Synthesis And Application Of Nucleic Acid Modified Organic Functional Materials

DNA has a wide range of applications in biosensing,nanomedicine,and smart materials due to its specific molecular recognition and stimuli-responsive properties.In order to detect and quantify the recognition and responsiveness of DNA to targets,materials with optical,electrical,and magnetic properties have to be connected with DNA.The covalent grafting technology of DNA and inorganic functional nanomaterials has been well developed.However,covalent conjugation between DNA and organic functional materials still has many problems,especially for very hydrophobic organic materials,which needs further exploration.Organic conjugated fluorescent small molecules are a kind of very important functional material and show applications in a broad range of fields,such as fluorescence sesing,photothermal therapy,photoacoustic imaging,and photodynamic therapy.Among many organic conjugated fluorescent small molecules,such as cyanines,naphthalene diimides,and pyrene,and AIE molecules,all these conjugated molecules show distinct physical and chemical properties,which will significantly affect the choice of a proper conjugation method for DNA coupling.Here in this thesis,we work on exploring the conjugation method between DNA and hydrophobic organic molecules,and three different strategies were investigated and compared.Furthermore,by the method of"no copper catalytic liquid phase click reaction",the conjugation product of near-infrared dye IR783 and DNA was synthesized and studied for biomedical applications.The main research contents are as follows:The conjugate product of pyrene and DNA was synthesized by using the"cationic surfactant DDAB-assisted solution method".Amine functionalized DNA was first synthesized by DNA synthesizer,which was transferred to organic phase by utilizing surfactant DDAB.Therefore,the amidation reaction between DNA and 1-pyrenebutanoic acid was efficiently carried out in organic phase.One-side and double-side modified DNA products with AIE molecule tetraphenylethylene?TPE?were synthesized by"Cu?I?catalyzed click reaction method"in solid phase.This method utilized the DNA synthesizer to synthesize functionalized DNA sequences but without cleavage from the solid support CPG.Thereafter,the DNA attached CPG was dispersed in organic solvent.The DNA on CPG surface with go through a Cu?I?-catalyzed click reaction to react with azide-modified TPE.Both the one-side and double-side were synthesized by this method.This is a facile method with a high conjugation yield,but which is highly dependent on using a DNA synthesizer.The conjugation product of IR783 and DNA was synthesized by using the"non-Cu-catalyzed click reaction"method in liquid phase.The method converted the amine-modified DNA DBCO-modified DNA.Hereafter,covalent attachment of DBCO-DNA to N₃-IR783 was achieved in the liquid phase using a"non-Cu-catalyzed click reaction".This method not only shows high conjugation efficiency and convenient operation,but also avoided the participation of metal ions such as Cu,which reduced the risk of biological toxicity.Based on the IR783-DNA,a nano-system with pH responsive fluorescence was constructed by coupling with graphene oxide?GO?.The i-motif forming sequence with pH responsive capability was utilized to construct the nanosystem IR783-DNA-Cy3 i-motif-Anchor-GO,which showed application potentials in pH-dependent fluorescence imaging and photothermal therapy.Through the exploration and comparison of the three conjugation strategies,we made a systematic summary on the conjugation between DNA and hydrophobic organic molecules.The combination between organic fluorescence molecules with superior optical properties and DNA with many uniqueness in molecular recognition and responsiveness will develop many new hybrid materials with application potentials in biosensor,theranostics and smart materials.The investigations in this thesis will provide great reference value for the development of this kind of new hybrid materials.