title: d-PET-controlled "off-on" Polarity-sensitive Probes for Reporting Local Hydrophilicity within Lysosomes.
abstract: Polarity-sensitive fluorescent probes are powerful chemical tools for studying biomolecular structures and activities both in vitro and in vivo. However, the lack of "off-on" polarity-sensing probes has limited the accurate monitoring of biological processes that involve an increase in local hydrophilicity. Here, we design and synthesize a series of "off-on" polarity-sensitive fluorescent probes BP series consisting of the difluoroboron dippyomethene (BODIPY) fluorophore connected to a quaternary ammonium moiety via different carbon linkers. All these probes showed low fluorescence quantum yields in nonpolar solution but became highly fluorescent in polar media. BP-2, which contains a two-carbon linker and a trimethyl quaternary ammonium, displayed a fluorescence intensity and quantum yield that were both linearly correlated with solvent polarity. In addition, BP-2 exhibited high sensitivity and selectivity for polarity over other environmental factors and a variety of biologically relevant species. BP-2 can be synthesized readily via an unusual Mannich reaction followed by methylation. Using electrochemistry combined with theoretical calculations, we demonstrated that the "off-on" sensing behavior of BP-2 is primarily due to the polarity-dependent donor-excited photoinduced electron transfer (d-PET) effect. Live-cell imaging established that BP-2 enables the detection of local hydrophilicity within lysosomes under conditions of lysosomal dysfunction.
authors: State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China.
authors: Hao
authors: H
authors: Zhu
authors: State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China.
authors: Jiangli
authors: J
authors: Fan
authors: State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China.
authors: Huiying
authors: H
authors: Mu
authors: State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China.
authors: Tao
authors: T
authors: Zhu
authors: State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China.
authors: Zhen
authors: Z
authors: Zhang
authors: State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China.
authors: Jianjun
authors: J
authors: Du
authors: State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China.
authors: Xiaojun
authors: X
authors: Peng
mesh_terms: D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry; D060833:Cellular Microenvironment; D004563:Electrochemistry; D004579:Electron Transport; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008247:Lysosomes / Q000378:metabolism*; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D011789:Quantum Theory; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013050:Spectrometry, Fluorescence
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes; D000644:Quaternary Ammonium Compounds