Breaking and making of the S-S linkage via nucleophilic substitution. An ab initio study

The energetics of nucleophilic opening and closing of protonated disulphide bridges [GRAPHICS] has been studied for the case of two sulphur-containing (H2S and CH3SH) nuc leophiles. The energetics of this reaction was compared to that of the nucl eophilic opening and closing of disulphide bridges with thiolate ions: [GRAPHICS] In the former case a not so good nucleophile is combined with an excellent leaving group, and in the latter case a superior nucleophile is combined wi th a relatively poor leaving group. The barrier heights for these S(N)2-typ e reactions were found to be comparable as calculated by ab initio MO metho ds. In addition, two oxygen-containing nucleophiles (H2O, HCONH-CH[CH2OH]-CONH2 ) have also been studied in the following reaction: [GRAPHICS] The water molecule is not nucleophilic enough to open the disulphide bridge . However, in a serine residue, in which the oxygen of the side-chain OH gr oup is activated through backbone/side-chain hydrogen bonding, the hydroxy group is sufficiently nucleophilic to open the disulphide bridge, just like the sulphur-containing nucleophiles mentioned above. (C) 1998 Elsevier Sci ence B.V. All rights reserved.