Cyclic organic peroxides: synthesis and mechanism of reduction

Abstract

The fenton-like reductive cleavage of organic peroxides by FeII species is a chemical reaction whose mechanistic pathway has not been yet fully understood. However, it is known that there is production of radical species centered at both the oxygen and carbon. The mechanism should therefore involve a ²-scission after the formation of the initial oxyradicals through a still unknown way. This research project suggests the synthesis of cyclic peroxides of the classes 1,2-dioxetane and 1,2,4-trioxolane, and the mechanistic study of the reductive cleavage of those peroxides by FeII, from thermodynamic and kinetic studies backed by reaction products determination by direct and indirect methods. The evaluation of the generating capacity of radicalar species from the reductive cleavage reaction will be done according to the structure of those formed species and their yields, and the peroxides will be tested against Plasmodium microorganisms. The mechanism of action of those peroxidic drugs involve the reductive cleavage of the peroxide by a free heme group inside the Plasmodium parasite, which results in the formation of carbon-centered radicals, that can attack and alkylate biomolecules that are vital to the survival of the parasite, which is destroyed or inactivated. The determination of the operating mechanism and the energetics of cyclic peroxides made in this project will be correlated to the antimalarial activity of those peroxides. (AU)