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Computational Study of Aqueous Reactions in Tocopherol Regeneration

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journal contribution
posted on 12.09.2006, 00:00 by R. Lui, A. L. Cooksy
The α-tocopheroxyl radical, resulting from the scavenging of the peroxyl radical by α-tocopherol (vitamin E) in the cell membrane, will further react with the peroxyl radical to form tocopherones. A computational study is presented of the aqueous proton-transfer reactions of the α-8a-(hydro-dioxy)tocopherone and α-8a-(methyl-dioxy)tocopherone to produce 1-benzopyrylium, the subsequent hydrolysis to 2H-1-benzopyran-6(8aH)-one, and the terminating rearrangement of 8a-hydroxytocopherone to 2,5-cyclohexadiene-1,4-dione. The alkyl tail of true tocopherol is replaced by methyl in these studies. Calculations of the structures and energies along the reaction pathways were first performed at the BP86/TZVP/DGA1 level with a COSMO solvent model, and additional solvent corrections from COSMO-RS theory were subsequently added. The proposed mechanism is found to be thermodynamically and kinetically feasible in water. The ion-mediated steps are found to have free-energies of activation under 3 kcal mol-1, with kinetics likely to be diffusion-limited. The unimolecular rearrangement is the slow step, with a predicted reaction rate constant of 0.056 min-1 at 298 K, in excellent agreement with the experimental value of 0.046 min-1. Kinetic and thermodynamic properties of the ion-mediated steps are shown to rely strongly on the use of an accurate continuum solvation model. Distinct entropy and enthalpy contributions are determined from the temperature dependence of the predicted free energies.