Photodynamic effect of light-harvesting, long-lived triplet excited state Ruthenium(II)-polyimine-coumarin complexes: DNA binding, photocleavage and anticancer studies

- RuII-polyimine complexes with long-lived triplet state were used for first time for DNA binding and DNA photocleavage.
- The complexes show more efficient DNA photocleavage as compared with the conventional Ru(II) complexes.
- DNA cleavage efficiency is dependent on both singlet oxygen quantum yields and visible light-harvesting ability of complexes.
- The cytotoxic assay demonstrates that the complexes Ru-1 and Ru-2 can effectively suppress the cancer proliferation.
- The cellular uptake suggests that these complexes can enter into the cytoplasm and accumulate in the nuclei.

Two coumarin based RuII-polyimine complexes (Ru-1 and Ru-2) showing intense absorption of visible light and long-lived triplet excited states (~ 12-15 μs) were used for study of the interaction with DNA. The binding of the complexes with CT-DNA were studied by UV-vis, fluorescence and time-resolved nanosecond transient absorption (ns-TA) spectroscopy. The results suggesting that the complexes interact with CT-DNA by intercalation mode of binding, showing the binding constants (Kb) 6.47 × 104 for Ru-1 and 5.94 × 104 M− 1 for Ru-2, in contrast no such results were found for Ru-0. The nanosecond transient absorption spectra of these systems in the presence of CT-DNA showing a clear perturbation in the bleaching region was observed compare to buffer alone. Visible light photoirradiation DNA cleavage was investigated for these complexes by treating with the supercoiled pUC19 DNA and irradiated at 450 nm. The reactive species produced upon irradiation of current agents is singlet oxygen (1O2), which results in the generation of other reactive oxygen species (ROS). The complexes shown efficient cleavage activity, converted complete supercoiled DNA to nicked circular at as low as 20 μM concentration in 30 min of light irradiation time. Significant amount of linear form was generated by Ru-1 at the same conditions. Even though Ru-0 has significant 1O2 quantum yield but shown lower cleavage activity compared to other two analogs is due the miserable interaction (binding) with DNA. The cytotoxicity in vitro of the complexes toward HeLa, BEL-7402 and MG-63 cells was assessed by MTT assay. The cellular uptake was observed on BEL-7402 cells under fluorescence microscope. The complexes shown appreciable cytotoxicity towards the cancer cell lines.

Singlet oxygen (1O2) mediated DNA photocleavage by well-designed light-harvested coumarin based RuII complexes (Ru-1 & Ru-2) at physiological conditions by the irradiation of monochromatic light at 450 nm for 30 min.111