DeutschesFachbuch.de : Concepts and Models in Bioinorganic Chemistry

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Contents
ForewordV
PrefaceVII
List of ContributorsXIX
AbbreviationsXXIII
1 The Biodistribution of Metal Ions 1
Robert J. P. Williams
1.1 Introduction 2
1.2 Rates of Exchange 5
1.3 The Limitations of Water as a Solvent 5
1.4 Equilibrium: Values of Binding Constants 7
1.5 Quantitative Metal Ion Equilibria: Donor Strength 7
1.6 The Effect of Size and Charge of Metal Ions 8
1.7 The Effect of Electron Affinity 11
1.8 Control over Ligand Concentration 14
1.9 The Compartments of Organisms 16
1.10 Transport 18
1.11 The Irreversible Binding of Fe, Co, Ni, Mg, and Mo (W)19
1.12 Vanadium, Molybdenum, and Tungsten 20
1.13 Rates of Exchange 21
1.14 Summary 22
References 23
2 Medicinal Inorganic Chemistry 25
Katherine H. Thompson and Chris Orvig
2.1 Introduction 26
2.2 Key Developments 27
2.2.1 Therapeutic Agents 27
2.2.1.1 Arsphenamine: The First Comprehensive Structure-Activity Relationship 28
2.2.1.2 Lithium in Psychiatry: The Dose-Response Relationship 29
2.2.1.3 Cisplatin: Targeted Toxicity 31
2.2.1.4 The Discovery of Essential Trace Elements 32
2.2.1.5 Treatment of Copper- and Iron-Overload Disorders: Metal Ions as Targets 33
2.2.1.6 Radiopharmaceuticals: Utilizing the Nuclear Properties of Metal Ions 34
2.2.2 Diagnostic Agents 35
2.2.2.199 mTc-Labeled Diagnostic Agents 36
2.2.2.2 Targeted Myocardial Imaging with 99 mTc-Sestamibi 36
2.2.2.367 Ga-Citrate Scintigraphy: Computed Tomography 37
2.2.2.4111 In-DTPA-Octreotide-Peptide Binding for Improved Tissue Targeting 37
2.2.2.5 Gadolinium-based MRI Contrast Enhancement 38
2.3 Summary of Key Concepts 39
2.4 Selected Current Research Directions 39
2.4.1 Therapeutic Agents 39
2.4.1.1 Vanadyl Insulin Mimetic Agents: Anticipating Biomolecular Interaction 39
2.4.1.2 Multifunctional Antimalarial Metallopharmaceuticals 40
2.4.1.3 Using Oxidation State to Advantage: Pt(IV) Compounds 41
2.4.2 Diagnostic Agents 41
2.5 Open Questions 42
References 44
3 The Chemical Toxicology of Metals and Metalloids 47
Graham N. George
3.1 Introduction 48
3.2 Arsenic 48
3.2.1 Dietary Sources of Arsenic 51
3.2.2 Arsenic-Selenium Antagonism: Two Wrongs That Do Make a Right!52
3.3 Mercury 52
3.3.1 Mercury in Food 55
3.3.2 Mercury-Selenium Antagonism and Synergism 56
3.3.3 Mercury Chelation Therapy 57
3.4 Chromium 58
3.5 The Promise of New Techniques 58
References 59
4 Theoretical Modeling of Redox Processes in Enzymes and Biomimetic Systems 63
Arianna Bassan, Tomasz Borowski, Marcus Lundberg, and Per E. M. Siegbahn
4.1 Introduction 64
4.2 Computational Model 66
4.3 Nonheme Iron Active Sites That Perform Alkane Hydroxylation and Olefin Oxidation ...
4.4 Keto Acid-Dependent Dioxygenases and Their Synthetic Analogues 72
4.5 Copper Complexes in Enzymes and Synthetic Systems 76
4.5.1 Enzymes with Copper Dimer Complexes 76
4.5.2 Enzymes with Copper Monomer Complexes 80
4.6 Manganese Complexes That Oxidize Water to Dioxygen 81
4.6.1 The Electronic Structure of the Highly Oxidized State 84
4.6.2 The O-O Bond-Formation Reaction 86
4.7 Conclusions 88
References 88
5 Charge Transport in Biological Molecules 93
Yitao Long and Heinz-Bernhard Kraatz
5.1 Introduction 94
5.1.1 A Brief History of Biological Electron Transfer 95
5.1.2 Theoretical Considerations 96
5.2 Electron Transfer in Proteins 98
5.2.1 Studies Involving Metal-labeled Proteins 99
5.2.1.1 Redox Properties 100
5.2.1.2 Studies Involving Azurin 100
5.3 Electron Transfer in Peptides 103
5.4 Charge Transfer in DNA 107
5.4.1 Fundamental Properties 107
5.4.2 Molecular Diagnostics 107
5.4.2.1 Sequence Detection 107
5.4.2.2 Protein-DNA Interactions 109
5.5 Summary and Open Questions 110
References 111
6 Bioorganometallic Chemistry 113
