Monitoring of Biological One-Electron Reduction by 19F NMR Using Hypoxia Selective Activation of an 19F-Labeled Indolequinone Derivative

详细信息    查看全文

• 作者：Kazuhito Tanabe ; Hiroshi Harada ; Michiko Narazaki ; Kazuo Tanaka ; Kenichi Inafuku ; Hirokazu Komatsu ; Takeo Ito ; Hisatsugu Yamada ; Yoshiki Chujo ; Tetsuya Matsuda ; Masahiro Hiraoka ; Sei-ichi Nishimoto
• 刊名：Journal of the American Chemical Society
• 出版年：2009
• 出版时间：November 11, 2009
• 年：2009
• 卷：131
• 期：44
• 页码：15982-15983
• 全文大小：112K
• 年卷期：v.131,no.44(November 11, 2009)
• ISSN：1520-5126

文摘

Biological reduction of fluorine-labeled indolequinone derivative (IQ-F) was characterized by ¹⁹F NMR for quantitative molecular understanding. The chemical shift change in ¹⁹F NMR allowed monitoring of the enzymatic reduction of IQ-F. Upon hypoxic treatment of IQ-F with NADPH:cytochrome P450 reductase, IQ-F was activated via catalytic one-electron reduction to release nonafluoro-tert-butyl alcohol (F-OH), while the formation of F-OH was significantly suppressed under aerobic conditions. Similar hypoxia-selective reduction of IQ-F occurred within A549 cells, which expresses NADPH:cytochrome P450 reductase. The kinetic analysis was also performed to propose a reaction mechanism. The molecular oxygen slightly prevents the binding of IQ-F to reductase, while the rate of net reaction was decreased due to oxidation of a semiquinone anion radical intermediate generated by one-electron reduction of IQ-F. The disappearance of IQ-F and appearance of F-OH were imaged by ¹⁹F fast spin echo, thus visualizing the hypoxia-selective reduction of IQ-F by means of MR imaging.