Sulfonamide DPA-Based Mononuclear Cobalt(II) Complexes: Evaluation of ROS-Driven Cytotoxicity

Four novel mononuclear Co(II) complexes [Co(L1-L4)Cl₂] (1-4) have been synthesized and thoroughly characterized, where L1 is N,N-bis(pyridin-2-ylmethyl)naphthalene-1-sulfonamide, L2 is N,N-bis(pyridin-2-ylmethyl)naphthalene-2-sulfonamide, L3 is 5-(dimethylamino)-N,N-bis(pyridin-2-ylmethyl)naphthalene-1-sulfonamide, and L4 is 4-methyl-N,N-bis(pyridin-2-ylmethyl)benzenesulfonamide. Comprehensive spectroscopic and analytical studies confirm that the ligands coordinate to the cobalt center in a bidentate fashion through the pyridyl nitrogen atoms, forming a rare eight-membered chelate ring. Fluorescence studies revealed a ligand-dependent modulation of photophysical behavior upon coordination. Complexes derived from L1 and L2 exhibited significant fluorescence quenching, whereas those containing L3 and L4 showed pronounced enhancement, indicating differing photoinduced electronic interactions between the ligands and the cobalt center. The cytotoxic potential of the complexes was further evaluated against two human breast cancer cell lines, MDA-MB-231 and MCF-7. Among the series, complex 2 exhibited the most pronounced cytotoxic effect, with IC₅₀ values of 95.9 µM and 91.3 µM against MDA-MB-231 and MCF-7 cells, respectively. The enhanced activity of complex 2 is likely due to its ability to generate reactive oxygen species (ROS). These findings suggest that complex 2 may serve as a superior potential scaffold for the development of cobalt-based cytotoxic agents with tunable electronic and photophysical properties.