Mechanistic aspects of the dithiocarbamate-induced mobilization of cadmium.
The examination of some of the species involved in the in vivo processes in which dithiocarbamates mobilize cadmium from its intracellular deposits indicates that several competing reactions occur. Rates of hydrolytic decomposition of a series of dithiocarbamates capable of mobilizing cadmium in vivo have been determined, and the solubility behavior and nuclear magnetic resonance (NMR) spectra of their cadmium complexes have been examined. Some of the dithiocarbamates most effective in this mobilization process are shown to undergo slow conversion to oxazolidine-2-thiones in the presence of cadmium. All of the cadmium complexes involved in the mobilization process are shown to undergo rapid ligand exchange. While dissociative mechanisms based on the turnover of metallothionein are inconsistent with the experimental data, at least two associative mechanisms are possible. These involve attack on the metallothionein by the dithiocarbamate itself or by a compound derived from it by known metabolic processes.
Topping
R J
RJ
Department of Chemistry, Vanderbilt University, Nashville, Tennessee.
Jones
M M
MM
Gale
G R
GR
Smith
A B
AB
D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D002614:Chelating Agents; D004050:Ditiocarb / Q000031:analogs & derivatives / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D012995:Solubility
D002614:Chelating Agents; D008024:Ligands; D002104:Cadmium; D008668:Metallothionein; D004050:Ditiocarb