Structure-activity relationship of the free-radical-scavenging reaction by vitamin E (alpha-, beta-, gamma-, delta-Tocopherols) and ubiquinol-10: pH dependence of the reaction rates.
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).
Mukai
Kazuo
K
Department of Chemistry, Faculty of Science, Ehime University, Matsuyama 790-8577, Japan, and Eisai Company, Ltd., Koishikawa 4-6-10, Bunkyo-ku, Tokyo 112-8088, Japan. mukai@chem.sci.ehime-u.ac.jp
Tokunaga
Aiko
A
Itoh
Shingo
S
Kanesaki
Yu
Y
Ohara
Keishi
K
Nagaoka
Shin-Ichi
S
Abe
Kouichi
K
D000818:Animals; D000431:Ethanol / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008823:Micelles; D013329:Structure-Activity Relationship; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry; D014810:Vitamin E / Q000737:chemistry*
D016166:Free Radical Scavengers; D008823:Micelles; D014451:Ubiquinone; D014810:Vitamin E; D000431:Ethanol; C026663:ubiquinol-10