Note: Intro -- Bioorganometallics -- Preface -- Contents -- List of Contributors -- 1 A Novel Field of Research: Bioorganometallic Chemistry, Origins, and Founding Principles -- 1.1 Introduction -- 1.2 Organometallics and Therapy -- 1.2.1 The Founding Father -- 1.2.2 The First Significant Organometallic Drug -- 1.2.3 Arsenic Compounds after Ehrlich -- 1.2.4 Organometallic Mercury Compounds -- 1.2.5 The Current Re-evaluation: Considerations of Efficacy, Toxicity and Selectivity -- 1.3 Toxicology and the Environment -- 1.4 Bioanalytical Methods Based on Special Properties of Organometallic Complexes -- 1.5 Naturally-occurring Organometallics and Synthetic Models -- 1.6 Organometallic Chemistry and Aqueous Solvents -- 1.7 Conclusions -- References -- 2 Ruthenium Arene Anticancer Complexes -- 2.1 Introduction -- 2.2 Metal-based Anticancer Complexes -- 2.3 Chemistry of Ru Arenes -- 2.3.1 Synthesis -- 2.3.2 Structure -- 2.3.3 Chirality -- 2.4 Biological Activity -- 2.4.1 Antibacterial -- 2.4.2 Anticancer -- 2.4.3 Biodistribution and Metabolism -- 2.5 Mechanism of Action -- 2.5.1 Nucleobase and DNA Binding -- 2.5.2 Amino Acids and Proteins -- 2.5.3 Aquation -- 2.6 Conclusions -- References -- 3 Organometallics Targeted to Specific Biological Sites: the Development of New Therapies -- 3.1 Introduction -- 3.2 Overview of Previous Developments -- 3.3 Metal Complex SERMs (Selective Estrogen Receptor Modulators) -- 3.3.1 Inorganic Complexes of Platinum -- 3.3.2 Carborane Derivatives with Estrogenic Properties -- 3.3.3 Titanocene Dichloride Derivative of Tamoxifen -- 3.3.4 Cyclopentadienyl Rhenium Tricarbonyl Derivatives of Tamoxifen Derivatives -- 3.3.5 Ferrocene Tamoxifen Derivatives (Ferrocifens) -- 3.3.6 Ruthenocene Tamoxifen Derivatives -- 3.3.7 Conclusion for SERMs -- 3.4 The Alkyne Cobalt Carbonyl Complexes. , 3.5 Ferroquine, a New Weapon in the Fight Against Malaria: the Archetypical Bioorganometallic Approach -- 3.5.1 The Problem of Malaria -- 3.5.2 Ferroquine: a Bioorganometallic Approach -- 3.5.3 Conclusion for Ferroquine -- 3.6 Other Examples of Organometallics Complexes Tested for their Biological Activities -- 3.7 Conclusions -- References -- 4 Radiopharmaceuticals -- 4.1 What are Radiopharmaceuticals? -- 4.1.1 Radiopharmaceutical Drug Finding and Drug Development -- 4.1.2 Organometallic Complexes in Radiopharmaceutical Routines -- 4.2 Organometallic Aquo-ions -- 4.3 The Prototype [(99)Tc(OH(2))(3)(CO)(3)](+), Synthesis and Properties -- 4.3.1 Coordination Chemistry with [(99)Tc(OH(2))(3)(CO)(3)](+) -- 4.3.2 Organometallic Chemistry in Water with [(99)Tc(OH(2))(3)(CO)(3)](+) -- 4.4 Combining [(99)Tc(OH(2))(3)(CO)(3)](+) with Targeting Vectors -- 4.5 Perspectives -- References -- 5 Conjugates of Peptides and PNA with Organometallic Complexes: Syntheses and Applications -- 5.1 Introduction -- 5.2 Conjugates of Organometallics with Small Peptides -- 5.2.1 Organometallics as Templates for the Induction of Secondary Structural Elements in Peptides -- 5.2.1.1 Derivatives of 1,1'-Ferrocene Dicarboxylic Acid -- 5.2.1.2 Other Derivatives -- 5.2.2 Peptides as Ligands for Organometallics -- 5.3 Conjugates of Organometallics with Natural Peptides -- 5.3.1 Organometallic Derivatives of Enkephalins -- 5.3.2 