Index

232 tet 42–3 antidiabetic drugs 219–30 antimalarials 211 AAS see atomic absorption spectroscopy AOs see atomic orbitals Ab peptide 230, 232–5 APL see acute promyelocytic leukemia absorption spectra 16–28 apoferritin 292–3 band assignments 24–8 APP see amyloid precursor protein band intensity/selection rules 19–21, 26–7 area under curve (AUC) 113–14, 157 Beer–Lambert law 17–18 arginine 51 110–11, 114 Arrhenius equation 34–5 75–6 (ATO) 290–2 crystal field theory 17–18, 20–8 ascorbic acid 155–6, 157–8 gold compounds 192, 205, 209–10 51 group theory 22 aspartic acid 51, 53 Jahn–Teller distortions 18–19, 20 associative mechanism 35–6, 41 129 ATO see arsenic trioxide ruthenium anticancer drugs 157, 159–60 atomic absorption spectroscopy (AAS) 66–7, 114 spectroscopic/free ion terms 20–4 atomic orbitals (AOs) 11–16 splitting parameters 24–8 ATP7A/B protein mutations 84, 87, 235, 236 Tanabe–Sugano diagrams 22–6, 27 AUC see area under curve titanium III hexahydrate 17–19 auranofin 193–200, 203–5 vanadium antidiabetic drugs 220, 223–7 aurocyanide 210–11 accelerator mass spectrometry (AMS) 132 aurothioglucose 193–4 acquired immunodeficiency syndrome see HIV/AIDS aurothiosulfate 193–4 acquired resistance 118, 158 activation by reduction hypothesis 155 b-cyclodextrin 270–1 acute promyelocytic leukemia (APL) 290–2 b-sheets 51, 202, 204 adenine 58–9 BBR3464 137, 140–1 Alzheimer disease (AD) 230–5, 257–8 BCM-ESR see blood-circulation monitoring–electron AMD3100 238–42 spin resonance Ames tests 67 Beer–Lambert law 17–18 amino acid structure 50–1 BEOV 219–20, 221–5 ammonium tetrathiomolybdate (TTM) 235–6 bicyclams 238–42 AMS see accelerator mass spectrometryCOPYRIGHTEDbis(acetylaceonato)oxovanadium(IV) MATERIAL 220, 226–9 amyloid beta (Ab) peptide 230, 232–5 bis(4,7-dimethyl-1,10-phenanthroline) amyloid cascade hypothesis 230 sulfatooxovanadium(IV) 228–30 amyloid precursor protein (APP) 230 bis(ethylmaltolato)oxovanadium(IV) 219–20, 221–5 animal studies 67 bis(maltolato)oxovanadium(IV) 220, 221–5 anti-HIV/AIDS drugs 210–11, 238, 242 bis(picolinato)oxovanadium(IV) 220, 226–8 antiarthritic drugs 192–205 BL see Burkitt’s lymphoma antibodies 283, 300–2 bladder 121, 132, 207

Metals in Medicine James C. Dabrowiak 2009 John Wiley & Sons, Ltd Index 312 blood-circulation monitoring–electron spin resonance chromium 151–3, 286 (BCM-ESR) 226–7 chrysotherapy 193, 199–200 BMOV 220, 221–5 circular dichroism (CD) 124–6 Bohr magnetons (BM) 28–9 gold compounds 202, 204, 209–10 Boltzmann distribution equation 264 ruthenium anticancer drugs 159–60 182 cisplatin 73–107 [bpV(phen)] 220, 226–9 absorption spectra 75–6 breast cancer 119, 130, 132–3, 156, 163 crystal structure 96–7 budotitane 168–9, 170–5 cytotoxicity 83–9 Burkitt’s lymphoma (BL) 117–18 discovery 73–4 byperglycemia 221 DNA repair 90–1 DNA as target 91–8 cadmium–selenium semiconductors 302–3, 305 drug transport 86–8 289–90 formulation, administration and carbon nanotubes 283–6, 298, 305–6 pharmacokinetics 80–1 carbonate reactions 64–5, 116–17, 120–2 heteronuclear single quantum coherence NMR 77–8, carboplatin 88–9, 109–22 81–2, 91–3 carbonate reactions 116–17, 120–2 modification by glutathione and metallothionein 89 clinical uses 109 nanomedicine 284–6, 287–8, 292–3 cytotoxicity 117–19 nephrotoxicity 81 DNA as target 119–22 non-DNA targets 98–101 