Absolute kinetic characterization of 17-beta-estradiol as a radical-scavenging, antioxidant synergist

We directly measured the absolute reactivity of 17-beta -estradiol (E-2) an d several phenolic model compounds for E-2 toward t-butoxy radical U-BuO .) by nanosecond time-resolved optical spectroscopy. Compared to other phenol s, E-2, is a moderate, but not strong deactivator of oxyradicals. The absol ute bimolecular rate constant for H-atom transfer from E-2 to t-BuO . is 1. 3 +/- 0.3 x 10(9) M-1 s(-1) (23 degreesC, benzene). We estimate the O-H bon d strength of 17-beta -estradiol to be approximately 85 +/- 2 kcal/mol and calculate the reaction rate constant of E-2 toward peroxy radical to be 10( 5) M-1 s(-1) at 37 degreesC. The conjugate phenoxy radical of 17-beta -estr adiol, E2O ., is unusually reactive toward a-tocopherol and ascorbate by H- atom transfer in homogeneous solution (10(8)-10(9) M-1 s(-1)). Our findings suggest that E-2 functions in vivo as a highly localized, synergistic biol ogical antioxidant. This may partly explain the clinical effectiveness of o varian steroids in delaying the manifestations of Alzheimer's Disease as we ll as in protecting against cardiovascular pathologies. In the absence of c omplementary antioxidant synergists, E2O . is expected to be a pro-oxidant. (C) 2001 Academic Press.