Comprehensive Organometallic Chemistry IV

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Comprehensive Organometallic Chemistry IV. Volume 15: Applications IV. Bio-Organometallics, Metallo-Therapy, Metallo-Diagnostics, Medicine and Environmental Chemistry
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Contents of Volume 15
Editor Biographies
Contributors to Volume 15
Preface
15.01 Introduction to Applications IV. Bio-Organometallics, Metallo-Therapy, Metallo-Diagnostics, Medicine and Environmental Chemistry
15.02 Hydrogenases and Model Complexes in Bioorganometallic Chemistry
	15.02.1. Hydrogenases and models in bioorganometallic chemistry
		15.02.1.1. Introduction
			15.02.1.1.1. The aim of this book chapter
			15.02.1.1.2. General overview
			15.02.1.1.3. Metal hydrides
			15.02.1.1.4. The role of proton-coupled electron transfer in H2/2H+ interconversion
		15.02.1.2. [FeFe] hydrogenases and their model compounds
			15.02.1.2.1. Structure and mechanism
			15.02.1.2.2. H-cluster assembly
			15.02.1.2.3. [FeFe] hydrogenase model chemistry
				15.02.1.2.3.1. Di-cyanide containing models and variations of the bridging di-thiolate ligand
				15.02.1.2.3.2. Replicating the rotated structure
				15.02.1.2.3.3. Mimicking the [4Fe4S]H cluster - redox active ligands
				15.02.1.2.3.4. Ligand and metal protonation sites of [2Fe]H models
				15.02.1.2.3.5. Bridging versus terminal hydrides and their involvement in catalysis
				15.02.1.2.3.6. Artificial maturation and semi-synthetic [FeFe] hydrogenases
		15.02.1.3. [NiFe] hydrogenase and their model compounds
			15.02.1.3.1. Structure and functions of [NiFe] hydrogenases
			15.02.1.3.2. Mechanisms for proton and hydrogen conversion in [NiFe] hydrogenases
			15.02.1.3.3. Unique oxygen tolerance in [NiFe] and [NiFeSe] hydrogenases
			15.02.1.3.4. Biomimetic Ni containing analogs
				15.02.1.3.4.1. [NiFe] analogs based on heterobimetallic Ni complexes
				15.02.1.3.4.2. Understanding O2 tolerance in [NiFe] and [NiFeSe] hydrogenases
				15.02.1.3.4.3. Bioinspired Ni only complexes
			15.02.1.3.5. Future challenges in developing [NiFe] model complexes
		15.02.1.4. [Fe] hydrogenase and their model compounds
			15.02.1.4.1. Enzymatic activity, inhibitors and isolatable cofactors
			15.02.1.4.2. Early `iron free hypothesis and refutation
			15.02.1.4.3. Spectroscopic studies
			15.02.1.4.4. Structure and mechanism of [Fe] hydrogenase
			15.02.1.4.5. Model complexes of the FeGP cofactor
	Acknowledgment
	References
15.03 Nitrogenases and Model Complexes in Bioorganometallic Chemistry
	15.03.1. Introduction
	15.03.2. Nitrogenase
		15.03.2.1. The Fe protein and the F-cluster
		15.03.2.2. The MoFe protein
			15.03.2.2.1. The P-cluster
			15.03.2.2.2. Atomic and electronic structure of the FeMo cofactor resting state
	15.03.3. Interaction of FeMoco with substrates
		15.03.3.1. Nitrogen
			15.03.3.1.1. The kinetic model of N2 reduction
			15.03.3.1.2. The E1 state
			15.03.3.1.3. The E2 and E4 states
				15.03.3.1.3.1. The oxidative addition/reductive elimination model of the E4 state
				15.03.3.1.3.2. Computational models of the E4 state
			15.03.3.1.4. The E7 and E8 states
			15.03.3.1.5. The alternating and distal mechanisms
		15.03.3.2. Alternative substrates
			15.03.3.2.1. Protons, H+
			15.03.3.2.2. Acetylene
			15.03.3.2.3. Carbon monoxide and selenocyanate
			15.03.3.2.4. Cyanide
			15.03.3.2.5. The surroundings of the FeMoco, and extracted FeMoco
		15.03.3.3. Alternative nitrogenases
			15.03.3.3.1. Reactivity of V-nitrogenase towards carbon monoxide
	15.03.4. Biosynthesis of FeMoco
