Syntheses, Structures, CT-DNA Binding And Antitumor Studies Of Some Ruthenium-heterocyclicaminocarboxylic Complexes

Compared with platinum-based anticancer drugs, ruthenium complexeshave received much attention due to its efficiency, low toxicity and few side effects.Therefore, in recent years syntheses, structures, CT-DNA binding and antitumorstudies of ruthenium complexes have become the focus of attention oforganometallic and academic medicine. In this paper, based on the development andthe application of metal complexes, we summarized recent research and the actionmechanism of metal-based anticancer complexes, especially focused on thecomparision the action mechanism of ruthenium metal with that of cisplatin.Meanwhile, we described the current research technique for anticancer drugs indetails, and explained the reason why we aimed on the present study.Ruthenium complexes [Ru(PPh3)2(C5H4O2N2)(CO)H](1),[Ru(PPh3)2(CO)2Cl2](2),[Ru(PPh3)2(C14H4O8N2)Na6](3) and [Ru(PPh3)2(C6H5NO2S)Cl2](4) weresynthesized. The structure of complex1has been literature reported, but withdifferent synthetic methed and different cell parameters in this subject. And weunexpectedly got a reported complex [Ru(PPh3)2(CO)2Cl2](2) by different syntheticmethods. These four complexes were characterized by IR,1H and31P{1H} NMR,mass spectroscopy, elemental analyses and complexes1,2and3were characterizedby single crystal X-ray diffraction study as well. Unfortunately, good quality X-raysingle crystal of complex4was not obtained. It was observed that Ru atom in allcomplexes was in a pseudo-octahedral geometry. Unlike1and2are monomers,complex3is promisingly as a cluster structure briged with a Na2xOxcage.The interactions of four complexes with calf thymus DNA were investigated byUV-Vis absorption spectroscopy, emission spectroscopy and competitive bindingstudies. In electronic absorption spectroscopy experiments, by increasing theconcentration of DNA or the concentration of complexes, the presence of redshiftand hyperchromic effect with respect to λmax were detected. All experimentssuggested that the interactions of four complexes interacted with DNA, leading tothe destruction of the DNA double helix, and the interaction modes of complexes1 and3are more complicated than those of complexes2and4.DNA-steady-state emission spectral studies displayed that all four complexesemitted luminescence in the Tris buffer at ambient temperature in the absence ofDNA, with maximum intensities at603and605nm respectively upon excitation at300nm. And the emission intensities of complexes1,2,3and4increase to3.416,1.404,2.439and2.351times respectively, compared to those without DNA uponaddition. It indicated that these four complexes bound to DNA by intercalation.Complex1has stronger affinity to DNA than complex3,4and2. In order to furtherstudy the binding properties of these complexes with DNA, competitive bindingexperiments were carried out as well. Fluorescence quenching constants ofcomplexes1,2,3and4were calculated by Stern-Volme equation to give1.1×103L·mol-1,1.0×103L·mol-1,1.3×103L·mol-1and1.1×103L·mol-1, respectively. TheirEB-DNA competitive experiments resulted in an obvious reduction in the emissionintensity, suggesting that all four ruthenium complexes displaced EB in EB-DNAmixture to bind with DNAby intercalation.However, the binding mode for1and3is more complicated than that of4and2.In summary, their binding mode could be a groove-surface combination orelectrostatic interaction in addition to the intercalative mode.The anti-cancer study of complexes1,2and3were also carried out in vitro inthis paper. The abilities of these three Ru complexes to inhibit or poison SGC gastriccancer cells, A549lung cancer cells and MCF-7breast cancer cells suggesting thatcomplex1has the best inhibition rate (28.37%) to MCF-7in5μmol/L concentration,while complex2has the best inhibition rate (9.57%) to MCF-7in20μmol/Lconcentration, and3showed good inhibition to all three cancer cells, its bestinhibition rates to SGC and A549are50.21%and28.7%in5μmol/L concentration,and the best inhibition rate to MCF-7is50.53%in20μmol/L concentration. Insummary, inhibiting effect of complex3is better than that of1and2, the sensitivityof three cancer cells to complexes are obviously different.