Studies On Metal Complex Based On The 1,10-dioxa-4,7,13,16-tetraazacyclooctadecane And Its Derivatives As Artificial Nuclease

Phosphodiester bonds of nucleic acid are extremely rigid in mild conditions since its half life is as long as millions of years, but the nucleic acid could be easily splitted by natural nucleases. However, the application of natural nucleases is limited by its disadvantages. Therefore, there is increasing interest in synthesizing artificial nucleases, which are kinds of enzyme toward catalyzing organic compound hydrolysis, such as the carboxylic acid, phosphate esters and amides etc in the biological body. Thus, design, synthesis and in-depth study of reaction mechanism of the artificial nucleases contribute to their potential applications in molecular biological technology and drug development. Complexes made of various aza-crown ethers and transition metal ions or rare earth metal ions have made great progress in the fields of drug development, molecular biological technology, creating novel therapeutics or laboratory agents for manipulating nucleic acids and so on.In order to explore the reaction of DNA and complexes made of transition metal ions or rare earth metal ions and aza-crown ethers(1,10-dioxa-4,7,13,16-tetraazacyclooctade- cane) and its derivatives, the following aspects were included in this paper:(1) Interaction of plasmid pUC19 DNA and complex(ZnL1) composed of aza-crown ether(L1) and transition metal ion(Zn2+) was measured by gel-electrophoresis. The results showed that the complex(ZnL1) could cleave supercoiled form DNA(pUC19 DNA) to linear form DNA. The cleavage efficiency of three transition metal complexes(ZnL1, CuL1, NiL1) follows the order: ZnL1>CuL1>NiL1, and this might be ascribed to their different ionic radius. Zn2+ ion can provide more open space and then lead to less steric hindrance in the metal complex.(2)The cleavage efficiency of lanthanum(III) complexes made of two similar aza-crown ethers(LaL1, LaL4) was measured by UV spectrometry and gel-electrophoresis. The results inidcated that LaL1 exhibited better cleavage efficiency due to the N atoms in the ligand. Compared to O atoms, N atom has stronger electro-donating ability, which may be contributed to the superior stability.(3)Two kinds of aza-crown ethers containing hydroxypropyl group(L2), amide group(L3) were successfully synthesized and identified by Liquid Chromatogram Mass spectrum(LC-MS). Complexes made of rare earth metal ions and these two aza-crown ethers were identified by fluorescent spectrometry. Interaction between DNA and transition complexes or rare earth complexes was studied by gel-electrophoresis. The results displayed that the cleavage efficiency of transition complexes followed the order: ZnL3>ZnL2, CuL3>CuL2 and the transition complexes consist of aza-crown ether with amide group showed better cleavage efficiency.The cleavage efficiency of rare earth complexes followed the order: LnL3>LnL2. The result might be attributed to the N atom in the amide group, which could reduce the electron density and then stabilize the transition state, and thus, rare earth aza-crown ethers containing amide group(L3) exhibited higher efficiency.