Chelation Therapy for Metal Intoxication: Comments from a Thermodynamic Viewpoint

Chelation therapy plays a prominent role in the clinical treatment of metal intoxication. In this paper the principal causes of metal toxicity are exposed, and the chemical and biomedical requisites of a chelating agent are sketched. The chelating agents currently in use for scavenging toxic metal ions from humans belong to few categories: those characterized by coordinating mercapto groups, by oxygen groups, poliaminocarboxylic acids, and dithiocarbamates. Considering that the complex formation equilibria have been studied for less than 50% of chelators in use, some reflections on the utility of stability constants are presented, together with an evaluation of ligands under the stability profile. The competition between endogenous and toxic target metal ions for the same chelating agent is furthermore examined. A thorough examination of stability constant databases has allowed to select, for each toxic metal, the ligands distinguished by the best pMe values. Even though this selection does not consider the biomedical requisites of a chelating agent, it gives a clear picture both of the pMe values that can be attained, and of the most appropriate chelators for each metal ion.