Heme Axial Base Effects on Heme-Peroxo-Copper Adduct Formation, Properties, and Reactivity

Over the course of the next century, a fundamental understanding of the critical factors that control the efficiency, and selectivity of the four proton, four electron reduction of O2 to H2O will likely continue to grow in importance for inorganic and materials chemists. This may be driven in large part by the necessity and promise of sustainable and economically feasible alternative energy technologies which will undoubtedly rely on fundamental chemical insights into the discrete metal-oxy species formed in the course of reductive O—O bond activation and cleavage in both homogeneous and heterogeneous media. Bio-inorganic chemists seek to address these important problems by looking to natural systems, wherein lie excellent examples of efficient, selective O2 reduction provided by Heme-Copper Oxidases (HCOs). This superfamily of integral membrane proteins serve as the terminal electron acceptors of the mitochondrial electron transport chain where they bind and reduce O2 to H2O at a hetero-binuclear active site consisting of a tris-histidyl ligated CuB ion, and a heme iron cofactor. The discrete steps of this reductive O—O bond cleavage reaction are coupled to transmembrane proton pumping and oxidative phosphorylation. A long standing interest of our group has been to utilize heme-peroxo-copper adducts as model systems to understand in detail the factors which result in O2 reduction to water by drawing upon structure function relationships in the binuclear active site. The metal bridging peroxide formulation (heme)-FeIII-(O22-)-CuII has never been observed during turnover, however it has been explored computationally and is an informative starting point as a model. In the chapters below we present a design approach wherein the heme axial base moiety attached to the porphyrin periphery is changed from a covalently attached pyridyl base, to an imidazole base, and we describe the effects of these axial base functionalities on heme-peroxo-copper adduct formation, and stability. Finally, we report the synthesis, and characterization of a small library of mononuclear heme-ferric peroxides which serve to sharpen relevant questions related to heme-peroxo-copper adduct reactivity towards exogenous reductant