AbstractThe competitive complexation of Ca2+, Fe2+, Cu2+, Zn2+, and Pb2+ toward ethylene diamine tetraacetate (EDTA), dimercaprol and D‐penicillamine, three liganding agents commonly used in chelation therapy against heavy metal, especially lead, poisonings is examined by means of B3LYP calculations, natural population analyses, and the topological analysis of the electron localization function. It is shown that Pb2+ can displace any of Ca2+, Fe2+, Cu2+, or Zn2+ chelated by any of dimercaprol or D‐penicillamine, but can only displace Ca2+ if EDTA is concerned. The first two chelators thus appear as better entities than EDTA to be used in chelation therapy, where in vivo selective complexation is essential. Moreover, the comparison of the bonding characteristics of Pb2+ with those of the other cations allows deriving three features to be taken into account in designing new chelators expecting to have an increased selectivity toward this cation. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008