Sulfur radical cation-peptide bond complex in the one-electron oxidation of S-methylglutathione.

Neighboring group participation was investigated in the *OH-induced oxidation of S-methylglutathione in aqueous solutions. Nanosecond pulse radiolysis was used to obtain the spectra of the reaction intermediates and their kinetics. Depending on the pH, and the concentration of S-methylglutathione, pulse irradiation leads to different transients. The transients observed were an intramolecularly bonded [>S thereforeNH2]+ intermediate, intermolecularly S thereforeS-bonded radical cation, alpha-(alkylthio)alkyl radicals, alpha-amino-alkyl-type radical, and an intramolecularly (S thereforeO)+-bonded intermediate. The latter radical is of particular note in that it supports recent observations of sulfur radical cations complexed with the oxygen atoms of peptide bonds and thus has biological and medical implications. This (S thereforeO)+-bonded intermediate had an absorption maximum at 390 nm, and we estimated its formation rate to be >or=6x10(7) s(-1). It is in equilibrium with the intermolecularly S thereforeS-bonded radical cation, and they decay together on the time scale of a few hundred microseconds. The S thereforeS-bonded radical cation is formed from the monomeric sulfur radical cation (>S*+) and an unoxidized S-methylglutathione molecule with the rate constant of 1.0x10(9) M(-1) s(-1). The short-lived [>S thereforeNH2]+ intermediate is a precursor of decarboxylation, absorbs at approximately 390 nm, and decays on the time scale of hundreds of nanoseconds. Additional insight into the details of the association of sulfur radical cations with the oxygen atoms of the peptide bonds was gained by comparing the behavior of the S-methylglutathione (S thereforeO+-bonded five-membered ring) with the peptide gamma-Glu-Met-Gly (S thereforeO+-bonded six-membered ring). Conclusions from experimental observations were supported by molecular modeling calculations.