Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 131, Issue 44, Pages 15982-+Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja904953b
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan
- National Institute of Biomedical Innovation (NIBIO), Japan
- Grants-in-Aid for Scientific Research [21300162] Funding Source: KAKEN
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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.
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