title: Fluorescent Probe HKSOX-1 for Imaging and Detection of Endogenous Superoxide in Live Cells and In Vivo.
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.
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Jun Jacob
authors.initials: JJ
authors.lastname: Hu
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Nai-Kei
authors.initials: NK
authors.lastname: Wong
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Sen
authors.initials: S
authors.lastname: Ye
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Xingmiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lu
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Angela Qian
authors.initials: AQ
authors.lastname: Zhao
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Alvin Chun-Hang
authors.initials: AC
authors.lastname: Ma
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Anskar Yu-Hung
authors.initials: AY
authors.lastname: Leung
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shen
authors.affiliation: †Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
mesh_terms: D000476:Alkanesulfonates / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D005452:Fluoresceins / Q000138:chemical synthesis / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D045325:HCT116 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000737:chemistry* / Q000166:cytology; D051379:Mice; D015394:Molecular Structure; D013481:Superoxides / Q000032:analysis*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D000476:Alkanesulfonates; D005452:Fluoresceins; D005456:Fluorescent Dyes; C000605801:HKSOX-1; D013481:Superoxides