Theoretical study of nucleophilic substitution at the disulfide bridge of cyclo-L-cystine

The reaction of cyclo-L-cystine with thiolate is examined at the B3LYP/6-31+G* level. The two isomers of cyclo-1-cystine differ in their dihedral angle about the disulfide bond; the M isomer (with dihedral angle of -90.1degrees) is found to be slightly lower in energy. The nucleophilic substitution reaction at sulfur follows the addition-elimination mechanism, exemplified by the hypercoordinate sulfur intermediate on the reaction surface. The reaction is exergonic (DeltaG = -6.16 kcal mol(-1)), and both the entrance and exit transition state lie below the reactant energies.