结合热力学、理论和生物学研究研究 N-(2-乙酰氨基)亚氨基二乙酸作为潜在的钍脱色剂,Inorganic Chemistry

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结合热力学、理论和生物学研究研究 N-(2-乙酰氨基)亚氨基二乙酸作为潜在的钍脱色剂
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2023-11-03 , DOI: 10.1021/acs.inorgchem.3c02296
Shikha Sharma ₁ , Manjoor Ali ₂ , Amit Kumar ₂ , Neetika Rawat ₁

Affiliation

减轻放射性金属内照射对人体毒性影响的最有效方法是金属配体 (ML) 螯合疗法。钍 (Th) 诱发的致癌以及由于长期内部暴露而对人类造成的其他健康危害，需要开发有效的 Th 解体剂。在这方面，进行了化学和生物学研究来评估N- (2-乙酰氨基)亚氨基二乙酸 (ADA)，这是一种相对经济有效、易于获得且生物安全的 Th 脱去络合剂。在目前的工作中，使用电位测定法、量热法、电喷雾电离质谱法和理论研究，对 ADA 与 Th(IV) 的络合进行了详细的热力学研究，以了解 Th-ADA 相互作用，然后对 Th 脱色进行了生物学评估。热力学研究揭示了强 Th-ADA 复合物的形成，这在熵和熵上都是有利的。有趣的是，为获得热力学有利的配位模式而进行的密度泛函理论计算显示，ML 中 ADA 的密度低于 ML ₂，这是不常见的趋势，这可以通过氢键稳定 ML 来解释。Th-ADA 复合物的热函异常趋势也反映了同样的情况。使用人红细胞、人全血和肺细胞进行的生物学实验表明，ADA 具有良好的细胞相容性和显着防止 Th 诱导的溶血的能力。研究发现，从红细胞、人体血液和正常肺细胞中去除 ADA 的效果与 FDA 批准的脱色剂二乙烯三胺五乙酸盐 (DTPA) 相当。本研究提供了有关 ADA 的 Th 络合化学及其从人类红细胞、血液和肺细胞中去除 Th 功效的重要数据。

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Combined Thermodynamic, Theoretical, and Biological Study for Investigating N-(2-Acetamido)iminodiacetic Acid as a Potential Thorium Decorporation Agent

The most effective approach to mitigate the toxic effects of internal exposure of radiometals to humans is metal–ligand (ML) chelation therapy. Thorium (Th)-induced carcinogenesis as well as other health hazards to humans as a result of chronic internal exposure necessitates the development of efficient Th-decorporating agents. In this regard, chemical and biological studies were carried out to evaluate N-(2-Acetamido)iminodiacetic acid (ADA), a comparatively cost-effective, readily available, and biologically safe complexing agent for Th decorporation. In the present work, detailed thermodynamic studies for complexation of ADA with Th(IV) have been carried out to understand Th-ADA interaction, using potentiometry, calorimetry, electrospray ionization mass spectrometry, and theoretical studies, followed by its biological assessment for Th decorporation. Thermodynamic studies revealed the formation of strong Th-ADA complexes, which are enthalpically as well as entropically favored. Interestingly, density functional theory calculations, to obtain a thermodynamically favored mode of coordination, showed the uncommon trend of lower denticity of ADA in ML than in ML₂, which has been explained on the basis of stabilization of ML by hydrogen bonding. The same was also reflected in the unusual trend of enthalpy for Th-ADA complexes. Biological experiments using human erythrocytes, whole human blood, and lung cells showed good cytocompatibility and ability of ADA to significantly prevent Th-induced hemolysis. Th removal of ADA from erythrocytes, human blood, and normal lung cells was found to be comparable with that of diethylenetriamine pentaacetate (DTPA), an FDA approved decorporating agent. The present study contributed significant data about Th complexation chemistry of ADA and its Th decorporation efficacy from human erythrocytes, blood, and lung cells.

更新日期：2023-11-03

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