Engineering\nHClO Ratiometric Fluorescent Probe by\nInducing Molecular Aggregation to Suppress TICT Formation for Monitoring\nDrug-Induced Liver Injury

Developing highly specific hypochlorite (HClO) ratiometric\nfluorescent\nprobes for elucidating drug-induced liver injury (DILI) and related\nbiological issues is of great significance. Phenothiazine-derived\ncoumarin (PTZC) fluorophores have been shown to exhibit high specificity\nin response to HClO; however, such fluorophores emit dim fluorescence\nin aqueous media due to the intrinsic twisted intramolecular charge\ntransfer (TICT) effect, resulting in only a turn-on mode response\nto HClO. In this work, we present a molecular design strategy of suppressing\nthe TICT formation by inducing PTZC fluorophores to form nanoaggregates\nin aqueous media for the HClO ratiometric fluorescent probe design.\nThe probe <b>PBFF</b> developed based on this strategy can form\nconsiderable nanoaggregates in aqueous media to inhibit the TICT formation\nwithout suffering from the aggregation-caused quenching effect, thus\nallowing it to emit intense fluorescence in aqueous media (Φ<sub><i>f</i></sub> = 0.20). Importantly, <b>PBFF</b> can\nspecifically and sensitively (LOD = 15.7 nM) respond to HClO, showing\ndistinct ratiometric fluorescence changes. Further experimental results\nshow that <b>PBFF</b> can sensitively monitor in situ DILI progression\nthrough HClO-induced fluorescence ratio changes. This strategy of\nsuppressing TICT formation by inducing molecule aggregation in aqueous\nmedia will advance the development of ratiometric fluorescent probes\nin the future.