Design,Synthesis And Application Of Fluorescent Probes For Bioactive Small Molecules

Bioactive small molecules,including reactive oxygen species?H₂O₂,ClO^-,.OH,¹O₂,etc.?,reactive nitrogen species?HNO,NO,ONOO^-,NO₂^-,etc.?,energy substances?ATP?and other small molecules?spermine,amantadine,etc.?,play vital roles in organisms.Traditional methods for detecting these bioactive small molecules,like high performance liquid chromatography,electrochemical method,capillary electrophoresis and spectrophotometry,suffered from complicated operation,high cost,low sensitivity,and poor selectivity.In contrast,fluorescent probes feature the unique advantages of simple operation,high sensitivity,good selectivity,low detection limit and applicability for live cell imaging.In view of the significance of bioactive small molecules and the unique advantages of fluorescent probes,we designed and synthesized some fluorescent probes for H₂O₂,HNO,ATP and spermine/1-adamantanamine respectively and the main results are briefed as follows:1.The first fluorescent probe?HCyHP?for H₂O₂ detection in hypoxic cancer cells was designed by combining the merits of hemicyanine dye and the high specificity of the boronate-to-phenol switch.The probe HCyHP displayed colorimetric and fluorescent turn-on dual mode sensing ability toward H₂O₂ with high specificity.In vitro imaging data demonstrated that HCyHP can selectively light-up H₂O₂ in hypoxic cancer cells.In vivo imaging of H₂O₂ in tumor-bearing live mice was also realized.Additionally,selective detection of D-glucose in diluted serum samples with the aid of glucose oxidase was also realized.2.A mitochondria-targeting and near-infrared?NIR?fluorescent probe?DCMHNO?for HNO detection was synthesized.The fluorescence of DCMHNO in PBS solution was almost quenched due to the weak intramolecular charge transfer?ICT?effect.While after reaction with HNO,DCMOH with strong ICT effect and NIR emission?700 nm?was generated.The probe DCMHNO showed fast response?about 4 min?,superior sensitivity?detection limit of 13 nM?,excellent selectivity and high pH stability towards HNO.Moreover,DCMHNO can be used for real time and in situ imaging of HNO in live cells,tissues and mice.3.An AIE based tetraphenylethylene derivative?TPPTPE?was synthesized for light-up sensing of ATP in aqueous solution.The emission of TPPTPE in solution was very weak due to the fast non-radiative decay of the singlet excited state that is facilated by free rotations about the phenyl rings.However,after aggregated on the surface of ATP molecules through electrostatic interactions and hydrophobic interactions,the intramolecular motion of TPPTPE was greatly restricted and the emission was turned on.The measuring range for ATP can be tuned by varing the concentration of TPPTPE.Moreover,TPPTPE can be used for monitoring ATP both in living cancer cell lines and in living normal cell lines.4.Supramolecular systems formed between an AIE-active molecule TPPTPE and cucurbit[n]uril?CB[n]?were used to construct selective fluorescent probes for spermine and 1-adamantanamine?AD?,respectively.The design strategy based on supramolecular chemistry avoided tedious and time-consuming synthetic and purification procedures,and may provide some guideline for the development of new fluorescent probes for important biological species.