Mimicking Elementary Reactions of Manganese Lipoxygenase Using Mn-hydroxo and Mn-alkylperoxo Complexes

Manganese lipoxygenase (MnLOX) is an enzyme that converts polyunsaturated fatty acids to alkyl hydroperoxides. In proposed mechanisms for this enzyme, the transfer of a hydrogen atom from a substrate C-H bond to an active-site Mn(III)-hydroxo center initiates substrate oxidation. In some proposed mechanisms, the active-site Mn(III)-hydroxo complex is regenerated by the reaction of a Mn(III)-alkylperoxo intermediate with water by a ligand substitution reaction. In a recent study, we described a pair of Mn(III)-hydroxo and Mn(III)-alkylperoxo complexes supported by the same amide-containing pentadentate ligand ((6Me)dpaq). In this present work, we describe the reaction of the Mn(III)-hydroxo unit in C-H and O-H bond oxidation processes, thus mimicking one of the elementary reactions of the MnLOX enzyme. An analysis of kinetic data shows that the Mn(III)-hydroxo complex [Mn(III)(OH)((6Me)dpaq)](+) oxidizes TEMPOH (2,2′-6,6′-tetramethylpiperidine-1-ol) faster than the majority of previously reported Mn(III)-hydroxo complexes. Using a combination of cyclic voltammetry and electronic structure computations, we demonstrate that the weak Mn(III)-N(pyridine) bonds lead to a higher Mn(III/II) reduction potential, increasing the driving force for substrate oxidation reactions and accounting for the faster reaction rate. In addition, we demonstrate that the Mn(III)-alkylperoxo complex [Mn(III)(OO(t)Bu)((6Me)dpaq)](+) reacts with water to obtain the corresponding Mn(III)-hydroxo species, thus mimicking the ligand substitution step proposed for MnLOX.