) tablets 47
2.6.2 Sodium chloride eye drops 47
References 48
Further Reading 48
3 Alkaline Earth Metals 49
3.1 Earth alkaline metal ions 49
3.1.1 Major uses and extraction 50
3.1.2 Chemical properties 51
3.2 Beryllium and chronic beryllium disease 52
3.3 Magnesium: competition to lithium? 53
3.3.1 Biological importance 53
3.3.2 Clinical applications and preparations 54
3.4 Calcium: the key to many human functions 55
3.4.1 Biological importance 56
3.4.2 How does dietary calcium intake influence our lives? 57
3.4.3 Calcium deficiency: osteoporosis, hypertension and weight management
57
3.4.4 Renal osteodystrophy 58
3.4.5 Kidney stones 59
3.4.6 Clinical application 59
3.4.7 Side effects 61
3.5 Barium: rat poison or radio-contrast agent? 61
3.6 Exercises 63
3.7 Case studies 65
3.7.1 Magnesium hydroxide suspension 65
3.7.2 Calcium carbonate tablets 65
References 66
Further Reading 66
4 The Boron Group - Group 13 67
4.1 General chemistry of group 13 elements 67
4.1.1 Extraction 68
4.1.2 Chemical properties 69
4.2 Boron 70
4.2.1 Introduction 70
4.2.2 Pharmaceutical applications of boric acid 71
4.2.3 Bortezomib 71
4.3 Aluminium 71
4.3.1 Introduction 71
4.3.2 Biological importance 72
4.3.3 Al3+ and its use in water purification 73
4.3.4 Aluminium-based adjuvants 73
4.3.5 Antacids 74
4.3.6 Aluminium-based therapeutics - alginate raft formulations 75
4.3.7 Phosphate binders 76
4.3.8 Antiperspirant 76
4.3.9 Potential aluminium toxicity 77
4.4 Gallium 77
4.4.1 Introduction 77
4.4.2 Chemistry 77
4.4.3 Pharmacology of gallium-based drugs 78
4.4.4 Gallium nitrate - multivalent use 78
4.4.5 Gallium 8-quinolinolate 79
4.4.6 Gallium maltolate 79
4.4.7 Toxicity and administration 80
4.5 Exercises 81
4.6 Case studies 83
4.6.1 Boric acid - API analysis 83
4.6.2 Aluminium hydroxide tablets 83
References 84
Further Reading 84
5 The Carbon Group 85
5.1 General chemistry of group 14 elements 85
5.1.1 Occurrence, extraction and use of group 14 elements 85
5.1.2 Oxidation states and ionisation energies 87
5.1.3 Typical compounds of group 14 elements 87
5.2 Silicon-based drugs versus carbon-based analogues 89
5.2.1 Introduction of silicon groups 90
5.2.2 Silicon isosters 91
5.2.3 Organosilicon drugs 93
5.3 Organogermanium compounds: balancing act between an anticancer drug and
a herbal
supplement 94
5.3.1 Germanium sesquioxide 95
5.3.2 Spirogermanium 97
5.4 Exercises 99
5.5 Cases studies 101
5.5.1 Simethicone 101
5.5.2 Germanium supplements 101
References 102
Further Reading 102
6 Group 15 Elements 103
6.1 Chemistry of group 15 elements 103
6.1.1 Occurrence and extraction 103
6.1.2 Physical properties 104
6.1.3 Oxidation states and ionisation energy 105
6.1.4 Chemical properties 106
6.2 Phosphorus 106
6.2.1 Adenosine phosphates: ATP, ADP and AMP 107
6.2.2 Phosphate in DNA 107
6.2.3 Clinical use of phosphate 108
6.2.4 Drug interactions and toxicity 112
6.3 Arsenic 112
6.3.1 Salvarsan: the magic bullet - the start of chemotherapy 113
6.3.2 Arsenic trioxide: a modern anticancer drug? 116
6.4 Exercises 119
6.5 Case studies 121
6.5.1 Phosphate solution for rectal use 121
6.5.2 Forensic test for arsenic 121
References 122
Further Reading 122
7 Transition Metals and d-Block Metal Chemistry 123
7.1 What are d-block metals? 123
7.1.1 Electronic configurations 123
7.1.2 Characteristic properties 124
7.1.3 Coordination numbers and geometries 125
7.1.4 Crystal field theory 129
7.2 Group 10: platinum anticancer agents 132
7.2.1 Cisplatin 134
7.2.2 Platinum anticancer agents 140
7.3 Iron and ruthenium 147
7.3.1 Iron 148
7.3.2 Ruthenium 155
7.4 The coinage metals 159
7.4.1 General chemistry 159
7.4.2 Copper-containing drugs 160
7.4.3 Silver: the future of antimicrobial agents? 163
7.4.4 Gold: the fight against rheumatoid arthritis 165
7.5 Group 12 elements: zinc and its role in biological systems 168
