Structure-activity relationship of the free-radical-scavenging reaction by vitamin E (α-, β-, γ-, δ-tocopherols) and ubiquinol-10:: pH dependence of the reaction rates

The reaction rates (k(s)) of vitamin E (alpha-, beta-, gamma-, delta-tocopherols, TocH), ubiquinol-10, and related antioxidants (tocol, ubiquinol-0, and hydroquinone) with aroxyl (ArO center dot) radical have been measured in micellar solution by stopped-flow spectrophotometer. The k(s) values increased in the order of hydroquinone < tocol < delta-TocH < ubiquinol-0 < gamma-TocH approximate to beta-TocH < ubiquinol-10 < alpha-TocH at pH 4 similar to 8. The antioxidants which have lower oxidation potentials showed higher reactivities. The k(s) values of alpha-, beta-, gamma-, delta-tocopherol, and tocol remained constant between pH 4 and 10, and decreased rapidly at pH 11 similar to 12 by increasing pH value. From the pH dependence of k(s) values, the pK(a) values (= 13.1 similar to 12.6) have been determined for these tocopherols. The k(s) values of ubiquinol-10 also remained constant between pH 4 and 9, and increased rapidly at pH 9.5. Ubiquinol-10 is dibasic acid and can exist in three different molecular forms, depending on the pH value. By comparing the k(s) values with the mole fraction of each molecular form of ubiquinol-10, the reaction rate k(s1) (= 1.21 x 10(5) M(-1)s(-1)) for the undissociated form, k(s2) (= 1.04 x 10(6) M(-1)s(-1)) for monoanion and k(s3) (= 0 M (-1)s (-1)) for dianion, and the pK(a1) and pK(a2) values (= 11.4 and 12.7) were determined. The k(s2) value is 8.6 times as large as the k(s1) value. Similar analyses were performed for ubiquinol-0 and hydroquinone. It was found that the relative ratio of k(s) values (100:21:20:2.9) of alpha-, beta-, gamma-, delta-tocopherols in micellar dispersion has good correlation with the relative biopotency ratios for rat fetal resorption, rat hemeolysis, and chicken muscle dystrophy. The relative antioxidant activities of alpha-tocopherol and ubiquinol-10 have been discussed based on the k(s) values obtained and their concentrations in serum and several tissues (heart, muscle, liver, kidney, and brain).