Study On Syntheses, Crystal Structures, DNA And BSA Binding Activity Of Novel Coordination Compounds With Oxamido-bridged And Polypyridine Ligands

Studies on DNA and BSA interaction of small molecules have got more and more interests in life science. DNA is an important genetic substance in organism. As the basis of genetic expression, it plays an important role in the process of storing, copying and transmitting germ messages. On the one hand, DNA targeted compounds may become very important nucleic acid probe; on the other hand, many anti-cancer drugs in clinical use are based on DNA for acting targets. Moreover, when drugs are in blood, serum albumins play an important role in the transport and deposition of a variety of exogenous compounds. The absorption, distribution, metabolism and excretion properties, as well as the stability and toxicity of chemical substances, can be significantly affected because of their binding to serum albumins. Therefore, studies on the binding of chemicals with protein will allow us to interpret of the metabolism and transporting process of them. BSA has been studied extensively, partly due to its structural homology with human serum albumin (HSA). Investigation of DNA and BSA interaction of small molecules is not only helpful to explore and develop new nucleic acid probe, but also help us understand the process of drugs in the body, which can provide the theory of designing for clinical more effective anti-cancer drugs.Obeject:To design and synthesize oxamido bridging dicopper complex and transition metal polypyridine complex do screening for the discovery of new anticancer drugs.Methods:First, adopt ethyl oxamate as the raw material, synthesize H2oxbp (N,N’-bis(2-(diethylamino)ethyl)oxalamide) through one-step chemical reaction, and further synthesize metal complexes of1and2; moreover, we synthesized one zinc complex3by1,1,3-tpbd ligand. By infrared spectroscopy, NMR, X-ray diffraction and other methods, we determine the structures of ligands and their complexes. The interaction of Cu(II) complexes with DNA was investigated by UV-vis, fluorescence emission spectrometry, CD and agarose gel electrophoresis. And fluorescence emission spectrometry was used to explore the interaction with BSA.Result:Cu(oxbp) and their copper complexes have been synthesized. The chemical structures were determined. The hypochromisms and red-shifts observed in UV absorption spectra of both complexes. The intrinsic binding constants Kb is1.14x103M-1for1and3.35×103M-1for2. The addition of different complex concentrations to the EB-bound calf thymus (CT-DNA) solution caused an obvious reduction in emission intensities. The apparent binding constant (Kapp) at room temperature are calculated to be3.16×105M-1for complex1and4.9×105M-1for complex2. Agarose gel electrophoresis experiments show that:it caused nuclease action under the conditions of oxidant and reductant, pUC19DNA can be converted from Form I into Form Ⅱ, and with the increasing of complex concentration, DNA sequence increases the degree of fracture. DNA cleavge inhibitors experiment shows that azide and EDTA inhibits DNA cleavage by1; azide, EDTA and KI significantly diminish the nuclease activity of complex2. When BSA was titrated with different amounts of complex, a remarkable intrinsic fluorescence decrease of BSA was observed. Both1and2bind to BSA with a medium affinity through a static mode which is tentatively assigned binding to Trp134in BSA. Fluorescence emission spectrometry of3with polypydine also shows reduction in emission intensities, Kapp is6.6×104M-1.Conclusion:UV absorption spectra suggest the two complexes interact with CT-DNA basically through the intercalative mode. Flurescence spectroscopy indicates that complex insert CT-DNA competitively and replace EB. Agarose gel electrophoresis experiments show that:it caused nuclease action, the way of DNA cleavaged by complexes is the oxidation cleavage. The active oxygen species involved in the reaction are singlet oxygen (1O2) for complex1and a singlet oxygen-like entity, hydrogen peroxide or metal ions in the complex2cleavage process. Fluorescence spectrometry of BSA with complexes demonstrates that both1and2bind to BSA with a medium affinity through a static mode which is tentatively assigned binding to Trpl34in BSA. Such oxamido bridge complexes with anticancer activity are wealthy of further researching and development. The structure of the compounds can be further modified. Flurescence spectroscopy of3also indicates that complex insert CT-DNA competitively and replace EB.