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

该项目的目标是合成双功能配体， 对Pb（II）和Bi（III）的高亲和力主要是由于 硫供体原子的存在，尽管使用其它杂原子是优选的。 被认为是有用的。 简单的硫醇盐配体，如 二巯基琥珀酸已经显示出形成高的 与两种离子的稳定性（1：2 Bi[DMSA]络合物的Kf为log 43.87）， 然而，适合于连接到 单克隆抗体还不能获得。 因此，系统 结合多个硫醇供体基团的化学探索 现有的和新的无环和环状螯合剂， 进行中。 已经合成了合适的前体分子， 测试引入硫醇作为金属结合位点的方法 以形成用于蛋白质修饰的新螯合剂。 特别 令人感兴趣的是本发明的多硫醇类似物的制备。 大环聚氮杂羧酸酯配体如1，4，7，10- 四氮杂环十二烷四乙酸（DOTA）。 的存在有可能 Pb（II）络合物稳定性的显著增强与 硫醇缓和过渡高能态的能力 在212 Pb的β衰变事件（T1/2=10.6 h）期间， 这种放射性核素作为体内发生器的临床应用 治疗剂量的α发射体212 Bi。 此外，这种基本设计的配体具有足够的 配位位点和供体特征可能被评估为 用于α粒子发射器211 At的螯合剂。 而 传统上与具有卤素的特征有关 由于其在周期表中的位置， 文献报告清楚地表明， 金属行为 与简单的单-和双- 配位螯合剂显示了开发这些的潜力。 具有适当的多齿的特性。 基础研究正在 开始探索这些可能性。

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.