Selectivity and rate of complex formation with metal radionuclides are crucial parameters for the utilization of ligating systems in nuclear medicine. One of the very suitable metals used in these applications is copper, which has a number of radioisotopes with useful properties. The thermodynamic and kinetic properties of Cu(II) complexes with 10 macrocyclic 1,4,8-trimethylcyclam-based ligands having one coordinating acid pendant arm (Me₃cyclam–R) were investigated in solution, allowing a direct comparison of the influence of the particular pendant arm on the properties of the complexes. They include the derivative with R = CH₂CO₂H (HL¹) and a family containing various phosphorus acids R = CH₂P(O)(OH)–X, where X = OEt (HL²); X = OH (H₂L³); X = H (HL⁴); X = CH₂CH₂CO₂H (H₂L⁵); X = CH₂P(O)(H)OH (H₂L⁶); X = CH₂P(O)(OH)₂ (H₃L⁷); X = CH₂N(CH₂C₆H₅)₂ (HL⁸); X = CH₂NH₂ (HL⁹) and X = CH₂N(CH₂CO₂H)₂ (H₃L¹⁰). For comparison, 1,4,8,11-tetramethylcyclam (TMC: R = Me) was used. The formation kinetics showed that ligands endowed with a coordinating pendant arm bind Cu(II) ions much faster when compared to TMC. At pH < 4, the fastest complexation was observed for acetate derivative HL¹. At higher pH and, especially, at pH relevant for living and biocompatible systems (pH ≈ 6–7), the ligands with methylene(phosphonatomethyl)phosphinate and methylenephosphonate pendant arms (H₃L⁷ and H₂L³) showed the fastest complexation. Acid-assisted dissociation of Cu(II) complexes with the ligands endowed with a coordinating pendant arm is similar for all studied systems (τ_1/2 = 7–35 min, 1 M HClO₄, 25 °C). In contrast, the inertness of the Cu(II)–TMC complex is much lower (τ_1/2 = 22 s under the same conditions). Potentiometric study of the selected ligands has confirmed a high thermodynamic selectivity of the studied ligands for Cu(II) binding over complexation of Ni(II) and Zn(II) (the differences between the stability constants reach 6–7 orders of magnitude). Fast complexation of Cu(II) at radio-level concentrations was observed, showing that the best ligands for potential in vivo use are those containing phosphonate or mixed geminal phosphinate–phosphonate pendant groups. One of the ligands (H₂L³) and three Cu(II) complexes (of H₂L⁵, H₃L⁷ and H₃L¹⁰) were structurally characterized by means of X-ray diffraction study. The predicted conformation I of the macrocycle was confirmed in all three complexes.

中文翻译：

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优化铜放射性同位素络合的选择性和速率：具有不同配位侧链臂的1,4,8-三甲基环素基配体的形成和解离动力学研究†

与金属放射性核素形成复合物的选择性和速率是核医学中结扎系统利用的关键参数。在这些应用中使用的非常合适的金属之一是铜，它具有许多具有有用性质的放射性同位素。在溶液中研究了具有10个具有一个配位酸侧基臂（Me ₃ cyclam–R）的10,1,4,8-三甲基环己基大环配体的Cu（II）配合物的热力学和动力学性质，从而可以直接比较配合物特性的特定侧链。它们包括具有R = CH ₂ CO ₂ H（H L ¹）的衍生物和包含各种磷酸R = CH的家族₂ P（O）（OH）–X，其中X = OEt（H L ²）；X = OH（H ₂ L ³）; X = H（H L ⁴）; X ＝ CH ₂ CH ₂ CO ₂ H（H ₂ L ⁵）；X ＝ CH ₂ CH ₂ CO ₂ H（H ₂ L ⁵）。X = CH ₂ P（O）（H）OH（H ₂ L ⁶）; X = CH ₂ P（O）（OH） ₂（H ₃ L ⁷）; X ＝ CH ₂ N（CH ₂ C ₆ H ₅） ₂（H L ⁸）；X = CH ₂ NH ₂（H L ⁹）和X ＝ CH ₂ N（CH ₂ CO ₂ H）₂（H ₃ L ¹⁰）。为了比较，使用了1,4,8,11-四甲基环酰胺（TMC：R = Me）。形成动力学表明，与TMC相比，配有配位侧链的配体结合Cu（II）离子的速度更快。在pH <4时，乙酸酯衍生物H L ^1的络合最快。在较高的pH值下，尤其是在与生命系统和生物相容性系统相关的pH值（pH≈6-7）下，具有亚甲基（膦酰基甲基）次膦酸酯和亚甲基膦酸酯侧链的配体（H ₃L ⁷和H ₂ L ³）显示最快的络合。的Cu的酸解离辅助（II）配合物与赋予了配位侧链臂的配位体是对所有研究的系统相似（τ _1/2 = 7 - 35分钟，1M的HClO ₄，25℃）。相反，Cu（II）–TMC络合物的惰性要低得多（在相同条件下，τ1 _/2 = 22 s）。所选配体的电位测量研究证实，所研究的配体对Cu（II）的结合具有很高的热力学选择性，而Ni（II）和Zn（II）的络合作用II）（稳定性常数之间的差异达到6–7个数量级）。观察到放射性水平浓度的Cu（II）快速络合，表明可能在体内使用的最佳配体是那些含有膦酸酯或双膦酸酯-膦酸酯侧基的混合配体。通过X射线衍射研究在结构上表征了一种配体（H ₂ L ³）和三种Cu（II）配合物（H ₂ L ⁵，H ₃ L ⁷和H ₃ L ¹⁰）。预测构象I 在所有三个复合物中都证实了大环的变化。