Equilibrium Thermodynamics of Macropa Complexes with Selected Metal Isotopes of Radiopharmaceutical Interest,Inorganic Chemistry

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Equilibrium Thermodynamics of Macropa Complexes with Selected Metal Isotopes of Radiopharmaceutical Interest
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2023-09-13 , DOI: 10.1021/acs.inorgchem.3c01983
Magdalena K Blei _{1,

2} , Lukas Waurick _{2,

3} , Falco Reissig ₁ , Klaus Kopka _{1,

2,

4,

5} , Thorsten Stumpf _{2,

3} , Björn Drobot ₃ , Jerome Kretzschmar ₃ , Constantin Mamat _{1,

2}

Affiliation

To pursue the design of in vivo stable chelating systems for radiometals, a concise and straightforward method toolbox was developed combining NMR, isothermal titration calorimetry (ITC), and europium time-resolved laser-induced fluorescence spectroscopy (Eu-TRLFS). For this purpose, the macropa chelator was chosen, and Lu³⁺, La³⁺, Pb²⁺, Ra²⁺, and Ba²⁺ were chosen as radiopharmaceutically relevant metal ions. They differ in charge (2+ and 3+) and coordination properties (main group vs lanthanides). ¹H NMR was used to determine four pK_a values (±0.15; carboxylate functions, 2.40 and 3.13; amino functions, 6.80 and 7.73). Eu-TRLFS was used to validate the exclusive existence of the 1:1 Mⁿ⁺/ligand complex in the chosen pH range at tracer level concentrations. ITC measurements were accomplished to determine the resulting stability constants of the desired complexes, with log K values ranging from 18.5 for the Pb-mcp complex to 7.3 for the Lu-mcp complex. Density-functional-theory-calculated structures nicely mirror the complexes’ order of stabilities by bonding features. Radiolabeling with macropa using ligand concentrations from 10^–3 to 10^–6 M was accomplished by pointing out the complex formation and stability (²¹²Pb > ¹³³La > ¹³¹Ba ≈ ²²⁴Ra > ¹⁷⁷Lu) by means of normal-phase thin-layer chromatography analyses.

中文翻译：

Macropa 配合物与放射性药物感兴趣的选定金属同位素的平衡热力学

为了设计放射性金属体内稳定的螯合系统，结合核磁共振、等温滴定量热法 (ITC) 和铕时间分辨激光诱导荧光光谱 (Eu-TRLFS)，开发了一种简洁明了的方法工具箱。为此，选择大螯合剂，并选择Lu ³⁺ 、La ³⁺ 、Pb ²⁺ 、Ra ²⁺和Ba ²⁺作为放射性药物相关金属离子。它们的电荷（2+ 和 3+）和配位特性（主族与镧系元素）不同。使用¹ H NMR测定四个pKa_值(±0.15；羧酸酯官能团，2.40和3.13；氨基官能团，6.80和7.73)。 Eu-TRLFS 用于验证 1:1 M ^{n +} /配体复合物在选定 pH 范围内、示踪剂水平浓度下的唯一存在。完成 ITC 测量以确定所需复合物的稳定性常数，log K值范围从 Pb-mcp 复合物的 18.5 到 Lu-mcp 复合物的 7.3。密度泛函理论计算的结构很好地反映了配合物通过键合特征的稳定性顺序。通过正相薄层指出配合物的形成和稳定性（ ²¹² Pb > ¹³³ La > ¹³¹ Ba ≈ ²²⁴ Ra > ¹⁷⁷ Lu），使用配体浓度从 10 ^–3到 10 ^–6 M 完成了 Macropa 放射性标记。色谱分析。

更新日期：2023-09-13

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