formulation, administration and pharmacokinetics 113–14 phosphaplatins 98 hydrolysis in water 112–13 physical and chemical properties 75–80 nanomedicine 292–3 proteins as targets 100–1 prodrug character 114–15 reactions in biological media 81–3, 129 reactions in biological media 114–17, 129 reactions of metal complexes 36–9 structure 110 resistance 117–19, 122, 167, 181 synthesis and properties 109–13 resistance mechanisms 87, 89–91 uptake 117–19 speciation profile in water 76–7, 81 cardiolite 255–6 structure 74 CAs see contrast agents supercoiled DNA 93, 94–6 caspases 210 synthesis 37–9 cathepsins 165, 200–1, 212 trans effect 78–9, 89 CB[7] 176–7 tubulin 100 CD see circular dichroism uptake 83–9, 119 cell-culture assays 65–6, 304–5 zinc finger proteins 98–100 cellular guardians 56–7 clinical trials 68–9 center of gravity rule 4–5 clioquinol (CQ) 231–2 centers of inversion 6–7, 20, 23 cobalt 151–2 ceretec 255–8 colorectal cancer 158 ceruloplasmin 236–7 computed tomography (CT) 295–6 CFSE see crystal field stabilization energy see also single photon emission computed tomography CFT see crystal field theory configuration interactions 7 CH1 cells 163 conjugate bases 52 Chagas disease 211–12 contrast agents (CAs) 251, 263–75 chaperone proteins 161 clinically-used 266–70 charge transfer transitions 16, 19 iron oxide particles 273–5 chelate effect 41–2 nanomedicine 283, 296–300 chelation therapy 230–2 next generation 270–3 chemokine receptor antagonists 238–42 structure and properties 266–8 chloride reactions 63 coordination polymers see metal–organic frameworks 313 Index copper compounds cytotoxicity 65–6 Ab peptide complexes 230, 232–5 carboplatin 117–19 Alzheimer disease 230–5 cisplatin 83–9 Menkes disease 235–8 gallium anticancer drugs 180–1 metal-chelating agents 230–2 gold compounds 196–9, 207–8 radical production in AD 234–5 nanomedicine 285–6, 291–2, 304–6 structure and properties 231–3, 236–7 oxaliplatin 130 Wilson disease 235–8 ruthenium anticancer drugs 163–4 copper homeostasis 86–7 titanium anticancer drugs 176–7 Cotton effect 124, 126 vanadium compounds 228–9 coulombic interactions 9 CQ see clioquinol density functional theory 236 cross peaks 78 deoxyribonucleic acid (DNA) crystal field stabilization energy (CFSE) binding sites 62–3 equilibria 35–6 carboplatin 119–22 gallium anticancer drugs 177 cisplatin 90–8 gold compounds 191–2 crosslinks 62–3, 90, 91–5, 97, 210–11 high- and low-spin complexes 10–11 cytotoxity 66 Jahn–Teller effect 18 drug uptake 67 ruthenium anticancer drugs 149 gold compounds 200–3, 208–10 titanium anticancer drugs 168 intercalation 62–3 crystal field theory (CFT) 1–11 metallo-drug action 58–63 absorption spectra 17–18, 20–8 nanomedicine 286 center of gravity rule 4–5 repair mechanisms 90–1 common coordinate geometries 1–2, 5–7 ruthenium anticancer drugs 157, 164–5 five-fold degenerate d-orbitals 3 structure 58–62 free ions 3–4 supercoiled 93, 94–6 group theory 5 titanium anticancer drugs 170, 175 high- and low-spin complexes 9–11, 26 desferrioxamine (DFO) 231 ligand field theory 28 Dhara synthesis 37–9 MOT comparison 13 diabetes mellitus (DM) 219–30 octahedral crystal field 2–7, 10–11, 13 diagnostic nuclear medicine 251–63 oxidation state of metal 8, 9 clinically used imaging agents 255–9 principal quantum number 8 imaging agents for selective targeting 260–2 