The Cleavage And Interaction Of Azacrown Ether Complexes To Nucleic Acids

Nucleic acid, one of the important components of organisms, is the carrier of genetic information, the material foundation of gene expression. It plays key role in the growth, development and propagation of organisms. The interaction between metal complexes (especially macrocyclic complexes) and DNA attracted much attention increasingly because of its biological effects, for example, hydrated cisplatin has strong anticanceractivity for it can coordinate with guanine of DNA chain. So, researching the interaction and mechanism, summarizing the rules of metal complexes binding with DNA, has very important meaning in exploring complexes' application in antitumor drugs, molecular biology, bioengineering technology and related fields.Macrocyclic polyamine complexes and metalloporphyrins have been applied extensively as nuclease because of their special structures. Though azacrown ether complexes have similar structures with macrocyclic polyamine complexes, they are seldom concerned in nuclease research for their poor cutting effect. Nevertheless, it has great significance in designing, synthensizing, studying and improving molecular nucleophilicity, sequence selectivity, and cleavage efficiency of azacrown ether complexes. In order to investigate the interaction of azacrown ether complexes with DNA, a new kind of azacrown ether complexes were selected. The binding modes and cleavage to DNA of the azacrown ether complexes were systematically studied. The main results of our research are summarized as follows:In chapter 1, the components and structures of nucleic acids, binding modes and research methods of complexes binding with nucleic acids were reviewed, and the application of macrocyclic polyamine complexes, azacrown ether complexes and metalloporphyrins in the cleavage of nucleic acids were discussed.In chapter 2, the binding of the complexes with calf thymus DNA was investigated using spectroscopy methods and viscosity measurements. The results suggest that the azacrown ether copper (II) can bind to DNA by intercalation, azacrown ether cerium (IV) may bind to DNA by partial intercalation, while azacrown ether nickel (II), cobalt (II), zinc (II) maybe bind by electrostatic attraction or groove-face interaction.In chapter 3, the cleavage of azacrown ether copper (II), nickel (II), cobalt (II), zinc (II) to DNA are examined by agarose gel electrophoresis. The main results are as the follows: (1) Induced by the four complexes in the presence of H₂O₂, DNA was completely converted from Form I to Form II and/or Form III in short time; though the complexes are incapable of cleaving DNA without H₂O₂, they still cleave DNA if incubated for longer time at 37℃. The extent of DNA modification is independent of the concentration of complexes. (2)The ions of copper (II), nickel (II), cobalt (II), zinc (II) and related azacrown ether complexes can cut DNA. Under the same condition, except cobalt complex has the same cleavage activity as cobalt ion, other three complexes have stronger cleavage ability than related ions. The cleavage activity has larger difference in the four complexes, in the presence of H₂O₂, the cleavage activity of the four complexes are as the follows: Co-L > Cu-L～Zn-L > Ni-L; while the activity without H₂O₂ sequence like this: Co-L～Zn-L > Cu-L～Ni-L.(3)Compared with azacrown ether complexes, the EDTA complexes of the four ions can barely cut DNA, except EDTA-Ni has weak cleavage.(4)In the presence of H₂O₂, the cleavage mechanism might involve free radical mechanism; without H₂O₂ as catalyst, the cleavage mechanism maybe concerns hydrolysis mechanism. Certainly it perhaps exits free radical mechanism.In chapter 4, based on the experimental results, the main conclusions of our research were given, as summarised as follows: Azacrown ether copper(II) can bind to DNA by intercalation and has great cutting effect, it may be applied as chemical nuclease or anticancer drugs as hydrated cisplatin; azacrown ether cerium(IV) may bind to DNA by partial intercalation, the rusults provide basic data for further research on rare earth elements; Azacrown ether nickel (II), cobalt(II), zinc(II) can cleave DNA with high efficiency, though they bind weakly to DNA, it has great difference with other complexes and has greater research value.