Photoactive monofunctional platinum(II) anticancer complexes of multidentate phenanthridine-containing ligands: photocytotoxicity and evidence for interaction with DNA.

Pt(II) complexes supported by chelating, multidentate ligands containing π-extended, planar phenanthridine (benzo[c]quinoline) donors ( R LPtCl) 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 CF3 LPtCl with DNA through intercalation-mediated turn-on luminescence in O 2 -saturated aqueous buffer. Brief irradiation with visible light (490 nm) was also found to drastically increase the activity of CF3 LPtCl, with photocytotoxicity increased up to 87% against a variety of human cancer cell lines. Mechanistic studies highlight significantly improved cellular uptake of CF3 LPtCl compared with cisplatin, with localization in the nucleus and mitochondria triggering effective apoptosis. Photosensitization experiments with 1,3-diphenylisobenzofuran demonstrate that CF3 LPtCl efficiently mediates the generation of singlet dioxygen ( 1 O 2 ), highlighting the potential of R LPtCl in photodynamic therapy.