Hantzsch Ester Modified Asymmetric BODIPY Probe with Ultra‐high Sensitivity for Ultra‐fast Detection of Endogenous Hypochlorite in Living Cells

Abstract

Comprehensive SummaryHypochlorite (ClO–) is an important reactive oxygen species produced by the immune system to fight off invading pathogens, but its over‐expression can interfere with normal physiological process and induce serious diseases. Although a variety of molecular probes have been reported for detecting ClO–, the development of advanced fluorescent tools with faster response and higher sensitivity to precisely monitor ClO– remains a challenge. In this work, two Hantzsch ester (a derivative of 1,4‐dihydropyridine) derived fluorescent probes MeDHP‐BCl and MeDHP‐PhBCl were constructed based on asymmetric BODIPY‐matrix. These probes exhibit significant fluorescence turn‐on in the ultra‐sensitive (detection limit < 1 nmol/L) and ultra‐fast response (≤ 5 s) to ClO–. The reaction has been determined to be a highly selective N‐chlorination of Hantzsch ester which cannot be activated by various common bioactive species, including nitric oxide (NO) that could oxidize Hantzsch ester under aerobic physiological conditions in most reports. MeDHP‐PhBCl possessed a relatively longer fluorescence emission wavelength and higher quantum yield after activation, while more notably, MeDHP‐BCl displayed lower cytotoxicity and more remarkable fluorescence increment in the response to ClO–, enabling selective and precise visualization of endogenous ClO– over‐expression in living RAW264.7 cells.