7.5.1 General chemistry 169
7.5.2 The role of zinc in biological systems 170
7.5.3 Zinc: clinical applications and toxicity 173
7.6 Exercises 177
7.7 Case studies 179
7.7.1 Silver nitrate solution 179
7.7.2 Ferrous sulfate tablets 179
7.7.3 Zinc sulfate eye drops 180
References 181
Further Reading 181
8 Organometallic Chemistry 183
8.1 What is organometallic chemistry? 183
8.2 What are metallocenes? 185
8.3 Ferrocene 187
8.3.1 Ferrocene and its derivatives as biosensors 188
8.3.2 Ferrocene derivatives as potential antimalarial agent 189
8.3.3 Ferrocifen - a new promising agent against breast cancer? 191
8.4 Titanocenes 194
8.4.1 History of titanium-based anticancer agents: titanocene dichloride
and budotitane 195
8.4.2 Further developments of titanocenes as potential anticancer agents
197
8.5 Vanadocenes 200
8.5.1 Vanadocene dichloride as anticancer agents 202
8.5.2 Further vanadium-based drugs: insulin mimetics 203
8.6 Exercises 207
8.7 Case study - titanium dioxide 209
References 210
Further Reading 210
9 The Clinical Use of Lanthanoids 211
9.1 Biology and toxicology of lanthanoids 211
9.2 The clinical use of lanthanum carbonate 213
9.3 The clinical application of cerium salts 214
9.4 The use of gadolinium salts as MRI contrast agents 215
9.5 Exercises 219
9.6 Case study: lanthanum carbonate tablets 221
References 222
Further Reading 222
10 Radioactive Compounds and Their Clinical Application 223
10.1 What is radioactivity? 223
10.1.1 The atomic structure 223
10.1.2 Radioactive processes 224
10.1.3 Radioactive decay 224
10.1.4 Penetration potential 227
10.1.5 Quantification of radioactivity 227
10.2 Radiopharmacy: dispensing and protection 232
10.3 Therapeutic use of radiopharmaceuticals 233
10.3.1 131Iodine: therapy for hyperthyroidism 233
10.3.2 89Strontium 234
10.3.3 Boron neutron capture therapy (BNCT) 235
10.4 Radiopharmaceuticals for imaging 235
10.4.1 99mTechnetium 237
10.4.2 18Fluoride: PET scan 240
10.4.3 67Gallium: PET 241
10.4.4 201Thallium 242
10.5 Exercises 245
10.6 Case studies 247
10.6.1 A sample containing 99mTc was found to have a radioactivity of 15
mCi at 8 a.m. when the sample was tested. 247
10.6.2 A typical intravenous dose of 99mTc-albumin used for lung imaging
contains a radioactivity of 4 mCi 247
10.6.3 Develop a quick-reference radioactive decay chart for 131I 247
References 248
Further Reading 248
11 Chelation Therapy 249
11.1 What is heavy-metal poisoning? 249
11.2 What is chelation? 250
11.3 Chelation therapy 252
11.3.1 Calcium disodium edetate 252
11.3.2 Dimercaprol (BAL) 253
11.3.3 Dimercaptosuccinic acid (DMSA) 254
11.3.4 2,3-Dimercapto-1-propanesulfonic acid (DMPS) 254
11.3.5 Lipoic acid (ALA) 254
11.4 Exercises 257
11.5 Case studies 259
11.5.1 Disodium edetate 259
11.5.2 Dimercaprol 259
References 261
Further Reading 261
Index 263
About the Companion Website xv
1 Introduction 1
1.1 Medicinal inorganic chemistry 1
1.1.1 Why use metal-based drugs? 2
1.2 Basic inorganic principles 3
1.2.1 Electronic structures of atoms 3
1.2.2 Bonds 9
1.3 Exercises 17
References 18
Further Reading 18
2 Alkali Metals 19
2.1 Alkali metal ions 19
2.1.1 Extraction of alkali metals: an introduction to redox chemistry 20
2.1.2 Excursus: reduction - oxidation reactions 21
2.1.3 Chemical behaviour of alkali metals 27
2.2 Advantages and disadvantages using lithium-based drugs 29
2.2.1 Isotopes of lithium and their medicinal application 29
2.2.2 Historical developments in lithium-based drugs 29
2.2.3 The biology of lithium and its medicinal application 30
2.2.4 Excursus: diagonal relationship and periodicity 31
2.2.5 What are the pharmacological targets of lithium? 33
2.2.6 Adverse effects and toxicity 34
2.3 Sodium: an essential ion in the human body 34
2.3.1 Osmosis 35
2.3.2 Active transport of sodium ions 37
2.3.3 Drugs, diet and toxicity 38
2.4 Potassium and its clinical application 40
