Selective and an efficient oxidative conversion of glutathione to glutathione disulfide with N-bromosuccinimide in aqueous acidic solution: kinetic and mechanistic chemistry

Abstract

Oxidative conversion of thiols to disulfides is an important chemical transformation in organic synthesis. A tripeptide, glutathione (GSH), composed of glutamate, cysteine and glycine, has been found to be the most abundant low molecular weight thiol in most biological systems. Its importance in mammal systems is believed to be related to its functions in oxidative metabolism and detoxification. It is noted that despite the importance of this substrate, less information is available in the literature on the oxidation of this substrate viewed from its kinetic and mechanistic studies. N-Bromosuccinimide (NBS) is a mild and selective oxidant for many organic compounds, and hence, it has been used as an oxidant for the present redox system. Consequently, the kinetics of oxidation of GSH with NBS in aqueous HClO₄ medium has been investigated at 283 K. The reaction rate exhibits first-order dependence on [NBS]_o and fractional-order dependence each on [GSH]_o and [H⁺]. The effect of added succinimide, ionic strength and dielectric constant of the medium on the rate of the reaction has been studied. The solvent isotope effect was studied using D₂O. The reaction was studied at different temperatures and thermodynamic parameters have been computed. Glutathione disulfide is characterized as the oxidation product of GSH. The protonated species RN⁺HBr (here R = (CH₂O)₂−) of the NBS is assumed to be the reactive oxidizing species. The reaction constants involved in the mechanism were evaluated. The observed results have been explained by a plausible mechanism, and the related rate law has been deduced.

Keywords:

• glutathione
• N-bromosuccinimide
• oxidation
• kinetics
• acid medium

Acknowledgements

One of the authors (Ramalingaiah) is grateful to the Principal and Management of PES Trust, Mandya, for encouragement.