Photoactive monofunctional platinum(II) anticancer complexes of multidentate phenanthridine-containing ligands:...

Pt(II) complexes supported by chelating, multidentate ligands containing π-extended, planar phenanthridine (benzo[c]quinoline) donors (^RLPtCl) exhibit a promising in vitro therapeutic index compared with phenanthriplatin, a leading preclinical anticancer complex containing a monodentate phenanthridine ligand. Here, we report evidence for non-specific interactions of ^CF3LPtCl with DNA through intercalation-mediated turn-on luminescence in O₂-saturated aqueous buffer. Brief irradiation with visible light (490 nm) was also found to drastically increase the activity of ^CF3LPtCl, with photocytotoxicity increased up to 87% against a variety of human cancer cell lines. Mechanistic studies highlight significantly improved cellular uptake of ^CF3LPtCl compared with cisplatin, with localization in the nucleus and mitochondria triggering effective apoptosis. Photosensitization experiments with 1,3-diphenylisobenzofuran demonstrate that ^CF3LPtCl efficiently mediates the generation of singlet dioxygen (¹O₂), highlighting the potential of ^RLPtCl in photodynamic therapy.