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

该项目的目标是合成双功能配体，这些配体具有 对铅(II)和铋(III)的高亲和力主要是由于 硫供体原子的存在，尽管使用其他杂原子是 被认为是有用的。简单的硫酸盐配体，如 二硫代丁二酸已被证明形成高密度的络合物 与两种离子的稳定性(1：2铋[DMSA]络合物的KF为log43.87)， 适用于连接的合适的多齿螯合剂 目前还没有可用的单抗。因此，系统化 多个硫醇给电子基团结合的化学探索 现有的和新的无环和环络合剂是 继续进行。合成了合适的前体分子，用于 测试引入硫醇作为金属结合部位的方法学 形成用于蛋白质修饰的新型螯合剂。特别的 令人感兴趣的是制备聚醇类似物 大环多氮杂羧酸配体，如1，4，7，10- 四氮杂环十二烷四乙酸(DOTA)。这种可能性是存在的 铅(II)络合物稳定性的显著提高与 硫醇调节短暂高能态的能力 在~(212)Pb(t_(1/2)=10.6小时)的β衰变过程中， 这种放射性核素作为体内产生器的临床应用 治疗剂量的阿尔法发射体212Bi。 此外，这种基本设计的配体具有足够的 协调位置和供体特征可能被评估为 α粒子发射器211At的螯合剂。而当 传统上与具有卤素特性有关 化学由于其在元素周期表中的位置，大量 文献报告清楚地表明，拥有相当数量的 金属行为。简单的单、双-络合物的形成 齿状螯合剂表明有可能开发这些 具有适当多齿的属性。基础研究现在正在进行 发起了探索这些可能性的活动。

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.