Chlorination-induced pK(a) decrease: an improved strategy to design ratiometric hypochlorite fluorescent probes with ideally high selectivity

Based on the selective ClO--triggered chlorination reaction and the subsequent pK(a) decrease of phenols, a new strategy was developed for rationally designing ratiometric ClO- fluorescent probes with high selectivity. By investigating the fluorescence responses of 6-cyano-2-naphthol toward ClO- and the pK(a)-dependent response mechanism, we developed a rapid, sensitive and selective two-photon ratiometric fluorescent probe, Naph-DFOB, to detect ClO-. This probe displayed a ratiometric fluorescence change (from 509 nm to 628 nm) toward ClO- and was successfully applied to image intracellular ClO- in living cells with two-photon excitation. Using Naph-DFOB as a useful tool, the investigation of lipopolysaccharide (LPS)-induced acute lung injury in a mouse model was effectively performed.