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This paper presents recent progress in our laboratory on the interaction of Ru(II)/Co(III) polypyridine complexes with DNA. The first part describes the effect on DNA binding of modulating the intercalative ligand and the size of the ancillary ligand of the complex. DNA binding modes and binding affinity can be modulated by ligand design. The second part focuses on the enantioselective DNA binding behavior of the Ru(II) complexes using absorption spectra, emission spectra, viscosity measurements, equilibrium dialysis and CD titrations. The enantiomers of the various Ru(II) complexes show diverse enantioselectivity on binding to DNA. Different equilibrium rates were observed for the enantiomers of the complex in a time-dependent dialysis experiment. The interesting effect of the “molecular switch” for DNA was observed for several Ru(II) complexes. Their DNA binding properties, together with the possible mechanism involved in the effect, are discussed in the last part.

A series of polypyridyl complexes have been synthesized. All polypyridyl complexes and some of the soluble ligands have been assayed for antitumor activity in vitro against the HL-60 (the human leucocytoma) cells, BEL-7402 (the human liver carcinoma) cells, KB (the human nasopharyngeal carcinoma) cells and HELA (the human adenocarcinoma of cervix) cells. The results indicate that several complexes have relative activity against different cell lines. Especially, the complexes [Co(bpy)2(pip)]3+, [Co(phen)2(pip)]3+, [Ru(bpy)2(pztp)]2+ and [Ru(pztp)2(bpy)]2+ show relative high activity against four tumor cell lines. Moreover, they are slightly more effective than cisplatin. At the concentration of 100 μg/mL, the complexes show inhibitory rate of 72∼86% for the cancer cells and have no toxicity for MDCK and Vero cells. It is indicated that these complexes can inhibit cancer cells selectively.

A novel asymmetric ligand 3-(pyrazin-2-yl)-as-triazino[5,6-f ]1,10-phenanthroline (pztp) and its mono- and bi-nuclear complexes [Ru(bpy)2(pztp)]2+ 1 and [(bpy)2Ru(pztp)Ru(bpy)2]4+ 2 (bpy = 2,2′-bipyridine) have been synthesized and characterized by UV/VIS, IR, 1H NMR and mass spectra. The electrochemical behaviours of complexes 1 and 2 were observed and displayed oxidation potentials at 1.37 and 1.39 and 1.60 V vs. saturated calomel electrode, respectively. The binding of the two complexes with calf thymus DNA has also been investigated by a spectrophotometric method and viscosity measurements. The results indicated that the two complexes interact with DNA in sharply different ways. The mononuclear complex 1 intercalates into DNA base pairs despite its small hypochromicity value, while the binuclear complex 2 binds to DNA via electrostatic interaction. The circular dichroism signals of the dialysates of the racemic complexes against calf thymus DNA are discussed.

This paper presents recent progress in our laboratory on the interaction of Ru(II)/Co(III) polypyridine complexes with DNA. The first part describes the effect on DNA binding of modulating the intercalative ligand and the size of the ancillary ligand of the complex. DNA binding modes and binding affinity can be modulated by ligand design. The second part focuses on the enantioselective DNA binding behavior of the Ru(II) complexes using absorption spectra, emission spectra, viscosity measurements, equilibrium dialysis and CD titrations. The enantiomers of the various Ru(II) complexes show diverse enantioselectivity on binding to DNA. Different equilibrium rates were observed for the enantiomers of the complex in a time-dependent dialysis experiment. The interesting effect of the “molecular switch” for DNA was observed for several Ru(II) complexes. Their DNA binding properties, together with the possible mechanism involved in the effect, are discussed in the last part.

A series of enantiomerically pure polypyridyl ruthenium(II) complexes, delta- and lambda-[Ru(bpy)2 (HPIP)](PF6)2 (delta-1 and lambda-1; bpy=2,2'-bipyridine, HPIP = 2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline), delta and lambda-[Ru(bpy)2(HNAIP)](PF6)2 (delta-2 and lambda-2; HNAIP = 2-(2-hydroxy-1-naphthyl)imidazo[4,5-f][1,10]phenanthroline), delta- and lambda-[Ru(bpy)2 (HNOIP)](PF6)2 (delta-3 and lambda-3; HNOIP = 2-(2-hydroxy-5-nitrophenyl)imidazo[4,5-f][1,10]phenanthroline), and delta- and lambda-[Ru(bpy)2(DPPZ)](PF6)2 (delta-4 and lambda-4; DPPZ= dipyridophenazine), have been synthesized. Binding behavior of these chiral complexes to calf thymus DNA (CT-DNA) has been investigated by electronic absorption, steady-state emission, and circular dichroism spectroscopies, as well as by viscosity measurements and equilibrium dialysis binding studies. Several points came from the results. (1) The DNA-binding properties were distinctly different for the [Ru(bpy)2L]2+ (L=HPIP, HNAIP, HNOIP) series of ruthenium(II) complexes, which indicates that the photophysical behavior of the complexes on binding to DNA can be modulated through ligand design. (2) Different binding rates of individual enantiomers of complexes 1 and 4 to DNA were observed through dialysis experiments. The lambda enantiomer bound more rapidly than the lambda enantiomer and their different intercalative binding geometries were suggested to be responsible. (3) Both delta-2 and lambda-2 bound weakly to CT-DNA; delta-2 may bind through a partial intercalation mode, whereas lambda-2 may bind in the DNA groove. (4) There was no noticeable enantioselectivity for complexes 1, 3, and 4 on binding to CT-DNA. Both of their enantiomers can intercalate into DNA base pairs. It is noted that delta-3 and lambda-3 exhibited almost identical spectral changes on addition of CT-DNA, and a similar binding manner of the isomers to the double helix was proposed.