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

PB(II) 和 BI(III) 的含硫醇配体

• 批准号: 2464445
• 负责人: MARTIN W BRECHBIEL
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2464445
• 关键词: bismuth; chelating agents; chemical synthesis; lead; ligands; metal complex; sulfur; thiols

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.

该项目的目标是合成双功能配体，其具有 对 Pb(II) 和 Bi(III) 的高亲和力主要是由于 硫供体原子的存在，尽管使用其他杂原子 被认为是有用的。 简单的硫醇盐配体，例如 二巯基丁二酸已被证明可形成高复合物 两种离子的稳定性（1:2 Bi[DMSA] 复合物的 Kf 为 log 43.87）， 然而合适的多齿螯合剂适合连接 目前还没有单克隆抗体。 因此，系统性地 探索化学结合多个硫醇供体基团 现有的和新的无环和环状螯合剂是 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 形成用于蛋白质修饰的新螯合剂。 特别是 人们感兴趣的是聚硫醇类似物的制备 大环多氮杂羧酸酯配体，例如1,4,7,10- 四氮杂环十二烷四乙酸（DOTA）。 可能性是存在的 Pb(II)络合物稳定性的显着增强加上 硫醇缓和短暂高能状态的能力 在 212Pb 的 β 衰变事件（T1/2=10.6 h）期间会导致 这种放射性核素作为体内发生器的临床用途 α发射体212Bi的治疗剂量。 此外，这种基本设计的配体具有足够的 协调位点和捐助者特征可能被评估为 α粒子发射体211At的螯合剂。 尽管 传统上与拥有卤素的特性有关 化学由于其在元素周期表中的位置，大量 文献报道清楚地表明拥有相当多的 金属行为。 与简单的单分子和双分子形成配合物 齿状螯合剂表明这些物质具有开发利用的潜力 具有适当的多齿的特性。 目前正在进行基础研究 开始探索这些可能性。