Pulse radiolysis of silybin: One-electron oxidation of the flavonoid at neutral pH

Abstract

One-electron oxidation of silybin, a flavonoid drug used in human therapy of liver, was investigated by pulse radiolysis at neutral pH. Phenoxyl radicals formed from the substrate by oxidising N.3 radicals were identified by comparing the transient optical absorption spectra with those obtained from model compounds. The orto-methoxy-phenolic structure (ring B) is the exclusive target for one-electron oxidation of silybin. The 5.7-dihydroxy-chromanone moiety (ring A) withstands free-radical attack at neutral pH due to the chelatic H-bond (pKa = 10.2) existing between the 5-OH and 4-oxo groups. Hydroxyl radicals react with silybin at diffusion controlled rate (k = 1.8 x 1010 dm3 mol-1 s-1). The reactivity of silybin towards free radicals at neutral pH is conform with the assumption that the physiological activity of the flavonoid is due to its chain-breaking antioxidant behaviour. © 1992.