Molecular Orbital Study on Binding Ability of Tocopherols and Catechins to Three-membered Reactive Sites of Mutagens

Molecular orbital study was conducted so as to clarify the reactivity of nucleophilic substitution between phenoxide anions of tocopherols (Vitamin E) and catechins and the three-membered oxirane ring (binding site to biomolecules) of some mutagens. All stationary points including transition state structures (TSs) were optimized with no geometrical constraint at the PM3 level and energies of all species including TSs were evaluated at the Becke3LYP/3-21G level based on PM3 geometry. The reactions of model compounds of three tocopherols (β-, γ-, and δ-tocopherol) and catechins with ethylene oxide were examined. The tocopherols and catechins were found to possess nucleophilic reactive sites to which electrophilic mutagens each having oxirane ring could bind.Activation energy (ΔE≠) for the rate-determining C-C bond forming step for electrophilic substitution of phenoxide anions of three tocopherol models with ethylene oxide was found to range in 43-53kJ/mol. Predicted reactivity followed the order βγ<δ-tocopherol. The most stable TS was that for the reaction of δ-tocopherol model and had the lowest ΔE≠ (+43.3kJ/mol), at which electrophilic reaction occurs at the C-7 position. In catechin models, TS whose O-5 phenoxide anion reacts with ethylene oxide at the C-8 position had the lowest ΔE≠ (+40.5kJ/mol). These considerably small ΔE≠ suggest tocopherols and catechins to be capable of directly capturing electrophilic mutagens having the reactive oxirane ring and eliminating their activities so as to bind to biomolecules.