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Monitoring of biological one-electron reduction by (19)F NMR using hypoxia selective activation of an (19)F-labeled indolequinone derivative.

Abstract
Biological reduction of fluorine-labeled indolequinone derivative (IQ-F) was characterized by (19)F NMR for quantitative molecular understanding. The chemical shift change in (19)F 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 (19)F fast spin echo, thus visualizing the hypoxia-selective reduction of IQ-F by means of MR imaging.
AuthorsKazuhito Tanabe, Hiroshi Harada, Michiko Narazaki, Kazuo Tanaka, Kenichi Inafuku, Hirokazu Komatsu, Takeo Ito, Hisatsugu Yamada, Yoshiki Chujo, Tetsuya Matsuda, Masahiro Hiraoka, Sei-ichi Nishimoto
JournalJournal of the American Chemical Society (J Am Chem Soc) Vol. 131 Issue 44 Pg. 15982-3 (Nov 11 2009) ISSN: 1520-5126 [Electronic] United States
PMID19842623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fluorine Radioisotopes
  • Indolequinones
Topics
  • Cell Line
  • Fluorine Radioisotopes
  • Humans
  • Hypoxia (metabolism)
  • Indolequinones (chemistry)
  • Magnetic Resonance Spectroscopy (methods)
  • Oxidation-Reduction

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