Synthesis and Kinetic Study of Antioxidant Activity of New Tocopherol (Vitamin E) Compounds

Article abstract of DOI:10.1021/jo00264a010

New tocopherol (vitamin E) compounds (5,7-diethyltocol (3), 5,7-diisopropyltocol (4), 7-tert-butyl-5-methyltocol (5), and 8-tert-butyl-5-methyltocol (6)) have been synthesized by condensation of isophytol with the corresponding alkylhydroquinone.The second-order rate constans, k_s, for the reaction of 10 kinds of tocopherol derivatives including α-, β-,γ-, and δ-tocopherols with substituted phenoxyl radical in ethanol have been measured in the temperature range 10.0-35.0 deg C, with a stopped-flow spectrophotometer, as a model reaction of tocopherols with unstablefree radicals (LOO radical, LO radical, and HO radical) in biological systems.The result indicates that the rate constants, k_s, increase as the total electron-donating capacity of the alkyl substituents on the aromatic ring increases.For the tocopherol derivatives, log k_s was found to correlate roughly with the sum of the Hammett's ? constants (Σ?) or the Brown's ?⁺ constants (Σ?⁺), but the two cases could not be distinguished.Half-peak oxidation potentials (E_p/2) for tocopherol compounds have also been measured by using a cyclic voltammetry technique.The log of the second-order rate constants, k_s, obtained for tocopherols was found to correlate with their half-peak oxidation potentials (E_p/2).The antioxidant activities of tocopherol derivatives 2-5 having two alkyl substituents, such as methyl, ethyl, isopropyl, and tert-butyl groups, at the ortho positions of the OH group are similar to each other, suggesting that the effect of steric hindrance on the reaction rate is small.Further, the reactivities of these tocopherols 2-5 are about half that of α-tocopherol.From detailed analysis of the temperature dependence of k_s values of the tocopherols, the activation energy, E_act, for the reaction has been determined.The observed activation energies were found to be related linearly to the half-peak oxidation potentials.From the results, the property of the transition state in the above free radical scavenging reaction by tocopherols has been discussed.Electron spin resonance measurements were performed for the tocopheroxyl radicals 3-6 in toluene, and the proton hyperfine coupling constants and g_iso values were determined.