Theoretical design of novel fluorophores for near-infrared fluorescent probes of peroxynitrite

On the basis of the experimentally reported near-infrared (NIR) fluorescent probe for peroxynitrite anions (ONOO-) DDAO-PN (DDAO = 1,3-dichloro-7-oxygen-9,9-dimethyl-2(9H)-acridinone, PN = 4- methylene benzeneboronic acid pinacol ester, DDAO-PN connecting 7-oxygen of DDAO with 4- methylene of PN), six DDAO derivatives DDAO-Px (x = 1-6) were designed. The fluorescence response mechanism and characteristics of the DDAO-PN probe to ONOO- were explored and the molecular structures, molecular orbital, and electron transfer during excitation and emission in DDAO-PN and DDAO-Px (x = 1-6) were comparatively analyzed in detail through the density functional theory (DFT) and time-dependent DFT calculations. The significant intramolecular charge transfer (ICT) effect in DDAO-PN were found to be released when PN (as the recognition domain of ONOO- in the recognition process) was removed, rendering DDAO-PN being an effective "off-on" NIR ONOO- fluorescent probe. The introduction of different electron-donating/accepting substituents in DDAO-Px significantly changed the electronic structures and thus the fluorescent properties, which finally modified the probe efficiency. This work clarifies the structure-property relationship in DDAO-Px type NIR probes and thus provides theoretical guidance for designing new NIR fluorescent probe.