Ru(II) Complexes with Absorption in the Photodynamic Therapy Window: 1O2 Sensitization, DNA Binding, and Plasmid DNA Photocleavage

Two Ru(II) complexes, [Ru(pydppn)(bim)(py)](2+) [2; pydppn = 3-(pyrid-2 '-yl)-4,5,9,16-tetraaza-dibenzo[a,c]naphthacene; bim = 2,2 '-bisimidazole; py = pyridine] and [Ru(pydppn)(Me(4)bim)(py)](2+) [3; Me(4)bim = 2,2 '-bis(4,5-dimethylimidazole)], were synthesized and characterized, and their photophysical properties, DNA binding, and photocleavage were evaluated and compared to [Ru(pydppn)(bpy)(py)](2+) (1; bpy = 2,2 '-bipyridine). Complexes 2 and 3 exhibit broad (MLCT)-M-1 (metal-to-ligand charge transfer) transitions with maxima at similar to 470 nm and shoulders at similar to 525 and similar to 600 nm that extend to similar to 800 nm. These bands are red-shifted relative to those of 1, attributed to the pi-donating ability of the bim and Me(4)bim ligands. A strong signal at 550 nm is observed in the transient absorption spectra of 1-3, previously assigned as arising from a pydppn-centered (3)pi pi* state, with lifetimes of similar to 19 mu s for 1 and 2 and similar to 270 ns for 3. A number of methods were used to characterize the mode of binding of 1-3 to DNA, including absorption titrations, thermal denaturation, relative viscosity changes, and circular dichroism, all of which point to the intercalation of the pydpppn ligand between the nucleobases. The photocleavage of plasmid pUC19 DNA was observed upon the irradiation of 1-3 with visible and red light, attributed to the sensitized generation of O-1(2) by the complexes. These findings indicate that the bim ligand, together with pydppn, serves to shift the absorption of Ru(II) complexes to the photodynamic therapy window, 600-900 nm, and also extend the excited state lifetimes for the efficient production of cytotoxic singlet oxygen.