""""""""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 heteroatom donor groups are envisioned. Simple thiolate ligands such as dimercaptosuccinic acid (DMSA) form complexes of high stability (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 cyclic chelating agents proceeds. Appropriate precursor molecules have been synthesized for developing the chemistry for introduction of metal binding sites to form new chelating agents for protein modification. Of particular interest is the preparation of poly(2-mercatoethylene) analogues of the macrocyclic polyazacarboxylate ligands, such as 1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) and homologs. 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 Pb-212 (T1/2=10.6h) would lead to the clinical use of this radionuclide as an in vivo generator for delivery of therapeutic doses of the alpha-emitter Bi-212. As new chelating agents are synthesized and the individual Pb(II) and Bi(III) complexes shown to be kinetically inert, evaluation of stability throught the decay event is. Additionally, ligands of this fundamental design possess adequate coordination sites and donor character to be evaluated as potential chelating agents for the alpha-particle emitter At-211. While traditionally assumed to possess characteristics of halogen chemistry due to its location in the periodic table, substantial literature reports clearly indicate considerable metallic behavior to this element. Therefore, as new ligands are developed for Pb(II), these ligands continue to be evaluated for their chelating ability of At-211.""""""""
