Synthesis, Structure And Interation With DNA And BSA Of Transition-Metal Complexes With 2-Substitued Imidazole Or Benzimidazole And Demethyleantharic Acid

Cancer, one of the world’s deadliest diseases, has already become the major concern of medical scientists. The number of metal complexes in current clinical use for the treatment of cancer is extremely limited, so studying novel anticancer drugs have been a hot spot in the field of biochemistry research. Demethylcantharate is the derivatives of anticancer drug of cantharidin, has both strong anticancer activity and low cytotoxicity to some extent. Imidazoles compounds have broad applications, including anticancer, antioxidant, antibacterial and so on biological activity. We have designed and synthesized different kinds of novel metal complexes with 2-substitued imidazoles compounds and demethylcantharate, based on a simple and effective idea that introducing ligands with good biological active into transition metal complexes. The interactions of these complexes with DNA and bovine serum albumin (BSA) were studied, the scavenging capacities of the hydroxyl free radical were tested. Meanwhile, their antiproliferative activities were tested with MTT essay in vitro. The main work is as following:Four novel complexes [Co(2-MeIm)(DCA)(H2O)2] (1), [Cu(2-MeIm)2(DCA)]2-(H2O)2 (2), [Zn2(2-MeIm)2(DCA)2]n·(H2O)n (3), [Ni(2-MeIm)(DCA)(H2O)2] (4) (2-MeIm=2-methylimidazole, C4H6N2; DCA2-= 7-oxabicyclo [2.2.1]heptane-2,3-dicarboxylate, demethylcantharate, C8H8O5) were synthesised and characterized by elemental analysis and infrared spectra. The structures of complexes 1-3 were determined by X-ray diffraction. The complex 1 is mononuclear complex of the coordination center is octahedron. The asymmetric unit of complex 2 contains two independent molecules, the coordination center of complex 2 is square pyramid. The complex 3 is a multicore polymer, the coordinated environment with four-coordinated and six-coordinated. The interaction between complexes 1-4 and DNA was studied by means of ultraviolet-visible absorption spectra, fluorescence spectra and viscosity measurements. In addition, the capacity that complexes 1-3 cut the supercoiled plasmid DNA was studied by means of agarose gel electrophoresis. The interaction between the complexes and bovine serum albumin (BSA) was investigated by fluorescence spectra and synchronous fluorescence spectroscopy. The antiproliferative activities of the complexes 1-3 against human hepatoma cells (SMMC7721) were tested in vitro. The hydroxyl radical scavenging effect of the complexes was investigated by fluorescence spectra. The results showed that the complexes could bind DNA in moderate intensity via partial intercalation, and the complex 2 possessed the strongest binding ability. The interacting intensity of complexes 2 and 3 was stronger than complexes 1 and 4. The complexes could quench the fluorescence of BSA strongly through static quenching, and was mainly caused by tryptophan residues in BSA. The antiproliferative activities of the complex 2 had the strongest activity against SMMC7721 cells and MCF-7 cells, and what was more intense than Na2(DCA). The complexes 2-4 have a more antioxidant system, can eliminate hydroxyl radical (HO·), and the complex 2 is the most effective of the three complexes for scaveging hydroxyl radical (HO).Four novel complexes:[Cu2(PBIm)2(DCA)2]-(H2O)2 (5), [Co(PBIm)(DCA)(H2O)](6), [Ni(PBIm)(DCA)(H2O)](7) [Mn2(PBIm)2(DCA)2](H2O)2 (8)(PBIm-2-(2’-pyridyl)-benzimidazole, C12H9N3; DCA2-=7-oxabicyclo [2.2.1]heptane-2,3-dicarboxylate, demethylcantharate, C8H8O5) were synthesised and characterized by elemental analysis, infrared spectra and ultraviolet-visible absorption spectra. The structures of complex 5 was determined by X-ray diffraction. The interaction between the compounds and DNA was studied by means of ultraviolet-visible absorption spectra, fluorescence spectra, viscosity measurements. In addition, the capacity that complexes 5-6 cut the supercoiled plasmid DNA was studied by means of agarose gel electrophoresis. The interaction between the complexes and bovine serum albumin (BSA) was investigated by fluorescence spectra and synchronous fluorescence spectroscopy. The antiproliferative activity of the complex 5 against human hepatoma cells (SMMC7721) was tested in vitro. The hydroxyl radical scavenging effect of the complexes was investigated by fluorescence spectra. The results showed that the complexes could bind DNA in moderate intensity via intercalation, and the complex 7 possessed the strongest binding ability.The complexes could quench the fluorescence of BSA strongly through static quenching from the formation of a ground-state complex between the fluorophore and quencher. The interacting intensity of complex 6 was stronger than other complexes. The antiproliferative activities of the complex 5 had a more activity against SMMC7721 cells and MCF-7 cells, and what was more intense than Na2(DCA). The complexes 5-8 have a more antioxidant system, can eliminate hydroxyl radical (HO·), and the complex 8 is the most effective of the three complexes for scaveging hydroxyl radical (HO·).