Kovacs, JuliaRogers, Dylan Meamber2023-08-142023-08-142023-08-142023Rogers_washington_0250E_25370.pdfhttp://hdl.handle.net/1773/50269Thesis (Ph.D.)--University of Washington, 2023Nature has developed enzymes over millennia that perform difficult chemical transformations in mild conditions, using structural controls to aid in the generation of powerful reactive intermediates. Metalloenzymes such as cysteine dioxygenase (CDO) and isopenicillin N synthase (IPNS) use thiolate ligands coordinated to their metal centers to bind dioxygen and produce strong oxidants in the form of FeIII-superoxo and and high-valent Fe-oxo species. The similar active sites of CDO and IPNS afford different chemistry due to small variations in their ligands stabilizing different intermediates. Similarly, nitrile hydratase (NHase) uses dioxygen to modify the thiolates in its coordination sphere to allow for the binding of nitriles and their transformations to amides. Dioxygen is produced by the oxygen-evolving complex (OEC) via the process of water splitting, a thermodynamically difficult process that Nature accomplishes via a cubane cluster of manganese and calcium atoms. This cluster separates that process into thermodynamically simpler steps which allow for the generation of dioxygen using the energy from light.To examine the factors that allow for the broadly different reactivity performed by CDO, IPNS, and NHase, a structurally constrained iron complex [FeIII(S2Me2N3(Et,Pr)]+ is produced and its interactions with oxo-atom donors to produce a sulfenate species is characterized and compared to the less constrained complex [FeIII(S2Me2N3(Pr,Pr)]+. At low temperatures, an oxo-atom donor adduct species is observed before formation of that sulfenate, and inhibition studies imply the existence of an intermediate FeV-oxo. This species is investigated via computational methods, and it is found that the constrained ligand produces a less stable oxo species. The reduced complex FeII(S2Me2N3(Et,Pr) and its reactivity with dioxygen are also characterized kinetically and thermodynamically by stopped-flow UV/visible spectroscopy, finding evidence that an FeIII-superoxo is formed. Compared to FeII(S2Me2N3(Pr,Pr), the superoxo is formed much more quickly and much more favorably. This superoxo species is transient and further reacts with either the solvent or itself, although the product species could not be characterized. Reactivity with oxygen in the presence of an excess of weak C–H bonds or with deuterated solvent was not found to change the rate of this species’ decay, indicating that the process occurring could be an intramolecular process. Computational studies support the possibility of a intramolecular process. The influence of a cis or trans thiolate is examined via the generation of the asymmetric mixed alkoxide/thiolate complexes FeII(SMe2OMe2N3(Pr,Pr)) and [FeIII(SMe2OMe2N3(Pr,Pr))]+ were synthesized, and their reactivity with oxo-atom donors and dioxygen was examined. Similar to the bis-thiolate complexes, intermediates were observed with oxo-atom donor and oxygen reactivity, but products could not be isolated. The preference for binding a substrate cis or trans to a thiolate was studied through computational methods, finding structural evidence that trans binding is preferred and predicted spectral evidence that cis binding is preferred. Factors influencing the structural flexibility of the OEC were examined using a series of model cubane complexes with varying ligand environments. By modifying the exogenous ligands of the cubane in small ways, dramatic changes are observed in the structural parameters of the cubane as a whole, demonstrating a potential way the OEC controls its structural arrangement during the process of water oxidation.application/pdfen-USCC BYInorganic chemistryChemistryOrganic chemistryChemistryThesis