Journal
INORGANIC CHEMISTRY
Volume 58, Issue 5, Pages 3349-3354Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.inorgchem.8b03442
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Funding
- National Natural Science Foundation of China [21771133, U1532259, 21422704, 21790370]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA02040600]
- Young Thousand Talents Program in China
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Uranium poses a threat for severe renal and bone damage in vivo. With the rapid development of nuclear industry, it is more urgent than ever to search for potential in vivo uranium chelators. In this work, 3-hydroxy-2-pyrrolidinone (HPD) is investigated as a new potential uranium decorporation ligand. The potentiometric titration measurements were carried out, and the stability constants were determined to be log beta(110) = 10.5(7), log beta(120) = 20.7(9), and log beta(130) = 28.2(4). The species distribution diagram shows that nearly all uranyl is complexed by HPD at pH 7.4 under the defined condition. A single crystal of uranyl and HPD complexes, [(UO2)(3)O(H2O)(3)(C4H6NO2)(3)]center dot NO3 center dot 12H(2)O (uranyl-HPD), was obtained via an evaporation method. The overall structure of uranyl-HPD is a trimer that consists of three uranyl units and three HPD ligands. The uranyl unit is equatorially coordinated by three oxygen atoms from two HPD agents, one coordinated water molecule, and one mu(3)-O atom that is shared by three uranyl units. The results of the cytotoxicity assay indicate that the ligand is less toxic than the chelators used clinically (i.e., DTPA-ZnNa3 and 3-hydroxy-1,2-dimethyl-4(1H)-pyridone (DFP)). The results of the uranium removal assay using the NRK-52E cell show that it could reduce as much as 58% of the uranium content at the cellular level. Furthermore, the in vivo uranium decorporation assays demonstrate that HPD can remove 52% of uranium deposited in the kidney but shows poor uranium removal efficacy in the bone.
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