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.
|
Authors | 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 |
Journal | Journal 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 |
PMID | 19842623
(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
|