title: Red-Fluorescent Activatable Probes for the Detection of Hydrogen Peroxide in Living Cells.
abstract: Many inflammatory processes are associated with an increase in the production of reactive oxygen species (ROS). Chemical probes that specifically detect ROS are potentially useful tools for the early diagnosis of inflammatory diseases as well as cancer. Herein we have developed a library of coumarin hybrids by condensation of various heterocyclic quaternary salts to a 7-hydroxycoumarin scaffold. From our library we identified one benzothiazole-coumarin hybrid as a red-fluorescent compound with emission maxima around 620 nm and a strong fluorogenic response. Furthermore, we proved that this scaffold is suitable for the preparation of activatable probes, such as by modification with a boronate group for selective sensing of hydrogen peroxide (H2O2). In vitro assays confirmed the reactivity and subsequent emission of our probe upon incubation with H2O2 with good selectivity over different ROS and reactive nitrogen species (RNS) as well as minimal toxicity in cells. Finally cell imaging experiments were performed in murine macrophages and validated the utility of the activatable probe for the detection of H2O2 in living cells.
authors.forename: Claudia
authors.initials: C
authors.lastname: Garcia-Guzman
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernandez
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Avlonitis
authors.forename: Mark
authors.initials: M
authors.lastname: Bradley
authors.affiliation: MRC Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinbugh, Edinburgh EH16 4TJ, UK. marc.vendrell@ed.ac.uk.
authors.forename: Marc
authors.initials: M
authors.lastname: Vendrell
mesh_terms: D000818:Animals; D002460:Cell Line; D003116:Color; D003374:Coumarins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000032:analysis*; D008264:Macrophages / Q000737:chemistry / Q000166:cytology; D051379:Mice; D017382:Reactive Oxygen Species / Q000032:analysis; D054852:Small Molecule Libraries / Q000737:chemistry
chemical_list: D003374:Coumarins; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D054852:Small Molecule Libraries; D006861:Hydrogen Peroxide