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

PB(II) 和 BI(III) 的含硫醇配体

• 批准号: 6123655
• 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/6123655
• 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 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."

“该项目的目的是合成双功能 对PB（II）和BI（III）具有高亲和力的配体， 主要是由于存在硫供体原子，尽管 设想了其他杂原子供体组的使用。简单的 硫醇酸盐配体，例如二焦糖酸（DMSA）形式 高稳定性的复合物（1：2 BI [DMSA]复合物的KF为 日志43.87），但合适的多齿螯合剂合适 对于与单克隆抗体的链接，尚不可用。像这样， 对化学的系统探索以结合多硫醇 供体组进入现有和新的环状螯合剂 收益。合成了适当的前体分子 用于开发用于引入金属结合位点的化学反应 形成用于蛋白质修饰的新螯合剂。特别 兴趣是制备聚（2-甲基乙基）类似物的 大环聚唑羧酸盐配体，例如 1,4,7,10-tetraazacyclododecane四乙酸（DOTA）和 同源物。存在大幅增强的可能性 Pb（II）复杂稳定性，结合硫醇的能力 在β衰变事件中调节暂时的高能状态 PB-212（T1/2 = 10.6H）的临床用途 放射性核素作为用于递送治疗的体内生成器 Alpha-Emitter BI-212的剂量。因为新的螯合剂是 所示的合成以及单个PB（II）和BI（III）复合物所示 要动力惰性，请通过衰减评估稳定性 事件是。此外，这种基本设计的配体具有 足够的协调站点和捐助者特征被评估为 α粒子发射极AT-211的潜在螯合剂。 传统上认为具有卤素的特征 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了相当大的金属行为 这个元素。因此，随着针对PB（II）开发新的配体， 这些配体继续评估其螯合能力 在211。”