Emission under Hypoxia: One‐Electron Reduction and Fluorescence Characteristics of an Indolequinone–Coumarin Conjugate

A characteristic feature of the reactivity of indolequinone derivatives, substituents of which can be removed by one‐electron reduction under hypoxic conditions, was applied to the development of a new class of fluorescent probes for disease‐relevant hypoxia. A reducing indolequinone parent molecule conjugated with fluorescent coumarin chromophores could suppress efficiently the fluorescence emission of the coumarin moieties by an intramolecular electron‐transfer quenching mechanism and a conventional internal‐filter effect. Under hypoxic conditions, however, the conjugate, denoted IQ‐Cou, underwent a one‐electron reduction triggered by X irradiation or the action of a reduction enzyme to release a fluorescent coumarin chromophore, whereupon an intense fluorescence emission with a maximum intensity at 420 nm was observed. The one‐electron reduction of IQ‐Cou was suppressed by molecular oxygen under aerobic conditions. IQ‐Cou also showed intense fluorescence in a hypoxia‐selective manner upon incubation with a cell lysate of the human fibrosarcoma cell line HT‐1080. The IQ‐Cou conjugate has several unique properties that are favorable for a fluorescent probe of hypoxia‐specific imaging.