2.4.1 Biological importance of potassium ions in the human body - action
potential 40
2.4.2 Excursus: the Nernst equation 40
2.4.3 Potassium salts and their clinical application: hypokalaemia 42
2.4.4 Adverse effects and toxicity: hyperkalaemia 43
2.5 Exercises 45
2.6 Case studies 47
2.6.1 Lithium carbonate (Li2CO3) tablets 47
2.6.2 Sodium chloride eye drops 47
References 48
Further Reading 48
3 Alkaline Earth Metals 49
3.1 Earth alkaline metal ions 49
3.1.1 Major uses and extraction 50
3.1.2 Chemical properties 51
3.2 Beryllium and chronic beryllium disease 52
3.3 Magnesium: competition to lithium? 53
3.3.1 Biological importance 53
3.3.2 Clinical applications and preparations 54
3.4 Calcium: the key to many human functions 55
3.4.1 Biological importance 56
3.4.2 How does dietary calcium intake influence our lives? 57
3.4.3 Calcium deficiency: osteoporosis, hypertension and weight management
57
3.4.4 Renal osteodystrophy 58
3.4.5 Kidney stones 59
3.4.6 Clinical application 59
3.4.7 Side effects 61
3.5 Barium: rat poison or radio-contrast agent? 61
3.6 Exercises 63
3.7 Case studies 65
3.7.1 Magnesium hydroxide suspension 65
3.7.2 Calcium carbonate tablets 65
References 66
Further Reading 66
4 The Boron Group - Group 13 67
4.1 General chemistry of group 13 elements 67
4.1.1 Extraction 68
4.1.2 Chemical properties 69
4.2 Boron 70
4.2.1 Introduction 70
4.2.2 Pharmaceutical applications of boric acid 71
4.2.3 Bortezomib 71
4.3 Aluminium 71
4.3.1 Introduction 71
4.3.2 Biological importance 72
4.3.3 Al3+ and its use in water purification 73
4.3.4 Aluminium-based adjuvants 73
4.3.5 Antacids 74
4.3.6 Aluminium-based therapeutics - alginate raft formulations 75
4.3.7 Phosphate binders 76
4.3.8 Antiperspirant 76
4.3.9 Potential aluminium toxicity 77
4.4 Gallium 77
4.4.1 Introduction 77
4.4.2 Chemistry 77
4.4.3 Pharmacology of gallium-based drugs 78
4.4.4 Gallium nitrate - multivalent use 78
4.4.5 Gallium 8-quinolinolate 79
4.4.6 Gallium maltolate 79
4.4.7 Toxicity and administration 80
4.5 Exercises 81
4.6 Case studies 83
4.6.1 Boric acid - API analysis 83
4.6.2 Aluminium hydroxide tablets 83
References 84
Further Reading 84
5 The Carbon Group 85
5.1 General chemistry of group 14 elements 85
5.1.1 Occurrence, extraction and use of group 14 elements 85
5.1.2 Oxidation states and ionisation energies 87
5.1.3 Typical compounds of group 14 elements 87
5.2 Silicon-based drugs versus carbon-based analogues 89
5.2.1 Introduction of silicon groups 90
5.2.2 Silicon isosters 91
5.2.3 Organosilicon drugs 93
5.3 Organogermanium compounds: balancing act between an anticancer drug and
a herbal
supplement 94
5.3.1 Germanium sesquioxide 95
5.3.2 Spirogermanium 97
5.4 Exercises 99
5.5 Cases studies 101
5.5.1 Simethicone 101
5.5.2 Germanium supplements 101
References 102
Further Reading 102
6 Group 15 Elements 103
6.1 Chemistry of group 15 elements 103
6.1.1 Occurrence and extraction 103
6.1.2 Physical properties 104
6.1.3 Oxidation states and ionisation energy 105
6.1.4 Chemical properties 106
6.2 Phosphorus 106
6.2.1 Adenosine phosphates: ATP, ADP and AMP 107
6.2.2 Phosphate in DNA 107
6.2.3 Clinical use of phosphate 108
6.2.4 Drug interactions and toxicity 112
6.3 Arsenic 112
6.3.1 Salvarsan: the magic bullet - the start of chemotherapy 113
6.3.2 Arsenic trioxide: a modern anticancer drug? 116
6.4 Exercises 119
6.5 Case studies 121
6.5.1 Phosphate solution for rectal use 121
6.5.2 Forensic test for arsenic 121
References 122
Further Reading 122
7 Transition Metals and d-Block Metal Chemistry 123
7.1 What are d-block metals? 123
7.1.1 Electronic configurations 123
7.1.2 Characteristic properties 124
7.1.3 Coordination numbers and geometries 125
7.1.4 Crystal field theory 129
7.2 Group 10: platinum anticancer agents 132
7.2.1 Cisplatin 134
7.2.2 Platinum anticancer agents 140
