초록
<P>Uranium accumulation in the kidneys and bones following internal contamination results in severe damage, emphasizing the pressing need for the discovery of actinide decorporation agents with efficient removal of uranium and low toxicity. In this work, cinnamic acid (3-phenyl-2-propenoic acid, CD), a natural aromatic carboxylic acid, is investigated as a potential uranium decorporation ligand. CD demonstrates markedly lower cytotoxicity than that of diethylenetriaminepentaacetic acid (DTPA), an actinide decorporation agent approved by the FDA, and effectively removes approximately 44.5% of uranyl from NRK-52E cells. More importantly, the results of the prompt administration of the CD solution remove 48.2 and 27.3% of uranyl from the kidneys and femurs of mice, respectively. Assessments of serum renal function reveal the potential of CD to ameliorate uranyl-induced renal injury. Furthermore, the single crystal of CD and uranyl compound (C<SUB>9</SUB>H<SUB>7</SUB>O<SUB>2</SUB>)<SUB>2</SUB>·UO<SUB>2</SUB> (denoted as UO<SUB>2</SUB>-CD) reveals the formation of uranyl dimers as secondary building units. Thermodynamic analysis of the solution shows that CD coordinates with uranyl to form a 2:1 molar ratio complex at a physiological pH of 7.4. Density functional theory (DFT) calculations further show that CD exhibits a significant 7-fold heightened affinity for uranyl binding in comparison to DTPA.</P><P>Cinnamic acid demonstrated low cytotoxicity even at high doses, effectively removed uranyl at cellular and in vivo levels, and had the potential to mitigate uranyl-induced kidney damage. Meanwhile, the analysis of the crystal structure, solution thermodynamics, and density functional theory calculations confirmed the high affinity of cinnamic acid for uranyl. This discovery highlights the significant potential of cinnamic acid in binding actinides and mitigating associated damage.</P><BR>[FIG OMISSION]</BR>