Topoisomerase I Inhibition, DNA Photocleavage Activity, and G-Quadruplex DNA 'Light Switch' Based on Nitro-Substituted Ruthenium Complexes

Two ruthenium complexes containing nitro-substituted ligand, [Ru(bpy)(2)(hnpip)](PF6)(2)(1) and [Ru(phen)(2)(hnpip)](PF6)(2)(2) (bpy = 2,2'-bipyridine; phen = 1,10-phenanthroline; hnpip = 2-(3-hydroxyl- 4-nitrophenyl)imidazo[4,5-f][1,10-phenanthroline] were synthesized and characterized. DNA binding behaviors were studied by luminescent titration, UV-vis titration, FRET (FRET = Fluorescence resonance energy transfer) and molecular docking experiments. Complex2exhibited light switch effect upon addition of G-quadruplex DNA and displayed fluorescent selectivity towards G-quadruplex DNA over other DNAs in the presence of K-4[Fe(CN)(6)]. Fluorescence experiments, FRET experiments and molecular docking results indicated that the selectivity may be attributed to protection of nitro group from water, DNA affinity and the difference in DNA structures. Furthermore, both complexes were found to cleave DNA under irradiation by the formation of singlet oxygen. DNA topoisomerase inhibition experiments indicated that complex2exhibited higher topoisomerase I inhibition activity (IC50= 18 mu M) than complex1(IC50= 50 mu M). Docking studies revealed that complex2stabilized Top1cc complex via pi-pi interaction and the formation of hydrogen bond.