7.3 Iron and ruthenium 147
7.3.1 Iron 148
7.3.2 Ruthenium 155
7.4 The coinage metals 159
7.4.1 General chemistry 159
7.4.2 Copper-containing drugs 160
7.4.3 Silver: the future of antimicrobial agents? 163
7.4.4 Gold: the fight against rheumatoid arthritis 165
7.5 Group 12 elements: zinc and its role in biological systems 168
7.5.1 General chemistry 169
7.5.2 The role of zinc in biological systems 170
7.5.3 Zinc: clinical applications and toxicity 173
7.6 Exercises 177
7.7 Case studies 179
7.7.1 Silver nitrate solution 179
7.7.2 Ferrous sulfate tablets 179
7.7.3 Zinc sulfate eye drops 180
References 181
Further Reading 181
8 Organometallic Chemistry 183
8.1 What is organometallic chemistry? 183
8.2 What are metallocenes? 185
8.3 Ferrocene 187
8.3.1 Ferrocene and its derivatives as biosensors 188
8.3.2 Ferrocene derivatives as potential antimalarial agent 189
8.3.3 Ferrocifen - a new promising agent against breast cancer? 191
8.4 Titanocenes 194
8.4.1 History of titanium-based anticancer agents: titanocene dichloride
and budotitane 195
8.4.2 Further developments of titanocenes as potential anticancer agents
197
8.5 Vanadocenes 200
8.5.1 Vanadocene dichloride as anticancer agents 202
8.5.2 Further vanadium-based drugs: insulin mimetics 203
8.6 Exercises 207
8.7 Case study - titanium dioxide 209
References 210
Further Reading 210
9 The Clinical Use of Lanthanoids 211
9.1 Biology and toxicology of lanthanoids 211
9.2 The clinical use of lanthanum carbonate 213
9.3 The clinical application of cerium salts 214
9.4 The use of gadolinium salts as MRI contrast agents 215
9.5 Exercises 219
9.6 Case study: lanthanum carbonate tablets 221
References 222
Further Reading 222
10 Radioactive Compounds and Their Clinical Application 223
10.1 What is radioactivity? 223
10.1.1 The atomic structure 223
10.1.2 Radioactive processes 224
10.1.3 Radioactive decay 224
10.1.4 Penetration potential 227
10.1.5 Quantification of radioactivity 227
10.2 Radiopharmacy: dispensing and protection 232
10.3 Therapeutic use of radiopharmaceuticals 233
10.3.1 131Iodine: therapy for hyperthyroidism 233
10.3.2 89Strontium 234
10.3.3 Boron neutron capture therapy (BNCT) 235
10.4 Radiopharmaceuticals for imaging 235
10.4.1 99mTechnetium 237
10.4.2 18Fluoride: PET scan 240
10.4.3 67Gallium: PET 241
10.4.4 201Thallium 242
10.5 Exercises 245
10.6 Case studies 247
10.6.1 A sample containing 99mTc was found to have a radioactivity of 15
mCi at 8 a.m. when the sample was tested. 247
10.6.2 A typical intravenous dose of 99mTc-albumin used for lung imaging
contains a radioactivity of 4 mCi 247
10.6.3 Develop a quick-reference radioactive decay chart for 131I 247
References 248
Further Reading 248
11 Chelation Therapy 249
11.1 What is heavy-metal poisoning? 249
11.2 What is chelation? 250
11.3 Chelation therapy 252
11.3.1 Calcium disodium edetate 252
11.3.2 Dimercaprol (BAL) 253
11.3.3 Dimercaptosuccinic acid (DMSA) 254
11.3.4 2,3-Dimercapto-1-propanesulfonic acid (DMPS) 254
11.3.5 Lipoic acid (ALA) 254
11.4 Exercises 257
11.5 Case studies 259
11.5.1 Disodium edetate 259
11.5.2 Dimercaprol 259
References 261
Further Reading 261
Index 263
Preface xiii
About the Companion Website xv
1 Introduction 1
1.1 Medicinal inorganic chemistry 1
1.1.1 Why use metal-based drugs? 2
1.2 Basic inorganic principles 3
1.2.1 Electronic structures of atoms 3
1.2.2 Bonds 9
1.3 Exercises 17
References 18
Further Reading 18
2 Alkali Metals 19
2.1 Alkali metal ions 19
2.1.1 Extraction of alkali metals: an introduction to redox chemistry 20
2.1.2 Excursus: reduction - oxidation reactions 21
2.1.3 Chemical behaviour of alkali metals 27
2.2 Advantages and disadvantages using lithium-based drugs 29
2.2.1 Isotopes of lithium and their medicinal application 29
2.2.2 Historical developments in lithium-based drugs 29
