The Reaction of Ebselen with Peroxynitrite

Abstract

Ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, rapidly reacts with peroxynitrite, the rate constant being of the order of 10⁶ M^-1 s^-1; the reaction yields the selenoxide of the parent molecule, 2-phenyl-1,2-benzisoselenazol-3(2H)-one 1-oxide, as the sole selenium-containing product; a stoichiometry of 1 mol of ebselen reacted and of the selenoxide formed per mole of peroxynitrite was observed. The reaction was studied in detail at neutral and alkaline pH (pH 10−11). It also proceeds at acidic pH where peroxynitrous acid (ONOOH) is predominant, the yield of the selenoxide being lower because peroxynitrous acid (pK_a = 6.8) decays rapidly. Reduction of the selenoxide in cells to regenerate ebselen would allow for a sustained defense against peroxynitrite. This novel reaction constitutes a potential cellular defense line against peroxynitrite, one of the important reactive species in inflammatory processes.