Article Dans Une Revue Inorganic Chemistry Année : 2025

Synthesis, Characterization, and Biological Evaluation of Iron(III)- N -Heterocyclic Carbene Complexes as Photosensitizers for Photodynamic Therapy and Chemotherapeutics against Cancer

Résumé

Photodynamic therapy (PDT) is a promising strategy for cancer treatment, yet the reliance on rare, expensive, and potentially toxic heavy metals limits the practical application of many current photosensitizers. In this study, we synthesized and evaluated a series of iron(III)-N-heterocyclic carbene (Fe(III)-NHC) complexes (1–7) bearing diverse substituents to explore their potential as cost-effective alternatives for cancer therapy. While none of the complexes exhibited significant singlet oxygen generation under light excitation, several (particularly complexes 1, 2, 3, and 7) showed strong cytotoxicity toward cancer cells even in the absence of photodynamic activation. Structure–activity analysis revealed that hydrophobic or moderately electron-donating groups enhanced cellular uptake and bioactivity, while polar or bulky substituents reduced efficacy of cellular uptake, as confirmed by ICP-MS and confocal fluorescence microscopy. Further biological studies suggested that the cytotoxic effects of these compounds may stem from mitochondrial damage, potentially caused by disruption of mitochondrial membrane potential through iron-mediated redox processes. These findings highlight the promise of Fe(III)-NHC complexes as potential chemotherapeutic agents and underscore the importance of rational ligand design in modulating their biological activity.

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hal-05211866 , version 1 (16-08-2025)

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Lei Zhou, Giulia Salluce, Pierre Mesdom, Marta Redrado, Lisa Gourdon-Grünewaldt, et al.. Synthesis, Characterization, and Biological Evaluation of Iron(III)- N -Heterocyclic Carbene Complexes as Photosensitizers for Photodynamic Therapy and Chemotherapeutics against Cancer. Inorganic Chemistry, 2025, ⟨10.1021/acs.inorgchem.5c03185⟩. ⟨hal-05211866⟩
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