2.2.3 The biology of lithium and its medicinal application 30
2.2.4 Excursus: diagonal relationship and periodicity 31
2.2.5 What are the pharmacological targets of lithium? 33
2.2.6 Adverse effects and toxicity 34
2.3 Sodium: an essential ion in the human body 34
2.3.1 Osmosis 35
2.3.2 Active transport of sodium ions 37
2.3.3 Drugs, diet and toxicity 38
2.4 Potassium and its clinical application 40
2.4.1 Biological importance of potassium ions in the human body - action
potential 40
2.4.2 Excursus: the Nernst equation 40
2.4.3 Potassium salts and their clinical application: hypokalaemia 42
2.4.4 Adverse effects and toxicity: hyperkalaemia 43
2.5 Exercises 45
2.6 Case studies 47
2.6.1 Lithium carbonate (Li2CO3) tablets 47
2.6.2 Sodium chloride eye drops 47
References 48
Further Reading 48
3 Alkaline Earth Metals 49
3.1 Earth alkaline metal ions 49
3.1.1 Major uses and extraction 50
3.1.2 Chemical properties 51
3.2 Beryllium and chronic beryllium disease 52
3.3 Magnesium: competition to lithium? 53
3.3.1 Biological importance 53
3.3.2 Clinical applications and preparations 54
3.4 Calcium: the key to many human functions 55
3.4.1 Biological importance 56
3.4.2 How does dietary calcium intake influence our lives? 57
3.4.3 Calcium deficiency: osteoporosis, hypertension and weight management
57
3.4.4 Renal osteodystrophy 58
3.4.5 Kidney stones 59
3.4.6 Clinical application 59
3.4.7 Side effects 61
3.5 Barium: rat poison or radio-contrast agent? 61
3.6 Exercises 63
3.7 Case studies 65
3.7.1 Magnesium hydroxide suspension 65
3.7.2 Calcium carbonate tablets 65
References 66
Further Reading 66
4 The Boron Group - Group 13 67
4.1 General chemistry of group 13 elements 67
4.1.1 Extraction 68
4.1.2 Chemical properties 69
4.2 Boron 70
4.2.1 Introduction 70
4.2.2 Pharmaceutical applications of boric acid 71
4.2.3 Bortezomib 71
4.3 Aluminium 71
4.3.1 Introduction 71
4.3.2 Biological importance 72
4.3.3 Al3+ and its use in water purification 73
4.3.4 Aluminium-based adjuvants 73
4.3.5 Antacids 74
4.3.6 Aluminium-based therapeutics - alginate raft formulations 75
4.3.7 Phosphate binders 76
4.3.8 Antiperspirant 76
4.3.9 Potential aluminium toxicity 77
4.4 Gallium 77
4.4.1 Introduction 77
4.4.2 Chemistry 77
4.4.3 Pharmacology of gallium-based drugs 78
4.4.4 Gallium nitrate - multivalent use 78
4.4.5 Gallium 8-quinolinolate 79
4.4.6 Gallium maltolate 79
4.4.7 Toxicity and administration 80
4.5 Exercises 81
4.6 Case studies 83
4.6.1 Boric acid - API analysis 83
4.6.2 Aluminium hydroxide tablets 83
References 84
Further Reading 84
5 The Carbon Group 85
5.1 General chemistry of group 14 elements 85
5.1.1 Occurrence, extraction and use of group 14 elements 85
5.1.2 Oxidation states and ionisation energies 87
5.1.3 Typical compounds of group 14 elements 87
5.2 Silicon-based drugs versus carbon-based analogues 89
5.2.1 Introduction of silicon groups 90
5.2.2 Silicon isosters 91
5.2.3 Organosilicon drugs 93
5.3 Organogermanium compounds: balancing act between an anticancer drug and
a herbal
supplement 94
5.3.1 Germanium sesquioxide 95
5.3.2 Spirogermanium 97
5.4 Exercises 99
5.5 Cases studies 101
5.5.1 Simethicone 101
5.5.2 Germanium supplements 101
References 102
Further Reading 102
6 Group 15 Elements 103
6.1 Chemistry of group 15 elements 103
6.1.1 Occurrence and extraction 103
6.1.2 Physical properties 104
6.1.3 Oxidation states and ionisation energy 105
6.1.4 Chemical properties 106
6.2 Phosphorus 106
6.2.1 Adenosine phosphates: ATP, ADP and AMP 107
6.2.2 Phosphate in DNA 107
6.2.3 Clinical use of phosphate 108
6.2.4 Drug interactions and toxicity 112
6.3 Arsenic 112
6.3.1 Salvarsan: the magic bullet - the start of chemotherapy 113
6.3.2 Arsenic trioxide: a modern anticancer drug? 116
6.4 Exercises 119
6.5 Case studies 121
6.5.1 Phosphate solution for rectal use 121
6.5.2 Forensic test for arsenic 121
References 122
