Molecular Probes for the Chemistry of Peroxynitrite

Princeton University, Princeton NJ

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Abstract

DESCRIPTION (provided by applicant): Peroxynitrite (ONOO) is a destructive biological oxidant which contributes to cellular damage associated with a wide range of human disease states. New catalysts for the detoxification of peroxynitrite (by isomerization to the benign nitrate anion) should provide valuable probes for understanding the complex interplay of reactive oxidants in biological systems. In addition these reagents could prove important as pharmaceutical agents. This proposal outlines a strategy for the development of iron-based catalysts for the rapid and selective isomerization of ONOO to N03-. The proposed "peroxynitritases" are binuclear iron complexes of the general formula [Fe(III)2(u-O)L(x)X(y)](Cl)(4)z. These cationic di-iron species are expected to participate in an efficient catalytic cycle for peroxynitrite isomerization mediated by mixed valent Fe(III)/Fe(IV) intermediates. Variation of the ligands X and L is facile, and should enable optimization of catalytic activity and catalyst stability. Mechanistic investigations of both the stoichiometric and catalytic reactions of [Fe(III)2(u-O)L(x)X(y)](Cl)(4)z with peroxynitrite will be undertaken in order to identify important intermediates and to fully characterize the catalytic cycle.