Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia V6T 2A3, Canada.
Inorg Chem. 2022 Jun 20;61(24):9119-9137. doi: 10.1021/acs.inorgchem.2c00636. Epub 2022 Jun 9.
A new decadentate chelator, Hampa, was designed to be a potential radiopharmaceutical chelator component. The chelator involves both amide and picolinate functional groups on a large non-macrocyclic, ether-bridged backbone. With its large scaffold, Hampa was paired with [Pb]Pb, [Bi]Bi, and La/[Ac]Ac ions. Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to study the non-radioactive metal complexes. A single crystal of Bi(ampa) was obtained; its asymmetric, 10-coordinate complex structure was revealed by X-ray diffraction. Optimal conformations of the metal complexes were assessed by density functional theory studies to provide further structural information. Solution studies providing thermodynamic insights into metal complex formation revealed Hampa coordinated Bi, Pb, and La ions to obtain pM values of 26, 14.8, and 15.1, respectively. Preliminary concentration-dependent radiolabeling experiments were carried out between Hampa and three different radiometals to evaluate their compatibility for radiopharmaceutical applications. The chelator radiolabeled [Pb]Pb, [Bi]Bi, and [Ac]Ac in short reaction times (7-30 min), at dilute concentrations, and under mild conditions. Thus, Hampa was proven to be a versatile chelator able to well coordinate a small range of radiometals frequently considered to be alpha therapeutic candidates.
一种新型的伸展型螯合剂 Hampa 被设计为一种有潜力的放射性药物螯合剂成分。该螯合剂在一个大的非大环、醚桥接的骨架上同时包含酰胺和吡啶甲酸官能团。由于其庞大的支架，Hampa 与 [Pb]Pb、[Bi]Bi 和 La/[Ac]Ac 离子进行了配对。使用核磁共振波谱和高分辨率质谱对非放射性金属配合物进行了研究。获得了 Bi(ampa) 的单晶；通过 X 射线衍射揭示了其不对称的 10 配位络合结构。通过密度泛函理论研究评估了金属配合物的最佳构象，以提供进一步的结构信息。提供金属络合物形成热力学见解的溶液研究表明，Hampa 与 Bi、Pb 和 La 离子配位，分别获得 pM 值为 26、14.8 和 15.1。进行了初步的浓度依赖性放射性标记实验，以评估 Hampa 与三种不同放射性金属的兼容性，用于放射性药物应用。该螯合剂在短反应时间（7-30 分钟）、稀释浓度和温和条件下标记 [Pb]Pb、[Bi]Bi 和 [Ac]Ac。因此，Hampa 被证明是一种多功能螯合剂，能够很好地配位一系列通常被认为是α治疗候选物的小范围放射性金属。
