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 CO 3 2− , HCO 3 − , Cl − , H 2 PO 4 − , HPO 4 2− , OH − , NO 2 − , NO 3 − , SCN − , I − , CH 3 COO − , Br − , H 2 O 2 , SO 4 2− , HS − , Na + , K + , Fe 2+ , TBHP, t-BuO, 1 O 2 , 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.