Rhenium(I) polypyridine complexes coordinated to an ethyl-isonicotinate ligand: Luminescence and in vitro anti-cancer studies

Abstract

In this work, fac-[Re(et-isonic)(NN)(CO)3]+ complexes, et-isonic = ethyl-isonicotinate, NN = 1,10-phenanthroline (phen), 4,7-diphenyl-1,10-phenanthroline (Ph2phen), 4,7-dichloro-1,10-phenanthroline (Cl2phen) or 4,7-dimethyl-1,10-phenanthroline (Me2phen), were synthesized to combine different substituent groups at coordinate phen ligand along with the coordination of a nicotinic acid derivative aiming the modulation of the photophysical and lipophilic properties. The electronic absorption spectra profile can be divided into two main regions: the high-energy region ascribed to the intraligand transition (IL), and the low-energy region assigned to the metal-to-ligand charge transfer transition (MLCT). Additionally, the complexes exhibited 3MLCT emission, sensitive to the nature of NN ligand, which can be used to photosensitize the generation of singlet oxygen as well as to localize them into the cell. The lipophilicity of the complexes increases as the substituent at coordinated phen ligand was changed from hydrogen to phenyl and these results reflected also in the same trend observed for the cytotoxicity results, in the absence of light, using breast cancer (MCF-7) and melanoma (SkMel-147 and SkMel-29) cell lines. In addition, the flow cytometry assay along with the Western Blotting analyses showed an overexpression on pro caspase-9, suggesting a Caspase proteolytic cascade through the intrinsic pathway in the apoptosis as the mechanism of action. In spite of the Re(I) complexes were capable of generating singlet oxygen in the presence of light, they were very effective in killing the cells by a different mechanism of action in the absence of light. Thus, these results provided a better understanding of the mechanism of anticancer action and highlight the potential application of rhenium(I) complexes in the development of a novel therapy process.