title: The dimethyl ester of meso-2,3-dimercaptosuccinic acid and its interactions with Cd2+ and rabbit liver metallothionein I.
abstract: The ion association complex formed with the cadmium chelate of the dimethyl ester of meso-2,3-dimercaptosuccinic acid and the tetramethylammonium cation, [(Me)4N]2[Cd(Di-MeDMSA)2], has been synthesized. The structures of the ion association complex and of the ligand (meso-DiMeDMSA) were determined by single-crystal X-ray diffraction. The two methyl ester groups and the two sulfhydryl groups in meso-DiMeDMSA were in a staggered conformation. The anion [Cd(DiMeDMSA)2]2- is essentially a distorted tetrahedron, with a mononuclear CdS4 kernel. The structure of the [Cd(DiMeDMSA)2]2- anion in solution was found to be similar to its structure in the solid state by multinuclear (1H, 13C, 113Cd) magnetic resonance spectroscopy. In the presence of rabbit liver metallothionein I (MT), meso-DiMeDMSA was found to coordinate Zn2+ and Cd2+ ions. 1H NMR spectroscopy proved to be an effective analytical technique for monitoring the competition between meso-DiMeDMSA and the protein for these metal ions. This was accomplished by probing the tertiary structure of MT with 1H NMR spectroscopy after incubation with meso-DiMeDMSA. In addition, the 1H NMR spectra of rabbit liver metallothionein I demonstrated that MT is more susceptible to oxidation at physiological pH after the metal ions have been removed. It appears that intra- as well as intermolecular disulfide cross-linkages are formed upon oxidation. When rabbit liver metallothionein I was incubated with meso-DiMeDMSA in a 20:1 (meso-DiMeDMSA:MT) mole ratio, 32% of the cadmium and 87% of the zinc bound to MT were removed.
authors.affiliation: Department of Chemistry, University of Arizona, Tucson 85721.
authors.forename: M
authors.initials: M
authors.lastname: Rivera
authors.forename: M A
authors.initials: MA
authors.lastname: Bruck
authors.forename: H V
authors.initials: HV
authors.lastname: Aposhian
authors.forename: Q
authors.initials: Q
authors.lastname: Fernando
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002104:Cadmium / Q000737:chemistry*; D002106:Cadmium Radioisotopes; D002614:Chelating Agents / Q000737:chemistry* / Q000494:pharmacology; D008099:Liver / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008668:Metallothionein / Q000737:chemistry*; D011485:Protein Binding; D011817:Rabbits; D012996:Solutions; D013054:Spectrophotometry, Atomic; D004113:Succimer / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D013696:Temperature; D014462:Ultrafiltration; D014961:X-Ray Diffraction; D015032:Zinc / Q000378:metabolism
chemical_list: D002106:Cadmium Radioisotopes; D002614:Chelating Agents; D012996:Solutions; D002104:Cadmium; C060658:dimethyl mercaptosuccinate; D008668:Metallothionein; D004113:Succimer; D015032:Zinc