Conformations of zinc chelates of meso- and rac-2,3-dimercaptosuccinic acid in aqueous solution.

Abstract

rac-2,3-Dimercaptosuccinic acid (DMSA) was found to be superior to meso-2,3-dimercaptosuccinc acid in mobilizing in vivo heavy metals such as Cd, Hg, and Pb. The disadvantage of using rac-DMSA alone as a clinical antidote for heavy metal poisoning is that it causes a greater loss of endogenous zinc than its meso isomer. The difference between the two diastereoisomers of DMSA in the excretion of endogenous zinc has been rationalized on the basis of the differences in the conformations of their zinc complexes. The zinc complexes of rac-DMSA in aqueous solution are more stable than the corresponding complexes of its meso isomer because the rac-DMSA ligands always adopt staggered anti conformations, in which the electrostatic repulsion between two bulky carboxylate groups is minimized; in contrast, unlike in the crystal lattice, meso-DMSA ligands always adopt staggered gauche conformations in their zinc complexes. The conformations of various monomeric and dimeric zinc complexes with rac- and meso-2,3-dimercaptosuccinic acid in aqueous solution were determined by IR spectroscopy and proton NMR spectroscopy as a function of zinc:ligand ratio, by proton NMR spectroscopy as a function of pD, and by variable-temperature 13C NMR spectroscopy. rac-DMSA in ZnL2(6-) coordinates with zinc ion via two thiolate groups and one carboxylate group, whereas in Zn2L2(4-) each ligand complexes two zinc ions by using one carboxylate group and one thiolate group in the beta-position to bind to the same zinc ion.(ABSTRACT TRUNCATED AT 250 WORDS)