title: From a theoretical concept to biochemical reactions: strain-induced bond localization (SIBL) in oxidation of vitamin E.
abstract: The regioselectivity of the oxidation of alpha-tocopherol (the main component of vitamin E) to an ortho-quinone methide (oQM) has been explained in the literature mostly by the ill-defined term "Mills-Nixon effect". In this paper we describe the preparation of eleven alpha-tocopherol derivatives, different from each other by the sum of annulation angles, but keeping the electronic factors unchanged. These compounds underwent Ag(2)O oxidation, forming two isomeric oQMs that were trapped by vinylmethyl ether. It was found that the isomeric product ratio changes smoothly as a function of the annulation angles, not abruptly from one regioisomer to the other on going from five- to six- and seven-membered rings, as predicted by the Mills-Nixon effect. The relative amounts of the products were determined at four different temperatures, and assuming that the product ratio represents the relative rates ratio, the relative enthalpy of activations could be obtained. Theoretically (at B3LYP/6-31G* theoretical level) four different intermediates were considered. Each of these underwent angular angles deformations to model the two regioisomers. At each deformation angle the energy difference between the two intermediates models was correlated to the experimental data for each of the four intermediates. It was found that the angle-deformed lithium (6-methyl-2-benzylium)phenolate correlated best (R>0.994) to the experimental data. This study confirms that the regioselectivity of the two isomeric oQMs in the oxidation of alpha-tocopherol and related compounds is simply a function of angular strain, best explained by the SIBL (strain-induced bond localization) model. In addition, this study provides evidence that the highest energy intermediate in the oxidation of vitamin E is a phenolate-benzyl cation.
authors.affiliation: Institute of Chemistry, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria. thomas.rosenau@boku.ac.at
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenau
authors.forename: Gerald
authors.initials: G
authors.lastname: Ebner
authors.forename: Amnon
authors.initials: A
authors.lastname: Stanger
authors.forename: Sharon
authors.initials: S
authors.lastname: Perl
authors.forename: Limor
authors.initials: L
authors.lastname: Nuri
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D013314:Stress, Mechanical; D014810:Vitamin E / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D014810:Vitamin E