Iron-Containing Enzymes -- Contents -- Chapter 1 Experimental and Computational Studies on the Catalytic Mechanism of Non-heme Iron Dioxygenases -- 1.1 Introduction -- 1.2 α-Ketoglutarate Dependent Dioxygenases (αKDD) and Halogenases (αKDH) -- 1.2.1 Taurine/α-Ketoglutarate Dioxygenase (TauD) -- 1.2.2 AlkB Repair Enzymes -- 1.2.3 Prolyl-4-hydroxylase (P4H) -- 1.2.4 α-Ketoglutarate Dependent Halogenases (αKDH) -- 1.3 Cysteine Dioxygenase (CDO) -- 1.4 Isopenicillin N Synthase (IPNS) -- 1.5 1-Aminocyclopropane-1-carboxylic Acid Oxidase (ACCO) -- 1.6 Rieske Dioxygenases -- 1.7 Extradiol and Intradiol Dioxygenases -- 1.8 Conclusion -- References -- Chapter 2 Non-heme Iron-Dependent Dioxygenases: Mechanism and Structure -- 2.1 Introduction -- 2.2 Dioxygenases Catalysing Oxidative C-C Cleavage Reactions -- 2.2.1 Intradiol Catechol Dioxygenases -- 2.2.2 Extradiol Catechol Dioxygenases -- 2.2.3 Carotenoid Cleavage Dioxygenases -- 2.2.4 Oxidative Cleavage of Aliphatic Substrates -- 2.3 Dioxygenases Catalysing Formation of Peroxides: Lipoxygenases -- 2.4 Dioxygenases Catalysing Hydroxylation Reactions -- 2.4.1 α-Ketoglutarate-Dependent Dioxygenases -- 2.4.2 Arene (Rieske) Dioxygenases -- 2.5 Conclusion and Summary -- References -- Chapter 3 Transient Iron Species in the Catalytic Mechanism of the Archetypal α-Ketoglutarate-Dependent Dioxygenase, TauD -- 3.1 Introduction -- 3.2 Structure of the TauD Active Site -- 3.2.1 Metal Binding to TauD Apoprotein -- 3.2.2 Substrate Binding to TauD -- 3.2.3 Characterization of the NO-Bound Quaternary Complex -- 3.3 The Fe(IV)-oxo Species -- 3.3.1 Experimental Detection of Fe(IV)-oxo -- 3.3.2 Electronic Configuration of the Fe(IV)-oxo Species -- 3.3.3 Hydrogen Atom Abstraction by Fe(IV)-oxo -- 3.3.4 Thermodynamics of Hydrogen Atom Abstraction by Fe(IV)-oxo -- 3.4 Fe(III)-O(H) Species and Oxygen Transfer -- 3.5 Conclusions.

Acknowledgements -- References -- Chapter 4 Density Functional Theory Studies on Non-heme Iron Enzymes -- 4.1 Introduction -- 4.1.1 Reactions Catalysed by Non-heme Iron Enzymes and their Biological Significance -- 4.1.2 Iron Binding Sites -- 4.2 Computational Methods -- 4.3 Dioxygen Binding and Generation of Peroxo Intermediates -- 4.3.1 O2 Binding with Oxidation of Fe(II) -- 4.3.2 O2 Binding with Oxidation of the Organic Substrate -- 4.3.3 O2 Binding with Oxidation of External Reductants -- 4.4 Strategies for O-O Bond Cleavage -- 4.4.1 Heterolytic O-O Bond Cleavage Leading to Fe(IV)=O -- 4.4.2 Homolytic O-O Bond Cleavage Leading to R-O -- 4.4.3 Heterolytic O-O Bond Cleavage in Fe(III)-OOH -- 4.5 Reactions of the High-Valent Intermediates -- 4.5.1 Oxygenation by Fe(IV)=O -- 4.5.2 Oxidation by Fe(IV)=O -- 4.5.3 Reactions of R-O -- 4.6 Origins of Chemoselectivity - The Role of Negative Catalysis -- 4.7 