Organometallic Derivatives of Peptide Hormones -- 5.3.2.1 Substance P and Neurokinin A -- 5.3.2.2 Angiotensin -- 5.3.2.3 Bradykinin -- 5.3.2.4 Gonadotropin-releasing Hormone -- 5.3.2.5 Secretin -- 5.3.3 Organometallic Derivatives of Other Peptides -- 5.3.3.1 Nuclear Localization Signal -- 5.3.3.2 Glutathione -- 5.3.3.3 Papain Inhibitors -- 5.3.3.4 Alamethicin -- 5.3.3.5 Others -- 5.3.4 Enzymatic Degradation of Organometallic Peptide Derivatives. , 5.4 Conjugates of Organometallics with PNA -- 5.4.1 Conjugates of PNA Monomers -- 5.4.2 Conjugates of PNA Oligomers -- 5.5 Applications -- 5.5.1 Organometallic Protecting Groups for Peptide Synthesis -- 5.5.1.1 Ferrocene-derived Protecting Groups -- 5.5.1.2 Aminocarbene-derived Protecting Groups -- 5.5.2 Peptide Synthesis -- 5.5.2.1 Template Synthesis of Peptides with Organometallics -- 5.5.2.2 Ugi Four-component Reaction -- 5.5.2.3 Ruthenium-mediated Coupling of Aryl Ethers for the Synthesis of Cyclic Peptides -- 5.5.3 Labeling of Peptides -- 5.5.3.1 HPLC with Electrochemical Detection (HPLC-ECD) -- 5.5.3.2 Radioactive Labels -- 5.5.4 Host-guest Chemistry and Biosensors -- References -- 6 Labeling of Proteins with Organometallic Complexes: Strategies and Applications -- 6.1 Introduction -- 6.2 Redox Probes -- 6.2.1 Amperometric Biosensors -- 6.2.1.1 Diffusional Mediators -- 6.2.1.2 Electron Relays -- 6.2.1.3 Electrical Wiring -- 6.2.2 HPLC and Immunoassays -- 6.2.3 Enzyme Structural Studies -- 6.2.4 Other applications -- 6.3 Luminescent Probes -- 6.3.1 Long-lived Probes -- 6.3.2 Electron Tunneling Studies -- 6.4 Heavy Metal Probes -- 6.4.1 Structural Analysis of Proteins by X-ray Crystallography -- 6.4.2 Cryo-electron Microscopy -- 6.4.3 Pharmacological Studies -- 6.5 Metallo-carbonyl Probes for Infrared Spectroscopy -- 6.6 Conclusions and Outlook -- References -- 7 Organometallic Bioprobes -- 7.1 Introduction -- 7.2 The Definition of the Terms Bioprobes and Molecular Bioprobes -- 7.3 Response Strategies for the Read-out of Information -- 7.4 Organometallic Components for Organometallic Bioprobes - Opening up the Advantages of IR-based Read-out Methods -- 7.5 Selectivity of Responses in IR-based Read-out Methods -- 7.5.1 Solvent-induced Effects -- 7.5.2 Responses to pH -- 7.5.3 Responses to Alkali Metal Ion Concentrations. , 7.5.4 Responses to π-Stacking Interactions between Organic Structures -- 7.6 Examples of Organometalcarbonyl Bioprobe Structures -- 7.7 Use of Organometallic Bioprobes with Proteins -- 7.8 Power of Genetics in the Design of Bioprobe Experiments -- 7.8.1 Remote and Local Response Capabilities -- 7.8.2 Functional and Dysfunctional Probes -- 7.8.3 Functional and Dysfunctional Receptors -- 7.8.4 Functional and Dysfunctional Probes and Receptors to Study the Induction of nod Gene Expression -- 7.9 Conclusions -- References -- 8 Organometallic Complexes as Tracers in Non-isotopic Immunoassay -- 8.1 Introduction -- 8.2 Principle of an Immunoassay -- 8.3 Obtaining Specific Antibodies -- 8.4 Synthesis of the Organometallic Tracers -- 8.4.1 Preparation of Tracers Labeled with Ferrocene -- 8.4.1.1 Preparation of a Tracer for Lidocaine -- 8.4.1.2 Preparation of a Tracer for Theophylline -- 8.4.1.3 Preparation of a Tracer for Triiodothyronine -- 8.4.1.4 Labeling of Antibodies (IgG) -- 8.4.2 Preparation of a Tracer for Diphenylhydantoin Labeled with a (Cyclopentadienyl)dicarbonyl Iron (Fp) Entity -- 8.4.3 Synthesis of Tracers Labeled with a Cymantrene (Cyclopentadienyl Manganese Tricarbonyl) Entity -- 8.4.3.1 Preparation of Tracers for Nortriptyline and Phenobarbital -- 8.4.3.2 Preparation of a Tracer for Chlortoluron -- 8.4.3.3 Preparation of a Tracer for Biotin -- 8.4.4 Synthesis of Diphenylhydantoin Bearing a Benchrotrene (Benzene chromium Tricarbonyl) Entity -- 8.4.5 Synthesis of Tracers Bearing an Alkyne Dicobalt Hexacarbonyl Moiety -- 8.4.5.1 Preparation of Tracers for Cortisol and Atrazine -- 8.4.5.2 Preparation of a Tracer for Carbamazepine -- 8.4.6 Synthesis of Cationic Tracers -- 8.4.6.1 Tracers Labeled with a Cobaltocenium Entity -- 8.4.6.2 Cationic Tracers Including a Ferrocene Entity. , 8.4.7 Synthesis of a Tracer Bearing a Rhenium Tricarbonyl Fragment -- 8.5 Examples of Mono- and Multi-metalloimmunoassays (MIA) -- 8.5.1 Metalloimmunoassay Using Atomic Absorption Spectroscopy -- 8.5.2 Detection by Fourier-transform Infrared Spectroscopy (Carbonyl Metalloimmuno Assay, CMIA) -- 8.5.2.1 Mono-immunoassays by CMIA -- 8.5.2.2 Multi-immunoassay by CMIA -- 8.5.2.3 New Developments in the CMIA Method -- 8.5.3 Electrochemical Detection -- 8.5.3.1 Homogeneous Ferrocene-mediated Amperometric Immunoassay -- 8.5.3.2 Homogeneous Electrochemical Immunoassay (Square Wave Voltammetry) -- 8.5.3.3 Electrochemical Flow Immunoassay System -- 8.5.4 Detection by Fluorescence Polarization (FP) -- 8.6 Use of Organometallic Complexes as Substrates or Co-substrates for Enzyme Immunoassay -- 8.6.1 Organometallic Complexes Used as Enzyme Substrates -- 8.6.2 Organometallic Complexes Used as Enzyme Co-substrates (Redox Mediators) -- 8.6.2.1 Flow Injection Immunoassay with Electrochemical Detection -- 8.6.2.2 Dual Enzyme Immunoassay with Amperometric Detection -- 8.6.2.3 Dual Enzyme Immunoassay Using Electrochemical Microscopy Detection -- 8.7 Conclusions -- References -- 9 Genosensors Based on Metal Complexes -- 9.1 Introduction -- 9.2 Metal Complexes as DNA Probes -- 9.2.1 Cationic Metal Complexes -- 9.2.2 Metal Complexes Conjugated with a DNA Fragment or DNA-binding Ligand -- 9.3 Electrochemical Analysis of the Interaction of Metal Complexes with dsDNA -- 9.4 Gene Detection Based on a Cationic Metal Complex or Metal Complex Conjugated with DNA-binding Ligand -- 9.5 Gene Detection Based on Ferrocenyl Oligonucleotides as a Metal Complex Conjugated with DNA Fragments -- 9.6 Conclusions -- References -- 10 Supramolecular Host Recognition Processes with Biological Compounds, Organometallic Pharmaceuticals, and Alkali-metal Ions as Guests -- 10.1 Introduction. , 10.2 Host 1.

