Synthesis And Properties Of Fluorescence Probes Based On Aggregation-Induced Emission Effect For Application In DNA Detection

In recent years,bioluminescent probes have become a powerful tool for chemists in analytical chemical sensing and photochemical imaging because of their obvious advantages: they can directly observe a series of biological macromolecules(proteins,DNA,enzymes,polysaccharides,lipids)and small biomolecules(monosaccharides,amino acids,biothiols,adenosine triphosphate,etc.)at the molecular level,and can provide a viable photochemical analysis for complex biological structures and biological processes.However,under normal circumstances,some probes don’t emit light at high concentration due to the strong interaction between the fluorophore molecules.This means that aggregation may cause quenching(ACQ),which limits the practical application of these fluorescent probes.Tang team proposed a unique aggregation-induced emission(AIE)effect in 2001,which provides a direct solution to the problems of the ACQ phenomenon.As the name suggests,the phenomenon of aggregation-induced emission refers to the phenomenon that the fluorescence emission is enhanced after the molecule changes from a dispersed state to an aggregated state.When the fluorescent molecule with AIE effect has good solubility in a dilute solution,the maximum excitation wavelength does not emit fluorescence or only emits very weak fluorescence,but it is highly emission in high concentration state and solid film state excitation.Based on this property,AIEgens would be a great potential as a class of excellent bioluminescent probes.DNA with a wealth of genetic information has injected vitality into both biology and chemistry,since Watson and Crick revealed the structure of DNA.This complex macromolecule is extremely important for biological genetic processes,development and function.Since fluorescence is widely used as a convenient and efficient means in the field of DNA detection,the design of small-molecule fluorescent probes that can interact with DNA is becoming more and more important.In this paper,we mainly designed and synthesized some AIEgens that had aggregation-induced emission effect,and studied some application in DNA detection.(1)A quaternary ammonium salt molecule with two hydrophilic groups and a classical AIE group tetraphenylthiol as the core was synthesized.The studies showed that the fluorescence signal is very weak in the good solvent DMSO,and it shows a very strong fluorescent signal in the poor solvent toluene.These results means that the molecule has a typical aggregation-induced emission effect.The Silore-R molecule with positive charges has excellent solubility in aqueous solution and weak background fluorescence signals in aqueous solution.Since the silole core of Silore-R has a positive charge,it has strong interaction with DNA with negative charges.When the AIEgen interacted with DNA,the AIE groups are close to each other,which caused the fluorescence to turn on.The studies showed that the flurescence intensity had a good linearity with the concentrations of DNA.Moreover,the AIEgen was further used to detect GAA trinucleotide repeat,and a dual-signal biosensor was designed based on the AIEgen and molecular beacon(MB).The method can detect sequence concentrations and estimated repeat length with good selectivity and simple operation.The strategy provide a feasible method for sequence detection and length estimate of repeat,and open perspective for the development of early diagnostic method of neurodegenerative diseases.(2)Four AIEgens containing acridine group were synthesized by combining DNA recognition molecule acridine with AIEgen.First,these derivatives were synthesized based on triphenylamine and tetraphenylethylene core respectively,through a rigid conjugated group and an olefin chain.It was found that only the compounds with triphenylamine as the core have a typical AIE effect.In addition,two kinds of molecules with tetraphenylene ethylene as core and acridine bonded through flexible chain were synthesized.It was found that both molecules had typical AIE effect.Their interaction of AIEgen and DNA were studied preliminarily,however,unfortunately AIE phenomenon wasn’t observed clearly by fluorescence spectroscopy.It is possible that the AIE group prevents the insertion of acridine into the double-stranded DNA due to the steric hindrance,and the AIE groups cannot be close to each other and the fluorescence cannot be turned on.Another,a super-molecular aggregation state had been formed in the aqueous solution because of weak water solubility,and the additionally added double-stranded DNA cannot make it more aggregate.Next,we expect to synthesize some water-soluble near infrared AIEgens with large conjugate area to increase the emission wavelength and with small steric hindrance to avoid interference of the intercalation of acridine groups into ds DNA as much as possible.