A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead

Abstract

The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (α-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg²⁺, Cd²⁺, and Pb²⁺ are reviewed since insight into these reactions can provide a basis for further development of therapeutics.

Keywords: BAL; DMPS; DMSA; metal chelator; metal ion.

Figure 1

Speciation plots of TGA (top) and TMA (bottom).

Figure 2

Speciation plots of British anti-Lewisite (BAL).

Figure 3

Speciation plots of DMSA.

Figure 4

Speciation plots of methyl-DMSA (top) and dimethyl-DMSA (bottom).

Figure 5

Speciation plots of DMPS.

Figure 6

Speciation plots of d-penicillamine (DPEN).

Figure 7

Speciation plots of Lipoic acid (top) and dihydrolipoic acid (DHLA) (bottom).

Figure 8

The molecular formula of DMSA–Hg complex proposed by Rivera et al. [193].

Figure 9

Calculated structures of the two diastereomers of the smallest possible DMSA:Hg²⁺ complex. The carbon atoms are depicted as dark gray, oxygen atoms as red, hydrogen atoms as white, mercury atoms as light gray, and sulfur atoms as yellow. Reproduced from reference [144].

Figure 10

Mercury in green, sulfur in yellow, and oxygen in red. Coordinates obtained from the Cambridge Structural Database (Reference Code LIMNUQ; the image was created with Mercury3.5.