		15.03.4.1. Radical-SAM enzymes and alkylated Fe4S4 clusters
	15.03.5. Model complexes
		15.03.5.1. Functional models of catalytic N2 reduction
		15.03.5.2. Iron-sulfur clusters
		15.03.5.3. Iron complexes with sulfur and N2 ligands
		15.03.5.4. Iron complexes with sulfur and NxHy ligands
		15.03.5.5. Iron carbides
		15.03.5.6. Iron complexes with other carbon ligands
		15.03.5.7. Iron hydrides
		15.03.5.8. Modeling second-sphere effects
	15.03.6. Outlook
	15.03.7. Note Added in Proof
	Acknowledgment
	References
15.04 Bioorganometallic Chemistry of Vitamin B12-Derivatives
	15.04.1. Introduction
	15.04.2. The structure of organometallic B12-derivatives
		15.04.2.1. Cobalamins and other ``complete´´ B12-derivatives
		15.04.2.2. ``Incomplete´´ B12-derivatives
		15.04.2.3. Cobamides as molecular switches
	15.04.3. Organometallic chemistry of B12-derivatives
		15.04.3.1. Formation and cleavage of the (CoC)-bond in B12-derivatives
		15.04.3.2. Thermally induced CoC bond homolysis
		15.04.3.3. The nucleophile induced heterolysis and formation of the CoC bond
		15.04.3.4. Radical induced abstraction of cobalt-bound alkyl groups
	15.04.4. Redox-chemistry of B12-derivatives
	15.04.5. Enzymatic organometallic processing of cobalamins
	15.04.6. Enzymatic reactions catalyzed by organometallic B12-cofactors
		15.04.6.1. B12-dependent methyl transferases
			15.04.6.1.1. B12-dependent methionine synthase
			15.04.6.1.2. B12- and S-adenosylmethionine-dependent radical methyl transferases
		15.04.6.2. Organometallic chemistry of enzymes dependent on coenzyme B12
			15.04.6.2.1. Coenzyme B12-dependent isomerases
			15.04.6.2.2. Coenzyme B12-dependent ribonucleotide reductase
		15.04.6.3. B12-dependent dehalogenases
	15.04.7. Gene-regulatory roles of organometallic B12-derivatives
		15.04.7.1. B12-riboswitches
		15.04.7.2. Photo-regulation of gene expression by coenzyme B12
	15.04.8. Organometallic cobalamins as antivitamins B12
	15.04.9. Metbalamins: Transition-metal analogues of cobalamin
	15.04.10. Summary and outlook
	Acknowledgment
	References
15.05 Bioorganometallics: Artificial Metalloenzymes With Organometallic Moieties
	15.05.1. Introduction
	15.05.2. Artificial metalloenzymes based on the biotin-streptavidin technology
		15.05.2.1. C-H activation
		15.05.2.2. Suzuki cross-coupling
		15.05.2.3. Transfer hydrogenation
		15.05.2.4. Ring closing metathesis (RCM)
		15.05.2.5. Hydroamination and hydroarylation
	15.05.3. Artificial metalloenzymes based on human carbonic anhydrase
		15.05.3.1. Imine transfer hydrogenation
		15.05.3.2. Metathesis
	15.05.4. Artificial metalloenzymes based on myoglobin
		15.05.4.1. Carbene insertion and cyclopropanation
	15.05.5. Artificial metalloenzymes based on thermophilic cytochrome P450 (CYP119)
		15.05.5.1. Carbene insertion into C-H bond
		15.05.5.2. Cyclopropanation
		15.05.5.3. C-H amination
	15.05.6. Artificial metalloenzymes based on POP scaffold
		15.05.6.1. Si-H insertion
		15.05.6.2. Cyclopropanation
	15.05.7. Artificial metalloenzymes based on nitrobindin
		15.05.7.1. Rh alkyne polymerization
		15.05.7.2. Ru metathesis
		15.05.7.3. C-H functionalization
		15.05.7.4. Other reactions with nitrobindin scaffold
	Acknowledgment
	References
	Relevant Website
15.06 Opportunities for interfacing organometallic catalysts with cellular metabolism
	15.06.1. Introduction
		15.06.1.1. Synthesis-Toward a concerted effort of synthetic chemists and biologists?
		15.06.1.2. Opportunities and challenges of interfacing organometallic reactions with cellular metabolism
		15.06.1.3. Scope of this book chapter
	15.06.2. The role of non-enzymatic transition-metal catalysis in the emergence and maintenance of biochemistry
