Bioinspired Catalysis -- Contents -- List of Contributors -- Preface -- Part I Primordial Metal-Sulfur-Mediated Reactions -- Chapter 1 From Chemical Invariance to Genetic Variability -- 1.1 Heuristic of Biochemical Retrodiction -- 1.2 Retrodicting the Elements of Life -- 1.3 Retrodicting Pioneer Catalysis -- 1.4 Retrodicting Metabolic Reproduction and Evolution -- 1.5 Retrodicting Pioneer-Metabolic Reactions -- 1.6 Early Evolution in a Spatiotemporal Flow Context -- Acknowledgments -- References -- Chapter 2 Fe-S Clusters: Biogenesis and Redox, Catalytic, and Regulatory Properties -- 2.1 Introduction -- 2.2 Fe-S Cluster Biogenesis and Trafficking -- 2.3 Redox Properties of Fe-S Clusters -- 2.4 Fe-S Clusters and Catalysis -- 2.4.1 Redox Catalysis -- 2.4.2 Nonredox Fe-S Cluster-Based Catalysis -- 2.5 Fe-S Clusters and Oxidative Stress -- 2.6 Regulation of Protein Expression by Fe-S Clusters -- 2.6.1 Eukaryotic Iron Regulatory Protein 1 (IRP1) -- 2.6.1.1 IRP1 and Fe-S Cluster Biogenesis -- 2.6.1.2 Reactive Oxygen Species and IRP1 Fe-S Cluster Stability -- 2.6.1.3 X-Ray Structural Studies of IRP1-IRE Complexes -- 2.6.2 Bacterial Fumarate Nitrate Reduction Regulator (FNR) -- 2.6.3 The ISC Assembly Machinery Regulator IscR -- 2.7 Conclusion -- References -- Part II Model Complexes of the Active Site of Hydrogenases - Proton and Dihydrogen Activation -- Chapter 3 [NiFe] Hydrogenases -- 3.1 Introduction -- 3.2 Introduction to [NiFe] Hydrogenases -- 3.3 Nickel Thiolate Complexes as Analogs of [NiFe] Hydrogenase -- 3.4 [NiFe] Hydrogenase Model Complexes -- 3.4.1 Amine [N2Ni(μ-S2)Fe] Complexes -- 3.4.2 Phosphine [P2Ni(μ-S2)Fe] Complexes -- 3.4.3 Thiolate [SxNi(μ-Sy)Fe] Complexes -- 3.4.4 Polymetallic [Ni(μ-S)zFey] Complexes -- 3.5 Analogs of [NiFe] Hydrogenase Incorporating Proton Relays.

3.5.1 Nickel Complexes Incorporating Protonation Sites -- 3.5.2 [NiFe] Complexes Incorporating Protonation Sites -- 3.6 Perspectives and Future Challenges -- Acknowledgments -- References -- Chapter 4 [FeFe] Hydrogenase Models: an Overview -- 4.1 Introduction -- 4.2 Synthetic Strategies toward [FeFe] Hydrogenase Model Complexes -- 4.3 Properties of Model Complexes -- 4.3.1 Biomimetic Models of the "Rotated State" -- 4.3.2 Electron Transfer in [FeFe] Hydrogenase Models -- 4.3.3 Protonation Chemistry of [FeFe] Hydrogenase Models -- 4.3.3.1 Hydride Formation -- 4.3.3.2 Ligand Protonation and Proton Relays -- 4.3.4 Water-Soluble Hydrogenase Mimics -- 4.4 Conclusion -- References -- Chapter 5 The Third Hydrogenase -- 5.1 Introduction -- 5.2 Initial Studies of Hmd -- 5.3 Discovery that Hmd Contains a Bound Cofactor -- 5.4 Discovery that Hmd is a Metalloenzyme -- 5.5 Crystal Structure Studies of [Fe] Hydrogenase -- 5.6 Mechanistic Models of [Fe] Hydrogenase -- 5.6.1 Studies Before the Most Recent Assignment of the FeGP Cofactor -- 5.6.2 Studies After the Most Recent Assignment of the FeGP Cofactor -- 5.6.3 Synthesized Model Complexes of the FeGP Cofactor -- References -- Chapter 6 DFT Investigation of Models Related to the Active Site of Hydrogenases -- 6.1 Introduction -- 6.2 QM Studies of Hydrogenases -- 6.3 QM Studies of Synthetic Complexes Related to the Active Site of Hydrogenases -- 6.3.1 DFT Studies about Structural and Redox Properties of Synthetic Complexes Related to the Active Site of [FeFe] Hydrogenases -- 6.3.2 DFT Studies about the Reactivity of Synthetic Models Related to the Active Site of [FeFe] Hydrogenases.

