Electronic Effect-Tuned Cooperativity of Multiple Noncovalent Interactions for Specific Detection of ADB-Type Synthetic Cannabinoids

ADB-type synthetic cannabinoids (SCs), as a major category of new psychoactive substances, have posed global concerns due to their high abuse potential and detrimental health and social stability effects, and their rapid and accurate <i>in situ</i> analysis is particularly challenging when they appear in concealed forms. Here, the strategy of electronic effect tuning cooperativity of multiple noncovalent interactions was proposed for the specific detection of ADB-type SCs, a class of structurally stable yet reactive inert analytes. The optimized probe HBO-Ph, for the first time, achieved ratiometric fluorescence detection of ADB-type SCs by effectively suppressing excited-state intramolecular proton transfer and promoting intramolecular charge transfer, showcasing unparalleled detection capabilities with a low detection limit of 24.3 nM and a rapid response in 1 s. Moreover, a sensor featuring a solid-liquid separation architecture was designed to enable the rapid detection of ADB-type SCs in real-world situations, unaffected by 24 possible interfering substances. This cooperative regulation method is expected to shed light on the exploration of noncovalent interaction-based probe design strategies and provide a new approach to analyzing target molecules with limited active sites, thereby greatly promoting the present drug detection technologies.