A novel target and pH dual-activatable fluorescent probe for precisely detecting hypochlorite in lysosomes

Anal Chim Acta. 2020 Jan 15:1094:122-129. doi: 10.1016/j.aca.2019.10.004. Epub 2019 Oct 17.

Abstract

Hypochlorite (HClO) is involved in various physiological and pathological processes as well as regulation of lysosomal functions. Thus, it is appreciated to develop efficient molecule tools for precisely detecting HClO in lysosomes. Although several lysosomal-targetable fluorogenic probes for HClO have been developed to date, they still suffered from the discounted sensing performance under lysosomal acidic condition. Herein, on the basis of the "AND" logic gate strategy, a novel dual-activatable fluorogenic probe CS has been rationally designed by simultaneously incorporating HClO recognition site and pH-sensitive group with lysosomal-targetable characteristic into a coumarin fluorophore. Different from the single-activated ones previously reported, CS exhibited good sensitivity, high specificity and fast response towards HClO under the acidic conditions but was out of operation in the neutral or alkaline environment. Importantly, it had been successfully applied for spatial-resolution imaging of exogenous or endogenous HClO in lysosomes.

Keywords: Coumarin; Fluorescent probe; Hypochlorite acid; Imaging; Lysosome.

MeSH terms

  • Coumarins / chemical synthesis
  • Coumarins / chemistry*
  • Coumarins / toxicity
  • Density Functional Theory
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / toxicity
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Hypochlorous Acid / analysis*
  • Limit of Detection
  • Lysosomes / metabolism*
  • Microscopy, Confocal / methods
  • Microscopy, Fluorescence / methods
  • Models, Chemical
  • Spectrometry, Fluorescence / methods

Substances

  • Coumarins
  • Fluorescent Dyes
  • Hypochlorous Acid