Working from basic chemical principles, Metals in Medicine 2nd Edition describes a wide range of metal–based agents for treating and diagnosing disease. Thoroughly revised and restructured to reflect significant research activity and advances, this new edition contains extensive updates and new pedagogical features while retaining the popular feature boxes and end–of–chapter problems of the first edition. Topics include: Metallo–Drugs and their action Platinum drugs for treating cancer Anticancer agents beyond cisplatin including ruthenium, gold, titanium and gallium Responsive Metal Complexes Treating arthritis and diabetes with metal complexes Metal complexes for killing bacteria, parasites and viruses Metal ion imbalance and its links to diseases including Alzheimer s, Wilson s and Menkes disease Metal complexes for detecting disease Nanotechnology in medicine Now in full colour, Metals in Medicine 2nd Edition employs real–life applications and chapter–end summaries alongside feature boxes and problems. It provides a complete and methodical examination of the use of metal complexes in medicine for advanced undergraduate and postgraduate students in medicinal inorganic chemistry, bioinorganic chemistry, biochemistry, pharmacology, biophysics, biology and bioengineering. It is also an invaluable resource for academic researchers and industrial scientists in inorganic chemistry, medicinal chemistry and drug development. INDICE: Feature Boxes .Preface .Acknowledgements .About the Companion Website .1. Inorganic Chemistry Basics .1.1 Introduction .1.2 Crystal field theory .1.2.1 Octahedral crystal field .1.2.2 Other crystal fields .1.2.3 Factors affecting the crystal field splitting parameter, .1.2.3.1 Spectrochemical series .1.2.3.2 Principal quantum number, n .1.2.3.3 Metal ion oxidation state .1.2.4 High– and low–spin complexes .1.3 Molecular orbital theory .1.3.1 MO diagram of molecular hydrogen .1.3.2 MO diagram for [Co(NH3)6]3+ .1.4 Absorption spectra of metal complexes .1.4.1 Band intensity/selection rules .1.4.2 Absorption spectra of multielectron systems .1.5 Magnetic properties of metal complexes .1.6 Structure and reactivity of metal complexes .1.6.1 Forward and reverse rates and equilibrium .1.6.2 Water exchange rates for metal ions .1.6.3 Transition State Theory, the kinetic rate constant and equilibrium .1.6.4 Trans effect and substitution reactions .1.6.5 Stability of metal complexes .1.6.6 Chelate effect .1.6.7 Macrocyclic effect .1.6.8 Hard soft acids bases .1.7 Summary .Discussion questions .Problems .References .Further reading .2. Metallo–Drugs and Their Action .2.1 Introduction .2.2 Proteins as targets for metallo–drugs .2.2.1 Protein structure .2.2.2 Metal binding sites on proteins .2.3 DNA as a target for metallo–drugs .2.3.1 Structure of DNA and RNA .2.3.2 Metal binding sites on DNA .2.4 Reaction of metal complexes in the biological milieu .2.4.1 Reactions with chloride .2.4.2 Reactions with phosphate .2.4.3 Reactions with carbonate .2.5 Evaluating the pharmacological effects of agents .2.5.1 Measuring the cytotoxicity of a drug .2.5.2 Measuring drug uptake .2.5.3 Animal studies .2.6 From discovery to the clinic .2.6.1 Pre–clinical phase of the drug approval process .2.6.2 Investigational new drug (IND) application .2.6.3 Phase I clinical trials .2.6.4 Phase II clinical trials .2.6.5 Phase III clinical trials .2.6.6 New drug application (NDA) .2.6.7 Post–Marketing .2.6.8 Cost of research and development .2.7 Summary .Discussion questions .Problems .References .Further reading .3. Platinum Drugs for Treating Cancer .3.1 Introduction .3.2 Cisplatin .3.2.1 Physical and chemical properties of cisplatin .3.2.2 Formulation, administration, pharmacokinetics and adverse reactions of cisplatin .3.2.3 Reaction of cisplatin in blood .3.2.4 Uptake (influx) of cisplatin by cells .3.2.5 Removal (efflux) of cisplatin from cells. Resistance .3.2.6 DNA as a target for cisplatin .3.2.7 Non–DNA targets for cisplatin .3.3 Carboplatin .3.3.1 Synthesis and properties of carboplatin .3.3.2 Formulation, administration, pharmacokinetics and adverse reactions of carboplatin .3.3.3 Carboplatin activation. Breaking the ring .3.3.4 Reaction of carboplatin with blood proteins .3.3.5 Cytotoxicity and uptake of carboplatin .3.3.6 Interaction of carboplatin with cellular targets .3.4 Oxaliplatin .3.4.1 Synthesis and properties of oxaliplatin .3.4.2 Formulation, administration and pharmacokinetics and adverse reactions of oxaliplatin .3.4.3 Reaction of oxaliplatin in blood .3.4.4 Uptake of oxaliplatin by cells .3.4.5 Interaction of oxaliplatin with cellular targets .3.5 Regionally used platinum drugs .3.5.1 Nedaplatin .3.5.2 Lobaplatin .3.5.3 Heptaplatin .3.6. Platinum agents in preclinical development .3.6.1 Sterically hindered agents .3.6.2 Compounds with the trans geometry .3.6.3 Biologically active cargo molecules .3.6.4 Monofunctional platinum complexes .3.6.5 Multinuclear platinum compounds .3.6.6 Platinum (IV) prodrugs .3.6.7 Platinum compounds that do not attack DNA .3.6.8 Lipoplatin .3.7 Summary .Discussion questions .Problems .References .4. Anticancer Agents Beyond Cisplatin .4.1 Introduction .4.2 Ruthenium .4.2.1 Chemistry of ruthenium in the biological milieu .4.2.2 Structure, synthesis and properties of ruthenium antitumor agents .4.2.3 Synthesis and biological properties of NAMI–A .4.2.4 Control of tumor growth by NAMI–A .4.2.5 Clinical trials with NAMI–A .4.2.6 Interaction of NAMI–A with potential biological targets .4.2.7 Synthesis and reactivity of KP1019 .4.2.8 Anticancer and biological activity of KP1019 .4.2.9 Interaction of KP1019 with biological molecules .4.2.10 Synthesis and properties of ruthenium arene (half–sandwich) compounds .4.2.11 Biological activity of the arene complexes .4.3. Gold anticancer agents .4.3.1 Structures, synthesis and properties of gold anticancer agents .4.3.2 Cellular targets of the gold anticancer agents .4.4 Titanium compounds for treating cancer .4.2.1 Structure, synthesis and properties of titanocene dichloride .4.2.2 Interaction of titanocene dichloride with potential biological targets .4.2.3 Structure, synthesis and properties of budotitane .4.2.4 Antitumor activity and clinical trials with budotitane .4.2.5 Biological interactions of budotitane .4.2.6 Titanium anticancer drugs in development .4.3 Gallium for treating cancer .4.3.1 Chemistry of gallium in biological media .4.3.2 Structures, synthesis and properties of gallium anticancer agents .4.3.3 Uptake, cytotoxicity and reactivity of gallium agents in the biological system .4.3.4 Gallium anticancer agents in development .4.4 Other anticancer active metal complexes .4.5 Summary .Discussion questions .Problems .References .Further reading .5. Responsive Metal Complexes .5.1 Introduction .5.2 Prodrug activation by redox .5.2.1 Platinum .5.2.2 Cobalt .5.2.3 Copper .5.2.4 Iron .5.3 Prodrug activation by pH .5.4 Prodrug activation by enzymes .5.5 Prodrug activation by light .5.2.1 Photo–release of a cytotoxic metal complex .5.2.2 Photo–release of bound drug molecules .5.2.3 Photo–release of cell–signaling molecules .5.6 Photodynamic therapy (PDT) .5.6.1 Porphyrins .5.6.2 Phthalocyanines .5.6.3 Texaphyrins .5.6.4 Bacteriopheophorbides .5.7 Summary .Discussion questions .Problems .References .Further reading .6. Metal Complexes for Treating Arthritis and Diabetes .6.1. Introduction .6.2 Chemistry of gold in biological media .6.3 Gold compounds for treating arthritis .6.3.1 Structures, synthesis and properties of gold antiarthritic drugs .6.3.2 Formulation, administration and pharmacokinetics of gold antiarthritic drugs .6.3.3 Reactions of gold drugs in biological media .6.3.4 Interaction of gold drugs with cellular targets .6.4 Vanadium compounds for treating diabetes .6.4.1 Diabetes mellitus (DM) .6.4.2 Bis(ethylmaltolato)oxovanadium(IV), BEOV and bis(maltolate)oxovanadium(IV), BMOV .6.4.3 Other vanadium complexes with insulin mimetic properties .6.5. Summary .Discussion questions .Problems .References .Further reading .7. Metal Complexes for Killing Parasites, Bacteria and Viruses .7.1 Introduction .7.2 Malaria .7.2.1 Antimalarial drugs .7.2.2 Metallo–antimalarial agents .7.3 Leishmaniasis .7.3.1 Antileishmanial drugs .7.3.2 Antileishmanial drugs in development .7.4 American trypanosomiasis (Chagas disease) .7.4.1 Trypanocidal drugs .7.4.2 Metallo trypanocidal drugs in development .7.5 Human African trypanosomiasis .7.6 Tuberculosis .7.6.1 The antituberculous drug isoniazid .7.6.2 Metallo antituberculous drugs in development .7.7 Peptic ulcer disease .7.7.1 Bismuth anti–ulcer drugs .7.7.2 Metallo anti–ulcer drugs in development .7.7.3 Metallo–drugs for treating minor gastrointestinal disorders .7.8 Syphilis .7.9 Bacterial infections .7.10 Acquired immunodeficiency syndrome (AIDS) .7.11 Summary .Discussion questions .Problems .References .8. Metal Ion Imbalance in the Body .8.1 Introduction .8.2 Alzheimer s disease (AD) .8.2.1 The amyloid cascade hypothesis .8.2.2 The metal ion hypothesis .8.2.3 The oxidative stress hypothesis .8.2.4 Metal chelating agents for treating Alzheimer s disease .8.3. Lithium and the brain .8.4. Wilson s disease (WD). Copper overload .8.5 Menkes disease (MD). Copper deficiency .8.6 Beta thalassemia. Iron overload .8.6.1 Desferrioxamine B .8.6.2 Deferiprone .8.6.3 Deferasirox .8.7 Iron deficiency anemia .8.8 Calcium imbalance .8.9 Chelation therapy .8.10 Summary .Discussion questions .Problems .References .Further reading .9. Metal Complexes for Detecting Disease .9.1 Introduction .9.2 Technetium in diagnostic nuclear medicine .9.2.1 Clinically used 99mTc imaging agents .9.2.2 Technetium drugs for selective targeting .9.2.3 Innovations in synthesis. The [Tc(CO)3]+ core .9.3 Metal compounds as contrast agents for MRI .9.3.1 Clinically used MRI contrast agents .9.3.2 Contrast agents in development .9.4 Radiotherapy .9.5. Summary .Discussion questions .Problems .References .Further reading .10. Nanomedicine .10.1. Introduction .10.2 Circulation, uptake and elimination of nanoparticles .10.2.1 The mononuclear phagocyte system (MPS) .10.2.2 Enhanced permeation and retention effect (EPR) .10.2.3 Cell targeting groups .10.2.4 Uptake of NPs by cells .10.2.5 Biodistribution of nanoparticles in the body .10.3 Nanoscience for treating cancer .10.3.1 Gold nanoparticles (AuNPs) .10.3.2 Mesoporous silica nanoparticles (MSNPs) .10.3.3 Nano metal organic frameworks (NMOFs) .10.4. Nanoparticles for detecting disease .10.4.1 Magnetic resonance imaging (MRI) .10.4.2 Fluorescence spectroscopy (FL) .10.5. Theranostic nanoparticles .10.6. Cytotoxicity of nanoparticles .10.7. Summary .Discussion questions .Problems .References .Index
- ISBN: 978-1-119-19130-8
- Editorial: Wiley–Blackwell
- Encuadernacion: Rústica
- Páginas: 480
- Fecha Publicación: 07/07/2017
- Nº Volúmenes: 1
- Idioma: Inglés