Efficient design of benzothiazole-based fluorescent probes for benzodiazepines detection by precisely mimicking their binding interactions with the GABAA receptor.

To address the lack of visual detection methods for the screening of abused benzodiazepines (BZDs), this study proposes a biomimetic probe design strategy. Specifically, molecular docking simulations of the γ-aminobutyric acid type-A receptor and BZD complexes revealed multiple shared π … π interactions with the TYR-58, PHE-77, PHE-100, and TYR-160 residues, along with a hydrophobic interaction with the VAL-203. The emulation of these receptor-ligand π … π interactions guided the biomimetic design of the styrylbenzothiazole-based fluorescent probes featuring a large π-conjugation structure. The optimal probe (E)-4-(2-(5-methoxybenzo[d]thiazol-2-yl)vinyl)benzonitrile (BCN), recognizes BZDs by forming π … π interactions with its phenyl/triazole moieties and weak hydrogen bond interactions with the imine and triazole nitrogen atoms, or carbonyl oxygen. Moreover, the BCN-functionalized sensing chip enables ratiometric fluorescence detection of typical BZDs (e.g., bromazolam, triazolam, diazepam, and oxazepam) via a target-assisted rightward shift of the excited-state cis-to-trans isomerization equilibrium. And this chip could enable visual qualitative detection of diazepam in actual tablet samples and four typical BZDs in complex matrices such as urine and wastewater.