Note: Bioorganometallic Chemistry: Applications in Drug Discovery, Biocatalysis, and Imaging -- Contents -- List of Contributors -- Preface -- Part One: Medicinal Chemistry -- 1. Organometallic Complexes as Enzyme Inhibitors: A Conceptual Overview -- 1.1 Introduction -- 1.2 Organometallic Compounds as Inert Structural Scaffolds for Enzyme Inhibition -- 1.3 Organometallic Compounds Targeting Specific Protein Residues -- 1.4 The Bioisosteric Substitution -- 1.5 Novel Mechanisms of Enzyme Inhibition with Organometallic Compounds -- 1.6 Organometallic Compounds as Cargo Delivers of Enzyme Inhibitors -- 1.7 Organometallic Enzyme Inhibitors for Theranostic Purposes -- 1.8 Conclusion -- Acknowledgments -- Abbreviations -- References -- 2. The Biological Target Potential of Organometallic Steroids -- 2.1 Introductory Note on Nuclear Receptors -- 2.1.1 Early History -- 2.1.2 Primary Structure of Nuclear Receptors -- 2.1.3 Estrogen Receptors -- 2.1.4 Androgens -- 2.1.5 Glucocorticoids -- 2.1.6 Progesterone and Progestogens -- 2.1.7 Mineralocorticoids and Aldosterone -- 2.1.8 Selective Modulators of Nuclear Receptors -- 2.1.8.1 Selective Estrogen Receptor Modulators (SERMs) -- 2.1.8.2 Selective Androgen Receptor Modulators (SARMs) -- 2.1.8.3 Selective Progesterone Receptor Modulators (SPRMs) -- 2.1.9 Mechanism of Action of Nuclear Receptors -- 2.1.10 Endocrine Disruptors -- 2.2 Steroids and Organometallics: An Overview of the Transitional Period from the Use of Organometallics in Synthesis to the Emergence of Bioorganometallics -- 2.2.1 Early Examples of Organometallic Estradiol Derivatives with Biological Potential: Modified Hormone Shown to Bind to Estrogen Receptor α -- 2.2.2 Examples of Estrogens Modified by Organometallics at the 11β-Position -- 2.2.3 Targeting Prostate Cancer with Organometallic Androgens and Antiandrogens. , 2.2.4 Approach Toward Organometallic Radiopharmaceuticals -- 2.2.4.1 Steroidal Derivatives -- 2.2.4.2 Nonsteroidal Complexes -- 2.3 Epilog -- Acknowledgments -- References -- 3. Chirality in Organometallic Anticancer Complexes -- 3.1 Introduction -- 3.2 Chirality in Arene Complexes -- 3.3 CIP System for the Nomenclature of Chiral-at-Metal Arene Complexes -- 3.4 Chiral Organometallic Complexes as Anticancer Agents -- 3.4.1 Chiral Carbene Complexes -- 3.4.2 Chiral Metallocene Complexes -- 3.4.3 Chiral Half-Sandwich Arene Complexes -- 3.4.4 Chirality at Metal in Supramolecular Complexes -- 3.5 Half-Sandwich Complexes with Chiral Metal Centers -- 3.5.1 Factors Influencing the Chirality at the Metal Center -- 3.5.1.1 Use of Chiral Ligands for Chiral Resolution at the Metal Center: Diastereoisomerism -- 3.5.1.2 CH-π Interactions: β-Phenyl Effect and Hydrogen Bond Interactions -- 3.5.1.3 Effect of the Temperature, Solvent and Ligands on the Metal Configuration -- 3.6 Conclusions -- Acknowledgments -- References -- 4. Gold Organometallics with Biological Properties -- 4.1 Introduction: The Use of Gold in Medicine -- 4.2 Anticancer Gold Organometallics and Proposed Biological Targets -- 4.2.1 Cyclometalated Gold(III) Complexes with C,N-Donor Ligands -- 4.2.1.1 Types of Cycloaurated Complexes, Synthetic Methods, and Reactivity -- 4.2.1.2 Cycloaurated Complexes with Biological Activities -- 4.2.2 Gold N-Heterocyclic Carbene (NHC) Complexes -- 4.2.3 Gold Alkynyl Complexes -- 4.3 Conclusions and Perspectives -- List of Abbreviations -- References -- 5. On the Molecular Mechanisms of the Antimalarial Action of Ferroquine -- 5.1 History and Development -- 5.2 Mechanism(s) of Action of 4-Aminoquinoline Antimalarials -- 5.3 Mechanism(s) of Action of Ferroquine as an Antimalarial -- 5.3.1 Antimalarial Activity -- 5.3.2 Metabolic Pathway of Ferroquine. , 5.3.3 Redox