Quantitative and systematic designing of fluorophores enables ultrasensitive distinguishing carbonyls

Although the use of sophisticated fluorescent probes can improve the detection sensitivity, either the lack of quantitative design for fluorophores or the deficiency of selectivity towards individual species makes it extremely difficult to distinguish homologs accurately. Herein, this study reports a quantitative strategy for the systematic engineering of fluorophores via density functional theory (DFT). A series of seven 1,8-naphthylamide hydrazine (NH-1–7) compounds was elaborately tailored on the basis of the PET mechanism, EPS charge population and the maximum HOMO overlap principle. The results showed that the obtained NH-4 exhibited 300-fold “off–on” signal towards carbonyls with extraordinary reactivity and high solubility. Importantly, the ultra-low limits of detection (LOD) towards multi-carbonyl homologs could reach 1.0 × 10−12 M on the ultra-high pressure liquid chromatography (UHPLC) in an 8 min analysis window. This systematic and quantitative engineering of fluorophores lays a bridge between efficient development of novel fluorophores and trace level detection in various matrixes.