Design,Synthesis And Properties Of Specific Formaldehyde Fluorescent Probes

Formaldehyde(FA)is a kind of colorless irritant gas,and is also a kind of indoor and outdoor pollutant closely related to people’s life and work.In addition,formaldehyde is a reactive carbonyl species(RCS)involved in a variety of physiological and pathological processes in the organism.Levels of formaldehyde above the normal physiological range have been associated with a variety of diseases,including cancer,neurodegenerative diseases and heart disease.Probe has attracted more and more attention due to its high selectivity and in situ imaging.Formaldehyde fluorescent probes have also been further developed.However,most probes lack targeting capability and cannot be used for dynamic imaging of formaldehyde in vivo.Therefore,it is of great significance to develop a fluorescent probe capable of specific recognition and real-time reversible detection of formaldehyde.Based on this,we designed and developed three cases of formaldehyde fluorescence probes that can be used for biological in situ imaging,and they were successfully applied to cell membrane imaging or reversible detection of formaldehyde in biological samples(1)A membrane targeting formaldehyde fluorescent probe Mem-FA,was designed and synthesized.By introducing the dodecylamine group to the naphthalene anhydride to make it have the ability to target the cell membrane,and then introducing the hydrazine as the recognition group,the probe Mem-FA could detect formaldehyde sensitively.The reaction between the probe Mem-FA and formaldehyde resulted in the change of hydrazine into methylenehydrazine,the PET process was inhibited and the fluorescence was recovered.The probe can detect formaldehyde sensitively and selectively.In addition,co-localization experiments showed that Mem-FA has good membrane targeting performance,and can also be used to distinguish endogenous formaldehyde from exogenous formaldehyde.The probe also shows excellent performance in the detection of basal formaldehyde and endogenous stimulated formaldehyde in cells and zebrafish,especially for the detection of formaldehyde related to the 1C cycle.Therefore,we hope that this probe can be applied to more internal and external source formaldehyde related analysis and detection.(2)A reversible ratiometric fluorescent probe CB-FA was designed and synthesized to detect formaldehyde in real time.The probe is a long-wavelength ratiometric fluorescent probe based on coumarin.The hydrogen sulfite(HSO3~-)can react with the unsaturated bond on the probe to produce an intermediate,which can specifically recognize electrophilic formaldehyde and turn it into a probe.After formaldehyde was added,the intermediate reacted quickly to it,which could make the fluorescence intensity reach the platform within 2minutes.The fluorescence intensity at 485 nm was reduced,and the fluorescence intensity at685 nm was recovered,and the emission wavelength was shifted by 200 nm,which was conducive to reducing the interference between the two emission peaks.The spectroscopic experiments show that probe CB-FA can identify formaldehyde with high selectivity.In addition,CB-FA can monitor the dynamic changes of formaldehyde in cells and zebrafish,providing an effective method for real-time analysis of formaldehyde.(3)On the basis of the second probe,a reversible near infrared fluorescent probe NIR-FA with longer emission wavelength was designed and synthesized to detect the reversible process of formaldehyde.The design and synthesis of the probe is based on coumarin and benzopyran.The fluorescence emission wavelength of the probe is in the near infrared region(788 nm),and the light damage to cells is less.After the Michael addition reaction with HSO3~-,the probe emission wavelength was blue shifted by 273 nm.After the reaction with formaldehyde,the probe was regenerated by removing HSO3~-.Therefore,it shows the effect of ratiometric measurement.The probe responds quickly,sensitively and high selectivityly to formaldehyde.The probe can not only ratio image the exogenous formaldehyde added in cells,but also sensitive detect the endogenous formaldehyde produced by tetrahydrofolate preincubation in cells.Therefore,probe NIR-FA provides an effective imaging tool for the real-time detection of exogenous and endogenous formaldehyde.