First Steps in the Oxidation of Sulfur-Containing Amino Acids by Hypohalogenation: Very Fast Generation of Intermediate Sulfenyl Halides and Halosulfonium Cations

Sulfur-containing amino acids show an extraordinary binding towards HOCl/ClO−. During the process, the Cl is transferred from the O to the S of the amino acid. Met reacts with HOCl one order of magnitude faster than the non-S containing amino acids (k(Met+HOCl)=8.7·108 mol−1 dm3 s−1). Instead, Cys reacts as its thiolate (RS−), two orders-of-magnitude faster (k(RS−+HOCl)=1.2·109 mol−1 dm3 s−1). Cys reacts also with ClO− (k(RS−+ClO−)=1.9·105 mol−1 dm3 s−1). Such processes take place much more readily than the corresponding N-halogenation of the non-sulfur containing amino acids. To our knowledge, these are the first kinetic measurements of the rate of formation of sulfenyl halides and halosulfonium cations in aqueous solution. Sulfenyl chlorides and chlorosulfonium ions derived from amino acids are elusive, and sulfide-type amino acids (Met) eventually yield sulfoxides (MetO), while thiol-type amino acids (Cys) lead to disulfides (Cys^Cys) and sulfonic acids (Cya). The fate of sulfur-containing amino acids upon oxidation with HOCl/ClO− seems to be related to their mutagen-inactivation ability.