A nuclear magnetic resonance study of the equilibria and kinetics of the reaction of penicillamine with cystine and related disulfides

Abstract

The thiol/disulfide exchange reactions of penicillamine (PSH) with cystine and several related disulfides (RSSR) have been studied by 1H nmr. The reactions take place in two steps:[Formula: see text]The equilibria and kinetics of the reactions of PSH with cystine were characterized over the pH range 5–8, while the reactions with the disulfides of cysteamine, homocysteine, 2-mercaptoethanol, mercaptoacetic acid, 3-mercaptopropionic acid, and mercaptosuccinic acid were studied at neutral pH. From the pH dependence of the rate of the reaction of PSH with cystine, the reactive species are identified as penicillamine with its amino group protonated and its thiol group deprotonated and cystine and penicillamine–cysteine mixed disulfide with their amino groups protonated. For all the disulfides studied, the extent to which the first reaction occurs is within a factor of 2–3 of that predicted by a random distribution, while the extent to which the second reaction occurs is considerably less than for a random distribution. This is attributed to steric effects due to the two methyl groups next to the sulfur of penicillamine.

Selenium-77 nuclear magnetic resonance studies of selenols, diselenides, and selenenyl sulfides

“…The exchange-averaged 'H resonances observed for solutions containing selenol and diselenide are in sharp contrast with the separate resonances observed for thiol and for disulfide in both 'H and I3C spectra of solutions containing thiol and disulfide (18)(19)(20), indicating that selenol/diselenide exchange is much faster than thiol/disulfide exchange.…”

“…By analogy with results from 'H and 13C nmr studies of thiol/disulfide exchange reactions (18)(19)(20), we expected to observe separate resonances for selenol and diselenide. However, 'H resonances were either broadened or exchange-averaged, depending on pH and the relative concentrations of selenol and diselenide, and 77Se resonances could not be detected for selenol/diselenide mixtures.…”

Reaction of Thiols with N-Bonded Sulfenamide Complexes of Cobalt(III): Steric Effect and Reaction Pathway

“…Of more relevance to the current study is the work of Theriault and Rabenstein on the reactions of penicillamine and cysteine and their disulfides. The reaction of penicillamine with cystine at pH 5−8 was found to reach equilibrium on the time-scale of minutes and gives a specific rate constant of 18 M -1 s -1 for reaction with the thiolate form of penicillamine.…”