NUCLEAR-MAGNETIC-RESONANCE STUDY OF THE KINETICS OF THE PENICILLAMINE BIS(PENICILLAMINE) SELENIDE SYMMETRICAL EXCHANGE-REACTION

The kinetics of reaction of the thiolate form of D-penicillamine (beta,beta-dimethylcysteine, PSH) with bis(D-penicillamine)selenide (PSSeSP) have been characterized over a wide pH range in aqueous solution by NMR line broadening techniques. Because of the steric bulk of the substituents on the beta-carbon of penicillamine, the rate of nucleophilic reaction at the sulfur of PSSeSP is much less than at selenium, making it possible for the first time to characterize quantitatively the kinetics for reaction of a thiolate at the selenium of the bis(alkylthio) selenide of a biological molecule. Rate constants are reported for reaction of the amino and ammonium forms of PS- with the various amino protonated forms of PSSeSP, e.g. the rate constant for reaction of the (NH3+, CO2-,S-) form of PSH with the (NH3+, NH3+, CO2-, CO2-) form of PSSeSP is 9.7 x 10(5) L/mol.s. The PSH/PSSeSP interchange reactions are approximately 10(6) faster than the analogous reaction of 2-methyl-2-propanethiol with bis(tert-butylthio) selenide. The large magnitude of the rate constants suggests that nucleophilic reaction at the selenium of bis(alkylthio) selenides, which are thought to be formed initially in the incorporation of inorganic selenium into living systems, could be important in their conversion to other selenium-containing biomolecules.