reactions of metal complexes 35–6 nanomedicine 288, 295–6 spectrochemical series 7–8 next generation imaging agents 262–3 splitting parameters 5, 7–9, 24–8 single photon emission computed tomography 253–4, Tanabe–Sugano diagrams 22–6, 27 256–63, 274–7 þ transition metal series 2–3 [Tc(CO)3] core 262–3 CT see computed tomography technetium compounds 252–63, 276–7 CTR1 84–7 diamagnetism 28–9, 219–20 cucurbit[7]uril (CB[7]) 176–7 dicyanogold 199 CXCR4 239–42 difference electron density maps 160 cyclams 43–4, 238 disease-modifying arthritis rheumatoid drugs 205 (DMARDs) 193, 201 cysteine dissociative mechanism 35–6, 41 cisplatin 82–3, 98 disulfide exchange 56–7 gold compounds 192, 196–201, 203–4, 211–12 disulfide linkages 192, 193, 196 metal-binding sites 54–5 DM see diabetes mellitus oxaliplatin 128, 133–5 DMARDs see disease-modifying arthritis sartraplatin 139 rheumatoid drugs Index 314 dotarem 266–9 structure and properties 179–80 drug approval process 67–9 synthesis 179–80 DW12 150, 152, 162–7 uptake 180–1 gallium maltolate 179–80 EDTA see ethylenediaminetetraacetic acid gel electrophoresis effective magnetic susceptibility 28 carboplatin 120–2 Ehrlich ascites tumor cells 168, 228 cisplatin 93 electron microscopy 99 gold compounds 200 electron paramagnetic resonance (EPR) 220, 223–7 vanadium compounds 229 electron shielding 78 glial foot 256 electronegativity 15, 37 glucagon 221 electrospray ionisation mass spectrometry (ESI-MS) 129 glucose homoeostasis 221 encapsulation 290–3 glutamic acid 51–3 endocytosis 285, 304 glutamine 51 EPR see electron paramagnetic resonance glutathione (GSH) 56–7 equilibrium constants 29–31 carboplatin 115, 120 cisplatin in water 76–7, 81 cell-culture assays 65 metallo-drug action 52 cisplatin 89, 100 stability of metal complexes 40–1 copper compounds 236 water exchange rates 31–3 gold compounds 199 ESI-MS see electrospray ionisation mass spectrometry oxaliplatin 128–30 ethylenediaminetetraacetic acid (EDTA) 41–2 ruthenium anticancer drugs 150, 158, 165–6 exchange energy 9–10 vanadium compounds 229 GNPs see gold nanoparticles Fenton chemistry 234 gold compounds 191–217 ferritins 292–3 anti-HIV/AIDS drugs 210–11 ferrocenes 152, 154 antiarthritic drugs 192–205 ferromagnetism 29 anticancer drugs 205–10 fibrils 232, 234 antimalarials 211 five-coordinate transition states 35–6 cathepsins as target 200–1 five-fold degenerate d-orbitals 3 Chagas disease 211–12 fluorescence microscopy 263 chrysotherapy 193, 199–200 fluorescence resonance energy transfer (FRET) 84–6 cytotoxicity 196–9, 207–8 5- (5-FU) 122 DNA as target 200–3, 208–10 formyl peptide receptors (FPR) 262–3 formulation, administration and pharmacokinetics 195–6 forward rate constants 29–31 hydrolysis 196–7 free ions 3–4, 21–4 reactions in biological media 191–2, 196–9, 207–8 FRET see fluorescence resonance energy transfer structure and properties 193–5, 205–7 5-FU see 5-fluorouracil synthesis 193–5, 205–7 fullerenes 305 uptake 196–9, 207–8 zinc finger proteins 201–5 gadolinium compounds 266–73, 296–300 gold nanoparticles (GNPs) 293–7, 305 gallium anticancer drugs 177–82 group theory 5, 14, 22 aqueous chemistry 177–9 GSH see glutathione cytotoxicity 180–1 guanidine 55 gallium maltolate 179–80 guanine 58–9 KP46 179–80 next generation 181–2 Haber–Weiss reaction 234 proteasomes as targets 181–2 hard acids/bases 