Oxidation of the drug tiopronin by Cerium(IV) in perchloric acid media: Kinetic and mechanistic analyses

Abstract

Although several analytical methods based on the Ce(IV) oxidations were developed for determinations of the drug tiopronin (MPG) and some biothiols, the kinetic and mechanistic aspects of oxidations of the thiol-containing molecules by Ce(IV) were poorly deciphered if not all. The oxidation of MPG by Ce(IV) has thus been characterized kinetically in perchloric acid media in this work. The oxidation reaction follows overall second-order kinetics: -d[Ce(IV)]tot/dt=k′[MPG]tot[Ce(IV)]tot, where k′ stands for the observed second-order rate constant and [Ce(IV)]tot and [MPG]tot pertain to the total concentrations of Ce(IV) and MPG, respectively. The relation between k′ and [H+] has been established in the region of 0.030M≤[H+]≤2.00M. Several additional reaction features are revealed by the rapid scan spectra, product identification and stoichiometric study. All these features are rationalized by a proposed reaction mechanism which involves Ce4+, Ce(OH)3+, and Ce(OH)22+ attacking on the sulfur atom of MPG in parallel and forming the rate-determining steps. These steps are followed by up to seven fast reactions. Rate constants of the rate-determining steps have been derived showing a reactivity trend: Ce4+>Ce(OH)3+>Ce(OH)22+. This trend, being observed for the first time in this work, suggests an outer-sphere electron transfer taking place in the rate-determining steps, which is strongly bolstered by the dependence of the Ce(IV)/Ce(III) redox potential on [H+] measured previously. Our kinetic and mechanistic analyses indicate that a rather complex reaction mechanism is operating behind the simple second-order kinetics.