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

Abstract

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.

Natural Products of Licorice for Uranium Decorporation with Low Toxicity and High Efficiency

“…The protonation constants of the free ligand, GL (denoted as LH 3 in this part), were determined by potentiometric titrations, analyzed by eq and refined with the nonlinear least-squares program (Hyperquad 2013). , The three protonation constants, p K a 1 , p K a 2 , and p K a 3 were measured to be 5.27, 9.18, and 9.6, respectively (Table ). The species distribution of LH 3 based on formation constants was calculated with Hyss (Figure a), and the speciation diagram of LH 3 illustrates that LH 2 – was the dominant species at physiological pH (7.4).…”

Cinnamic Acid: A Low-Toxicity Natural Bidentate Ligand for Uranium Decorporation

“…Chelation therapy is currently the most important medical procedure used to remove toxic metals from the organs and tissues of the human body and to treat diseases by utilizing metal-chelating agents. − However, the effectiveness of some commercial chelating agents in uranium elimination is limited. For instance, FDA-approved calcium trisodium and zinc trisodium diethylenetriaminepentaacetate (CaNa 3 DTPA and ZnNa 3 DTPA, respectively) can remove Am­(III) and Pu­(IV) from the body, but they show a poor effect in uranium removal and exhibit noticeable kidney and liver toxicity. − In addition, sodium bicarbonate (NaHCO 3 ) is recommended for uranium internalization for radiological and nuclear emergencies according to the World Health Organization’s latest guidelines .…”