		15.06.2.1. Primordial metabolic pathways
		15.06.2.2. Microbial extracellular electron transfer
		15.06.2.3. The curious case of lignocellulose degradation by brown-rot fungi
	15.06.3. Identifying biocompatible catalysts
		15.06.3.1. Screening under biologically-relevant conditions
		15.06.3.2. Using pro-fluorophores to determine catalyst activity and localization in vivo
		15.06.3.3. Assessing biocompatibility by interfacing catalyst activity with cellular metabolism
		15.06.3.4. Means to make bio-incompatible catalysts biocompatible
	15.06.4. Interfacing biocompatible catalysts with cellular metabolism
		15.06.4.1. Employing biocompatible catalysis for the biocontainment of genetically-modified organisms
		15.06.4.2. Adding to the repertoire of biocompatible CX-bond forming reactions
		15.06.4.3. Approaches to the synthesis of value-added compounds
	15.06.5. Conclusions and future directions
	References
15.07 Oligonucleotide Complexes in Bioorganometallic Chemistry
	Glossary
	15.07.1. Introduction
	15.07.2. Complexes of oligonucleotides with organometallic compounds
		15.07.2.1. Non-coordinating interactions
		15.07.2.2. Coordinating interactions
			15.07.2.2.1. Interplay of coordination, intercalation and groove binding
			15.07.2.2.2. Preferred coordination sites on nucleic acids
			15.07.2.2.3. Cross-linking
	15.07.3. Organometallic and organometalloid oligonucleotides
		15.07.3.1. Synthesis of organometallic and organometalloid oligonucleotides
			15.07.3.1.1. Electrophilic aromatic substitution
			15.07.3.1.2. Oxidative addition
			15.07.3.1.3. Ligand-directed cyclometalation
			15.07.3.1.4. Post-synthetic conjugation in solution
			15.07.3.1.5. On-support conjugation
			15.07.3.1.6. Solid phase synthesis using organometallic and organometalloid building blocks
			15.07.3.1.7. Enzymatic polymerization
		15.07.3.2. Organometallic and organometalloid oligonucleotides as synthetic intermediates
			15.07.3.2.1. Halodemercuration and halodestannylation
			15.07.3.2.2. Palladium-catalyzed cross-coupling reactions
		15.07.3.3. Reversible ligation of organoboron oligonucleotides
		15.07.3.4. Metal-mediated base pairing of organometallic oligonucleotides
			15.07.3.4.1. Hg(II)-mediated base pairing
			15.07.3.4.2. Pd(II)-mediated base pairing
		15.07.3.5. Organometallic nucleobases as affinity tags
		15.07.3.6. Organomercury nucleotides as isomorphous heavy atom derivatives in X-ray crystallography
		15.07.3.7. Sensor and imaging applications
			15.07.3.7.1. Electrochemical labeling of hybridization probes
			15.07.3.7.2. Detection of single-nucleotide polymorphisms
			15.07.3.7.3. Biomolecule sensors
			15.07.3.7.4. Cation sensors
			15.07.3.7.5. Intracellular imaging
		15.07.3.8. Toward therapeutic applications
			15.07.3.8.1. Organometallic oligonucleotides and drug delivery
			15.07.3.8.2. Biostability of organometallic and organometalloid oligonucleotides
			15.07.3.8.3. Affinity and selectivity of organometallic and organometalloid oligonucleotides for intracellular targets
			15.07.3.8.4. Boron neutron capture therapy
	15.07.4. Summary and outlook
	Acknowledgment
	References
15.08 Organometallic Receptors and Conjugates With Biomolecules in Bioorganometallic Chemistry
	15.08.1. Introduction
	15.08.2. Analytical techniques to assess the accumulation and distribution of organometallics
		15.08.2.1. In vitro
		15.08.2.2. In vivo
	15.08.3. Approaches to study organometallic-protein interactions
		15.08.3.1. Metalloproteomics
		15.08.3.2. Protein target identification
		15.08.3.3. Metabolomics and multi-omics approaches
