Absolute kinetic characterization of 17-beta-estradiol as a radical-scavenging, antioxidant synergist.
We directly measured the absolute reactivity of 17-beta-estradiol (E2) and several phenolic model compounds for E2 toward t-butoxy radical (t-BuO*) by nanosecond time-resolved optical spectroscopy. Compared to other phenols, E2 is a moderate, but not strong deactivator of oxyradicals. The absolute bimolecular rate constant for H-atom transfer from E2 to t-BuO* is 1.3 +/- 0.3 x 10(9) M(-1) x s(-1) (23 degrees C, benzene). We estimate the O-H bond strength of 17-beta-estradiol to be approximately 85 +/- 2 kcal/mol and calculate the reaction rate constant of E2 toward peroxy radical to be 10(5) M(-1) x s(-1) at 37 degrees C. The conjugate phenoxy radical of 17-beta-estradiol, E2O*, is unusually reactive toward alpha-tocopherol and ascorbate by H-atom transfer in homogeneous solution (10(8)-10(9) M(-1) x s(-1)). Our findings suggest that E2 functions in vivo as a highly localized, synergistic biological antioxidant. This may partly explain the clinical effectiveness of ovarian steroids in delaying the manifestations of Alzheimer's Disease as well as in protecting against cardiovascular pathologies. In the absence of complementary antioxidant synergists, E2O* is expected to be a pro-oxidant.
Winterle
J S
JS
Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, California 95064, USA. cmc@got.net
Mill
T
T
Harris
T
T
Goldbeck
R A
RA
D000544:Alzheimer Disease / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000737:chemistry* / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D019800:Phenol / Q000737:chemistry; D013053:Spectrophotometry; D014810:Vitamin E / Q000737:chemistry
D000975:Antioxidants; D016166:Free Radical Scavengers; D014810:Vitamin E; D019800:Phenol; D004958:Estradiol; D001205:Ascorbic Acid