[reaction: see structure] The antioxidant activity of curcumin (1, 7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) was determined by inhibition of controlled initiation of styrene oxidation. Synthetic nonphenolic curcuminoids exhibited no antioxidant activity; therefore, curcumin is a classical phenolic chain-breaking antioxidant, donating H atoms from the phenolic groups not the CH(2) group as has been suggested (Jovanovic et al. J. Am. Chem. Soc. 1999, 121, 9677). The antioxidant activities of o-methoxyphenols are decreased in hydrogen bond accepting media.

The reaction rates (ks) of vitamin E (alpha-, beta-, gamma-, delta-tocopherols, TocH), ubiquinol-10, and related antioxidants (tocol, ubiquinol-0, and hydroquinone) with aroxyl (ArO(.-)) radical have been measured in micellar solution by stopped-flow spectrophotometer. The ks values increased in the order of hydroquinone < tocol < delta-TocH < ubiquinol-0 < gamma-TocH approximately beta-TocH < ubiquinol-10 < alpha-TocH at pH 4 approximately 8. The antioxidants which have lower oxidation potentials showed higher reactivities. The ks values of alpha-, beta-, gamma-, delta-tocopherol, and tocol remained constant between pH 4 and 10, and decreased rapidly at pH 11 approximately 12 by increasing pH value. From the pH dependence of ks values, the pKa values (= 13.1 approximately 12.6) have been determined for these tocopherols. The ks 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 ks values with the mole fraction of each molecular form of ubiquinol-10, the reaction rate ks1 (= 1.21 x 10(5) M(-1)s(-1)) for the undissociated form, ks2 (= 1.04 x 10(6) M(-1)s(-1)) for monoanion and ks3 (= 0 M(-1)s(-1)) for dianion, and the pKa1 and pKa2 values (= 11.4 and 12.7) were determined. The ks2 value is 8.6 times as large as the ks1 value. Similar analyses were performed for ubiquinol-0 and hydroquinone. It was found that the relative ratio of ks 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 ks values obtained and their concentrations in serum and several tissues (heart, muscle, liver, kidney, and brain).

The reaction rates ( k s) of tocopherol metabolites (alpha-, gamma-, and delta-CEHC) and Trolox with aroxyl radical have been measured in ethanol and micellar solution by a stopped-flow spectrophotometer, and the k s values obtained were compared with those reported for tocopherols (alpha-, beta-, gamma-, and delta-tocopherol, TocH) and tocol. The rate constants ( k s) increased in the order of Tocol < delta-CEHC < delta-TocH < gamma-CEHC < Trolox approximately gamma-TocH approximately beta-TocH < alpha-CEHC < alpha-TocH in ethanol. The antioxidants that have lower oxidation potentials ( E p) showed higher reactivities. The k s values of alpha-, beta-, gamma-, and delta-tocopherol and tocol in micelle remained constant between pH 4 and pH 10 and decreased rapidly at pH 11~12 by increasing pH value. On the other hand, the k s values of alpha-CEHC, gamma-CEHC, and Trolox showed notable pH dependence. As a result of the detailed analysis of the pH dependence of the rate constants ( k s), the structure-activity relationship in the free radical-scavenging action of the tocopherol metabolites and Trolox has been clarified.