Fluorescent Probe HKSOX-1 for Imaging and Detection of Endogenous Superoxide in Live Cells and In Vivo

J Am Chem Soc. 2015 Jun 3;137(21):6837-43. doi: 10.1021/jacs.5b01881. Epub 2015 May 19.

Abstract

Superoxide anion radical (O2(•-)) is undoubtedly the most important primary reactive oxygen species (ROS) found in cells, whose formation and fate are intertwined with diverse physiological and pathological processes. Here we report a highly sensitive and selective O2(•-) detecting strategy involving O2(•-) cleavage of an aryl trifluoromethanesulfonate group to yield a free phenol. We have synthesized three new O2(•-) fluorescent probes (HKSOX-1, HKSOX-1r for cellular retention, and HKSOX-1m for mitochondria-targeting) which exhibit excellent selectivity and sensitivity toward O2(•-) over a broad range of pH, strong oxidants, and abundant reductants found in cells. In confocal imaging, flow cytometry, and 96-well microplate assay, HKSOX-1r has been robustly applied to detect O2(•-) in multiple cellular models, such as inflammation and mitochondrial stress. Additionally, our probes can be efficiently applied to visualize O2(•-) in intact live zebrafish embryos. These probes open up exciting opportunities for unmasking the roles of O2(•-) in health and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanesulfonates / chemical synthesis
  • Alkanesulfonates / chemistry*
  • Animals
  • Cell Line
  • Cell Survival
  • Fluoresceins / chemical synthesis
  • Fluoresceins / chemistry*
  • Fluorescent Dyes / analysis
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • HCT116 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Macrophages / chemistry*
  • Macrophages / cytology
  • Mice
  • Molecular Structure
  • Superoxides / analysis*
  • Zebrafish / embryology*

Substances

  • Alkanesulfonates
  • Fluoresceins
  • Fluorescent Dyes
  • HKSOX-1
  • Superoxides