44–5, 62, 192, 208 reactions in biological media 177–9, 180–1 HEK see human embryotic kidney ribonucleotide reductase as target 180–1 Henderson–Hasselbalch equation 52, 77 315 Index hepatotoxicity 136 imidazolium ions 53–4 heptaplatin 135–6 immunocytological assay (ICA) 90 herceptin 300–2 IND see investigational new drugs heteronuclear multiple quantum coherence (HMQC) induced optical activity 159–60 NMR 78 inductively-coupled plasma mass spectrometry heteronuclear single quantum coherence (HSQC) NMR (ICP-MS) 66–7, 114, 115 BBR3464 140 insulin 220–1 carboplatin 111, 116, 120 intercalation 62–3, 165, 175, 177 cisplatin 77–8, 81–2, 91–3 intermediate acids/bases 192, 202, 208 zinc–bicyclam 240 interstrand crosslinks (ISCs) 90, 91–5, 97, 210–11 hexacarbonylchromium 151, 153 intestinal amebiasis 231 high mobility groups (HMG) 96 investigational new drugs (IND) 68 high-performance capillary electrophoresis (HPCE) 158 ionophores 231–2 high-performance liquid chromatography (HPLC) 113, iron oxide particles 273–5 128–30 ISCs see interstrand crosslinks high-resolution transmission electron micrography (HRTEM) 298 Jablonski diagrams 294 high-spin complexes 9–11, 26 Jahn–Teller distortions 18–19, 20, 237, 242 highest occupied molecular orbitals (HOMO) 151, 153, jj coupling 21 163, 302–3 JM1657 238 histidine Jurkat leukemia cells 91, 117–19 cisplatin 82 copper compounds 237–8 kinetic rate constants 33–7 gold compounds 201, 203 kinky hair disease 235–8 metal-binding sites 51, 53 KP46 179–80 HIV/AIDS 210–11, 238, 242 KP1019 150, 158–61 HMG see high mobility groups HMQC see heteronuclear multiple quantum coherence lactate dehydrogenase (LDH) 89 hOCT see human organic cation transporter lactoferrins 160–1 HOMO see highest occupied molecular orbitals Laporte selection rule 19, 21, 26–7 HPCE see high-performance capillary electrophoresis LCAO see linear combination of molecular orbitals HPLC see high-performance liquid chromatography LDH see lactate dehydrogenase HRTEM see high-resolution transmission electron leishmaniasis 212 micrography Lewis lung carcinoma 156 HSAB concept 44–5, 62, 191–2, 202, 208 ligand field theory 28 HSQC see heteronuclear single quantum coherence ligand-to-metal charge transfer (LMCT) 16, 19, 21 human embryotic kidney (HEK) 88 linear combination of molecular orbitals (LCAO) 12 human immunodeficiency virus see HIV/AIDS linear crystal field 2, 7 human organic cation transporter (hOCT) 88–9 liposomes 290–3 Hund’s rule 9 LMCT see ligand-to-metal charge transfer hydrogen bonding 51 lobaplatin 135–6 hyperparathyroidism 256 longboat delivery systems 284 low-spin complexes 9–11, 26 ibritumomab tiuxetan 277 lowest unoccupied molecular orbitals (LUMO) 151, 153, ibuprofen 286–7 163, 302–3 IC50 assays 66 lung cancer 164 ICA see immunocytological assay lysine 51, 54 ICP-MS see inductively-coupled plasma mass spectrometry macrocyclic effect 42–4, 207, 268 imaging agents see technetium compounds maghemite 298–9, 305 imidazoles 53–4 magnetic quantum number 11 Index 316 magnetic resonance imaging (MRI) 251, 263–75 metastasis 156, 261–2 clinically-used contrast agents 266–70 metathesis reactions 206 contrast agents 251, 263–75 methionine instrumentation schematic 267 binding-sites 54–5 iron oxide particles 273–5 carboplatin 115, 120 nanomedicine 283, 296–300 cisplatin 82–3 next generation contrast