title: Synthesis and properties of the monomethyl ester of meso-dimercaptosuccinic acid and its chelates of lead (II), cadmium(II), and mercury(II).
abstract: The monomethyl ester of meso-dimercaptosuccinic acid (MoMeDMSA) and its chelates with lead(II), cadmium(II), and mercury(II) have been synthesized. The mercury(II) chelate of MoMeDMSA is formed by the coordination of the two sulfur atoms in MoMeDMSA, whereas the lead(II) and cadmium(II) chelates are formed by the coordination of one sulfur and one oxygen atom. The solubilities of the chelates are pH dependent; the mercury(II) chelate dissolves when the uncoordinated carboxylic acid dissociates, but the lead(II) and cadmium(II) chelates are solubilized only after the uncoordinated mercapto group is dissociated. The cadmium(II) chelate is dimeric and the lead(II) and mercury(II) chelates are monomeric at the concentrations and conditions used in this study. The acid dissociation constants of the chelating agent and the uncoordinated groups in its metal chelates have been determined in 50% v/v methanol-water. These acid-base properties in addition to the polarity of the chelating agent contribute to the effectiveness in the in vivo mobilization of intracellular in vivo deposits of cadmium. The biliary excretion of cadmium in rats increased by a factor of 173 upon administration of the relatively toxic, nonpolar dimethyl ester of DMSA whereas the administration of the less toxic, more polar monomethyl ester increased the biliary excretion of cadmium by a factor of 63. On the other hand, meso-DMSA which is highly polar and less toxic is known to be without effect on biliary excretion of cadmium. The monomethyl DMSA, therefore, appears to have properties that are intermediate between those of DMSA and its dimethyl ester, as far as both chelating properties and biliary excretion of cadmium are concerned.
authors.affiliation: Department of Chemistry, University of Arizona, Tucson 85721.
authors.forename: M
authors.initials: M
authors.lastname: Rivera
authors.forename: D J
authors.initials: DJ
authors.lastname: Levine
authors.forename: H V
authors.initials: HV
authors.lastname: Aposhian
authors.forename: Q
authors.initials: Q
authors.lastname: Fernando
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism; D002104:Cadmium / Q000737:chemistry* / Q000493:pharmacokinetics; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007854:Lead / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008628:Mercury / Q000737:chemistry*; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D013055:Spectrophotometry, Infrared; D004113:Succimer / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D002614:Chelating Agents; D002104:Cadmium; C060658:dimethyl mercaptosuccinate; D007854:Lead; C071157:dimercaptosuccinic acid monomethyl ester; D004113:Succimer; D008628:Mercury