	15.08.4. Organometallic conjugates with biomolecules
		15.08.4.1. Strategies to synthesize organometallic-peptidic conjugates
			15.08.4.1.1. Amide coupling
			15.08.4.1.2. Direct metalation of amino acids
			15.08.4.1.3. Sonogashira coupling
			15.08.4.1.4. Alkyne-azide coupling
			15.08.4.1.5. Maleimide-thiol coupling
			15.08.4.1.6. NHC coupling
			15.08.4.1.7. Miscellaneous
		15.08.4.2. Targeting strategies
			15.08.4.2.1. Blood
			15.08.4.2.2. Membrane receptors
			15.08.4.2.3. Cell penetrating peptides
			15.08.4.2.4. Subcellular targeting
			15.08.4.2.5. Miscellaneous
	15.08.5. Conclusions
	References
15.09 Organometallic Chemistry of Anticancer Ruthenium and Osmium Complexes
	15.09.1. Introduction
	15.09.2. Early discoveries and design of bioactive organometallic compounds
	15.09.3. Sandwich metal complexes-ruthenocenes and osmocenes
	15.09.4. Half-sandwich metal(II)-arene complexes of ruthenium and osmium
		15.09.4.1. RAPTA inspired half-sandwich complexes
		15.09.4.2. RAED-inspired organoruthenium and -osmium complexes
		15.09.4.3. N-heterocyclic carbene (NHC) complexes
		15.09.4.4. Cyclometalated Ru(II) and Os(II) arene complexes
		15.09.4.5. Bioconjugates of half-sandwich organoruthenium and osmium complexes
	15.09.5. Multinuclear Ru and Os organometallics
	15.09.6. Cytotoxic organometallic clusters of Ru and Os
	15.09.7. Conclusions
	Acknowledgment
	References
15.10 Organometallic Chemistry of Drugs Based on Technetium and Rhenium
	15.10.1. Introduction
		15.10.1.1. General aspects about technetium and rhenium drugs
		15.10.1.2. Properties of technetium in molecular imaging
		15.10.1.3. Rhenium in radiotherapy and in ``cold´´ drugs
	15.10.2. Technetium imaging agents
		15.10.2.1. Cancer targeting
		15.10.2.2. Labelled peptides and proteins
		15.10.2.3. Alzheimer\'s disease and β-amyloid targeting with 99mTc
		15.10.2.4. Cell nucleus targeting and Auger electrons
		15.10.2.5. Labelled nanoparticles - Multi modality imaging
	15.10.3. Small molecules with rhenium and 99mTc homologs
		15.10.3.1. De novo matched-pair complexes with Re and 99mTc
		15.10.3.2. Homologs of Re and 99mTc with pendent pharmacophores or substrates
		15.10.3.3. Pharmacomimetics with integrated complexes
	15.10.4. Miscellaneous
	15.10.5. Concluding remarks
	Acknowledgment
	References
15.11 Organometallic Chemistry of Drugs Based on Iron
	Abbreviations
	15.11.1. Introduction
	15.11.2. Antimalarial compounds containing ferrocene
		15.11.2.1. Ferrocene and its biological activity
			15.11.2.1.1. Ferroquine and its derivatives as antimalarial agents
				15.11.2.1.1.1. Antimalarial mechanism of action of ferroquine
				15.11.2.1.1.2. Ferroquine-based antimalarials
				15.11.2.1.1.3. Ferrocenyl derivatives of artemisinin: A natural product inspiration
	15.11.3. Anticancer activity of ferrocene-based compounds
		15.11.3.1. Ferrocifens
		15.11.3.2. Ferroquine repurposed as a potential anticancer agent
		15.11.3.3. Ferrocenyl hybrids containing other scaffolds
		15.11.3.4. Small molecule bimetallic ferrocenyl derivatives
		15.11.3.5. Multinuclear, macromolecular ferrocenyl compounds
	15.11.4. Organometallic ferrocene compounds against neglected tropical diseases
		15.11.4.1. Trypanosomiasis: Human African trypanosomiasis and Chagas disease
			15.11.4.1.1. Trypanocidal ferrocenyl compounds derived from clinical antitrypanosomal drug scaffolds
			15.11.4.1.2. Trypanocidal ferrocenyl compounds inspired by bioactive scaffolds contained in the MMV pathogen box
			15.11.4.1.3. Heteronuclear ferrocenyl antitrypanosomal compounds targeting NADH-fumarate reductase, epimastigote necrosis ...