agents 270–3 gold compounds 192 principles 264–6 oxaliplatin 128, 133 magnetic spin quantum number 11, 19 sartraplatin 139 magnetite 274 metvan 228–30 magnevist 266–9, 298 microstates 21 malaria 211 99 maltol 176 MIL-100/MIL-101 286–8 mammary carcinoma 156, 163 mismatch repair (MMR) 90 manganese compounds 152, 267, 269–70 MLCT see metal-to-ligand charge transfer manganism 270 Mobil Crystalline Material-41 (MCM-41) 288–9, 306 MCM-41 see Mobil Crystalline Material-41 MOFs see metal–organic frameworks MDA-MB-231 breast cancer 132–3 molecular orbital theory (MOT) 11–16 MDR see multidrug resistance absorption spectra 19 melanoma 156 CFT comparison 13 Menkes disease 86, 235–8 charge transfer transitions 16, 19 6- 205 electronegativity 15 mesoporous silica nanoparticles (MSNs) 288–90, 306 group theory 14 metal-chelating agents 230–2 hexaminocobalt III MO diagram 13–16 metal–organic frameworks (MOFs) 286–8 linear combination of molecular orbitals 12 metal-to-ligand charge transfer (MLCT) 16, 19, 21 molecular hydrogen MO diagram 11–13 metallo-drug action 49–72 nanomedicine 294–5, 302–3 animal studies 67 nonbonding orbitals 16 binding sites 51–6, 62–3 octahedral molecular orbital 13–16 carbonate reactions 64–5 organometallic chemistry 151–4 cellular guardians 56–7 ruthenium anticancer drugs 163 chloride reactions 63 molybdenum decay scheme 252–3 cytotoxicity 65–6 monoclonal antibodies 283, 300–2 disulfide exchange 56–7 MOT see molecular orbital theory DNA structure 58–62 mozobil 238–42 DNA as target 58–63 MRI see magnetic resonance imaging drug approval process 67–9 MS-325 271–3 drug uptake 66–7 MSNs see mesoporous silica nanoparticles pharmacological evaluation 65–7 MT see metallothionein phosphate reactions 64 multicompartment model 114 profits 69 multidrug resistance (MDR) 87, 132–3 protein structure 50–1 myocardial ischemia 256 proteins as targets 49–57 myochrysine 193–5, 201, 204 redox reactions 56–7 resonance stabilization 55–6 Na þ /H þ exchanger protein (NHE1) 98 metallo-enzymes 49 NADH see nicotinamide adenine dinucleotide metallothionein (MT) NAMI-A 150, 153–8 binding-sites 57 nanomedicine 283–310 cisplatin 89 cell-culture assays 304–5 copper compounds 235, 236 contrast agents for MRI 283, 296–300 oxaliplatin 129 cytotoxicity 285–6, 291–2, 304–6 317 Index

diagnostic nuclear medicine 288, 295–6 one electron energies 7 encapsulation 290–3 optical rotatory dispersion (ORD) 124–6 gold nanoparticles 293–7, 305 orbital angular momentum quantum number 11, 19 magnetic resonance imaging 283, 296–300 organic anion transporter 1 (OAT1) 258 mesoporous silica nanoparticles 288–90, 306 Osmium anticancer drugs 167 metal–organic frameworks 286–8 ovarian cancer 163–4, 182 293–5, 297 oxaliplatin 88–9, 122–34 anticancer drugs 284–6, 287–8, 292–3 cytotoxicity 130 quantum dots 300–3, 305 DNA as target 130–3 single-walled carbon nanotubes 283–6, 298, 305–6 formulation, administration and treatment of disease 283–95 pharmacokinetics 127 nanoscale coordination polymers (NCP) 288 nucleosome core particles 132, 134 NBDs see nucleotide-binding domains optical activity 123–6 NCF see nephrogenic cystic fibrosis reactions in biological media 128–30 NCP see nanoscale coordination polymers; nucleosome structure and stereochemistry 122–6, 127, 131–2 core particles synthesis and properties 126–7 NDA see new drug