Biomimetic Oxidations Involving Metal Peroxides

Yoder, Jeffrey

Abstract

The proposed research is designed to test the feasibility of the participation of metal hydroperoxo species in oxidations catalyzed by metalloenzymes such as cytochrome P450 and methane monooxygenase. It has been recently proposed that metal hydroperoxides can indeed function as active oxidants in biological systems, in contrast to the accepted mechanistic paradigm which holds that high-valent metal oxo species are required. These metal hydroperoxides have been suggested to oxidize alkanes via insertion of either """"""""O"""""""" or """"""""OH"""""""" directly into a C-H bead. Substrate oxygenation, therefore, occurs concomitant with O-O bond breackage and, importantly, without change in the metal's oxidation state. Existing transition metal peroxide complexes typically effect hydrocarbon functionalization via free-radical autoxidation, a pathway that is facilitated by metal-centered oxidation state changes, and thus few valid biomimetic systems exist. Main group metals can mimic the electrophilic nature of the enzyme active sites and are also typically redox-insert, thus it is proposed that peroxide complexes of the group 12 and 13 metals can be utilized to model the enzyme catalyzed oxidations. Discrete hydro- and alkylperoxide complexes of zinc(II), aluminum(III), and gallium(III) will be synthesized; the proposed compounds can be made from known species in one or two steps. Detailed mechanistic studies will be carried out on alkane oxidations effect by these species, including the measurement of reaction rate constants and determination of kinetic deuterium isotope effects. The results of these studies will be compared with data obtained from oxidations catalyzed by metalloenzymes to test the validity of assigning high oxidation reactivity to biological hydroperoxide species.