Maximo-Canadas_2025_ACS.Omega_10_47266

The efficient detection of nerve agents is paramount in civilian and war contexts. In this work, we investigated theoretically the mechanisms of fluorescence quenching and charge transfer (CT) in two recently synthesized small molecule fluorescent probes for detecting nerve agents, NMU-1 and 10-hydroxybenzo-[h]-quinoline (HBQ-AE), which are based on the pyridine group as the identifying unit. These fluorescent molecules change their emission pattern upon binding to an organophosphorus compound. We employed density functional theory (DFT), implicit methods for describing the water solvent, and a path integral approach to calculate fluorescence rates and emission spectra from first-principles for analyzing the interaction between the nerve agent simulant diethyl chlorophosphite (DCP) and NMU-1 or HBQ-AE. Upon interacting with DCP, both HBQ-AE and NMU-1 experience strong fluorescence quenching, with intensity reductions of -99.65 and -99.95%, respectively, due to enhanced CT induced by DCP's electron-accepting nature and formation of a positively charged nitrogen within the probes. Although the measured fluorescence enhancement in HBQ-AE/DCP systems was attributed to the HBQ-DCP product, our results show a different picture: the true fluorescent species is the hydrolysis product HBQ + H, whose calculated emission differs by a blue shift of only 0.23 eV from the experimental data, rather than the HBQ-DCP product as previously thought. For acetylcholinesterase (AChE) detection, fluorescence is confirmed to originate from the HBQ-Keto, with a blue shift deviation of 0.12 eV. The NMU-1 calculations also confirm the experiments, showing a 0.24 eV deviation, thus confirming its quenching-based detection of DCP. Therefore, HBQ-AE is a fluorescence turn-on sensor via its emissive hydrolysis product HBQ+H. In contrast, NMU-1 is a turn-off sensor, as both NMU-DCP and NMU+H are essentially nonemissive. Our theoretical approach is general, accurate, and can be applied to different problems involving fluorescent probes and binding agents.