Nils Metzler-Nolte and Kay Severin
6.1 Introduction 115
6.2 Organometallic Complexes in Nature 116
6.3 Synthetic Organometallic Complexes with Bioligands 119
6.4 Organometallic Pharmaceuticals 123
6.5 Analytical Bioorganometallic Chemistry 125
6.6 Bioorganometallic Catalysis 130
6.7 Conclusions and Outlook 133
References 134
7 The Bioinorganic Side of Nucleic Acid Chemistry: Interactions with Metal Ions 137
Bernhard Lippert and Jens Müller
7.1 Introduction: Nucleic Acids and Metals 138
7.2 Modeling Metal-Nucleic Acid Interactions 142
7.2.1 Selected "Classical" Aspects 142
7.2.1.1 Metal-Binding Patterns 142
7.2.1.2 Metals at Close Distance 144
7.2.1.3 DNA Distortion by GG Adduct 146
7.2.1.4 Pt Binding and NMR 147
7.2.1.5 Subtle Consequences of Metal Coordination 148
7.2.1.5.1 Effect of Metal Coordination on H Bonding 148
7.2.1.5.2 Nucleobase Acidification 148
7.2.1.5.3 Metals and Nucleobase Tautomerism 149
7.2.1.6 Irreversible Nucleobase Modifications 150
7.2.2 More Recent Developments 151
7.2.2.1 Molecular Squares 151
7.2.2.2 M-DNA 152
7.2.2.3 Metal-Containing Antisense and Antigene Reagents 153
7.2.2.4 Others 154
7.3 Take-Home Message 154
7.4 Open Questions and Perspectives 155
References 156
8 Nuclease and Peptidase Models 159
Srecko I. Kirin, Roland Krämer, and Nils Metzler-Nolte
8.1 Introduction 159
8.2 Mechanistic Considerations 161
8.3 Substrates for Model Studies 163
8.4 Peptidase Models 166
8.5 Nuclease Models 167
8.5.1 Simple Mononuclear Metal Complexes 167
8.5.2 Dinuclear Metal Complexes 168
8.5.3 Metal-Functional Group Cooperation 170
8.6 Applications 172
References 173
9 Metalloporphyrins, Metalloporphyrinoids, and Model Systems 177
Bernhard Kräutler and Bernhard Jaun
9.1 Introduction: Biological Background 178
9.2 Model Systems and Model Compounds to Understand Biological Function 182
9.2.1 Iron Porphyrins: Hemes in Biological Electron Transfer, Oxygen Transport and Ac...
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Subject Index
A
A-cluster 321
AAS, see atomic absorption spectroscopy
ACE, see angiotensin-converting enzyme
acetate 67
acetyl coenzyme A (acetyl CoA) synthase (ACS) 117, 320
acid phosphatase, purple (PAP), see purple acid phosphatase
aconitase 290 ff.
ACS, see acetyl coenzyme A synthase or carbon monoxide dehydrogenase
activation of dioxygen, reductive, see reductive activation of dioxygen
active site 64
adamalysin (ADAM) 405
adenosine deaminase (ADA) DNA repair protein 420 ff.
ADH, see alcohol dehydrogenase
AdoCbl, see coenzyme B 12
agent, diagnostic, see diagnostic agent
agent, therapeutic, see therapeutic agent
ALAD, see 5-aminolevulinic acid dehydratase
alcohol dehydrogenase (ADH) 131, 400, 417 ff.
alkaline phosphatase 398, 426 ff.
alkane hydroxylation 68
amavadin 214
5-aminolevulinic acid dehydratase (ALAD) 420
aminopeptidase 398 f., 422, 425
ammonia 298
ammonia monooxygenase (AMO) 366
amyloid-beta (Aβ) peptide 365
anemia, antipernicious 199
[9]aneS 3, see 1,4,7-trithiacyclononane
angiotensin 400, 412
angiotensin-converting enzyme (ACE) 400, 412
anhydrase, carbonic, see carbonic anhydrase
anthrax 413
anticancer activity 140
antiferromagnetic coupling 271, 379 ff.
antiferromagnetic interaction 379 f.
antiferromagnetically coupled copper 380
antimalarial 40
AO, see ascorbate oxidase
archaebacteria 332
aromatic hydroxylation 382
arsenate reductase 49
arsenic 26 ff., 48 ff.
arsenic trioxide 48
arsenosugar 51
arsine (AsH 3) 49
arsphenamine 28, 50
arthritis 29
artificial metalloenzyme 130
artificial restriction enzyme 172
ascidians 214
ascorbate oxidase (AO) 366
AsH 3, see arsine
aspartate 67
Asperger's syndrome 55
aspzincins 404, 412 ff.
assay, sandwich, see sandwich assay
atomic absorption spectroscopy (AAS) 125
ATP synthesis 373
Auranofin™ 29
aureolysin 412 f.
autism 55
azapropanedithiolate ligand 339 ff.
