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.