Novel hepatocyte-targeting fluorescent probes for detection of hypochlorous acid: Synergistic effect of phosphate and galactose

Abstract

Two novel hepatocyte-targeting fluorescent probes were designed and synthesized. NPG-1 and NPG-2 show good selectivity and sensitivity toward ClO−, which were not disturbed by CO32−, HCO3−, Cl−, H2PO4−, HPO42−, OH−, NO2−, NO3−, SCN−, I−, CH3COO−, Br−, H2O2, SO42−, HS−, Na+, K+, Fe2+, TBHP, t-BuO, 1O2, HO, Cys, Hcy, GSH. The fluorescent “on-off” response of NPG-1 or NPG-2 towards ClO− could be recognized by the naked eye. The possible mechanism is that the methyl thioether group of NPG-1 or NPG-2 is oxidized to sulfoxide group by ClO−, inhibiting the intramolecular charge transfer (ICT) effect of naphthalimides. The hepatocyte-targeting capacity of the synthesized naphthalimide-based fluorescent probes follows N−OH < NP < NPG-1 < NPG-2 trend, suggesting that phosphate modification is an efficient hepatocyte-targeting strategy and co-modification with phosphate and galactose groups could synergistically improve hepatocyte-targeting effect of compounds. Our results demonstrated that the low-toxicity NPG-1 and NPG-2 probes could specifically detect hypochlorite of hepatocytes in real time.