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A series of octahedral Ru(II) polypyridyl complexes, [Ru(phen)2L]2+ (L = R-PIP and PIP = 2-phenylimidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elementary analysis, 1H NMR and ES-MS, as well as UV–visible spectra and emission spectra. The antitumor activities of these complexes and their corresponding ligands were investigated against mouse leukemia L1210 cells, human oral epidermoid carcinoma KB cells, human promyelocytic leukemia cells (HL-60) and Bel-7402 liver cancer cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. It was found that the complexes [Ru(phen)2L]2+ (L = R-PIP) exert rather potent activities against all of these cell lines, especially for the KB cells (IC50 = 4.7 ± 1.3 μM). The binding affinities of these Ru(II) complexes to CT-DNA (calf thymus DNA), as well as the DNA-unwinding properties on supercoiled pBR322 DNA were also investigated. The results showed that these Ru(II) polypyridyl complexes not only had an excellent DNA-binding property but also possessed a highly effective DNA-photocleavage ability. The structure–activity relationships and antitumor mechanism were also carefully discussed.

Theoretical studies on the related properties of Co(III) polypyridyl complexes [Co(phen)2L]3 + (L: dppz = dipyrido[3,2-a:2′,3′-c]phenazine; phen = 1,10-phenanthroline; dione = 1,10-phenanthroline-5,6-diketone) 1–3 interacting with DNA, including the DNA-binding, DNA-photocleavage and spectral properties, have been carried out. First, the full geometry-optimizations of these three complexes in their ground states were carried out in aqueous solution. The optimized structures of these three complexes were docked into DNA-base-pairs using the Dock6.0 program. Secondly, the binding modes of complexes 1–3 were revealed in detail and the trend in DNA-binding affinities was reasonably explained. Thirdly, the electronic absorption and emission spectra of docking model of the optimal complex 1 were calculated and simulated. The experimental intense absorption and emission bands of Co(Ш) complex 1 in the presence of DNA were explained in detail, in particular, the reason why the emission spectra of complex 1 in the presence of DNA are greatly stronger than those in the absence of DNA was theoretically elucidated. Finally, the DNA-photocleavage essential of complexes was explored and the DNA photocleavage efficiencies (φ), i.e., φ(1) > φ(2) > φ(3), was also reasonably explained.

Two new Ru(II) complexes [Ru(L)(4)(dppz)](2+) (L=imidazole (Im), 1-methylimidazole (MeIm); dppz=dipyrido[3,2-a:2',3'-c]phenazine), have been synthesized and characterized in detail by elemental analysis, (1)H NMR, Electrospray ionization mass spectrometry (ESI-MS) and UV-visible (UV-Vis) spectroscopic techniques. The interaction of these complexes with calf thymus DNA (CT-DNA) has been explored by using electronic absorption titration, competitive binding experiment, circular dichroism (CD), thermal denaturation and viscosity measurements. The experimental results show that: both the two complexes can bind to DNA in an intercalation mode; the DNA-binding affinity of complex [Ru(Im)(4)(dppz)](2+)1 (K(b)=2.5 x 10(6)M(-1)) is greater than that of complex [Ru(MeIm)(4)(dppz)](2+)2 (K(b)=1.1 x 10(6)M(-1)). Moreover, it is very interesting to find that the circular dichroic spectrum of DNA-complex 1 adduct, in which both bands centered at 277 nm and 236 nm are all negative, is very different from those of DNA-complex 2 adduct and other Ru(II) complexes binding to DNA in general intercalation mode. It may be due to the hydrogen-bonding effect or the contribution of induced CD signals of complex 1. Another interesting finding is that the hypochromism of the complexes is not linear relation to their DNA-binding affinities. In order to deeply study these experimental phenomena and trends, the density functional theory (DFT) and time-dependent DFT (TDDFT) computations were carried out, and on the basis of the DFT/TDDFT results and the frontier molecular orbital theory, the trend in DNA-binding affinities, the spectral properties as well as the interesting phenomena of larger extent of hypochromism but relatively smaller K(b) values for the title complexes have been reasonably explained.

Two new complexes, ([Ru(phen)(2)(6-OH-dppz)](2+)) (1) and ([Ru(phen)(2)(6-NO(2)-dppz)](2+)) (2) (phen=1,10-phenanthroline; 6-OH-dppz=6-hydroxyl-dipyrido[3,2-a:2',3'-c]phenazine; 6-NO(2)-dppz=6-nitro-dipyrido[3,2-a:2',3'-c]phenazine), have been synthesized and characterized by elemental analysis, ES-MS (electrospray mass spectra), (1)H NMR, UV-Vis (UV-visible) and CV (cyclic voltammetry). The DNA-binding behaviors of both complexes have been studied by spectroscopic methods and viscosity measurements. The results indicate that the two complexes all bind to calf thymus DNA (CT-DNA) in an intercalative mode, and the DNA-binding affinity of complex 2 is greater than that of complex 1. In addition, complex 1 can promote photocleavage of pBR322 DNA upon irradiation, whereas complex 2 can promote cleavage of pBR322 DNA both upon irradiation and in the dark, with more efficient cleavage occurring upon irradiation. Theoretical studies for these complexes have been also carried out with the density functional theory (DFT) method. The difference in the DNA-binding behaviors of the two complexes can be reasonably explained by the DFT calculations.