2009年11月
Monitoring of Biological One-Electron Reduction by F-19 NMR Using Hypoxia Selective Activation of an F-19-Labeled Indolequinone Derivative
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
- 巻
- 131
- 号
- 44
- 開始ページ
- 15982
- 終了ページ
- +
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/ja904953b
- 出版者・発行元
- AMER CHEMICAL SOC
Biological reduction of fluorine-labeled indolequinone derivative (IQ-F) was characterized by F-19 NMR for quantitative molecular understanding. The chemical shift change in F-19 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 F-19 fast spin echo, thus visualizing the hypoxia-selective reduction of IQ-F by means of MR imaging.
- リンク情報
- ID情報
-
- DOI : 10.1021/ja904953b
- ISSN : 0002-7863
- PubMed ID : 19842623
- Web of Science ID : WOS:000271513700009