Cucurbituril-mediated AIE: An unconventional indicator displacement assay for ketamine detection

Abstract Typical AIE luminogens with extensive π-electron conjugation are limited in use on account of their complex synthesis, high cost and environmental concerns. To this end, we report here a novel host-guest inclusion complex that is assembled from nonemissive ligands, and surprisingly exhibits notable AIE features in aqueous solution while maintaining good sensitivity for ketamine (KET) detection. Isothermal titration studies confirm that palmatine (PAL) binds to cucurbit[8]uril (Q8) in a 2:1 ratio with an equilibrium association constant of 1.75 × 1011 M−2, suggesting that the unconventional AIE effects can be attributed to the stacking of two PAL moieties inside a single Q8 cavity. Geometric constraints of the macrocycle result in dimeric coupling of PAL in the ground state with significant bathochromic shifts in absorption and emission, which can be readily excited to exhibit enhanced photoluminescence. The unusual upfield perturbation and broadening of Q8 signals in the 1H NMR spectrum upon binding with PAL convey decisive information that Q8 not only serves as a molecular container, but also participates in the electron delocalization during the AIE events. Upon addition of KET, fluorescence was switched off through guest exchange to generate KET@Q8 as well as free PAL. The significant AIE characteristics of 2*PAL@Q8 in combination with its specific molecular recognition towards KET gives rise to 5.0 ng/mL limit of detection with linear range from 16.8 to 500 ng/mL, and a pronounced selectivity over possible interfering substances in biological matrices. We demonstrate the first example of Q8-mediated AIE effects, where the photoluminescence of virtually nonemissive or feebly emissive ligands is remarkably intensified through clustering inside a macrocyclic host molecule, therefore offering great promise for further development into dedicated AIE-based sensors.