applications thioredoxin reductase as target 133–5 88–9, 135–6 uptake 119, 130 nephrogenic cystic fibrosis (NCF) 268 oxidoperoxo(1,10-phenanthroline)vanadium(V) nephrotoxicity 81 monoanion 220, 226–9 NER see nucleotide excision repair neuroblastoma cells 117–19, 181–2, 306 p-glycoprotein (P-gp) 87–8 neurofibrillary tangles 230 p21-activated kinase-1 (PAK1) 166–7 new drug applications (NDA) 69 p53 96, 140, 150 NHE1 see Na þ /H þ exchanger protein 100, 136 nicotinamide adenine dinucleotide (NADH) 56, 66 PAK1 see p21-activated kinase-1 nitric oxide signaling pathway 167 palliative care 251, 274–7 NJ see normal Jurkat paramagnetism 28–9 NMR see nuclear magnetic resonance contrast agents 273–5 NOESY see Nuclear Overhauser effect spectroscopy nanomedicine 295 nonbonding orbitals 16 ruthenium anticancer drugs 154 normal Jurkat (NJ) cells, carboplatin 117–18 vanadium antidiabetic drugs 219–20 nuclear magnetic resonance (NMR) spectroscopy passive diffusion 67 copper compounds 232–3 Pc see phthalocyanine gold compounds 197–8 PCR see polymerase chain reaction oxaliplatin 88–9, 130–1 PDT see photodynamic therapy ruthenium anticancer drugs 156 penicillamine 231, 235 titanium anticancer drugs 169–70, 173–5 pentagonal bipyramidal crystal field 2, 7 see also heteronuclear single quantum coherence NMR; peptide bonds 52 magnetic resonance imaging pertechnate ion 253, 258 nuclear medicine see diagnostic nuclear medicine pharmacokinetics Nuclear Overhauser effect spectroscopy (NOESY) 130 animal studies 67 nuclear spin angular momentum quantum number 264 carboplatin 113–14 nuclear spin quantum number 264 cisplatin 80–1 nucleosome core particles (NCP) 132, 134 gold compounds 195–6 nucleotide excision repair (NER) 90–1 oxaliplatin 127 nucleotide-binding domains (NBDs) 87 vanadium compounds 221–2, 229 pharmacological evaluation 65–7 OAT1 see organic anion transporter 1 phase changes 39 octahedral crystal field 2–7, 10–11, 13 phosphaplatins 98 octahedral molecular orbital 13–16 phosphate reactions 64 Index 318 phosphodiester bonds 59–60 R-S see Russell–Saunders photodynamic therapy (PDT) 229–30, 293–5, 297 RA see rheumatoid arthritis phthalocyanine (Pc) 293–4 radionuclides 251, 274–7 picoplatin 137, 139–40 rCBF see regional cerebral blood flow PKC see protein kinase C reactions of metal complexes 29–45 plaques 230 associative/dissociative mechanisms 35–6, 41 plasma ultra filtrate (PUF) 127–9 chelate effect 41–2 plasmids 94 hard-soft acids-bases 44–5 platinum anticancer drugs 109–47 kinetic rate constant and equilibria 33–7, 40–1 BBR3464 137, 140–1 macrocyclic effect 42–4 carboplatin 88–9, 109–22, 292–3 rate constants and equilibria 29–33 heptaplatin 135–6 stability of metal complexes 40–1 lobaplatin 135–6 substitution reactions 37–40 nanomedicine 284–6, 287–8, 292–3 trans effect 37–40 nedaplatin 88–9, 135–6 transition state theory 33–7 oxaliplatin 119, 122–34 water exchange rates and metal ions 31–4 picoplatin 137, 139–40 reactive oxygen species (ROS) 56 136–9 copper compounds 234–5 see also cisplatin gallium anticancer drugs 181 point group symmetry 20 gold compounds 199 polymerase chain reaction (PCR) 84 nanomedicine 294–5, 297, 305 porphyrins 43–4, 210, 272, 294, 297 ruthenium anticancer drugs 150, 164–5 pre-clinical phase 68 receptor-induced magnetization enhancement principal quantum number 8, 11 (RIME) 271 