Reaction of phenylaminoethyl selenides with peroxynitrite and hydrogen peroxide

Peroxynitrite, a reactive cytotoxic species generated by the reaction of su peroxide with nitric oxide, rapidly oxidizes phenylaminoethyl selenide (PAE Se) and its para-substituted derivatives with second-order rate constants r anging from 900 to 3000 M-1 s(-1) at neutral pH (pH 7.0) and 25 degrees C. These values are approximately 3 x 10(4) times greater than the correspondi ng rate constants for the reactions of selenides with hydrogen peroxide. Th e peroxynitrite reaction was also studied at alkaline pH. HPLC analysis con firms that both the peroxynitrite and hydrogen peroxide reactions produced the corresponding phenylaminoethyl selenoxide (PAESeO) as the sole selenium containing product, with a stoichiometry of 1 mol of PAESe oxidized per 1 mol of PAESeO formed per 1 mol of oxidant reacted. The influence of para-su bstituents on the rate constants was investigated using Hammett plots; in b oth cases the data are consistent with an S(N)2-type mechanism, wherein the selenium atom acts as the nucleophile. Our results provide further evidenc e that organoselenium compounds may play a protective role in the defense a gainst the many reactive oxidizing species produced in cellular metabolism. (C) 2000 Academic Press.