George Graham N, Prince Roger C, Gailer Jürgen, Buttigieg Gavin A, Denton M Bonner, Harris Hugh H, Pickering Ingrid J
Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E2, Canada.
Chem Res Toxicol. 2004 Aug;17(8):999-1006. doi: 10.1021/tx049904e.
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.
汞中毒的临床螯合疗法通常使用两种药物中的一种或两种——内消旋二巯基丁二酸(DMSA)和二巯基丙磺酸钠(DMPS),它们分别以Chemet和Dimaval的商品名出售。我们结合汞L(III)边X射线吸收光谱和密度泛函理论计算,研究了汞离子与每种螯合疗法药物相互作用的化学过程。我们发现,DMSA和DMPS都不会与汞离子形成真正的螯合物,并且就其结合汞离子的临床任务而言,这些药物应被视为次优选择。我们讨论了汞特异性螯合剂分子或“定制螯合剂”的设计标准,这可能是改进临床治疗的基础。