Rapid and Specific Dual-Mode Recognition of Cathinone Derivatives Enabled by π-Conjugation-Tuned Multinoncovalent Interactions

Cathinone derivatives, a major class of new psychoactive substances, pose severe public health threats, because of their high toxicity, addictiveness, and concealed circulation, rendering their rapid on-site detection a critical challenge. Herein, a π-conjugation-tuning strategy based on the excited-state intramolecular proton transfer (ESIPT) mechanism is proposed to modulate multinoncovalent interactions via π-conjugation regulation and enable rapid, specific dual-mode detection of cathinone derivatives. The optimized carbazole-imidazole-based ESIPT probe IM-3 exhibits a distinct dual-mode response upon binding to methcathinone (MC): fluorescence quenching via a photoinduced electron transfer (PET) process that suppresses the ESIPT emission, and a color change from yellow to colorless, both triggered by synergistic multinoncovalent interactions (π-π stacking and N-H···N hydrogen bonding). This sensing system achieves ultrafast detection within 0.8 s, with low limits of detection (LOD): 4.7 μM (fluorescence mode) and 6.6 μM (colorimetric mode), excellent selectivity against 19 potential interferents, and robust stability and reliable performance across a wide range of pH and temperature conditions. The portable sensor, constructed through probe immobilization on a solid-liquid separation platform, provides accurate methcathinone in samples ranging from spiked matrices (sewage, blood, chocolate, beverage) to an authentic specimen. This work establishes a strategy for detecting cathinone derivatives (a representative class of low-nucleophilicity inert analytes) via π-conjugation-tuned multinoncovalent interactions, and provides a foundation for the next-generation dual-mode probes exploration and practical on-site security screening technologies advancing.