			15.11.4.1.4. Ferrocifens and heterocyclic ferrocenyl compounds as trypanocidal agents
		15.11.4.2. Ferrocenyl compounds as potential agents against leishmaniasis
			15.11.4.2.1. Heterobimetallic ferrocenyl antimonials possessing anti-leishmanial activity by targeting DNA interaction
			15.11.4.2.2. Ferrocenyl quinolines inhibiting the growth of Leishmania parasites
			15.11.4.2.3. Quinazoline- and benzimidazole-based derivatives of ferrocene active against leishmaniasis
	15.11.5. Antiviral ferrocene-containing compounds
		15.11.5.1. Ferrocene-containing compounds as anti-HIV compounds
			15.11.5.1.1. Ferrocene-peptides inactivate HIV-1 by targeting viral proteins
			15.11.5.1.2. Ferrocenyl anti-HIV compounds inhibiting HIV-1 integrase
			15.11.5.1.3. Bimetallic ferrocene-based gold(I) complexes as anti-HIV compounds
		15.11.5.2. Ferrocenyl complexes active against strains of herpes and hepatitis viruses
			15.11.5.2.1. Artemisinin- and betulin-ferrocene hybrids active against herpes virus
			15.11.5.2.2. Ferrocene-based inhibitors of hepatitis C virus
	15.11.6. Ferrocene-containing compounds as antitubercular agents
		15.11.6.1. Isatin- and uracil-ferrocene hybrids as anti-TB agents
		15.11.6.2. Bimetallic heteronuclear ferrocene complexes with anti-TB potency
	15.11.7. Alzheimer\'s disease
	15.11.8. Non-ferrocenyl organometallic iron compounds with biological activity
		15.11.8.1. Homometallic iron(II) organometallic half-sandwich complexes
		15.11.8.2. Heterobimetallic iron(II) organometallic half-sandwich complexes
	15.11.9. Conclusions
	Acknowledgment
	References
	Relevant Websites
15.12 Organometallic Chemistry of Gold-Based Drugs
	15.12.1. Introduction
	15.12.2. Gold(I) N-heterocyclic carbenes
		15.12.2.1. Anticancer gold(I) NHC complexes and their modes of action
			15.12.2.1.1. Mononuclear and binuclear gold(I) NHC complexes
			15.12.2.1.2. Heteronuclear complexes featuring Au(I) NHCs moieties
		15.12.2.2. Gold(I) NHC complexes as antibacterial and antiparasitic
			15.12.2.2.1. Antibacterial complexes
			15.12.2.2.2. Antimalarial and antileishmanial complexes
	15.12.3. Cyclometalated Au(III) complexes
		15.12.3.1. Anticancer Au(III) cyclometalated complexes and their modes of action
	15.12.4. Conclusions and perspectives
	References
15.13 Manganese-Based Carbon Monoxide-Releasing Molecules: A Multitude of Organometallic Pharmaceutical Candidates Primed for Further Biological Analysis
	15.13.1. Introduction
		15.13.1.1. General introduction to manganese
	15.13.2. Carbon monoxide releasing-molecules
		15.13.2.1. Introduction to carbon monoxide releasing-molecules (CO-RMs)
		15.13.2.2. Overview of methods of CO-release and detection from CO-RMs
			15.13.2.2.1. Thermal CO-release
			15.13.2.2.2. Chemically triggered CO-release
			15.13.2.2.3. Light-induced CO-release
		15.13.2.3. Mn-based CO-RMs and their synthesis/properties
			15.13.2.3.1. Thermally/chemically triggered Mn-based CO-RMs
			15.13.2.3.2. Photoactivated manganese-based CO-RMs
				15.13.2.3.2.1. Development of phenylpyridine manganese tetracarbonyl CO-RMs: From basic motif to versatile functionality
				15.13.2.3.2.2. Lowering the energy of photo-excitation required to obtain CO-release
	15.13.3. Conclusions
	Acknowledgment
	References
15.14 Organometallic Synthesis in Flow
	15.14.1. Introduction
	15.14.2. Organolithium reagents in flow
		15.14.2.1. Preparation of organolithium reagents in flow
			15.14.2.1.1. By direct insertion
			15.14.2.1.2. By Halogen/lithium exchange
			15.14.2.1.3. By directed lithiation
		15.14.2.2. Reaction of organolithium reagents in flow
	15.14.3. Organomagnesium reagents in flow
		15.14.3.1. Preparation of organomagnesium reagents in flow
			15.14.3.1.1. By direct insertion
			15.14.3.1.2. By halogen-magnesium exchange
			15.14.3.1.3. By directed metalation
		15.14.3.2. Reactions of organomagnesium reagents in flow
	15.14.4. Organozinc reagents in flow
		15.14.4.1. Preparation of organozinc reagents in flow
	15.14.5. Organosodium and organopotassium reagents in flow
	15.14.6. Preparation and cross-couplings of organoboron reagents in flow
	15.14.7. Conclusion
	References
Index
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