A pulse radiolysis study of free radicals formed by one electron oxidation of the antimalarial drug pyronaridine

Ismail, FMD; Drew, MGB; Navaratnam, S; Bisby, RH

Abstract

Free radicals from one-electron oxidation of the antimalarial drug pyronaridine have been studied by pulse radiolysis. The results show that pyronaridine is readily oxidised to an intermediate semiiminoquine radical by inorganic and organic free radicals, including those derived from tryptophan and acetaminophen. The pyronaridine radical is rapidly reduced by both ascorbate and caffeic acid. The results indicate that the one-electron reduction potential of the pyronaridine radical at neutral pH lies between those of acetaminophen (707 mV) and caffeic acid (534 mV). The pyronaridine radical decays by a second order process which DFT calculations (UB3LYP/6-31+G* ) suggest is a disproportionation reaction. Important calculated dimensions of pyronaridine, its phenoxyl and aminyl radical as well as the iminoquinone are presented.

• Journal Article Type: Article
• Publication Date: Jan 1, 2009
• Deposit Date: Sep 28, 2011
• Publicly Available Date: Apr 5, 2016
• Journal: Research on Chemical Intermediates
• Print ISSN: 0922-6168
• Electronic ISSN: 1568-5675
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 35
• Issue: 4
• Pages: 363-377
• DOI: https://doi.org/10.1007/s11164-009-0051-7
• Keywords: Pyronaridine, free radical, pulse radiolysis, oxidation, DFT, antimalarial
• Publisher URL: http://dx.doi.org/10.1007/s11164-009-0051-7