Design, Synthesis And Application Of Fluorescent Probes Focused On Nucleic Acids And Its Mutations And DNA Asymmetric Catalysis Based On G-triplex Structure

Nucleic acid is the genetic material of life, the cornerstone of human survival and evolution. In this paper, we have designed and synthesized AIE (aggregation induced emission) effect of fluorescent probes for the detection of nucleic acids. Then from the starting DNA mutations, we designed and synthesized a series of fluorescent nucleotide probes for the detection of these mutations. Finally, we use the properties of G-triplex structure, asymmetric catalytic abilities for catalyzing Diels-Alder reaction.And we synthesized several substrates for this reaction.Nucleic acids are widely used in genetic engineering, forensics, and bioinformatics. Therefore, many methods have been developed for the detection of nucleic acids. We have designed a compound with aggregation induced emission (AIE effect) using for fluorescent detection of nucleic acids. Compound 1 has a styrene structure, and with positive charge, could combine with the nucleic acid carrying negative charge in an aqueous environment through electrostatic interaction, resulting fluorescence enhancement. We further applied compound 1 for DNA staining in gel electrophoresis. We also investigated the ability of compound 1 as nucleus dye. Compared with commercial obtained nucleus dye Hoechst33258, we found that compound 1 can be used as a nuclear dye.As one of the most common form in DNA mutations,5-hydroxymethyl-deoxyuridine prove to be breast cancer marker. We replaced the hydroxyl group of 5-hydroxymethyl-deoxyuridine with an azide group, and then design compounds 2,3,4 with alkynyl group. This mutation is detected by fluorescent enhancement via click reaction by azide and alkynyl group. Through selective fluorescence experiments, we exclude the interference of several other natural nucleosides, and try on the detection of 5-hydroxymethyl-deoxyuridine in DNA chain.5-hydroxymethyl-deoxycytidine is an important product in DNA methylation process, and proved to be related to cell differentiation and diseases. A new type of 1, 3-O, N-heterocycle, including two fluorescent derivatives 5,6, has been synthesised by the reaction of formyl group and the hydroxyl and amine groups of 5-hydroxymethyl-2’- deoxycytidine. After the annulation the fluorescence intensity was increased. To study the influence of electronic effect on the ring-forming reaction, we resorted to the methodology to study the yield of the reaction based on benzaldehyde with different substituents. Finally, the reaction was found that the nitro substituent brought the maximum benefit, the electron-withdrawing effect can increase the yield of the reaction.The structures of DNA are various. Double-stranded DNA itself has chirality, which played a very important role in asymmetric catalysis research. G-triplex DNA structure is a secondary structure of DNA. When complexed with copper ions, it could perform as an efficacy catalyst in asymmetric synthesis. We tested the catalytic ability of G-triplex complexes with copper ions and copper ions and G-triplex structure only, and we found that G-triplex complexed with copper ions had the best performance. We synthesize four catalytic substrates 7,8,9,10 for testing G-triplex complexed with copper ions.