6.3.3 DFT Studies about Regiochemistry of Protonation of Synthetic Complexes Related to the Active Site of [FeFe] Hydrogenases -- 6.3.4 DFT Studies about the Isomerization of Synthetic Complexes Related to the Active Site of [FeFe] Hydrogenases -- 6.4 Conclusions -- References -- Chapter 7 Mechanistic Aspects of Biological Hydrogen Evolution and Uptake -- 7.1 Introduction -- 7.2 [FeFe] Hydrogenases -- 7.2.1 Overview of the Catalytic Cycle -- 7.2.2 The Nature of the Bridgehead Atom -- 7.2.3 Structural Features of the Resting State (Hox) and Reduced State (Hred) of the Active Site -- 7.2.4 Relationship between Structural and Spectroscopic Properties of Hox, Hred, and Hsred -- 7.2.5 The Rotated State and Mixed Valency: Synthetic Systems -- 7.2.6 Hydrides -- 7.2.7 Hydrides and Electrocatalysis of Hydrogen Evolution -- 7.2.8 Dihydrogen Oxidation -- 7.2.9 Final Comments -- 7.3 [NiFe] Hydrogenases -- 7.3.1 Overview of the Catalytic Cycle -- 7.3.2 Structural Models of Ni-A, Ni-B, and Ni-SI States -- 7.3.3 Hydride Chemistry Related to Ni-C/Ni-R: Functional Models -- 7.3.4 Final Comments -- 7.4 [Fe] Hydrogenase -- 7.4.1 Overview -- 7.4.2 Biological Mechanism -- 7.4.3 Model Studies -- 7.4.4 Final Comments -- 7.5 Nitrogenase -- 7.5.1 Overview -- 7.5.2 Hydrogen Evolution by Mo-Nitrogenase -- 7.5.3 Paramagnetic Bridging Fe/Fe Hydrides -- 7.5.4 Final Comments -- References -- Part III Nitrogen Fixation -- Chapter 8 Structures and Functions of the Active Sites of Nitrogenases -- 8.1 Introduction -- 8.2 Properties of Mo Nitrogenase -- 8.2.1 Properties of Fe Protein and its Associated Cluster -- 8.2.1.1 The Fe Protein Structure -- 8.2.1.2 The [Fe4S4] Cluster -- 8.2.2 Properties of MoFe Protein and its Associated Clusters -- 8.2.2.1 The MoFe Protein -- 8.2.2.2 The P-Cluster -- 8.2.2.3 The FeMo-co -- 8.3 Catalysis by Mo Nitrogenase -- 8.3.1 The Thorneley-Lowe Model.

