State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
J Am Chem Soc. 2022 Jun 29;144(25):11054-11058. doi: 10.1021/jacs.2c00688. Epub 2022 Jun 14.
The sequestration of uranium, particularly from the deposited bones, has been an incomplete task in chelation therapy for actinide decorporation. Part of the reason is that all previous decorporation ligands are not delicately designed to meet the coordination requirement of uranyl cations. Herein, guided by DFT calculation, we elaborately design a hexadentate ligand (TAM-2LI-MAM), whose preorganized planar oxo-donor configuration perfectly matches the typical coordination geometry of the uranyl cation. This leads to an ultrahigh binding affinity to uranyl supported by an desorption experiment of uranyl phosphate. Administration of this ligand by prompt intraperitoneal injection demonstrates its uranyl removal efficiencies from the kidneys and bones are up to 95.4% and 81.2%, respectively, which notably exceeds all the tested chelating agents as well as the clinical drug ZnNa-DTPA, setting a new record in uranyl decorporation efficacy.
在锕系元素去污染的螯合疗法中,铀的隔离,特别是从沉积的骨骼中分离铀,一直是一项未完成的任务。部分原因是,以前所有的去污染配体都不是精心设计的,无法满足铀阳离子的配位要求。在此,我们在 DFT 计算的指导下,精心设计了一种六齿配体(TAM-2LI-MAM),其预先组织的平面氧供体构型与典型的铀阳离子配位几何形状完美匹配。这导致与铀酰配合物具有超高的结合亲和力,通过铀磷酸盐的解吸实验得到证实。通过腹腔内注射的方式给予该配体,其从肾脏和骨骼中去除铀的效率分别高达 95.4%和 81.2%,显著超过所有测试的螯合剂以及临床药物 ZnNa-DTPA,在铀去污染效果方面创下了新纪录。