Abstract
Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. Removing actinides deposited in bones after intake is one of the most significant challenges remaining in this field because of the instantaneous formation of highly stable actinide phosphate complexes upon contact with hydroxyapatite. Here we report a hydroxypyridinone-based ligand (5LIO-1-Cm-3,2-HOPO) exhibiting stronger affinity for U(VI) compared with the reported tetradentate hydroxypyridinone ligands. This is further revealed by the first principles calculation analysis on bonding between the ligand and uranium. Both in vitro uranium removal assay and in vivo decorporation experiments with mice show that 5LIO-1-Cm-3,2-HOPO can remove uranium from kidneys and bones with high efficiencies, while the decorporation efficiency is nearly independent of the treatment time. Moreover, this ligand shows a high oral decorporation efficiency, making it attractive for practical applications.
Highlights
Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy
In order to weaken the intramolecular hydrogen bond formed between the amide and hydroxide groups found in many tetradentate HOPO ligands, a ligand {N,N′[oxybis(ethane-2,1-diyl)]bis[2-(3-hydroxy-2-oxopyridin-1(2H)-yl) acetamide], denoted as 5LIO-1-Cm-3,2-HOPO, was designed by introducing the carboxylic group on the N site of pyridine ring
The hydroxyl group in A was protected with a benzyl moiety, and the ester group was activated via hydrolysis to afford product B. 5LIO-1-Cm-3,2-HOPOBn was obtained via amidation of the carboxylate group with the amine backbone
Summary
Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. In this work, we introduce a chelating agent (5LIO-1-Cm-3,2-HOPO) with an additional methyl group inserted between the amide and HOPO groups in order to significantly weaken these intramolecular hydrogen bonds This ligand exhibits significantly elevated coordination capability towards U(VI), as demonstrated by potentiometric titration experiment, synchrotron radiation-based extended X-ray adsorption fine structure (EXAFS) analysis, and density functional theory (DFT) simulation. Results of both in vitro and in vivo assays suggest that 5LIO-1-Cm-3,2-HOPO is a potential solution to the long-term challenge of efficiently removing uranium from bones
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