Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.14279/2246
Title: Ferryl–oxo heme intermediate in the antimalarial mode of action of artemisinin
Authors: Kapetanaki, Sofia M. 
Varotsis, Constantinos 
Major Field of Science: Medical and Health Sciences
Field Category: Medical Biotechnology
Keywords: Antimalarials;Artemisinin;Fourier transform infrared spectroscopy;Heme;Iron;Oxygen;Raman spectrometry
Issue Date: 2-Jan-2000
Source: FEBS letters, 2000, vol. 474, no. 2–3, pp. 238–241
Volume: 474
Issue: 2-3
Start page: 238
End page: 241
Journal: FEBS Letters 
Abstract: Fourier transform infrared (FTIR) and resonance Raman (RR) spectroscopies have been employed to investigate the reductive cleavage of the O-O bond of the endoperoxide moiety of the antimalarial drug artemisinin and its analog trioxane alcohol by hemin dimer. We have recorded FTIR spectra in the ν(O-O) and ν(as)(Fe-O-Fe) regions of artemisinin and of the hemin dimer that show the cleavage of the endoperoxide and that of the hemin dimer, respectively. We observed similar results in the trioxane alcohol/hemin dimer reaction. The RR spectrum of the artemisinin/hemin dimer reaction displays a vibrational mode at 850 cm-1 that shifts to 818 cm-1 when the experiment is repeated with 18O-O18 endoperoxide enriched trioxane alcohol. The frequency of this vibration and the magnitude of the 18O-O18 isotopic shift led us to assign the 850 cm-1 mode to the Fe(IV) = O stretching vibration of a ferryl-xoxo heme intermediate that occurs in the artemisinin/hemin dimer and trioxane alcohol/hemin reactions. These results provide the first direct characterization of the antimalarial mode of action of artemisinin and its trioxane analog, and suggest that artemisinin appears to react with heme molecules that have been incorporated into hemozoin and subsequently the heme performs cytochrome P450-type chemistry
URI: https://hdl.handle.net/20.500.14279/2246
ISSN: 00145793
DOI: 10.1016/S0014-5793(00)01592-1
Rights: © Wiley
Type: Article
Affiliation: University of Crete 
Affiliation : University of Crete 
Publication Type: Peer Reviewed
Appears in Collections:Άρθρα/Articles

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