Further Reading 122
7 Transition Metals and d-Block Metal Chemistry 123
7.1 What are d-block metals? 123
7.1.1 Electronic configurations 123
7.1.2 Characteristic properties 124
7.1.3 Coordination numbers and geometries 125
7.1.4 Crystal field theory 129
7.2 Group 10: platinum anticancer agents 132
7.2.1 Cisplatin 134
7.2.2 Platinum anticancer agents 140
7.3 Iron and ruthenium 147
7.3.1 Iron 148
7.3.2 Ruthenium 155
7.4 The coinage metals 159
7.4.1 General chemistry 159
7.4.2 Copper-containing drugs 160
7.4.3 Silver: the future of antimicrobial agents? 163
7.4.4 Gold: the fight against rheumatoid arthritis 165
7.5 Group 12 elements: zinc and its role in biological systems 168
7.5.1 General chemistry 169
7.5.2 The role of zinc in biological systems 170
7.5.3 Zinc: clinical applications and toxicity 173
7.6 Exercises 177
7.7 Case studies 179
7.7.1 Silver nitrate solution 179
7.7.2 Ferrous sulfate tablets 179
7.7.3 Zinc sulfate eye drops 180
References 181
Further Reading 181
8 Organometallic Chemistry 183
8.1 What is organometallic chemistry? 183
8.2 What are metallocenes? 185
8.3 Ferrocene 187
8.3.1 Ferrocene and its derivatives as biosensors 188
8.3.2 Ferrocene derivatives as potential antimalarial agent 189
8.3.3 Ferrocifen - a new promising agent against breast cancer? 191
8.4 Titanocenes 194
8.4.1 History of titanium-based anticancer agents: titanocene dichloride
and budotitane 195
8.4.2 Further developments of titanocenes as potential anticancer agents
197
8.5 Vanadocenes 200
8.5.1 Vanadocene dichloride as anticancer agents 202
8.5.2 Further vanadium-based drugs: insulin mimetics 203
8.6 Exercises 207
8.7 Case study - titanium dioxide 209
References 210
Further Reading 210
9 The Clinical Use of Lanthanoids 211
9.1 Biology and toxicology of lanthanoids 211
9.2 The clinical use of lanthanum carbonate 213
9.3 The clinical application of cerium salts 214
9.4 The use of gadolinium salts as MRI contrast agents 215
9.5 Exercises 219
9.6 Case study: lanthanum carbonate tablets 221
References 222
Further Reading 222
10 Radioactive Compounds and Their Clinical Application 223
10.1 What is radioactivity? 223
10.1.1 The atomic structure 223
10.1.2 Radioactive processes 224
10.1.3 Radioactive decay 224
10.1.4 Penetration potential 227
10.1.5 Quantification of radioactivity 227
10.2 Radiopharmacy: dispensing and protection 232
10.3 Therapeutic use of radiopharmaceuticals 233
10.3.1 131Iodine: therapy for hyperthyroidism 233
10.3.2 89Strontium 234
10.3.3 Boron neutron capture therapy (BNCT) 235
10.4 Radiopharmaceuticals for imaging 235
10.4.1 99mTechnetium 237
10.4.2 18Fluoride: PET scan 240
10.4.3 67Gallium: PET 241
10.4.4 201Thallium 242
10.5 Exercises 245
10.6 Case studies 247
10.6.1 A sample containing 99mTc was found to have a radioactivity of 15
mCi at 8 a.m. when the sample was tested. 247
10.6.2 A typical intravenous dose of 99mTc-albumin used for lung imaging
contains a radioactivity of 4 mCi 247
10.6.3 Develop a quick-reference radioactive decay chart for 131I 247
References 248
Further Reading 248
11 Chelation Therapy 249
11.1 What is heavy-metal poisoning? 249
11.2 What is chelation? 250
11.3 Chelation therapy 252
11.3.1 Calcium disodium edetate 252
11.3.2 Dimercaprol (BAL) 253
11.3.3 Dimercaptosuccinic acid (DMSA) 254
11.3.4 2,3-Dimercapto-1-propanesulfonic acid (DMPS) 254
11.3.5 Lipoic acid (ALA) 254
11.4 Exercises 257
11.5 Case studies 259
11.5.1 Disodium edetate 259
11.5.2 Dimercaprol 259
References 261
Further Reading 261
Index 263
About the Companion Website xv
1 Introduction 1
1.1 Medicinal inorganic chemistry 1
1.1.1 Why use metal-based drugs? 2
1.2 Basic inorganic principles 3
1.2.1 Electronic structures of atoms 3
1.2.2 Bonds 9
1.3 Exercises 17
References 18
Further Reading 18
2 Alkali Metals 19
2.1 Alkali metal ions 19
2.1.1 Extraction of alkali metals: an introduction to redox chemistry 20
