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.