Oxidative Damage of S‐Containing Amino Acids by the Environmental Radical NO3.: A Kinetic, Product and Computational Study

Abstract

AbstractMethionine, cysteine and cystine, which were acetylated at the N‐terminus and methylated at the C‐terminus, react rapidly with the environmental nitrate radical (NO3.) with rate coefficients of 7.7×109, 3.4×109 and 2.0×109 M−1 s−1, respectively, in acetonitrile. Methionine (Ac−Met−OMe) is successively oxidized via the sulfoxide (Ac−MetO−Me) to the sulfone (Ac−MetO2−OMe), with the latter step being also extremely fast with a rate coefficient of 1.2×109 M−1 s−1. Computations predict formation of an initial charge transfer complex between NO3. and the S or SO moiety in Ac‐Met‐OMe, Ac‐MetO‐OMe and cystine (Ac−Cys(S−S)Cys‐OMe), respectively, which is followed by simultaneous S−O bond formation and NO2. expulsion. Calculations for the reaction of cysteine (Ac‐Cys‐OMe) with NO3. revealed side‐chain oxidation to give a thiyl radical or a sulfenic acid as likely pathways. These findings highlight the potential harmful impact of NO2./O3 pollution on S‐containing amino acid residues in peptides.