Synthesis, structure, and properties of rac-2,3-dimercaptosuccinic acid, a potentially useful chelating agent for toxic metals.

rac-2,3-Dimercaptosuccinic acid (rac-DMSA) may be a more effective antidote for the treatment of heavy metal poisoning than meso-2,3-dimercaptosuccinic acid (meso-DMSA), which is used at present. A comparative study of these two chelating agents has been undertaken in order to investigate this possibility. The structures of rac-DMSA and the precursor in its synthesis, rac-2,3-bis(acetylthio)succinic acid, have been determined by single-crystal X-ray analysis and compared with the structures of the corresponding meso compounds. The concentration distributions of the various ionic and molecular species of rac-DMSA that are present in aqueous solutions in the pH range 1.8-12.8 have been calculated from the four acid dissociation constants that have been determined potentiometrically at an ionic strength of 0.10. The conformations of these species in aqueous solutions have been determined by 1H NMR spectroscopy as a function of pH. The rac-DMSA exists in the crystal lattice as a double-stranded structure in which each molecule is in a gauche configuration. The meso-DMSA, however, exists in a single strand in which each molecule has adopted an anti configuration and the individual molecules are joined together at each end by hydrogen bonds. These differences in the conformations of rac- and meso-DMSA may account for the significant difference in the solubilities of the two compounds in aqueous solutions. In acidic solutions at elevated temperatures of about 95 degrees C, rac-DMSA is slowly but irreversibly converted to meso-DMSA. This conversion does not occur at ambient temperatures.