A bifunctional ER-targeting fluorescent probe for the detection of SO2 and polarity in living cell and animals.

SO2 and solvent polarity are critical for physiological homeostasis, and their dysregulation is implicated in various diseases, including cancer. In this study, we report a novel intramolecular charge transfer (ICT), reaction based two channel ratiometric fluorescent probe, (E)-2-cyano-N-(3-((4-methylphenyl)sulfonamido)propyl)-3-(4-oxo-7,8,11,12-tetrahydro-4H,6H, 10H-pyrido[3,2,1-ij]thieno[2',3':4,5]pyrano[2,3-f]quinolin-2-yl)acrylamide (CTAT), for the simultaneous detection of SO2 and microenvironmental polarity via two fluorescence channels. CTAT exhibits reaction based two channel ratiometric responses (λ ex = 410 nm, λ em = 490 nm; λ ex = 510 nm, λ em = 660 nm) and distinct colorimetric fluorescence changes upon reaction with SO2, with a low detection limit of 0.144 µM. CTAT also sensitively reports solvent polarity: in 1,4-dioxane/PBS mixtures where it displays an emission peak at 660 nm, and its maximum fluorescence intensity (F max) correlates linearly with the polarity parameter Δf across the tested range. CTAT exhibits low phototoxicity and good biocompatibility, as well as strong endoplasmic reticulum targeting and as such was successfully applied to image endogenous and exogenous SO2 derivatives and polarity changes in HepG2 and L-02 living cells, zebrafish, and tissue samples. This research provides a new strategy and tool for diagnosing polarity-related diseases and for detecting SO2 in real environments.