This grant in the Organic and Macromolecular Chemistry Program supports research of Professors Lawrence Sayre and Fred Urbach, which aims at a mechanistic study concerning the role of copper as a catalyst in the oxidation of organic compounds. Such processes have far reaching consequences in both biochemical and industrial processes. The use of more simplified model systems to study these multifaceted processes that involve different oxidation states of copper at specific places in the catalytic cycle provides considerable insight into how nature achieves such chemical reactions. The planned research is divided into four sections. The first examines the dehydrogenation of unactivated amines and the oxidative cleavage of beta-hetero-atom-substituted amines. The second involves a model study for the copper amine oxidases in which a quinone-mediated transamination is followed by copper-mediated oxidation of the resulting aminophenol. The third aspect deals with oxidations of amino acids and simple N-acyl derivatives thereof. The fourth examines the regioselective copper-mediated oxidative N-dealkylation of oligopeptides at the C-terminus as possible mechanisms for the copper amidases which convert peptidylglycine to peptide carboxamides. Initial studies in these areas make it clear that multiple reaction pathways are possible in many cases. The planned work involves a deeper and more quantitative characterization of the reaction in terms of (1) the factors which control competitive reaction pathways, (2) substrate structure-reactivity effects, (3) the effect of varying the oxidation system ?e.g., Cu(I)-dioxygen vs. Cu(II)-peroxydisulfate vs. Cu(III)!, and (4) the effect of the metal coordination environment and other reaction conditions.
