Complexing properties of 2,3-dimercaptosuccinic acid and its monomethyl and dimethyl esters.

Abstract

Metal complexes of meso-dimercaptosuccinic (DMSA) acid were studied by potentiometric and infrared methods. The coordination sites were found to be metal dependent. In the cases of Pb²⁺ and Cd²⁺, one oxygen and one sulfur act as donors; in the case of Hg²⁺, two sulfur atoms act as donors. The solubilities of the chelates were found to be pH dependent. When the uncoordinated sulfhydryl and carboxylic acid groups dissociate, the chelates dissolve and remain in aqueous solution. In the case of racemic-DMSA, two types of Pb²⁺ chelates were isolated: one in which rac-DMSA is coordinated to Pb²⁺ via one oxygen and one sulfur atom and the other in which the Pb²⁺ is coordinated via two sulfur atoms. The monomethyl ester and the dimethyl ester of meso-DMSA (MoMeDMSA and DiMeDMSA, respectively) were synthesized and their metal chelates with Pb²⁺, Cd²⁺, and Hg²⁺ studied. Esterification of meso-DMSA was found to change its biological properties. Both compounds, MoMeDMSA and DiMeDMSA, increased the biliary excretion of cadmium, which strongly suggests that the two derivatives of meso-DMSA enter the hepatocyte. The acid dissociation constants of the chelating agents and the uncoordinated groups in its metal chelates were determined. The results suggested that these acid-base properties in addition to the polarity of the chelating agent contribute to the effectiveness in the mobilization of intracellular deposits of cadmium. The dimethyl ester of DMSA was found to compete effectively with metallothionein for Cd²⁺ and Zn²⁺ ions by ¹H NMR spectroscopy. The structures of the metal chelates formed upon interaction of DiMeDMSA and Cd²⁺, or Zn²⁺ in solution at physiological pH were determined by multinuclear magnetic resonance spectroscopy. Mononuclear complexes were found to be formed. In these complexes, the metal ions are tetrahedrally coordinated by four thiolate groups from two DiMeDMSA molecules.