prodrugs 114–15, 239 redox reactions 56–7 profits 69 regional cerebral blood flow (rCBF) 258 prophine 297 rehnium 275 proteasomes 181–2 reporter ligands 79 protein kinase C (PKC) 170 resistant Jurkat (RJ) cells 117–19 protein scaffolds 201–2 resonance stabilization 55–6 proteins retinoblastoma tumor suppressor 229 binding sites 51–6 reverse rate constants 29–31 cellular guardians 56–7 rhenium compounds 263 cisplatin 100–1 rheumatoid arthritis (RA) 192–205 copper compounds 230 ribonucleic acid (RNA) 58–62, 201 disulfide exchange 56–7 ribonucleotide reductase (RNR) 180–1 drug uptake 67 RIME see receptor-induced magnetization enhancement oxaliplatin 133–4 RJ see resistant Jurkat redox reactions 56–7 RNA see ribonucleic acid resonance stabilization 55–6 RNR see ribonucleotide reductase ruthenium anticancer drugs 165–7 ROS see reactive oxygen species structure 50–1 RPMI complex 81–2 as targets 49–57 Russell–Saunders (R-S) coupling 21 titanium anticancer drugs 175 ruthenium anticancer drugs 149–67 zinc–bicyclam 239–42 arene compound class 150, 152, 161–7 see also zinc finger proteins ascorbic acid 155–6, 157–8 pseudo first-order reactions 32–3, 112, 116, 128 clinical trials 157, 159 PUF see plasma ultra filtrate control of tumor growth 156 pyrimidine 58–9 cytotoxicity 163–4 DNA as target 157, 164–5 quantum dots (QDs) 300–3, 305 DW12 150, 152, 162–7 quantum mechanics (QM) 1, 9, 20–1 hydrolysis 154–6 319 Index

KP1019 150, 158–61 strong field ligands 8 metastasis 156 substitution reactions 37–40 NAMI-A 150, 153–8 super paramagnetic iron oxide (SPIO) 274, 298–9, 305 oxidation states of ruthenium 149–50 supercoiled DNA 93, 94–6 potential biological targets 157–8, 159–61, 164–7 superoxide dismutases (SOD) 234 proteins as targets 165–7 SWNTs see single-walled carbon nanotubes reactions in biological media 149–50, 153–6, 158, 163–4 T-S see Tanabe–Sugano structure and properties 150–3, 161–3 Tanabe–Sugano (T-S) diagrams 22–6, 27 synthesis 153–5, 158, 161–3 taxol 100 transferrins 158, 159–62, 164 Tc-HDP 276 Tc-HMPAO 255–8 sanochrysine 193–4 Tc-MAG3 255, 258–9 satraplatin 136–9 Tc-MDP 255–6 þ scanning electron microscopy (SEM) 295 [Tc(BIMI)6] 255–6 þ scintillation counting 119 [Tc(CO)3] core 262–3 SEC see size exclusion chromatography [TcO]depreotide 260–2 selenocysteine 133–5, 204–5, 291 technetium compounds self-complimentary strands 92 clinical trials 259 259 clinically used imaging agents 255–9 SEM see scanning electron microscopy diagnostic nuclear medicine 252–63, 274–7 semiconductors 302–3, 305 imaging agents for selective targeting 260–2 seven-coordinate transition states 35–6 molybdenum decay scheme 252–3 single photon emission computed tomography next generation 262–3 (SPECT) 253–4, 256–63, 275–7 single photon emission computed tomography 253–4, single-walled carbon nanotubes (SWNTs) 283–6, 298, 256–63, 274–7 305–6 structure and properties 255 þ size exclusion chromatography (SEC) 115 [Tc(CO)3] core 262–3 SKBR3 cells 163 TEM see transmission electron micrography SOD see superoxide dismutases terbium compounds 288 sodium aurothiomalate 193–5, 201, 204 teslascan 267, 269–70 sodium vanadate 219–20 testicular cancer 132–3 soft acids/bases 44–5, 62, 191–2 tetragonal crystal field 5–6 solganol 193–4 tetrahedral crystal field 2, 6–7 solid-state NMR 232–3 TGN see trans-Golgi network somatostatin