Conclusions -- References -- Chapter 5 Theoretical Spectroscopies of Iron-Containing Enzymes and Biomimetics -- 5.1 Introduction -- 5.2 Mössbauer Spectroscopy -- 5.2.1 Theoretical Prediction of Mössbauer Parameters -- 5.2.2 Examples from the Literature -- 5.3 Nuclear Resonance Vibrational Spectroscopy -- 5.3.1 Examples from the Literature -- 5.4 Electron Paramagnetic Resonance -- 5.4.1 Theoretical EPR Spectroscopy -- 5.4.2 Examples from the Literature -- 5.5 Absorption Spectroscopy -- 5.5.1 Theoretical Prediction of Absorption Spectroscopy -- 5.5.2 Examples from the Literature -- 5.6 X-Ray Spectroscopy -- 5.6.1 Theoretical Prediction of Metal and Ligand K-Edge Spectra -- 5.6.2 Examples from the Literature -- 5.7 Conclusion -- References -- Chapter 6 Bioinspired Non-heme Iron Catalysts in C-H and C=C Oxidation Reactions -- 6.1 Biological Precedents -- 6.1.1 Oxidative Iron Proteins -- 6.1.2 Cytochrome P450 -- 6.1.3 Rieske Dioxygenases.

6.2 Non-heme Iron Complexes as Bioinspired Catalysts -- 6.2.1 Oxidation of Alkanes (C-H Bonds) by Non-heme Iron Complexes -- 6.2.2 Oxidation of Alkenes (C=C Double Bonds) by Non-heme Iron Complexes -- 6.3 Reaction Mechanisms in Catalytic C-H and C=C Oxidation Reactions Mediated by Complexes with N-Rich Ligands -- 6.3.1 The Initially Formed FeIII-OOH and its Cleavage Products -- 6.3.2 Olefin Oxidations: Epoxidation and cis-Dihydroxylation -- 6.3.3 Alkane Oxidations -- 6.4 Conclusions -- References -- Chapter 7 Application of Magnetic Circular Dichroism, X-Ray Absorption Spectroscopy and Extended X-Ray Absorption Fine Structure in Determining Geometric and Electronic Structure of Non-heme Iron(IV)-oxo Enzymatic Intermediates and Related Synthetic Models -- 7.1 Introduction -- 7.1.1 Magnetic Circular Dichroism (MCD) -- 7.1.2 X-Ray Absorption Spectroscopy and Extended X-Ray Absorption Fine Structure -- 7.2 MCD of Iron(IV)-oxo Complexes -- 7.2.1 [FeIV=O(TMC)(NCCH3)]2+ -- 7.2.2 Iron(IV)-oxo MCD: Varying Axial and Equatorial Ligands -- 7.2.3 Vibronic Progression in MCD -- 7.3 XAS and EXAFS of Iron(IV)-oxo Intermediates and Synthetic Model Complexes -- 7.3.1 Enzymatic Catalytic Cycle Intermediates -- 7.3.2 Model Complexes -- 7.4 Parting Thoughts -- References -- Chapter 8 Structure, Mechanism and Function of Cytochrome P450 Enzymes -- 8.1 Introduction -- 8.2 Cytochromes P450 - A Brief History -- 8.3 Optical and Spectroscopic Features -- 8.4 Cytochrome P450 Catalytic Cycle -- 8.5 Biological Diversity -- 8.6 Cytochrome P450 Redox Partner Systems -- 8.7 Cytochrome P450 Structure -- 8.8 Physiological Roles of Cytochromes P450 -- 8.9 Cytochrome P450 Medicine and Biotechnology -- 8.10 Conclusions and Future Prospects -- References -- Chapter 9 Drug Metabolism by Cytochrome P450: A Tale of Multistate Reactivity -- 9.1 Introduction.

