Determination and metabolism of dithiol chelating agents. VIII. Metal complexes of meso-dimercaptosuccinic acid.
Metal complexes of meso-dimercaptosuccinic acid (DMSA) with Pb2+, Cd2+, and Hg2+ were studied by potentiometric and infrared methods. This dimercapto metal-binding agent was found to form complexes whose structures are dependent on the metal ion to be complexed. In the cases of Pb2+ and Cd2+, one oxygen and one sulfur act as the donor atoms; in the case of Hg2+, two sulfur atoms act as the donors. The solubilities of all metal chelates were found to be pH dependent. Complexes of cadmium and lead are insoluble in the pH range 1.0 to 7.1, but are solubilized when the noncoordinated sulfhydryl and carboxylic acid groups are ionized. The mercury complex is insoluble in the pH range 1.0 to 3.0. It dissolves when one of the noncoordinated carboxylic acid groups is ionized. The dimethyl ester of meso-DMSA (DiMe-meso-DMSA) was synthesized and its acid dissociation constants were determined (pK1 = 6.38 and pK2 = 8.00). Esterification of the carboxyl groups of meso-DMSA changes its coordination properties in that the two sulfur atoms of DiMe-meso-DMSA are used to coordinate with Hg2+, Cd2+, or Pb2+. Esterification of meso-DMSA also changes its biological properties. DiMe-meso-DMSA, when given to rats 3 days after Cd administration, greatly increased the excretion of Cd via bile. In contrast, meso-DMSA was devoid of such activity.
Rivera
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Department of Chemistry, University of Arizona, Tucson 85721.
Zheng
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W
Aposhian
H V
HV
Fernando
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D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites; D002104:Cadmium / Q000378:metabolism*; D002614:Chelating Agents / Q000138:chemical synthesis / Q000378:metabolism; D004951:Esterification; D007854:Lead / Q000378:metabolism*; D008297:Male; D008628:Mercury / Q000378:metabolism*; D011199:Potentiometry; D051381:Rats; D011919:Rats, Inbred Strains; D004113:Succimer / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D002614:Chelating Agents; D013438:Sulfhydryl Compounds; D002104:Cadmium; C060658:dimethyl mercaptosuccinate; D007854:Lead; D004113:Succimer; D008628:Mercury