Properties of FQ -- 5.3.4 Basic Properties and Accumulation -- 5.3.5 Importance of Redox Properties of Ferrocene on Antimalarial Activity of FQ -- 5.3.6 Inhibition of Hemozoin Formation -- 5.4 Conclusion -- Acknowledgments -- List of Abbreviations -- References -- 6. Metal Carbonyl Prodrugs: CO Delivery and Beyond -- 6.1 Introducing CO in Biology -- 6.1.1 Origin -- 6.1.2 Biological Action and Targets of CO -- 6.1.3 Therapeutic Outlook -- 6.1.4 Measuring CO in Biology -- 6.2 Therapeutic Delivery of CO -- 6.2.1 CO Gas and Inhalation -- 6.2.2 Prodrugs for CO Delivery: CO-Releasing Molecules (CORM) -- 6.2.2.1 Definitions and Concept -- 6.2.3 Early CORMs -- 6.2.3.1 Nonmetal-Based CORMs -- 6.2.3.2 Metal Carbonyl-Based CORMs -- 6.2.4 The Chemical Biology of Early CORMs -- 6.2.4.1 [Ru(CO)3]2+-Based CORMs -- 6.2.4.2 [Mo(CO)n]-Based CORMs -- 6.2.4.3 Miscellaneous Biologically Significant Observations on Early-Stage CORMs -- 6.3 Biological and Therapeutic Results Obtained with the Early-Stage CORMs -- 6.3.1 CORM and Inflammatory Response -- 6.3.2 Cardioprotective Effects of CORM -- 6.3.3 Central Nervous System and CORMs -- 6.3.4 Transplantation -- 6.3.5 Bactericide Effects of CORMs -- 6.3.6 CORMs: Tissue Regeneration and Modulation of Cell Proliferation/Differentiation -- 6.3.7 CORMs and Cancer Therapy? -- 6.4 Beyond the Early-Stage CORMs: Strategies for Finding New Candidates -- 6.4.1 Evaluation of CO Release from CORMs -- 6.4.2 Light Activated or photoCORMs -- 6.4.3 Chemically Activated CORMs -- 6.4.4 Bioactivated or Enzyme-Triggered CORMs (ET-CORMs) -- 6.5 Intracellular Detection of CORMs, Mechanistic Studies, and Other Unanswered Questions -- 6.6 Designing Pharmacologically Useful, Drug-like CORMs -- 6.6.1 The First Drug-like CORM -- 6.7 Final Remarks and Perspectives -- List of Abbreviations -- References. , 7. Dinitrosyl Iron Complexes with Natural Thiol-Containing Ligands: Physicochemistry, Biology, and Medicine -- 7.1 Introduction -- 7.2 The History of Detection and Identification of DNIC with Thiol-Containing Ligands in Microorganisms and Animal Tissues -- 7.3 Physicochemistry of DNIC with Natural Thiol-Containing Ligands -- 7.3.1 Mono- and Binuclear forms of DNIC with Natural Thiol-Containing Ligands -- 7.3.2 Two Approaches to the Synthesis of DNIC with Natural Thiol-Containing Ligands -- 7.3.3 Mechanisms of Formation of DNIC with Natural Thiol-Containing Ligands -- 7.3.4 The Electronic and Spatial Structures of DNIC with Thiol-Containing Ligands -- 7.3.5 DNIC with Thiol-Containing Ligands as NO and NO Donors -- 7.4 Biological Effects of DNIC with Thiol-Containing Ligands -- 7.4.1 S-Nitrosating Effect of DNIC with Thiol-Containing Ligands -- 7.4.2 Vasodilator and Hypotensive Effects of DNIC with Thiol-Containing Ligands -- 7.4.3 Inhibiting Effect of DNIC with Thiol-Containing Ligands on Platelet Aggregation -- 7.4.4 DNIC with Thiol-Containing Ligands Increase Erythrocyte Elasticity -- 7.4.5 DNIC with Thiol-Containing Ligands Accelerate Skin Wound Healing in Animals -- 7.4.6 Erective Activity of DNIC -- 7.4.7 DNIC and Apoptosis -- 7.4.8 DNIC with Glutathione Inhibits the Development of Experimental Endometriosis in Rats -- 7.4.9 Other Examples of Biological Effects of DNIC with Thiol-Containing Ligands -- 7.5 DNIC with Thiol-Containing Ligands as a Basis in the Design of Drugs with a Broad Range of Therapeutic Activities -- List of Abbreviations -- Acknowledgments -- References -- Part Two: Metalloproteins, Catalysis, and Energy Production -- 8. The Bioorganometallic Chemistry of Hydrogenase -- 8.1 Introduction -- 8.1.1 Hydrogenase -- 8.1.2 The Chemistry of Hydrogen -- 8.1.3 Dihydrogen Metal Complexes -- 8.1.4 First Coordination Sphere Ligands. , 8.2 Structure and Function -- 8.2.1 The Active Sites of the Hydrogenases -- 8.2.1.1 [NiFe]- and [FeFe]-Hydrogenase -- 8.2.1.2 [Fe]-Hydrogenase -- 8.2.2 The Mechanisms of the Hydrogenases -- 8.3 Natural Biosynthesis and Synthetic Analogs of the Active Sites -- 8.3.1 Natural Biosynthesis of Hydrogenase Active Sites -- 8.3.1.1 Biosynthesis of [NiFe]-Hydrogenase -- 8.3.1.2 Biosynthesis of [FeFe]-Hydrogenase -- 8.3.2 Synthetic Analogs -- 8.3.2.1 Models of the [NiFe]-Hydrogenase Active Site -- 8.3.2.2 Models of the [FeFe]-Hydrogenase Active Site -- 8.3.2.3 Models of the [Fe]-Hydrogenase Active Site -- 8.4 Comments and Conclusion -- References -- 9. Bio-Organometallic Systems for the Hydrogen Economy: Engineering of Electrode Materials and Light-Driven Devices -- 9.1 Introduction -- 9.2 Electrode Materials for Hydrogen Evolution and Uptake -- 9.2.1 Electrode Materials-Based on Hydrogenases -- 9.2.2 Hydrogen Fuel Cell Electrodes Based on Hydrogenases -- 9.2.3 Electrode Materials Based on Bio-inspired Molecular Catalysts -- 9.2.3.1 Covalent Attachment of Catalyst to Electrode Material -- 9.2.3.2 Noncovalent Attachment of Catalyst to Electrode Material via π-π Stacking Interaction -- 9.3 Light-Driven Systems for Hydrogen Evolution -- 9.3.1 Biological and Biohybrid Systems -- 9.3.2 Bio-inspired Catalysis Approaches -- 9.3.2.1 Iron-Based Catalysts -- 9.3.2.2 Nickel-Based Catalysts -- 9.3.2.3 First Approaches toward Molecular-Based Photoelectrodes -- 9.4 Artificial Photosynthetic Systems -- 9.5 Summary and Conclusions -- List of Abbreviations -- References -- 10. Artificial Metalloenzymes Containing an Organometallic Active Site -- 10.1 Introduction -- 10.2 Dative Anchoring -- 10.2.1 Metalloproteins as Protein Hosts -- 10.2.2 Other Protein Hosts -- 10.3 Supramolecular Anchoring -- 10.3.1 (Strept)avidin as Protein Hosts -- 10.3.2 Antibodies as Protein Hosts. , 10.3.3 Other Protein Hosts.

Note: Intro -- Medicinal Organometallic Chemistry -- Topics in Organometallic Chemistry Also Available Electronically -- Introduction -- References -- Contents -- Arsenic-Based Drugs: From Fowler´s Solution to Modern Anticancer Chemotherapy -- 1 Introduction -- 2 Malaria and Fevers -- 3 Trypanosomiasis -- 3.1 Atoxyl -- 3.2 Tryparsamide -- 3.3 Melaminophenyl Arsenicals -- 4 Syphilis -- 4.1 Arsphénamines -- 4.2 Arseno-Metallic Compounds -- 5 Treatment of Amebiasis, Worms, Trichomonas Vaginalis, and Vincent´s Angina -- 6 Blood Diseases and Disorders -- 7 Conclusion -- References -- Activation Mechanisms for Organometallic Anticancer Complexes -- 1 Introduction -- 2 Activation Through Cleavage of M-X Bonds -- 2.1 Titanocenes -- 2.2 Ruthenium and Osmium Arenes -- 2.2.1 Hydrolysis of the Ru-Z Bond -- 2.2.2 Hydrolysis of the Os-Z Bond -- 2.2.3 Sulfur Oxidation -- 2.2.4 Bifunctional Ru