9.2 Nomenclature of Cytochrome P450 Enzymes -- 9.3 Types of Drug Interactions -- 9.3.1 Induction -- 9.3.2 Inhibition -- 9.4 Important Isoforms of Human CYP -- 9.4.1 CYP1A2 Isoform -- 9.4.2 CYP2C8, CYP2C9 and CYP2C19 Isoforms -- 9.4.3 CYP2D6 Isoform -- 9.4.4 CYP3A4 Isoform -- 9.5 Examples of Generation of Various Metabolites from a Single CYP 450 -- 9.6 CYP 450 Structure -- 9.7 Catalytic Cycle of CYP 450 -- 9.8 Compound I of CYP 450: The Active Species -- 9.8.1 Axial Ligand Effect of Compound I -- 9.9 Reactivity of Compound I -- 9.10 Aliphatic C-H Hydroxylation by Compound I of CYP 450 -- 9.10.1 Rearrangement Mechanisms of Aliphatic Hydroxylation Reactions -- 9.11 C=C Epoxidation by Compound I of CYP 450 -- 9.12 Sulfoxidation Reaction by Compound I of CYP 450 -- 9.13 Aromatic Hydroxylation Reaction by Compound I of CYP 450 -- 9.14 Role of Water Molecule as Biocatalyst -- 9.15 Conclusion -- Acknowledgements -- References -- Chapter 10 Oxidation of Unnatural Substrates by Engineered Cytochrome P450cam -- 10.1 Introduction -- 10.2 Binding of the Substrate -- 10.3 CYP 450cam Reaction Cycle -- 10.4 Rational Design of the Active Site of CYP 450cam -- 10.5 Metabolism of Unnatural Substrates by CYP 450cam Variants -- 10.6 Binding of Unnatural Substrate, Hydroxylation, and Product Release -- 10.6.1 Small Hydrocarbons -- 10.6.2 Alkyl Benzenes -- 10.6.3 Polycyclic Aromatic Hydrocarbons (PAHs) -- 10.6.4 2-Ethylhexanol -- 10.6.5 Aromatic-Aliphatic Hydrocarbon, Phenylcyclohexane -- 10.6.6 Diphenylmethane -- 10.6.7 Valporic Acid -- 10.6.8 Terpenoids -- 10.6.9 Fused Benzene-Cycloalkane Compounds -- 10.6.10 Nitrogenous Compounds -- 10.6.11 Halogenated Compounds -- 10.7 Summary -- References -- Chapter 11 QM/MM Studies of Cytochrome P450 Systems: Application to Drug Metabolism -- 11.1 Introduction -- 11.2 CYPs and Drug Metabolism.

11.3 Quantum Mechanical/Molecular Mechanical (QM/MM) Methods -- 11.4 QM/MM Studies of CYPs -- 11.4.1 Catalytic Cycle of CYP101 (CYP 450cam) -- 11.4.2 Hydroxylation of Camphor by CYP 450cam -- 11.4.3 Compound I Reactivity and Selectivity -- 11.4.4 Aromatic Hydroxylation -- 11.4.5 Other QM/MM Studies of CYPs -- 11.5 Conclusions -- References -- Chapter 12 Mechanism and Function of Tryptophan and Indoleamine Dioxygenases -- 12.1 Introduction -- 12.2 Biological and Physiological Function of Indoleamine Dioxygenase and Tryptophan Dioxygenase -- 12.3 Structures of TDO and IDO -- 12.3.1 Comparison of Overall Structure -- 12.3.2 Active Site Environments -- 12.4 Turnover and Inhibition -- 12.4.1 Steady State Kinetics -- 12.4.2 Inhibition of TDO and IDO -- 12.5 Catalytic Cycle -- 12.5.1 Formation of the Active Ternary Complex -- 12.5.2 Electrochemical Control of Substrate Reactivity -- 12.5.3 Heme Coordination Environment -- 12.5.4 Mechanism of Oxygen Insertion -- 12.6 Summary and Conclusions -- References -- Subject Index.