Visible light-induced cytotoxicity studies on Co(ii) complexes having an anthracene-based curcuminoid ligand

Herein, two ternary cobalt(ii) complexes, namely [Co(9-accm)(phen)₂](OAc) (1) and [Co(9-accm)(dppz)₂](OAc) (2), where 9-accmH is 1,7-(di-9-anthracene-1,6-heptadiene-3,5-dione), phen is 1,10-phenanthroline and dppz is dipyrido[3,2-a:2',3'-c]phenazine, having an anthracene-based curcuminoid and phenanthroline bases were synthesized and fully characterized, and their in vitro photocytotoxicities were studied in cancer cells. To understand the role of the curcuminoid ligand 9-accm in photo-activated cytotoxicity, two control complexes, viz. [Co(dbm)(phen)₂](OAc) (3) and [Co(dbm)(dppz)₂](OAc) (4), where dbmH is 1,3-diphenyl-1,3-propanedione (dibenzoylmethane), were prepared and used for the control experiments. Complex 3 was structurally characterized by X-ray crystallography. The complexes displayed a quasi-reversible Co(i)/Co(ii) redox couple at ∼-1.1 V and an irreversible Co(ii)/Co(iii) couple at ∼1.3 V vs. Ag/AgCl in DMF-0.1 M [Buⁿ₄N](ClO₄). Highly intense 9-accm ligand-centred bands were observed at ∼250-450 nm, which masked the Co(ii)-based weak d-d bands in the DMF-Tris-HCl buffer (1 : 9 v/v). The complexes displayed a significant binding propensity for calf-thymus (ct) DNA with binding constants in the range from (2.42 ± 0.10) × 10⁵ to (3.24 ± 0.13) × 10⁶ M^-1. They also showed a moderate binding affinity for human serum albumin (HSA), displaying K_b values in the order of ∼10⁴-10⁵ M^-1. The complexes 1 and 2 showed prodigious photoenhanced cytotoxicity in human cervical cancer (HeLa) and breast cancer (MCF-7 and MDA-MB-231) cells with low dark toxicity, whereas they were non-toxic to immortalized lung epithelial normal cells (HPL1D). Flow cytometric studies showed a time-dependent uptake of the complexes 1 and 2 in HeLa cells. The complexes generated reactive oxygen species (ROS) upon excitation with low energy visible light, thereby killing the cancer cells. The results from DAPI staining, AO/EB dual staining and Annexin-V-FITC experiments suggested that the complexes induce cell death primarily via an apoptotic mechanism in HeLa cells.