Arenes -- 2.2.5 Chelate Ring Redox -- 2.2.6 Irradiation -- 2.3 Other Transition Metal Complexes -- 3 Metal Complexes as Catalytic Drugs -- 4 Structural Scaffolds -- 4.1 Ferrocenes and Ferrocenyl Derivatives -- 4.2 Glutathione-S-Transferase Inhibitors -- 4.3 Kinase Inhibitors -- 4.4 COX Inhibitors -- 5 Metal as a Carrier for Active Ligands -- 5.1 Side-Chain Hydrolysis -- 5.2 Ruthenium Cages -- 6 Photoactivation and Photosensitizers -- 7 Organotins -- 8 The Future for Medicinal Organometallics -- References -- Organometallic Antitumour Agents with Alternative Modes of Action -- 1 Introduction -- 2 DNA as a Target -- 3 Organoruthenium Compounds -- 4 Ruthenium-Arene PTA (RAPTA) Compounds -- 5 RAPTA Targets -- 6 Ruthenium-Arene Targeted Drugs -- 7 Organogold Compounds -- 8 Proposed Targets -- 9 Protein-Mediated Tumour Targeting -- 10 Concluding Remarks -- References -- Ferrocene Functionalized Endocrine Modulators as Anticancer Agents -- 1 Ferrocene and Medicinal Chemistry. , 2 Breast and Prostate Cancer -- 3 Hydroxyferrocifens -- 4 Ferrocenyl Raloxifen Derivatives -- 5 Ferrocenyl Oestradiol Derivatives -- 6 Anti-cancer Structure-Activity Relationship Studies of Hydroxyferrocifens -- 6.1 N, N-dimethylamino Side Chain -- 6.2 Presence and Position of the Phenol Group -- 6.3 Role of the Ferrocene Moiety -- 6.4 Conjugation -- 6.5 Phenyl Functionalisation -- 6.6 Placement of the Ferrocene Group -- 6.7 Cyclic Compounds -- 7 Mechanism -- 8 Formulation Studies -- 9 Ferrocenyl Androgens and Anti-androgens -- 10 Summary -- References -- Titanocenes: Cytotoxic and Anti-angiogenic Chemotherapy Against Advanced Renal-Cell Cancer -- 1 Introduction -- 2 Benzyl-Substituted Titanocenes via Hydridolithiation -- 3 Chiral Mixtures of Titanocenes via Carbolithiation -- 4 Achiral Titanocenes via Carbolithiation -- 5 Biological Evaluation -- 6 Conclusions and Outlook -- References -- Organometallics as Structural Scaffolds for Enzyme Inhibitor Design -- 1 Introduction -- 2 Metal Complexes as Structural Scaffolds -- 3 Organometallic Protein Kinase Inhibitors -- 3.1 Protein Kinases as Drug Targets -- 3.2 Staurosporine as an Inspiration for Organometallic Inhibitors -- 3.3 Crystal Structures of Organometallic Compounds Bound to the ATP Binding Site of Protein Kinases -- 3.4 Anticancer Properties of Organometallic Kinase Inhibitors -- 4 Conclusion -- References -- Bioorganometallic Chemistry and Malaria -- 1 Introduction -- 1.1 Malaria: The Burden and the Problems -- 1.2 The Digestive Vacuole of Parasite and Hemoglobin Digestion -- 1.3 Drug Resistance -- 2 Metal Complexes as Antimalarials: An Overview -- 2.1 Ferrocenic Molecules with Antimalarial Properties -- 2.2 Ferrocene Conjugates with Antimalarial Drugs Other Than Chloroquine -- 2.2.1 Artemisinin -- 2.2.2 Atovaquone -- 2.2.3 Mefloquine and Quinine. , 2.2.4 Ferrocenyl Pyrrolo[1,2-a]quinoxaline Derivatives -- 2.2.5 Ciprofloxacin -- 2.3 Ferrocene Conjugates with Chloroquine -- 2.3.1 Quinoline Ring Substitutions -- 2.3.2 Lateral Side Chain Modifications -- 2.3.3 N-N Spacer Modifications -- 2.3.4 Bisquinolines -- 3 Ferroquine: A New Candidate Antimalarial Drug -- 3.1 The Chemistry of Ferroquine -- 3.2 Ferroquine Derivatives -- 3.3 Specific Pharmacology -- 3.4 Metabolism, ADME, and