Red and NIR light-triggered enhancement of anticancer and antibacterial activities of dinuclear Co(ii)-catecholate complexes†

Abstract

Photoactive complexes of bioessential 3d metals, activable within the phototherapeutic window (650–900 nm), have gained widespread interest due to their therapeutic potential. Herein, we report the synthesis, characterization, and light-enhanced anticancer and antibacterial properties of four new dinuclear Co(II) complexes: [Co(phen)(cat)]₂ (Co-1), [Co(dppz)(cat)]₂ (Co-2), [Co(phen)(esc)]₂ (Co-3), and [Co(dppz)(esc)]₂ (Co-4). In these complexes, phen (1,10-phenanthroline) and dppz (dipyrido[3,2-a:2′,3′-c]phenazine) act as neutral N,N-donor ligands, while cat²⁻ and esc²⁻ serve as O,O-donor catecholate ligands derived from catechol (1,2-dihydroxybenzene) and esculetin (6,7-dihydroxy coumarin). Their high-spin paramagnetic nature and dimeric identity in solution were confirmed by magnetic susceptibility, UV-visible, emission, and mass spectral data. Co-1–Co-4 exhibited an absorption band within the 600–850 nm range, originating from a charge transfer transition. The electrically neutral complexes demonstrated sufficient solution stability both in the dark and under irradiated conditions. The dppz complexes Co-2 and Co-4 exhibited notable toxicity towards A549 lung carcinoma cells, with potency increasing significantly under brief (5 min) exposure to 660 nm (red) and 808 nm (NIR) laser light (IC₅₀ ∼ 8.9 to 14.9 μM). Notably, their toxicity towards normal NIH-3T3 fibroblast cells was minimal. Cellular assays highlighted that the induced cell death followed an apoptotic pathway, primarily due to mitochondrial damage. Co-2 and Co-4 also demonstrated significant antibacterial potency against Gram-(+) S. aureus and Gram-(−) P. aeruginosa, with effectiveness significantly enhanced upon 808 nm laser irradiation (MIC ∼ 15–142 μM). The increase in the anticancer and antibacterial efficacies was attributed to the generation of cytotoxic singlet oxygen (¹O₂) species upon red/NIR light exposure. Notably, 808 nm NIR irradiation produced more pronounced effects compared to 660 nm. This study is the first to report on cobalt complexes exhibiting red and NIR light-triggered enhancement of antibacterial and anticancer activities, illuminating the path for the development of long-wavelength absorbing cobalt complexes with enhanced therapeutic efficacy.