Rivera M, Bruck M A, Aposhian H V, Fernando Q
Department of Chemistry, University of Arizona, Tucson 85721.
Chem Res Toxicol. 1991 Sep-Oct;4(5):572-80. doi: 10.1021/tx00023a014.
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.
