Mimicking Elementary Reactions of Manganese Lipoxygenase Using Mn-hydroxo and Mn-alkylperoxo Complexes
| Autor: | Timothy A. Jackson, Elizabeth N. Grotemeyer, Adedamola A. Opalade |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipid Peroxides
Lipoxygenase hydrogen-atom transfer Pharmaceutical Science Ligands Redox Article Analytical Chemistry Reaction rate chemistry.chemical_compound QD241-441 Piperidines Biomimetics Coordination Complexes TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY Catalytic Domain alkylperoxo Drug Discovery Elementary reaction Pyridine Polymer chemistry Physical and Theoretical Chemistry Alkyl Substitution reaction chemistry.chemical_classification Manganese Molecular Structure Chemistry Ligand Organic Chemistry Substrate (chemistry) Oxygen manganese enzymes lipoxygenase ligand substitution Chemistry (miscellaneous) Fatty Acids Unsaturated Molecular Medicine Oxidation-Reduction Hydrogen |
| Zdroj: | Molecules Molecules; Volume 26; Issue 23; Pages: 7151 Molecules, Vol 26, Iss 7151, p 7151 (2021) |
| ISSN: | 1420-3049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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