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

Hypochlorite(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.