Toxicology -- 3.5 A Brief Industrial Development Story -- 4 Mechanism(s) of Action of Ferroquine -- 4.1 Inhibition of Hemozoin Formation -- 4.2 Specific Drug Targeting -- 4.3 A Critical Intramolecular Hydrogen Bond -- 4.4 Production of Reactive Oxygen Species -- 5 Conclusion -- References -- Biomedical Applications of Organometal-Peptide Conjugates -- 1 Introduction -- 2 Chemical Synthesis of Metal-Peptide Conjugates -- 2.1 Synthesis in Solution -- 2.2 Solid-Phase Peptide Synthesis -- 2.2.1 N-Terminal Derivatization -- 2.2.2 Side Chain Derivatization -- 2.2.3 C-Terminal Modification -- 3 Biomedical Applications -- 3.1 Radiopharmaceutical Applications -- 3.2 Anticancer Activity -- 3.3 Antibacterial Activity -- 3.4 Cell Uptake and Intracellular Localization -- 3.5 Biosensors and Molecular Recognition -- 4 Summary -- References -- Organometallic Radiopharmaceuticals -- 1 Introduction -- 2 Building Blocks for Organometallic Radiopharmaceuticals -- 3 Technetium Essential Organometallic Radiopharmaceuticals -- 4 Targeting Organometallic Radiopharmaceuticals -- 4.1 Fatty Acids -- 4.2 Targeting the Folate Receptor with Organometallic Complexes -- 4.3 Competing with PET: Carbohydrates Labeled with 99mTc Organometallic Complexes -- 4.4 Targeting Enzymes: 99mTc-Labeled Thymidine for TKs -- 4.5 Very Small and Essential Biomolecules: α-Amino Acids -- 4.6 Vitamin B12: An Organometallic Coenzyme for Organometallic Complexes. , 4.7 Targeting the Cell Nucleus -- 4.8 Drug Finding and Development: The Single Amino Acid Chelate Approach -- 5 New eta5-Coordinating Ligands: Cyclopentadienyl and Carborane Complexes -- 6 Conclusion and Perspectives -- References -- Carbon Monoxide: An Essential Signalling Molecule -- 1 Introduction -- 2 The Role of CO In Vivo -- 3 Sites of Action of CO -- 3.1 Guanylyl Cyclase -- 3.2 Na+ and KCa+ Channels -- 3.3 Hemes and Cytochromes -- 3.4 Other Possible Binding Sites for CO -- 4 CO-Releasing Molecules (CO-RMs) -- 4.1 Initial Discovery -- 4.2 Ruthenium CO-RMs -- 4.2.1 [Ru(CO)3Cl2]2 (CORM-2) -- 4.2.2 [Ru(CO)3Cl(glycinate)] (CORM-3) -- 4.2.3 Other Ruthenium Compounds -- 4.3 Iron CO-RMs -- 4.3.1 Heme-Based Carriers -- 4.3.2 [CpFe(CO)3]+ and Its Derivatives -- 4.3.3 [(eta4-2-pyrone)Fe(CO)3] -- 4.3.4 Other Iron CO-RMs -- 4.4 Manganese CO-RMs -- 4.4.1 [Mn2(CO)10], CORM-1 -- 4.4.2 [Mn(CO)5X], X=Cl, Br, I -- 4.4.3 [Mn(CO)4X2]-, X=Br, I, SC(O)Me [13, 204] -- 4.4.4 [Mn(CO)4(eta2-S2CR)], R=NEt2, NMeCH2CO2H, N(CH2CH2OH)2, OEt, and [Mn(CO)4{eta2-S2P(OEt)2}] [204] -- 4.4.5 [Mn2(CO)6X3]-, X=Cl, OAc [204] -- 4.4.6 Other Manganese Compounds -- 4.5 Vanadium -- 4.6 Chromium -- 4.7 Molybdenum -- 4.7.1 [Mo(CO)5X]-, X=Cl, Br, I, and [Mo{=C(OMe)Me}(CO)5] -- 4.7.2 [CpMo(CO)3(pyrone)]+ -- 4.7.3 Mo(CO)3L, L=nitrilotriacetate, 4-[[bis(2-pyridinylmethyl)amino]methyl]-benzoate, diethylenetriamine-N,N,N,N,N-pentaacetat -- 4.7.4 [NEt4][MoI3(CO)4] -- 4.8 Tungsten -- 4.9 Cobalt -- 4.10 Boron. Na[H3BCO2H], CORM-A1 -- 4.11 Organic Compounds as Sources of CO -- 5 Detection of CO Release -- 5.1 Manometric -- 5.2 Gas Chromatography -- 5.3 CO Electrode -- 5.4 Myoglobin -- 6 Mechanisms of CO Release -- 7 Some Potential Applications of CO Gas and CO-RMs in Medicine -- 8 Patents -- 9 The Future -- References -- Index.