Synthesis And Application Of Novel AIE Probes For Hydrogen Sulfide And Hypochlorous Acid Detection

Active small molecules in organisms play a crucial role in the physiological and pathological environment of cells.The excessive generation of reduced hydrogen sulfide(H2S)molecules and oxidized hypochlorous acid(HClO)molecules in lysosomes could induces cell death through calpain activation and lysosomal disruption.Therefore,the selective visualization of endogenous H2S and HCIO in lysosomes is particularly important for elucidation of the relationship with the underlying disease.Among many detection methods,fluorescence method has been widely used in chemical sensing and imaging because of its high sensitivity and selectivity,non-invasiveness to biological tissue,real-time in situ imaging,and high spatial and temporal resolution.Among them,chemical reaction-based Aggregation-induced emission(AIE)fluorescence sensors have become a research hotspot because they overcome the widely existing aggregation caused quenching(ACQ)phenomenon of traditional fluorescent probes.Based on this,in this paper,we designed and synthesized three chemical reaction-based AIE fluorescence sensors for high selectivity and high sensitivity fluorescence detection and cell imaging of H2S and HCIO.(1)First,a H2S probe(E)-2-(4-(dicyanomethylene)-2-(4-(((2,4-dinitrophenyl)sulfonyl)oxy)styryl)quinolin-1(4H)-yl)ethyl stearate(probe 5)was synthesized by using 2-methylquinoline derivative and 2,4-dinitrobenzenesulfonyl chloride.Subsequently,we prepared an amphiphilic block copolymer polyethylene oxide-b-polystyrene(PEO-b-PS)through the Reversible Addition-Fragmentation Chain Transfer Polymerization(RAFT).Probe 5 and PEO-b-PS were then prepared by coprecipitation into stable nanoparticles(AIED).The prepared AIED has the advantages of good water dispersibility,long-term stability(>15 weeks),good biocompatibility,high selectivity and high sensitivity(?43.8 nM)detection for H2S,etc.,and has been successfully employed to visualize the endogenous H2S in lysosomes in living cells.(2)A novel photoswitchable AIE nanoprobe(E)-2-(4-(dicyanomethylene)-2-(4-(((2,4-dinitrophenyl)sulfonyl)oxy)styryl)quinolin-1(4H)-yl)ethyl 3-(3',3'-dimethyl-6-nitrospiro[chromene-2,2'-indolin]-l'-yl)propanoate(DNBS-DCM-SP)was synthesized by combining H2S recognizing aggregation-induced emission(AIE)group with photochromic spiropyran moiety.In the presence of H2S,the electron-withdrawing DNBS moiety will deviate from DNBS-DCM-SP via a H2S-induced O-S bond cleavage,induced a sensitive turn-on fluorescence response at about 592 nm.In additon,the fluorescence of the H2S-activated AIE nanoprobe(DCM-SP)can be reversibly switched by selective fluorescence resonance energy transfer(FRET)from the AIE fluorophore(DCM)to ring-opened state of spiropyran via alternating UV/visible light irradiation.The prepared nanoprobe displays good sensitivity(?5.0 nM),and high specificity(especial against other thiols),high spatiotemporal resolution,and has been successfully employed to visualize the endogenous H2S in lysosomes in living cells and reversible dual-color fluorescence imaging.(3)An AIE probe(E)-2-(4-(dicyanomethylene)-2-(2-(pyren-1-yl)vinyl)quinolin-1-(4H)-yl)ethyl stearate was synthesized by combining 1-pyrenecarboxaldehyde(with?-? stacking effect)and 2-methylquinoline derivatives for HCIO ratiometric detection.Subsequently,lysosome-targeting surfactant MAA-CO720 was synthesized through one-step esterification reaction by using IGEPAL CO-720 and 4-morpholine acetic acid.Then the amphiphilic block copolymers PEO113-b-PS46,MAA-CO720 and SA-C2-PCD were prepared by the co-precipitation method into stable nanoparticles AIED-Lys for selective detection of lysosomal HClO.AIED-Lys itself shows only strong red fluorescence,but with the addition of HClO it can be observed that red fluorescence is significantly reduced and a new blue fluorescence is observed at the same time.This is because HClO will break the carbon-carbon double bond of the probe molecule SA-C2-PCD,resulting in a decrease of the AIE fluorescence of the probe molecule,and the resulting 1-pyrenecarboxaldehyde undergoes ?-? stacking,resulting in progressively enhanced blue fluorescence.The prepared AIED-Lys showed high water dispersibility,large Stokes shift(?200 nm),strong anti-interference ability,high selectivity and high sensitivity(?70.4 nM)to HClO,long-term stability(>10 weeks),and good biocompatibility,which can be applied to the visual detection of endogenous HClO in lysosomes.