Abstract
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 MnIII-hydroxo center initiates substrate oxidation. In some proposed mechanisms, the active-site MnIII-hydroxo complex is regenerated by the reaction of a MnIII-alkylperoxo intermediate with water by a ligand substitution reaction. In a recent study, we described a pair of MnIII-hydroxo and MnIII-alkylperoxo complexes supported by the same amide-containing pentadentate ligand (6Medpaq). In this present work, we describe the reaction of the MnIII-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 MnIII-hydroxo complex [MnIII(OH)(6Medpaq)]+ oxidizes TEMPOH (2,2′-6,6′-tetramethylpiperidine-1-ol) faster than the majority of previously reported MnIII-hydroxo complexes. Using a combination of cyclic voltammetry and electronic structure computations, we demonstrate that the weak MnIII-N(pyridine) bonds lead to a higher MnIII/II reduction potential, increasing the driving force for substrate oxidation reactions and accounting for the faster reaction rate. In addition, we demonstrate that the MnIII-alkylperoxo complex [MnIII(OOtBu)(6Medpaq)]+ reacts with water to obtain the corresponding MnIII-hydroxo species, thus mimicking the ligand substitution step proposed for MnLOX.
Highlights
Manganese lipoxygenase (MnLOX) is an enzyme that oxidizes C-H bonds of polyunsaturated fatty acids to generate alkyl hydroperoxide products [1,2,3,4]
We reported that the MnIII-hydroxo complex [MnIII(OH)(6Medpaq)]+ could be generated via the oxidation of the MnII-aqua complex [MnII(H2O)(6Medpaq)](OTf) using 0.5 equiv. iodosobenzene (PhIO) [30]
Because a number of MnIII-hydroxo complexes can be generated by aerobic oxidation of their MnII analogues [17,18,20,24,43,44,45], we explored the reaction of [MnII(H2O)(6Medpaq)](OTf) with O2
Summary
Manganese lipoxygenase (MnLOX) is an enzyme that oxidizes C-H bonds of polyunsaturated fatty acids to generate alkyl hydroperoxide products [1,2,3,4]. The carbon-based substrate radical can rearrange, after which it is trapped by O2 to generate an oxygen-centered radical This radical can abstract a hydrogen-atom from the MnII-aqua complex to yield product and regenerate the MnIII-hydroxo center (Path A in Scheme 1). The oxygen-centered radical can displace the aqua ligand and oxidize the MnII center to yield a MnIII-alkylperoxo complex (Path B in Scheme 1) Support for this alternate pathway is provided by an X-ray crystal structure of an Fe-alkylperoxo complex from soybean lipoxygenase [15]. In this path, the MnIII-alkylperoxo complex reacts with water via a ligand substitution reaction to yield the substrate and the MnIII-hydroxo center
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