Competition between Cd(II) and other divalent transition metal ions during complex formation with amino acids, peptides, and chelating agents

Cadmium is not an essential element for humans but its compounds are known for their toxicity. Besides the risks for workers in the industries using cadmium, this metal enters the food chain at different levels and can be absorbed by the body, replacing other metals with similar chemical activity. The same holds true for the cadmium inhaled via cigarette smoking. The study of the interactions of cadmium with biologically relevant molecules, such as amino acids, peptides or proteins, is paramount, as well as the study of chelating methods to cure or alleviate acute or chronic cadmium poisoning cases. As a matter of fact, 111/113Cd isotopes are used as NMR probes to determine complex-formation sites and geometries of metals in metalloproteins and metalloenzymes. In the present review, after a general introduction on the general properties of cadmium, the main uses of this metal, its compounds and artefacts is presented. The toxicity of cadmium for humans is also discussed. Moreover, this review collects the most significant results reported in the literature concerning the interaction of cadmium and other potentially competing divalent metal ions of biological relevance (Fe(II), Zn(II), Mn(II), Ni(II) and Cu(II)) with amino acids and peptides, with especial attention to His- and thiol-containing ligands. In the authors’ knowledge, a so wide critical collection of speciation models for such systems was never previously reported in the literature. Distribution and competition diagrams are built up in order to allow a comparison of the binding ability of different metals towards the same ligand or vice-versa, in a wide pH range and under different reagent concentrations and/or concentration ratios, thus giving hints to what can happen in vivo both inside and outside the cells, where pH and concentrations can be very different. On the other hand, the huge topic of complexes with phytochelatins and metallothioneins has been left to more specific (dedicated) papers. Finally, the issue of cadmium chelators with potential pharmacological applications is thoroughly reviewed