NEW INVESTIGATIONS OF NITRIC OXIDE, NITRITE AND HYPONITRITE INTERACTIONS WITH HEME/COPPER ASSEMBLIES
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Our long-time niche in synthetic biological inorganic chemistry has been to design ligands and generate coordination complexes of copper and/or iron ions, those reacting with dioxygen (O2) and/or nitrogen oxides (e.g., nitric oxide (NO(g)), nitrite (NO2–), and hyponitrite (N2O22–)). The purpose of investigation of synthetic models is to elucidate fundamental aspects of the chemistry, here metal/small-molecule adduct formation, structure, spectroscopy and correlation to structure, electronic-structure/bonding, reactivity and mechanism of action. As inspiration for the work presented in this dissertation, we turn to mitochondrial cytochrome c oxidase (CcO) which is responsible for dioxygen consumption and also regarded as the key target for NO(g) and nitrite within mitochondria. The very same binuclear active site is also capable of reductive coupling of two NO(g) molecules to generate nitrous oxide (N2O) where a heme and/or copper coordinated hyponitrite (N2O22–) moiety has been postulated (or even detected in some protein chemistry) as an intermediate in the reaction. Our synthetic heme/Cu assemblies possess redox activity toward these small molecules of biological interest. Chapter 1 provides an overview of our recent advances in studying synthetic heme/Cu complexes with respect to the design and synthetic generation of O2-adducts to elucidate fundamental aspects of the O2-reduction and subsequent O–O cleavage process as well as our new investigations on closely related heme/Cu constructs capable of mediating nitrite ion reduction to NO(g) or the reverse, oxidation of NO(g) to nitrite. In chapter 2, we first introduce a synthetic heme/Cu assembly that in its partially reduced form facilitates nitrite reduction to NO(g), while the fully oxidized form of the same assembly, a μ-oxo heme-FeIII−O−CuII(L) complex, oxidizes NO(g) to nitrite. Chapter 3 probes the key factors involved in the nitrite reductase chemistry wherein the nature of the heme and/or the copper ligand were synthetically modified. The ferrous heme is the reductant, but its reducing ability does not influence the overall reaction rate. It is proposed that the nitrite to cupric ion binding dictates how nitrite coordinates to the ferrous heme, via a N- or O-atom, which influences the overall kinetics. To elucidate the molecular mechanism of NO(g) oxidase chemistry, in Chapter 4, detailed spectroscopic and kinetic studies using various μ-oxo heme-FeIII−O−CuII(L) compounds were performed. The experimental results are in excellent agreement with theoretical calculations, revealing the nature of intermediates and key mechanistic steps. In Chapter 5, the first example of a cupric hyponitrite compound is reported. From X-ray analysis, a trans-geometry for the hyponitrite moiety is confirmed. The first example of a synthetic heme/Cu hyponitrite intermediate is described. Warming the intermediate to room temperature results in clean formation of the corresponding μ-oxo heme-FeIII−O−CuII(L) complex and N2O is released stoichiometrically.