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.

快速超灵敏检测化学战剂（chemical warfare agents, CWAs），尤其是神经毒剂与光气，对于国家安全至关重要。然而，由于结构-活性关系尚不明确，激发态分子内质子转移（excited-state intramolecular proton transfer, ESIPT）探针的合理设计仍受限于此，且区分多种化学战剂依然颇具挑战。为此，我们提出了一种电子效应驱动的策略，用以调控对位取代的2-(2'-羟基苯基)苯并恶唑（p-substituted 2-(2′-hydroxyphenyl)benzoxazole, HBO）探针的位点特异性亲核性与ESIPT特性。我们证实，适度的给电子基团（electron-donating groups, EDGs）可协同增强亲核性，同时维持较高的ESIPT效率。这种平衡使得优化后的探针（HBO-OMe）能够在3秒内实现对氯磷酸二乙酯（diethyl chlorophosphate, DCP，检出限LOD=61.1 nM）与光气（检出限LOD=17.4 nM）的超灵敏检测。此外，由HBO-OMe与HBO-Me组成的双探针荧光传感器阵列，是首个可区分5种神经毒剂（塔崩/GA、沙林/GB、梭曼/GD、环沙林/GF及VX）、纯光气以及15种干扰物的传感器。本研究确立了电子效应驱动的ESIPT探针结构-活性关系，并为复杂化学战剂的识别提供了一种基于阵列的实用解决方案。