2.1.2 Excursus: reduction - oxidation reactions 21
2.1.3 Chemical behaviour of alkali metals 27
2.2 Advantages and disadvantages using lithium-based drugs 29
2.2.1 Isotopes of lithium and their medicinal application 29
2.2.2 Historical developments in lithium-based drugs 29
2.2.3 The biology of lithium and its medicinal application 30
2.2.4 Excursus: diagonal relationship and periodicity 31
2.2.5 What are the pharmacological targets of lithium? 33
2.2.6 Adverse effects and toxicity 34
2.3 Sodium: an essential ion in the human body 34
2.3.1 Osmosis 35
2.3.2 Active transport of sodium ions 37
2.3.3 Drugs, diet and toxicity 38
2.4 Potassium and its clinical application 40
2.4.1 Biological importance of potassium ions in the human body - action
potential 40
2.4.2 Excursus: the Nernst equation 40
2.4.3 Potassium salts and their clinical application: hypokalaemia 42
2.4.4 Adverse effects and toxicity: hyperkalaemia 43
2.5 Exercises 45
2.6 Case studies 47
2.6.1 Lithium carbonate (Li2CO3) tablets 47
2.6.2 Sodium chloride eye drops 47
References 48
Further Reading 48
3 Alkaline Earth Metals 49
3.1 Earth alkaline metal ions 49
3.1.1 Major uses and extraction 50
3.1.2 Chemical properties 51
3.2 Beryllium and chronic beryllium disease 52
3.3 Magnesium: competition to lithium? 53
3.3.1 Biological importance 53
3.3.2 Clinical applications and preparations 54
3.4 Calcium: the key to many human functions 55
3.4.1 Biological importance 56
3.4.2 How does dietary calcium intake influence our lives? 57
3.4.3 Calcium deficiency: osteoporosis, hypertension and weight management
57
3.4.4 Renal osteodystrophy 58
3.4.5 Kidney stones 59
3.4.6 Clinical application 59
3.4.7 Side effects 61
3.5 Barium: rat poison or radio-contrast agent? 61
3.6 Exercises 63
3.7 Case studies 65
3.7.1 Magnesium hydroxide suspension 65
3.7.2 Calcium carbonate tablets 65
References 66
Further Reading 66
4 The Boron Group - Group 13 67
4.1 General chemistry of group 13 elements 67
4.1.1 Extraction 68
4.1.2 Chemical properties 69
4.2 Boron 70
4.2.1 Introduction 70
4.2.2 Pharmaceutical applications of boric acid 71
4.2.3 Bortezomib 71
4.3 Aluminium 71
4.3.1 Introduction 71
4.3.2 Biological importance 72
4.3.3 Al3+ and its use in water purification 73
4.3.4 Aluminium-based adjuvants 73
4.3.5 Antacids 74
4.3.6 Aluminium-based therapeutics - alginate raft formulations 75
4.3.7 Phosphate binders 76
4.3.8 Antiperspirant 76
4.3.9 Potential aluminium toxicity 77
4.4 Gallium 77
4.4.1 Introduction 77
4.4.2 Chemistry 77
4.4.3 Pharmacology of gallium-based drugs 78
4.4.4 Gallium nitrate - multivalent use 78
4.4.5 Gallium 8-quinolinolate 79
4.4.6 Gallium maltolate 79
4.4.7 Toxicity and administration 80
4.5 Exercises 81
4.6 Case studies 83
4.6.1 Boric acid - API analysis 83
4.6.2 Aluminium hydroxide tablets 83
References 84
Further Reading 84
5 The Carbon Group 85
5.1 General chemistry of group 14 elements 85
5.1.1 Occurrence, extraction and use of group 14 elements 85
5.1.2 Oxidation states and ionisation energies 87
5.1.3 Typical compounds of group 14 elements 87
5.2 Silicon-based drugs versus carbon-based analogues 89
5.2.1 Introduction of silicon groups 90
5.2.2 Silicon isosters 91
5.2.3 Organosilicon drugs 93
5.3 Organogermanium compounds: balancing act between an anticancer drug and
a herbal
supplement 94
5.3.1 Germanium sesquioxide 95
5.3.2 Spirogermanium 97
5.4 Exercises 99
5.5 Cases studies 101
5.5.1 Simethicone 101
5.5.2 Germanium supplements 101
References 102
Further Reading 102
6 Group 15 Elements 103
6.1 Chemistry of group 15 elements 103
6.1.1 Occurrence and extraction 103
6.1.2 Physical properties 104
6.1.3 Oxidation states and ionisation energy 105
6.1.4 Chemical properties 106
6.2 Phosphorus 106
6.2.1 Adenosine phosphates: ATP, ADP and AMP 107
6.2.2 Phosphate in DNA 107
