Redox reactions of thiol free radicals with the antioxidants ascorbate and chlorpromazine: role in radioprotection

Abstract

The interaction of the thiyl radical from glutathione, GS˙, and its corresponding peroxyl radical adduct, GSO₂˙, with the reducing agents, ascorbate and chlorpromazine, have been studied in aqueous solution at pH 5.0–5.5 using the technique of pulse radiolysis with spectrophotometric detection. The rate constants determined for interaction of GS˙ with ascorbate and chlorpromazine are 5.4 × 10⁸ and 9.0 × 10⁸ dm³ mol^–1 s^–1 respectively. The reaction is thought to proceed via an electron transfer process. Further, the redox potential of GS˙/GSH at pH 5.0 is estimated to be 0.91 V. In the presence of different concentrations of oxygen, it has been established that GSO₂˙, as observed at 540 nm, interacts with ascorbate and chlorpromazine by electron transfer with rate constants of 2.1 × 10⁸ and 5.0 × 10⁸ dm³ mol^–1 s^–1 respectively. From these kinetic observations it is inferred that GSO₂˙ is a weaker oxidant than GS˙. From these findings the role of these glutathione radicals should be taken into account when considering the biological role of thiols in oxidative damage in biological systems.