CONFORMATIONS OF ZINC CHELATES OF MESO-2,3-DIMERCAPTOSUCCINIC AND RAC-2,3-DIMERCAPTOSUCCINIC ACID IN AQUEOUS-SOLUTION

rac-2,3-Dimercaptosuccinic acid (DMSA) was found to be superior to mes o-2,3-dimercaptosuccinc acid in mobilizing in vivo heavy metals such a s Cd, Hg, and Pb. The disadvantage of using rac-DMSA alone as a clinic al antidote for heavy metal poisoning is that it causes a greater loss of endogenous zinc than its meso isomer. The difference between the t wo diastereoisomers of DMSA in the excretion of endogenous zinc has be en rationalized on the basis of the differences in the conformations o f their zinc complexes. The zinc complexes of rac-DMSA in aqueous solu tion are more stable than the corresponding complexes of its meso isom er because the rac-DMSA ligands always adopt staggered anti conformati ons, in which the electrostatic repulsion between two bulky carboxylat e groups is minimized; in contrast, unlike in the crystal lattice, mes o-DMSA ligands always adopt staggered gauche conformations in their zi nc complexes. The conformations of various monomeric and dimeric zinc complexes with rac- and meso-2,3-dimercaptosuccinic acid in aqueous so lution were determined by IR spectroscopy and proton NMR spectroscopy as a function of zinc:ligand ratio, by proton NMR spectroscopy as a fu nction of pD, and by variable-temperature C-13 NMR spectroscopy. rac-D MSA in ZnL(2)(6-) coordinates with zinc ion via two thiolate groups an d one carboxylate group, whereas in Zn(2)L(2)(4-) each ligand complexe s two zinc ions by using one carboxylate group and one thiolate group in the beta-position to bind to the same zinc ion. In contrast, meso-D MSA in ZnL(2)(6-) uses one thiolate group and two carboxylate groups t o bind to the zinc ion, and in Zn(2)L(2)(4-) each ligand binds to one zinc ion via two carboxylate groups and one thiolate group, and to the other zinc ion via the other thiolate group. In ZnL(2)(6-) of meso-DM SA, one of the carboxylate groups in the ligand binds to the zinc ion in an unsymmetrical bidentate manner.