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.

该项目的目的是合成具有的双功能配体 PB（II）和BI（III）的高亲和力主要是由于 硫供体原子的存在，尽管其他杂原子的使用是 设想是有用的。 简单的硫醇酸盐配体，例如 已显示二焦核酸酸会形成高的复合物 两个离子的稳定性（1：2 BI [DMSA]复合物的KF是log 43.87）， 但是适当的多齿螯合剂适合与 单克隆抗体尚不可用。 因此，系统性 探索化学以结合多个硫醇供体组的探索 进入现有的和新的无环和循环螯合剂是 程序。 适当的前体分子已合成 测试将硫醇作为金属结合位点引入的方法 形成用于蛋白质修饰的新螯合剂。 特别 兴趣是准备多键类似物 大环聚唑羧酸盐配体，例如1,4,7,10- 四二烷酸四乙烷四乙酸（DOTA）。 存在可能性 PB（II）复杂稳定性的显着增强与 硫醇适度暂时高能状态的能力 在212pb（T1/2 = 10.6 h）的Beta-Decay事件中，将导致 该放射性核素作为用于输送的体内生成器的临床用途 212Bi的α-发射剂的治疗剂量。 此外，该基本设计的配体具有足够的 协调地点和捐助者特征可能会被评估为 α粒子发射极211AT的螯合剂。 尽管 传统上与拥有卤素的特征有关 化学由于其位于元素周期表中的位置，很大 文献报告清楚地表明拥有大量 金属行为。 与简单的单声道和二线形成复合物 齿状螯合剂表明有可能开发这些剂 具有适当多径化的属性。 基本研究现在正在 启动以探索这些可能性。