Benzimidazole–Piperazine–Coumarin/Cucurbit[7]uril Supramolecular Photoinduced Electron Transfer Fluorochromes for Detection of Carnosol by Stimuli-Responsive Dye Displacement and pK(a) Tuning

[Image: see text] A new fluorescent dye (4PBZC) comprising coumarin (C), piperazine (P), and benzimidazole (BZ) was designed, prepared, and complexed to cucurbit[7]uril (CB7) to detect carnosol (CAR), an anti-breast cancer drug, in sub-nanomolar concentrations utilizing the supramolecular indicator displacement assay strategy, the CB7-assisted pK(a) shift, and the CB7-retarded photoinduced electron transfer process. The host–guest complexation was confirmed by UV–visible absorption, fluorescence, and (1)H NMR spectroscopy, which established the binding of 4PBZC to CB7. CB7 preferentially binds the indicator dye (4PBZC) via the protonated BZ residue compared to the neutral BZ one, demonstrated by a higher binding constant of the complex in its di-protonated form, which led to an increase in the pK(a) of the BZ moiety by ca. 3.0 units after the addition of CB7. In aqueous solution (pH 6), switching the emission signals between 4PBZH(+)C/CB7 (ON state) and 4PBZC (OFF state) was achieved by displacement of the protonated dye from the cavity of CB7 by the CAR analyte. An efficient sensor was obtained for the sensitive detection of CAR in aqueous solution with a low detection limit of 0.148 ng/mL (0.45 nM) and a linear range from 20 to 627 ng/mL.