Comparison of rac- and meso-2,3-dimercaptosuccinic acids for chelation of mercury and cadmium using chemical speciation models.

The formation constants of various mercury and cadmium chelates of the stereoisomers of 2,3-dimercaptosuccinic acid (DMSA) have been determined from potentiometric titrations in the presence of the competing ligand EDTA. The mercury chelates formed at pH 7.4 are the monomeric HgL of the DMSA diastereoisomers and HHgL2 of rac-DMSA. Mercury is completely complexes at pH greater than 3.0 in solutions containing more than 1 equiv of either rac- or meso-DMSA. At high concentrations (10 microM and above) mercury tends to bind to a greater extent to rac- than to meso-DMSA. At pH 7.4, the predominant cadmium meso-DMSA chelate species in solution is CdL, and HCdL is present at a much smaller concentration. With rac-DMSA, however, the predominant cadmium chelate species is HCdL at a low concentration of the ligand, and at a high concentration of the ligand the species CdL2 predominates. Cadmium is completely chelated at pH 7.4 in solutions containing more than 1 equiv of either rac- or meso-DMSA. At pH around 5.5, which corresponds to the pH of the kidney, however, a significant amount of free cadmium is present in solutions containing 1 equiv or less of either DMSA stereoisomer. From the results of an analysis of speciation models, probable kidney damage, that may result from free cadmium ion release in the kidney during chelation therapy, is inferred when meso-DMSA is used for mobilizing cadmium. In contrast, the release of free cadmium ion is negligible in the pH range in the kidney when rac-DMSA is used. On the basis of the speciation models, rac-DMSA is found to be far superior to meso-DMSA in the treatment of acute cadmium poisoning.