The principal objective of the proposed research is the development of the coordination chemistry of Cu(I), Cu(II), Cu(I)- dioxygen (O2) and Cu-ligand structure, spectroscopy and reactivity which is of relevance to the metal ion active site chemistry in a number of redox active copper enzymes. The appropriate coordination chemistry needs to be established so that realistic conclusions which are derived from studies on the proteins can be made. Our approach falls into the realm of biomimetic chemistry, where synthetic mononuclear and dinuclear copper complexes containing polydentate ligands are designed to mimic at least certain aspects of protein active sites, and systematic investigations can help to elucidate protein structrual and/or functional properties. The biologically essential copper enzymes of interest are the O2-carrier, hemocyanin, the monooxygenases tyrosinase, dopamine beta-hydroxylase and Cu-phenylalanine hydroxylase (PAH), and the blue and non-blue copper oxidases (e.g. laccase). In addition, copper-containing reductases which mediate reductive transformations of nitrite ion or nitrous oxide are of interest. Specific areas for study and aims of the proposed research fall into four categories: 1) Copper Monooxygenase Systems. Elucidate electronic substituent effects in model monooxygenase systems (arene hydroxylation) via synthetic and kinetic studies. A kinetic study of electronic substituent effects in tyrosinase is proposed. We plan to initiate studies of Cu-pterin chemistry of relevance to PAH. 2) Dioxygen-Copper Chemistry. Extensive structural, spectroscopic, kinetic and thermodynamic investigations involving the formation and reactivity of discrete Cun-O2 (n=1,2) complexes will be carried out. New systems which can more closely mimic protein active sites will be designed. 3) Biomimetic Reactivity. High priority will be given to studies of Cun-OOR/substrate reactions which will address fundamental questions of O2 activation resulting in oxygen incorporation into substrates. Synthetic and kinetic/mechanistic studies will seek to characterize key Cu/oxy intermediates such as are involved in monooxygenase or DNA cleaving systems. 4) Mononuclear Cu Complexes. These studies will seek to establish structural probes for Cu(I), and elucidate (LCu-X)n+ structure, spectroscopy, and ligand reactivity including reductive transformations involving nitrogen oxides. New Cu/O2 complexes and reactivity studies will be examined using these mononucleating ligands.
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