Study On Syntheses, Structure And The Interaction With Nucleic Acid And Protein Molecules Of Metal Complexes With Polypyridine Ligand

In recent years, the polypyridyl metal complexes have got more and more attentions because of their variety of structures and a wide range of uses. The complexes have extensive applications in the field of molecular recognition, nucleic acid probes, anticancer drugs and self-assembled molecular catalysts prospects. In this paper, we primarily focus on interaction between these complexes and biological macromolecules such as DNA and serum protein, which is used to illustrate the biological activity of such complexes. DNA as an important carrier of the genetic material of life, can guide the synthesis of proteins and enzymes through replication and transcription. Furthermore, in the organism, the protein as extremely important life substance, play a key role in the movement of lives and development. Serum albumin is the most abundant carrier protein in plasma. It can effectively bind to many connotations type substances in vivo and exogenous drug, which plays an important role in the storage and transportation. Therefore, study on the interaction of these complexes and protein can help us to better understand the process of the metabolism and transportation of drug in vivo. The research on the metal complexes with DNA, HSA/BSA is not only in favor of the exploration of the mechanism of chemical nuclease, but also the process of the transport, distribution and metabolic of drugs in body.Obeject:To design and synthesize novel polypyridyl metal complexes, and study the interaction of complexes with DNA, HSA/BSA which explore the mode of action between the metal complex and biological macromolecuoles. These results can provide some theoretical information of the metal complexes were used as nucleic acid probes and medical.Methods:First, adopt1,10-phenanthroline as the raw material, synthesize the ligand o-NPIP (2-(2-nitrophenyl)imidazo[4,5-f]1,10-phenanthroline). Then we synthesize Cu(Ⅱ), Ni(Ⅱ) two transition metal complexes, and Er(Ⅲ), Yb(Ⅲ) two rare earth metal complexes through the ligand o-NPIP and acetylacetone(acac). By infrared spectroscopy, NMR, X-ray diffraction, we determine the structure of the four complexes. The interaction of the four complexes with DNA and SA was investigated by UV-vis, fluorescence emission spectrometry and agarose gel electrophoresis.Result:We have synthesized four mononuclear complexes, respectively [Cu(acac)(o-NPIP)(NO3)](1),[Ni(acac)2(o-NPIP)](CH3OH)3(2),[Er(acac)2(o-NPIP)2](CH3CH2OH)2(3),[Yb(acac)2(o-NPIP)2](NO3)2(4). The crystal structures were determined by X-ray diffraction. The hypochromisms and red-shifts were observed in UV absorption spectra of complexes1-4, and the intrinsic binding constants Kb is3.04×104M-1,1.17×104M-1,1.67×104M-1,1.27×104M-1respectively. The fluorescence spectrum of EB-DNA shows different quenching with the addition of different complex concentrations. The apparent binding constant (Kapp) at room temperature are calculated to be1.448×106M-1,8.03×10-5M-1,8.35×105M-1,6.35×105M-for complexes1-4. Complexes1,3,4can cleave effectively pUC19DNA from Form Ⅰ to Form Ⅱ, and with the increasing concentrations of complexes, the cleavage activities become higher. DNA cleavage inhibitors experiment shows that azide and EDTA inhibits DNA cleavage by complexes1,3,4. In the fluorescence quenching experiment, with adding the complexes1-4, the fluorescence intensity of SA decreased gradually. For complexes1and2, Ksv increases with the rising temperature, but for complexes3and4, Ksv decreases with the rising temperature. The results of the Synchronous fluorescence spectra at△λ=15nm with four complexes show that the highest intensity of S A does not change, while at△λ=60nm, the spectral redshift is obtained obviously. The thermodynamic properties of complexes1-4are measured and the results show that△H>0, and△S>0.Conclusion:UV absorption spectra suggest the four complexes interact with CT-DNA basically through the intercalative mode. The fluorescence spectra of EB-DNA show that the four complexes can effectively compete and substitute EB. Agarose gel electrophoresis experiment show that the complexes1,3,4do not exhibit chemical nuclease activity without any external redox agent. When adding H2O2, complexes1,3,4show the medium DNA cleavage activity, and the cleavage action is oxidation. The DNA cleavage inhibitor experiments show that the chelating agent and hydrogen peroxide participate in the cleavage process for complexes1,3,4. The fluorescence quenching experiments and UV absorption determine that the quenching mechanism is static mechanism for complexes1-4. Synchronous fluorescence spectroscopy studies show that the four complexes affect the surrounding microenvironment of tryptophan residues due to the fluorescence quenching. The thermodynamic constant research shows that the four complexes bind to SA through hydrophobic interactions.