HEME/COPPER AND HEME/NONHEME IRON O2 AND NO REACTIVITY

Johns Hopkins University, Baltimore MD

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Abstract

The long-term research objective is to design, synthesize and investigate model compound systems which can help elucidate fundamental aspects of structure, metal-ligation, spectroscopy and reactivity relevant to the chemistry utilized by heme-copper oxidases (e.g., cytochrome c oxidases (CcOs)) and nitric oxide reductases. These evolutionarily related enzymes are involved in the bioenergetics of aerobic and anaerobic organisms, and have in common a heme/M (M = Cu or non-heme Fe) active site which reductively cleaves dioxygen (OZ) or nitric oxide (NO), respectively. The research can contribute to a better understanding of enzyme structure and mechanism, and provide fundamental insights into biological O2-activation, NO and nitrogen oxide chemistry and biochemistry, and issues related to nitrogen oxides in the environment. Major themes are the synthesis of discrete heme/M compounds, O2-chemistry of reduced heme/Cu assemblies, the coordination chemistry of heme/M complexes, NO reactivity studies, and use of phenol chemistry in heme/Cu mediated O2-reduction. Specific aims include (1) spectroscopic and structural characterization of heme-O2-Cu (peroxo) complexes using varied conditions of heme, axial base, or Cu-ligand, (2) study of heme/Cu/O2 adducts assembled from mononuclear components, (3) systematic comparisons of the reactivity of varying Fe-O2-Cu moieties, (4) development of the coordination chemistry of heme/M systems with mu-oxo, mu-OH- and other ligands (e.g., C1-, CN-) of interest as biochemical probes, (5) study of reduced heme/M complexes and their CO and isocyanide adducts, (6) thorough investigation and elaboration upon a NO reductase model system which produces nitrous oxide (N2O), (7) generation of new heme/Fe systems having varied Fe-ligands with three N-donors and/or with one O-donor, (8) study of nitric oxide reactivity with these and heme/Cu systems, since NO is a reversible inhibitor of CcO, (9) use of phenols as electron-proton donors and Cu-ligands in O2-reduction with heme/Cu assemblies, and (10) probing of the chemistry relevant to formation and function of an imidazole-phenol (His-Tyr) covalent link found in CcO.