Synthesis, Characterization And Interaction With DNA Of Some Novel Oxovanadium Complexes

Great interest has been aroused among researchers upon the interaction of metal complexes with DNA. Some metal complexes, in particular those with small molecular weight, have been used as DNA-structural probes, DNA-dependent electron transfer, sequence-specific cleaving agents and potential anti-cancer drugs. As a biocompatible element existing in human body, vanadium exhibits diverse biological activities such as antidiabetes, antibacterial, anti-tuberculosis and so on. The latest researches reveal that vanadium complexes also possess potentially anti-tumor activities. Therefore, it becomes indispensable to study the interaction of oxovanadium complexes with DNA and much effort has been done in these fields. Nevertheless, the mechanisms by which oxovanadium complexes interact with DNA molecules have not been clearly elucidated yet. In particular, the possible binding modes between these complexes and DNA are still needed further investigation. In addition, metal complexes with small molecular weight may possess potentially antioxidative activities for their similar structures with those of some natural antioxidants such as superoxide dismutase existing in cells of organism. So far, the in vitro antioxidative activities, especially the scavenging activities against hydroxyl radicals, of oxovanadium complexes have not been reported yet and thus been of great significance for seeking for some novel antioxidants. For these purposes, in the present dissertation, a series of novel oxovanadium complexes with small molecular weight have been synthesized and characterized. Their binding modes and binding affinities with calf thymus DNA (CT-DNA) have been studied in principal. The photocleavage activities of some oxovanadium complexes towards PBR322 DNA have been tested as well. Besides, preliminary researches on the in vitro scavenging activities of these oxovanadium complexes against hydroxyl radicals have been conducted. The principal contents of my research include:1. Six novel oxovanadium complexes incorporating Schiff bases, namely salicylaldehyde thiosemicarbazones as well as their derivatives, as primary ligands and the phenanthroline or bipyridine as auxiliary ligands were synthesized and characterized by elemental analysis, UV-Vis, ES-MS and 1H NMR.2. The binding modes as well as binding strength of these complexes with CT-DNA were studied using electronic absorption titration, fluorescence spectra, viscosity measurements, circular dichroism and thermal denaturation. The magnitude of their binding strength with CT-DNA was also elucidated from electronic effects as well as the size of aromatic conjugated system. The experimental results indicate that the binding affinity of oxovanadium complexes bearing aromatic chromophores with no groups was larger than that of those with electron-withdrawing groups substituted such as Cl, Br and so on. Meanwhile, the binding strength of oxovanadium complexes bearing phenanthroline as the auxiliary ligand was larger than that of those bearing bipyridine as the auxiliary ligand.3. The photocleavage efficiency of two oxovanadium complexes exhibiting stronger binding affinity with CT-DNA among all the vanadyl complexes was tested. It was found that two oxovanadium complexes, VO(s)(p) and VO(s)(b), could catalyze the photocleavage of plasmid pBR322 DNA and the photocleavage efficiency of VO(s)(p) was better than that of VO(s)(b).4. Using safranin as a substrate, the scavenging activities of all oxovanadium complexes against hydroxyl radicals produced by Fenton reaction were tested. The experimental results indicate that these complexes exhibit scavenging effects against hydroxyl radicals and with their increasing concentration, the scavenging ratio of these oxovanadium complexes against hydroxyl radicals was preliminarily increased and subsequently decreased, making the largest scavenging ratio in the concentrations of 4μM or 6μM.The above results provide experimental evidence for the investigation on the mechanism of interactions between small molecular compounds and DNA and simultaneously experimental basis for the exploitation of anti-tumor drugs targeting DNA molecule as well as seeking for some manually synthetic antioxidants with high biological activities and low toxicity.