The kinetics and equilibria of the oxidation of penicillamine by glutathione disulfide to form, in the first step, penicillamine–glutathione mixed disulfide and glutathione and, in the second step, penicillamine disulfide and glutathione have been studied over the pH range 4–9 by 1H nmr. The reactive species are found to be penicillamine with its amino group protonated and its thiol group deprotonated and glutathione disulfide and penicillamine–glutathione mixed disulfide with their two amino groups protonated. The rate and equilibrium constants for the first step are much larger than those for the second step, indicating a small tendency for penicillamine to form its symmetrical disulfide by thiol/disulfide exchange reactions. This and the smaller reducing power of penicillamine as compared to glutathione are attributed to steric hindrance from the methyl groups adjacent to the sulfur. The kinetics and equilibria of the oxidation of N-acetylpenicillamine by glutathione disulfide were studied at neutral pH. Conditional equilibrium and rate constants for the oxidation of penicillamine by glutathione disulfide at pH 7.4 are presented and discussed in terms of the metabolism of penicillamine.
Equilibrium Constants for the Hydrogen Isotopic Self-Exchange Reactions in the 4.2- to 50-K Temperature Range
