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.
Tanabe
Kazuhito
K
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510, Japan. tanabeka@scl.kyoto-u.ac.jp
Hirata
Nao
N
Harada
Hiroshi
H
Hiraoka
Masahiro
M
Nishimoto
Sei-Ichi
S
D003374:Coumarins / Q000737:chemistry*; D004583:Electrons; D000860:Hypoxia / Q000378:metabolism*; D045563:Indolequinones / Q000737:chemistry*; D010084:Oxidation-Reduction; D013050:Spectrometry, Fluorescence / Q000379:methods*
D003374:Coumarins; D045563:Indolequinones