Efficient design of benzothiazole-based fluorescent probes for benzodiazepines detection by precisely mimicking their...

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.