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Photoreactivity of biologically active compounds. XIX: Excited states and free radicals from the antimalarial drug primaquine

Kristensen, S, Edge, R, Tønnesen, HH, Bisby, RH and Navaratnam, S 2009, 'Photoreactivity of biologically active compounds. XIX: Excited states and free radicals from the antimalarial drug primaquine' , Journal of Photochemistry and Photobiology B: Biology, 94 (3) , pp. 147-157.

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        Abstract

        The formation and reactivity of excited states and free radicals from primaquine was studied in order to evaluate the primary photochemical reaction mechanisms. The excited primaquine triplet was not detected, but is likely to be formed with a short lifetime (< 50 ns) and with a triplet energy < 250 kJ/mol as the drug is an efficient quencher of the fenbufen triplet and the biphenyl triplet, and forms 1O2 by laser flash photolysis (PQΦΔ = 0.025). Primaquine photoionises by a biphotonic process and also forms the monoprotonated cation radical (PQH2+•) by one electron oxidation by OH• (kq = 6.6•109 M-1s-1) and Br2•- (kq = 4.7•109 M-1s-1) at physiological pH, detected as a long-lived transient decaying essentially by a second order process (k2 = 7.4•108 M-1s-1). PQH2+• is scavenged by O2, although at a limited rate (kq = 1.0•106 M-1s-1). The reduction potential (E°) of PQH2+• / PQH+ is < +1015 mV. Primaquine also forms PQH2+• at pH 2.4, by one electron oxidation by Br2•- and proton loss (kq = 2.7•109 M-1s-1). The non-protonated cation radical (PQ+•) is formed during one electron oxidation with Br2•- at alkaline conditions (kq = 4.2•109 M-1s-1 at pH 10.8). The estimated pKa-value of PQH2+•/ PQ+• is pKa ~ 7-8. Primaquine is not a scavenger of O2•- at physiological pH. Thus self-sensitization by O2•- is eliminated as a degradation pathway in the photochemical reactions. Impurities in the raw material and photochemical degradation products initiate photosensitized degradation of primaquine in deuterium oxide, prevented by addition of the 1O2 quencher sodium azide. Photosensitized degradation by formation of 1O2 is thus important for the initial photochemical decomposition of primaquine, which also proceeds by free radical reactions. Formation of PQH2+• is expected to play an essential part in the photochemical degradation process in a neutral, aqueous medium.

        Item Type: Article
        Themes: Subjects / Themes > Q Science > QD Chemistry
        Subjects outside of the University Themes
        Schools: Colleges and Schools > College of Science & Technology
        Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences
        Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences > Biomedical Research Centre
        Journal or Publication Title: Journal of Photochemistry and Photobiology B: Biology
        Publisher: Elsevier
        Refereed: Yes
        ISSN: 10111344
        Depositing User: RH Bisby
        Date Deposited: 16 Feb 2009 10:48
        Last Modified: 20 Aug 2013 16:55
        URI: http://usir.salford.ac.uk/id/eprint/1739

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