Synergistic Noncovalent Interaction Drives High-Performance Fluorescence Detection of Drug Analogs

Accurate and sensitive detection of illicit drugs, including methamphetamine (MA), is essential for maintaining public health and security. Stringent regulatory controls on MA have driven the adoption of <i>N</i>-methylphenethylamine (MPEA) as a prevalent experimental surrogate in scientific research. While fluorescence-based sensing demonstrates efficacy in detecting MPEA, its practical application remains constrained by selectivity and sensitivity. To overcome these limitations, we engineered a fluorescence sensing strategy based on synergistic noncovalent interaction and employed AgPDT (PDT = 4-pyridinethiol) as a recognition motif enabling both exceptional selectivity (<i>F</i> ₀/<i>F</i> shows a 450% enhancement versus structural analogs) and remarkable sensitivity (LOD = 1 nM) for MPEA detection. The excellent detection performance originates from optimized charge transfer and hydrogen bonding interactions between AgPDT and MPEA, synergistically enhancing the molecular recognition specificity. This ultrasensitive fluorescence-based detection system demonstrates significant potential for trace illicit drug analysis.