Mercury binding to the chelation therapy agents DMSA and DMPS and the rational design of custom chelators for mercury.

Graham N George, Roger C Prince, Jürgen Gailer, Gavin A Buttigieg, M Bonner Denton, Hugh H Harris, Ingrid J Pickering

Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E2, Canada. g.george@usask.ca

Chemical research in toxicology 2004 Aug

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Clinical chelation therapy of mercury poisoning generally uses one or both of two drugs--meso-dimercaptosuccinic acid (DMSA) and dimercaptopropanesulfonic acid (DMPS), commercially sold as Chemet and Dimaval, respectively. We have used a combination of mercury L(III)-edge X-ray absorption spectroscopy and density functional theory calculations to investigate the chemistry of interaction of mercuric ions with each of these chelation therapy drugs. We show that neither DMSA nor DMPS forms a true chelate complex with mercuric ions and that these drugs should be considered suboptimal for their clinical task of binding mercuric ions. We discuss the design criteria for a mercuric specific chelator molecule or "custom chelator", which might form the basis for an improved clinical treatment.

Citation

Graham N George, Roger C Prince, Jürgen Gailer, Gavin A Buttigieg, M Bonner Denton, Hugh H Harris, Ingrid J Pickering. Mercury binding to the chelation therapy agents DMSA and DMPS and the rational design of custom chelators for mercury. Chemical research in toxicology. 2004 Aug;17(8):999-1006