6.2.3 Clinical use of phosphate 108
6.2.4 Drug interactions and toxicity 112
6.3 Arsenic 112
6.3.1 Salvarsan: the magic bullet - the start of chemotherapy 113
6.3.2 Arsenic trioxide: a modern anticancer drug? 116
6.4 Exercises 119
6.5 Case studies 121
6.5.1 Phosphate solution for rectal use 121
6.5.2 Forensic test for arsenic 121
References 122
Further Reading 122
7 Transition Metals and d-Block Metal Chemistry 123
7.1 What are d-block metals? 123
7.1.1 Electronic configurations 123
7.1.2 Characteristic properties 124
7.1.3 Coordination numbers and geometries 125
7.1.4 Crystal field theory 129
7.2 Group 10: platinum anticancer agents 132
7.2.1 Cisplatin 134
7.2.2 Platinum anticancer agents 140
7.3 Iron and ruthenium 147
7.3.1 Iron 148
7.3.2 Ruthenium 155
7.4 The coinage metals 159
7.4.1 General chemistry 159
7.4.2 Copper-containing drugs 160
7.4.3 Silver: the future of antimicrobial agents? 163
7.4.4 Gold: the fight against rheumatoid arthritis 165
7.5 Group 12 elements: zinc and its role in biological systems 168
7.5.1 General chemistry 169
7.5.2 The role of zinc in biological systems 170
7.5.3 Zinc: clinical applications and toxicity 173
7.6 Exercises 177
7.7 Case studies 179
7.7.1 Silver nitrate solution 179
7.7.2 Ferrous sulfate tablets 179
7.7.3 Zinc sulfate eye drops 180
References 181
Further Reading 181
8 Organometallic Chemistry 183
8.1 What is organometallic chemistry? 183
8.2 What are metallocenes? 185
8.3 Ferrocene 187
8.3.1 Ferrocene and its derivatives as biosensors 188
8.3.2 Ferrocene derivatives as potential antimalarial agent 189
8.3.3 Ferrocifen - a new promising agent against breast cancer? 191
8.4 Titanocenes 194
8.4.1 History of titanium-based anticancer agents: titanocene dichloride
and budotitane 195
8.4.2 Further developments of titanocenes as potential anticancer agents
197
8.5 Vanadocenes 200
8.5.1 Vanadocene dichloride as anticancer agents 202
8.5.2 Further vanadium-based drugs: insulin mimetics 203
8.6 Exercises 207
8.7 Case study - titanium dioxide 209
References 210
Further Reading 210
9 The Clinical Use of Lanthanoids 211
9.1 Biology and toxicology of lanthanoids 211
9.2 The clinical use of lanthanum carbonate 213
9.3 The clinical application of cerium salts 214
9.4 The use of gadolinium salts as MRI contrast agents 215
9.5 Exercises 219
9.6 Case study: lanthanum carbonate tablets 221
References 222
Further Reading 222
10 Radioactive Compounds and Their Clinical Application 223
10.1 What is radioactivity? 223
10.1.1 The atomic structure 223
10.1.2 Radioactive processes 224
10.1.3 Radioactive decay 224
10.1.4 Penetration potential 227
10.1.5 Quantification of radioactivity 227
10.2 Radiopharmacy: dispensing and protection 232
10.3 Therapeutic use of radiopharmaceuticals 233
10.3.1 131Iodine: therapy for hyperthyroidism 233
10.3.2 89Strontium 234
10.3.3 Boron neutron capture therapy (BNCT) 235
10.4 Radiopharmaceuticals for imaging 235
10.4.1 99mTechnetium 237
10.4.2 18Fluoride: PET scan 240
10.4.3 67Gallium: PET 241
10.4.4 201Thallium 242
10.5 Exercises 245
10.6 Case studies 247
10.6.1 A sample containing 99mTc was found to have a radioactivity of 15
mCi at 8 a.m. when the sample was tested. 247
10.6.2 A typical intravenous dose of 99mTc-albumin used for lung imaging
contains a radioactivity of 4 mCi 247
10.6.3 Develop a quick-reference radioactive decay chart for 131I 247
References 248
Further Reading 248
11 Chelation Therapy 249
11.1 What is heavy-metal poisoning? 249
11.2 What is chelation? 250
11.3 Chelation therapy 252
11.3.1 Calcium disodium edetate 252
11.3.2 Dimercaprol (BAL) 253
11.3.3 Dimercaptosuccinic acid (DMSA) 254
11.3.4 2,3-Dimercapto-1-propanesulfonic acid (DMPS) 254
11.3.5 Lipoic acid (ALA) 254
11.4 Exercises 257
11.5 Case studies 259
11.5.1 Disodium edetate 259
11.5.2 Dimercaprol 259
References 261
Further Reading 261
Index 263