Unveiling\nthe Potential of Sulfur-Rich Macrocyclic\nChelators Against Cadmium Poisoning

Cadmium, an extremely toxic heavy metal, poses significant\nhealth\nrisks to humans. Despite persistent research efforts, the development\nof effective treatments for cadmium intoxication remains a challenge.\nThis study aims to establish the chemical groundwork for improved\nchelation therapy options against cadmium poisoning. Herein, the coordination\nchemistry of a series of sulfur-rich macrocycles featuring different\npolyamine backbones (NO3S, TACD3S, DO4S, TRI4S, and TE4S) was investigated.\nOur results demonstrate that DO4S exhibits exceptional Cd<sup>2+</sup> scavenging ability, forming the most thermodynamically stable complex\namong the studied chelators. The stability of the Cd<sup>2+</sup> complexes\ndecreases in the following order: DO4S (pCd = 19.8) ≫ NO3S\n(pCd = 11.0) ∼ TRI4S (pCd = 10.9) ≫ TE4S (pCd = 7.8)\n> TACD3S (pCd = 7.3). DFT calculations demonstrated that the backbone\npolarization properties dictate the observed reduced stability when\nshifting from DO4S to the other ligands. DO4S showed superior affinity\nwhen compared to the state-of-the-art Cd<sup>2+</sup> chelators such\nas EDTA (pCd = 16.7), DTPA (pCd = 17.4), and DMSA (pCd = 13.2). The\nfindings from this study underscore the potential of the examined\nchelating agents, with particular reference to DO4S, paving the way\nfor the development of advanced chelation therapies to combat cadmium\npoisoning.