Positron emission tomography (PET) is emerging as one of the most important diagnostic tools for brain imaging, yet the most commonly used radioisotopes in PET imaging, ¹¹C and ¹⁸F, have short half-lives, and their usage is thus somewhat limited. By comparison, the ⁶⁴Cu radionuclide has a half-life of 12.7 h, which is ideal for administering and imaging purposes. In spite of appreciable research efforts, high-affinity copper chelators suitable for brain imaging applications are still lacking. Herein, we present the synthesis and characterization of a series of bifunctional compounds (BFCs) based on macrocyclic 1,4,7-triazacyclononane and 2,11-diaza[3.3](2,6)pyridinophane ligand frameworks that exhibit a high affinity for Cu²⁺ ions. In addition, these BFCs contain a 2-phenylbenzothiazole fragment that is known to interact tightly with amyloid β fibrillar aggregates. Determination of the protonation constants (pK_a values) and stability constants (log β values) of these BFCs, as well as characterization of the isolated copper complexes using X-ray crystallography, electron paramagnetic resonance spectroscopy, and electrochemical studies, suggests that these BFCs exhibit desirable properties for the development of novel ⁶⁴Cu PET imaging agents for Alzheimer’s disease.

中文翻译：

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双功能化学试剂的配位化学设计用于阿尔茨海默氏病的⁶⁴ Cu PET成像

正电子发射断层扫描（PET）逐渐成为大脑成像的最重要诊断工具之一，但是PET成像中最常用的放射性同位素¹¹ C和¹⁸ F具有短的半衰期，因此其使用受到一定限制。相比之下，⁶⁴ Cu放射性核素的半衰期为12.7 h，非常适合给药和成像。尽管进行了大量的研究，但仍缺乏适用于脑成像的高亲和力铜螯合剂。在本文中，我们介绍了基于大环1,4,7-三氮杂环壬烷和2,11-二氮杂[3.3]（2,6）吡啶并oph烷配体骨架的一系列双功能化合物（BFC）的合成和表征铜²⁺离子。另外，这些BFC包含2-苯基苯并噻唑片段，该片段已知与淀粉样β原纤维聚集体紧密相互作用。这些BFC的质子化常数（p K _a值）和稳定性常数（logβ值）的测定，以及使用X射线晶体学，电子顺磁共振波谱和电化学研究对分离的铜络合物进行表征，表明这些BFC对开发用于阿尔茨海默氏病的新型⁶⁴ Cu PET显像剂具有理想的性能。