A. A. Martinos Center for Biomedical Imaging and the Institute for Innovation in Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Dalton Trans. 2020 Oct 20;49(40):14088-14098. doi: 10.1039/d0dt02787a.
Synthesis and characterisation of a dithiadiaza chelator NSNS2A, as well as copper complexes thereof are reported in this paper. Solution structures of copper(i/ii) complexes were calculated using density functional theory (DFT) and validated by both NMR and EPR spectroscopy. DFT calculations revealed a switch in the orientation of tetragonal distortion upon protonation, which might be responsible for poor stability of the Cu(II)NSNS2A complex in aqueous media, whilst the same switch in tetragonal distortion was experimentally observed by changing the solvent. The chelator was radiolabeled with 64Cu and evaluated using PET/MRI in rats. Despite a favorable redox potential to stabilize the cuprous state in vivo, the 64Cu(II)NSNS2A complex showed suboptimal stability compared to its tetraazamacrocyclic analogue, 64Cu(TE2A), with a significant 64Cu uptake in the liver.
本文报道了一种二硫代二氮杂冠醚 NSNS2A 的合成及性质，并对其铜配合物进行了研究。采用密度泛函理论（DFT）计算了铜（I/II）配合物的溶液结构，并通过 NMR 和 EPR 光谱进行了验证。DFT 计算表明，在质子化过程中，四方畸变的取向发生了转变，这可能是导致 Cu(II)NSNS2A 配合物在水相介质中稳定性差的原因，而通过改变溶剂，实验上也观察到了同样的四方畸变转变。该螯合剂用 64Cu 进行放射性标记，并在大鼠中进行了 PET/MRI 评估。尽管具有有利的氧化还原电位来稳定体内的亚铜状态，但与四氮杂大环类似物 64Cu(TE2A)相比，64Cu(II)NSNS2A 配合物的稳定性较差，在肝脏中有明显的 64Cu 摄取。