8.3.1.1 The Fe Protein Cycle -- 8.3.1.2 The MoFe Protein Cycle -- 8.3.2 Recent Development -- 8.3.2.1 Alternative Pathway of N2 Reduction -- 8.3.2.2 Plausible Structures of N2 Reduction Intermediates -- 8.3.2.3 Alternative Substrates of Nitrogenase -- 8.4 Unique Features of V Nitrogenase -- 8.4.1 Structural Features of Fe Protein and its Associated Cluster -- 8.4.1.1 The Fe Protein -- 8.4.1.2 The [Fe4S4] Cluster -- 8.4.2 Structural Features of VFe Protein and its Associated Clusters -- 8.4.2.1 The VFe Protein -- 8.4.2.2 The P-Cluster of VFe Protein -- 8.4.2.3 The FeVco -- 8.4.3 Catalytic Features of V Nitrogenase -- 8.5 Catalytic Properties of Isolated FeMo-co and FeVco -- Acknowledgments -- References -- Chapter 9 Model Complexes of the Active Site of Nitrogenases: Recent Advances -- 9.1 Introduction -- 9.2 Structural Models of Metal-Sulfur Clusters in the Nitrogenases -- 9.3 Functional Modeling at a Single Molybdenum Center -- 9.4 Functional Modeling at a Single Iron Center -- 9.5 The Hydrogen and Homocitrate Issues in Nitrogenase Model Chemistry -- 9.6 Sulfur- and Metal-Metal Interaction in Functional Models of Nitrogenase -- 9.7 Surface Chemistry and the Supramolecular Protein Environment -- 9.8 Conclusion and Outlook -- References -- Chapter 10 A Unified Chemical Mechanism for Hydrogenation Reactions Catalyzed by Nitrogenase -- 10.1 Introduction -- 10.1.1 Nitrogenase: the Enzyme -- 10.1.2 FeMo-co -- 10.1.3 Where Does the Catalysis Occur on FeMo-co? -- 10.2 Investigations of Mechanism -- 10.2.1 Density Functional Simulations -- 10.2.2 The Coordination Chemistry of FeMo-co -- 10.2.3 Electronic Structure of FeMo-co -- 10.3 Hydrogen Supply for the Reactions of Nitrogenase -- 10.3.1 Multiple Protons are Needed for Catalytic Reaction Cycles -- 10.3.2 The Proton Supply Chain -- 10.3.3 Hydrogenation of FeMo-co.

10.3.4 Hydrogen Atom Migration over FeMo-co -- 10.4 FeMo-co in Nitrogenase as a General Hydrogenating Machine -- 10.4.1 Modes of Substrate Binding to FeMo-co -- 10.4.2 Vectorial Hydrogenation of FeMo-co in Relation to Substrate Binding -- 10.4.3 The Intramolecular Hydrogenation Paradigm for the Catalytic Reactivity of FeMo-co -- 10.5 Chemical Mechanisms for the Catalysis of Substrate Hydrogenation at FeMo-co -- 10.5.1 How Does N2 Bond to FeMo-co? -- 10.5.2 Proposed Intimate Chemical Mechanism for the Catalysis of Hydrogenation of N2 to NH3 at FeMo-co -- 10.5.2.1 Possibilities -- 10.5.2.2 Preliminary Simulations -- 10.5.2.3 Complete 21-Step Choreography -- 10.6 Hydrogen Tunneling in the Nitrogenase Mechanism -- 10.6.1 Characteristics of H Atom Tunneling in Enzyme Reactions -- 10.6.2 Characteristics of H-Atom Transfer in Nitrogenase -- 10.7 Intramolecular Hydrogenation of Other Substrates -- 10.7.1 Formation of Dihydrogen -- 10.7.2 Hydrogenation of Alkynes -- 10.7.3 Hydrogenation of D2: the HD Reaction -- 10.7.4 Hydrogenation of CO and CO2 -- 10.8 Interpretation of the Structure of FeMo-co and Its Surrounds -- 10.9 Mimicking Nitrogenase -- 10.10 Summary and Epilog -- Acknowledgments -- References -- Chapter 11 Binding Substrates to Synthetic Fe-S-Based Clusters and the Possible Relevance to Nitrogenases -- 11.1 Introduction -- 11.2 Mechanism of Nitrogenases -- 11.2.1 Detecting Substrates and Intermediates Bound to the Enzyme -- 11.2.2 Exploring Intermediates in the Enzyme Mechanism Using Calculations -- 11.3 Studies on Synthetic Clusters -- 11.3.1 Evidence for Substrates Bound to Synthetic Clusters -- 11.3.2 Mechanisms of Substrates Binding to Fe-S-Based Clusters -- 11.3.3 Mechanisms Peculiar to Clusters -- 11.3.4 Influence of Cluster Composition on Substrate Binding.

11.3.5 Transient Binding of Substrates to Clusters.