Kinetics and mechanism of oxidation of the drug mephenesin by bis(hydrogenperiodato)-argentate(III) complex anion

Mephenesin is being used as a central-acting skeletal muscle relaxant. Oxidation of mephenesin by bis(hydrogenperiodato)argentate(III) complex anion, [Ag(HIO6)(2)](5-), has been studied in aqueous alkaline medium. The major oxidation product of mephenesin has been identified as 3-(2-methylphenoxy)-2-ketone-1-propanol by mass spectrometry. An overall second-order kinetics has been observed with first order in [Ag(III)] and [mephenesin]. The effects of [OH-] and periodate concentration on the observed second-order rate constants k ' have been analyzed, and accordingly an empirical expression has been deduced. k ' = (k(a) + k(b)[OH-])K-1/{f([OH-])[IO4-](tot) + K-1}, where [IO4-](tot) denotes the total concentration of periodate, k(a) = (1.35 +/- 0.14) x 10(-2)M(-1)s(-1) and k(b) = 1.06 +/- 0.01M(-2)s(-1) at 25.0 degrees C, and ionic strength 0.30 M. Activation parameters associated with k(a) and k(b) have been calculated. A mechanism has been proposed to involve two pre-equilibria, leading to formation of a periodato-Ag(III)-mephenesin complex. in the subsequent rate-determining steps, this complex undergoes inner-sphere electron transfer from the coordinated drug to the metal center by two paths: one path is independent of OH- whereas the other is facilitated by a hydroxide ion. in the appendix, detailed discussion on the structure of the Ag(III) complex, reactive species, as well as pre-equilibrium regarding the oxidant is provided. (c) 2007 Wiley Periodicals, Inc.