receptors (SSTRs) 260 thalassaemia 231 species distribution plots 178–9 thin-layer chromatography (TLC) 117 SPECT see single photon emission computed tomography thioredoxin reductase (TrxR) spectrochemical series 7–8 cisplatin 100 spin correlations 9–10 gold compounds 204 spin multiplicity 23 nanomedicine 291 spin selection rule 19–21, 26–7 oxaliplatin 133–5 spin-only magnetic susceptibility 28–9 thiourea 120 SPIO see super paramagnetic iron oxide thymine 58–9 splitting parameters 5, 7–9, 24–8 titanium anticancer drugs 167–77 squamous cell carcinoma 261–2 antitumor activity 174–5 square planar crystal field 2, 5–7 budotitane 168–9, 170–5 square pyramidal crystal field 2, 7 clinical trials 169, 174–5 SSTRs see somatostatin receptors cucurbit[7]uril 176–7 staurosporine 150, 152 cytotoxicity 176–7 stopped-flow kinetics 155, 196 DNA as target 170, 175 (STZ) 221, 226 geometric and optical isomerism 170, 171–4 Index 320 titanium anticancer drugs (Continued ) UV-visible absorption spectra next generation 175–7 carboplatin 110–11 potential biological targets 170 gold compounds 192, 205 proteins as targets 175 ruthenium anticancer drugs 157, 159–60 reactions in biological media 175 structure and properties 168–75 vanadium compounds synthesis 168–9, 173–4 anticancer drugs 228–30 titanocene dichloride 168–70 antidiabetic drugs 219–30 transferrins 169 BEOV/BMOV 219–20, 221–5 titanocene dichloride 168–70 clinical trials 219, 222–3, 229 TLC see thin-layer chromatography cytotoxicity 228–9 trans effect 37–40 disease profile 220–1 carboplatin 115 historical development 219 cisplatin 78–9, 89, 96–7 pharmacokinetics 221–2, 229 satraplatin 137–8 structure and properties 220 trans-Golgi network (TGN) 86 vanadate/vanadyl 219–20, 225, 227 factors 201–3 vanadocene dichloride/VO(salmet)(dpq)/ transferrins metvan 228–30 gallium anticancer drugs 180 VO(pic)2/VO(acac)2/[bpV(phen)] 220, 226–9 ruthenium anticancer drugs 158, 159–62, 164 vanadocene dichloride 228–30 titanium anticancer drugs 169 vanadyl 219–20, 225, 227 vanadium compounds 222, 226 vitamin B12 231 transition state theory 33–7 vitamin C 155–6, 157–8 transmission electron micrography (TEM) 293–4, 298 VO(acac)2 220, 226–9 transplatin VO(pic)2 220, 226–8 DNA as target 93–4, 96 VO(salmet)(dpq) 228–30 reactions of metal complexes 36–40 VPA 220, 226–9 synthesis 39–40 transporter proteins 67, 84, 87 water exchange rates 31–4 trastuzumab 300–2 Watson–Crick base pairings 61, 90, 92, 94–6 tricapped trigonal prism crystal field 2, 7 weak field ligands 8 triethylenetetramine (trientine) 235 Wilson disease 86, 235–8 trigonal bipyramidal crystal field 2, 7 writhe 94 trigonal crystal field 2, 7 triplatin tetranitrate 140–1 X-ray absorption near-edge spectroscopy (XANES) 139 triple orbital degeneracy 18 x-ray analysis trisenox 290 carboplatin 111 TrxR see thioredoxin reductase oxaliplatin 126–7, 131 tryptophan 51, 55 zinc–bicyclam 241 TTM see ammonium tetrathiomolybdate XANES see X-ray absorption near-edge spectroscopy tubulin 100 xenobiotics 56, 86–7 two-dimensional NMR 130–1 tyrosine 51, 54–5 yttrium 275, 277 ubiquitin 181–2 zevalin 277 ultra-small super paramagnetic iron oxide (USPIO) zinc finger proteins 98–100, 201–5 274, 298–9, 305 zinc–bicyclam 238–42 ultrafilterable platinum 81, 82, 114 zinc-gadolinium complexes 272–3

This index was prepared by Neil Manley.