Mercury binding to the chelation therapy agents DMSA and DMPS and the rational design of custom chelators for mercury.
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.
Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E2, Canada. g.george@usask.ca
Graham N
GN
George
Roger C
RC
Prince
Jürgen
J
Gailer
Gavin A
GA
Buttigieg
M Bonner
MB
Denton
Hugh H
HH
Harris
Ingrid J
IJ
Pickering
D002614:Chelating Agents / Q000737:chemistry* / Q000378:metabolism; D015913:Chelation Therapy; D008628:Mercury / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D008630:Mercury Poisoning / Q000188:drug therapy*; D013057:Spectrum Analysis / Q000379:methods; D004113:Succimer / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D014494:Unithiol / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use
D002614:Chelating Agents; D014494:Unithiol; D004113:Succimer; D008628:Mercury