Azopt™ 407
azurin (Az) 99 f., 366 ff., 387
B
B 3 LYP 66
B 12-dependent enzyme 203 f.
bacteria
- archae, see archaebacteria
- fermentative, see fermentative bacteria
- hydrogen-metabolizing, see hydrogen-metabolizing bacteria
- photosynthetic, see photosynthetic bacteria
bacteriochlorin 180, 195
bacteriophage T 7 lysozyme 400
BAL, see British anti-Lewisite
barium sulfate 27
β-barrel structure 103
BDE, see bond dissociation energy
benzoylformate (bf) 73
Bertrand diagram 29
bifunctional metalloenzyme 320
binding constant 12
binding site 7
bioavailability, oral 41
biodistribution of metal ion 2 ff.
biomimetic catalytic system 74, 384
biomimetic complex 64, 390
biomimetic imidazole ligand 385
biomimetic low-spin complex 390
biomimetic system 74, 385
bioorganometallic chemistry 115, 204 ff.
biosensor 116
bipolar disease 30
bismuth 27
bismuth subsalicylate 30
bispicolylglycine (BPG) 414 f.
blood-brain barrier 36
blue copper protein 365 ff., 387
BLYP 85
bond angle 7
bond dissociation energy (BDE) 390
bond length 7
botulism 413
BPG, see bispicolylglycine
BrCN 173
brinzolamide 407
British anti-Lewisite (BAL) 33, 48
bromination 226
bromocyclization 224
bromoperoxidase 219
buffering, electronic, see electronic buffering
C
C-C bond desaturation 272
C-cluster 319
C-H activation 199
C-H aromatic bond activation 382
C-H bond cleavage 390
CA, see carbonic anhydrase
CAO, see copper amine oxidase
cadmium 30
calcium 9 ff.
calixarene 410
camphor hydroxylase 178 ff.
cancer, testicular see testicular cancer
Capoten™ 400, 412
captopril 400, 412 ff.
carbon monoxide (CO) 189, 316, 335
- dehydrogenase/acetyl coenzyme A synthase (CODH/ACS) 117, 320
carbonate 6
carbonic anhydrase (CA) 400, 406 ff.
carbonyl ligand 335 ff., 339 f.
carbonyl metalloimmunoassay (CMIA) 128
Carboplatin™ 31, 141
carboxylate ligand 265
carboxylate shift 414
carboxypeptidase A (CPA) 166, 400, 405, 413 f.
carboxypeptidase A 2 400
carboxypeptidase T 405
Cardiolite™ 36 f.
catalytically active RNA (ribonucleic acid) 144
catalysis, RNA, see RNA catalysis
catechol oxidase (CO) 76, 370
CcO, see cytochrome c oxidase
cell 4
cephalosporin 423
ceruloplasmin (Cp) 366, 388
chaperone 9, 138
chaperone copper, see copper chaperone
charge separation 82
charge transfer, ligand-to-metal, see ligand-to-metal charge transfer (LMCT)
chelating agent 33
Chemet® 57
chemotherapy 30
chlorin 19, 180
chloroperoxidase 216
chlorophyll 11, 178 ff.
chloroquine (CQ) 41, 124
chromium 30, 58
chromodulin 58
ciprofloxacin 413
cisplatin 31, 139
citrate 298
clinical trials 123
CMIA, see carbonyl metalloimmunoassay
CO, see carbon monoxide or catechol oxidase
Co(I)-corrinoid 205
cobalamin 30, 117
cobaloxime 184, 206
cobalt 30
cobalt complex, Costa-type, see Costa-type cobalt complex
cobalt corrinoid 199 ff.
CODH, see carbon monoxide dehydrogenase
coenzyme 131
coenzyme B 193
coenzyme B 12 (AdoCbl) 186, 209
coenzyme F 430 178, 192 ff.
cofactor 48, 178 ff.
cofactor biogenesis 390
collagenase 405
σ-complex 75
complex
- biomimetic, see biomimetic complex
- Costa-type cobalt, see Costa-type cobalt complex
- peroxo, see peroxo complex
- windmill, see windmill complex
- zinc alkoxide, see zinc alkoxide complex
compound I (Cpd I) 190
computational model 66
coordination, metal, see metal coordination
coordination sphere, second, see second coordination sphere
copper, see also Cu, dicopper, tricopper or multicopper 26, 68, 363 ff.
- antiferromagnetically coupled, see antiferromagnetically coupled copper
- bis(µ-oxo) core 381
- mixed-valent, see mixed-valent copper
- oxidase (CAO) 366 ff.
- chaperone 365
- dimer complex 76
- monomer complex 80
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