Structural characterization of Cd²⁺ complexes in solution with DMSA and DMPS.

Meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) are chelating agents which have been used clinically to treat patients suffering from Pb(2+) or Hg(2+) exposure. Cd(2+) is a related environmental pollutant that is of increasing public health concern due to a demonstrated dose-response between urinary Cd level and an increased risk of diabetes. However, therapeutically effective chelating agents which enhance the excretion of Cd(2+) from humans have yet to be identified. Here we present a structural characterization of complexes of DMSA and DMPS with Cd(2+) at physiological pH using a combination of X-ray absorption spectroscopy, size exclusion chromatography and density functional theory. The results indicate a complex chemistry in which multi-metallic forms are important, but are consistent with both DMPS and DMSA acting as true chelators, using two thiolates for DMPS and one thiolate and one carboxylate for DMSA.