THIOL CONTAINING LIGANDS FOR PB(II) AND BI(III)

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The goal of the project is to synthesize bifunctional ligands which have high affinity for both Pb(II) and Bi(III) principally by virtue of the presence of sulfur donor atoms, although use of other heteroatoms is envisioned as being useful. Simple thiolate ligands such as dimercaptosuccinic acid have been shown to form complexes of high stability with both ions (Kf for the 1:2 Bi[DMSA] complex is log 43.87), yet appropriate multidentate chelating agents suitable for linkage to monoclonal antibodies are not yet available. As such, systematic exploration of the chemistry to incorporate multiple thiol donor groups into both existing and new acyclic and cyclic chelating agents is proceeding. Appropriate precursor molecules have been synthesized for testing the methodology for introduction of thiols as metal binding sites to form new chelating agents for protein modification. Of particular interest is the preparation of the polymercaptan analogues of the macrocyclic polyazacarboxylate ligands such as 1,4,7,10- tetraazacyclododecane tetraacetic acid (DOTA). The possibility exists that significant enhancement of the Pb(II) complex stability coupled with the ability of the thiols to moderate a transitory high energy state during the beta-decay event of 212Pb (T1/2=10.6 h) would lead to the clinical use of this radionuclide as an in vivo generator for delivery of therapeutic doses of the alpha-emitter 212Bi. Additionally, ligands of this fundamental design possess adequate coordination sites and donor character to potentially be evaluated as chelating agents for the alpha-particle emitter 211At. While traditionally associated with possessing the characteristics of halogen chemistry due to its location in the periodic table, substantial literature reports clearly indicate the possession of considerable metallic behavior. Formation of complexes with simple mono- and bi- dentate chelating agents indicate a potential for exploitation of these properties with the proper polydentate. Fundamental studies are now being initiated to explore these possibilities.