Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes

Two ruthenium(II) polypyridyl complexes were prepared with the {Ru(phen)(2)}(2+) moiety and a third sterically non-hindering bidentate ligand, namely 2,2′-dipyridylamine (dpa) and N-benzyl-2,2′-dipyridylamine (Bndpa). Hence, complexes [Ru(phen)(2)(dpa)](PF(6))(2) (1) and [Ru(phen)(2)(Bndpa)](PF(6))(2) (2) were characterized and their photochemical behaviour in solution (acetonitrile and water) was subsequently investigated. Compounds 1 and 2, which do not exhibit notably distorted octahedral coordination environments, contrarily to the homoleptic “parent” compound [Ru(phen)(3)](PF(6))(2), experience two-step photoejection of the dpa and Bndpa ligand upon irradiation (1050–430 nm) for several hours. DNA-binding studies revealed that compounds 1 and 2 affect the biomolecule differently upon irradiation; while 2 solely modifies its electrophoretic mobility, complex 1 is also capable of cleaving it. In vitro cytotoxicity studies with two cancer-cell lines, namely A549 (lung adenocarcinoma) and A375 (melanoma), showed that both 1 and 2 are not toxic in the dark, while only 1 is significantly cytotoxic if irradiated, 2 remaining non-toxic under these conditions. GRAPHICAL ABSTRACT: Light irradiation of the complex cation [Ru(phen)(2)(dpa)](2+) leads to the generation of transient Ru species that is present in the solution medium for several hours, and that is significantly cytotoxic, ultimately producing non-toxic free dpa and [Ru(phen)(OH(2))(2)](2+). [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00775-023-01998-z.