Ultrasensitive and Selective Detection of Chemical Warfare Agents via Electronic Modulation of Site-Specific Nucleophilicity

Rapid and ultrasensitive detection of chemical warfare agents (CWAs), particularly nerve agents and phosgene, is critical for national security. However, the rational design of excited-state intramolecular proton transfer (ESIPT) probes is limited by unclear structure–activity relationships, and discriminating between multiple CWAs remains challenging. Thus, we introduced an electronic effect-driven strategy to modulate site-specific nucleophilicity and ESIPT characteristics in p -substituted 2-(2′-hydroxyphenyl)benzoxazole (HBO) probes. We established that moderate electron-donating groups (EDGs) synergistically enhance nucleophilicity while maintaining high ESIPT efficiency. This balance enables the optimized probe (HBO-OMe) to achieve ultrasensitive detection of diethyl chlorophosphate (DCP) (LOD = 61.1 nM) and phosgene (LOD = 17.4 nM) within 3 s. Furthermore, a dual-probe (HBO-OMe/HBO-Me) fluorescent sensor array is the first sensor to discriminate between five nerve agents (Tabun/GA, Sarin/GB, Soman/GD, Cyclosarin/GF, and VX), pure phosgene, and 15 interferents. This work establishes an electronic effect-driven structure–activity relationship for ESIPT probes and provides a practical array-based solution for complex CWAs identification.