Evaluation of Cytotoxic Potential of Water-Soluble Photosensitive Pincer-Copper Complexes

Herein, the synthesis and characterization of four new water-soluble pincer-copper complexes of the type (R2NNN)CuCl2 (R = C6H5, p-OMe-C6H4, p-Me-C6H4, and p-F-C6H4) based on bis(imino)pyridine ligands have been reported. The complexes exhibited significant cytotoxicity against a monolayer of MCF-7 breast cancer cells following light irradiation. Notably, the complex (Ph2NNN)CuCl2 demonstrated the highest efficacy among the pincer-Cu complexes, with an IC50 of 11 μM in the presence of light and an IC50 of 25 μM in dark conditions, making it ideal for photodynamic therapy (PDT). The complex (Ph2NNN)CuCl2 demonstrated selectivity for MCF-7 cells, as indicated by its reduced cytotoxicity against HEK cells. The generation of singlet oxygen (1O2) led to photo-oxidation-mediated apoptosis, as evidenced by the Annexin V/PI assay and concomitant G2/M cell cycle arrest. Furthermore, cleaved PARP (cPARP) expression upon photoactivation also confirmed the induction of apoptosis. This work provides an avenue for future applications of strategically engineered water-soluble pincer-metal complexes in cancer phototherapy.