Hangman Metalloporphyrins as Heme Hydroperoxidase Models

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): The proposed research is designed to examine factors that influence enzymatic Compound I formation and reduction using model "Hangman" metalloporphyrin complexes. Heme hydroperoxidases generate a ferryl species two redox levels above FeIII - known as Compound I - by heterolytic cleavage of an O-O bond (in dioxygen or hydrogen peroxide). These materials subsequently react as oxidants in a variety of one and two-electron processes facilitating, for example, the dismutation of hydrogen peroxide in catalases. Factors that control both the formation of Compound I species and govern the redox (2-e- vs. l-e-) specificity exhibited by these intermediates are not well understood. Recently, a methodology for the preparation of "Hangman" porphyrins was developed. This architecture positions an acid-base group above an oxidizing active site via a rigid spacer. In this respect, the fine control over the secondary, H-bonding environment afforded by the Hangman scaffold provides an ideal and highly tunable model system to investigate Compound I-like reactivity. Procedures are described here for the synthesis of a "library" of new Hangman porphyrin compounds with varying electronic and thermochemical properties. Experiments are proposed to examine how these properties relate to "push" and "pull" effects on Compound I formation. Also, reactions of Compound I and II-like species with biologically relevant substrates will be performed to interrogate structural and electronic influences on mechanisms of Compound I reduction. The models described here are unique in that they will allow separation of the individual Compound I formation and reduction steps with careful control over the structural environment-a powerful mechanistic tool. Results of these studies will complement others' current work in this area on enzymatic systems.