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."

“该项目的目标是合成双功能 对 Pb(II) 和 Bi(III) 均具有高亲和力的配体， 主要是由于硫供体原子的存在，尽管 设想使用其他杂原子供体基团。简单的 硫醇盐配体，例如二巯基丁二酸 (DMSA) 形式 高稳定性配合物（1:2 Bi[DMSA] 配合物的 Kf 为 log 43.87)，但合适的多齿螯合剂合适 与单克隆抗体的连接尚不可用。像这样， 系统探索化学结合多种硫醇 供体基团进入现有和新的环状螯合剂 收益。已经合成了合适的前体分子 用于开发引入金属结合位点的化学方法 形成用于蛋白质修饰的新螯合剂。特别是 感兴趣的是聚（2-巯基乙烯）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）和 同系物。存在显着增强的可能性 Pb(II) 配合物的稳定性与硫醇的能力相结合 在β衰变事件期间缓和短暂的高能状态 Pb-212 (T1/2=10.6h) 的使用将导致该药物的临床应用 放射性核素作为体内发生器，用于递送治疗剂 α发射体Bi-212的剂量。由于新的螯合剂 合成并显示单独的 Pb(II) 和 Bi(III) 配合物 具有动力学惰性，通过衰变评估稳定性 事件是。此外，这种基本设计的配体具有 足够的协调地点和捐助者特征进行评估 α粒子发射体At-211的潜在螯合剂。 虽然传统上认为具有卤素的特性 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了相当大的金属行为 这个元素。因此，随着新的 Pb(II) 配体的开发， 继续评估这些配体的螯合能力 在-211。”