A Novel Redox Reaction of Ebselen with Alcohol in Basic Solution

Abstract

Ebselen is an organoselenium compound that exhibits a glutathione peroxidase-like activity. The kinetics of ebselen degradation in basic aqueous solution containing primary alcohol was investigated by HPLC. The reversible reaction of ebselen and its dimer (diselenide) was discovered as a novel redox reaction. This reaction followed first-order degradation in basic solution at a constant temperature, and the equilibrium constants of ebselen and diselenide depended on pH. Analysis of the degradation rate for the forward reaction-pH profile indicated that specific base catalysis occurs in ebselen. The mechanism of this redox reaction was investigated by HPLC, spectrophotometry and trapping the labile intermediate with trichloroethylene. Ebselen decomposes to diselenide via selenenic acid and selenol by reacting with primary alcohol. The deuterium isotope effect on the forward reaction indicated that the reaction rate depends on the strength of the hydrogen-carbon bond at the α-position of primary alcohol. On the other hand, the effect of nitrogen replacement on the reverse reaction showed that diselenide is converted into ebselen by oxidation with oxygen existing in the solution.