The Unusual Reaction of Semiquinone Radicals with Molecular Oxygen Luca Valgimigli,* ,# Riccardo Amorati, # Maria Grazia Fumo, # Gino A. DiLabio, ² Gian Franco Pedulli, # Keith U. Ingold, § and Derek A. Pratt* ,‡ Dipartimento di Chimica Organica “A. Mangini” Via San Giacomo 11, UniVersita ` di Bologna, 40126 Bologna, Italy, National Institute for Nanotechnology, National Research Council of Canada, 11421 Saskatchewan DriVe, Edmonton, AB, Canada T6G 2M9, National Research Council of Canada, 100 Sussex DriVe, Ottawa, ON, Canada K1A 0R6, and Department of Chemistry, Queen’s UniVersity, 90 Bader Lane, Kingston, ON, Canada K7L 3N6 luca.Valgimigli@unibo.it; pratt@chem.queensu.ca ReceiVed NoVember 16, 2007 Hydroquinones (benzene-1,4-diols) are naturally occurring chain-breaking antioxidants, whose reactions with peroxyl radicals yield 1,4-semiquinone radicals. Unlike the 1,2-semiquinone radicals derived from catechols (benzene-1,2-diols), the 1,4-semiquinone radicals do not always trap another peroxyl radical, and instead the stoichiometric factor of hydroquinones varies widely between 0 and 2 as a function of ring-substitution and reaction conditions. This variable antioxidant behavior has been attributed to the competing reaction of the 1,4-semiquinone radical with molecular oxygen. Herein we report the results of experiments and theoretical calculations focused on understanding this key reaction. Our experiments, which include detailed kinetic and mechanistic investigations by laser flash photolysis and inhibited autoxidation studies, and our theoretical calculations, which include detailed studies of the reactions of both 1,4-semiquinones and 1,2-semiquinones with O 2 , provide many important insights. They show that the reaction of O 2 with 2,5-di-tert-butyl-1,4-semiquinone radical (used as model compound) has a rate constant of 2.4 ( 0.9 × 10 5 M -1 s -1 in acetonitrile and as high as 2.0 ( 0.9 × 10 6 M -1 s -1 in chlorobenzene, i.e., similar to that previously reported in water at pH ∼7. These results, considered alongside our theoretical calculations, suggest that the reaction occurs by an unusual hydrogen atom abstraction mechanism, taking place in a two-step process consisting first of addition of O 2 to the semiquinone radical and second an intramolecular H-atom transfer concerted with elimination of hydroperoxyl to yield the quinone. This reaction appears to be much more facile for 1,4-semiquinones than for their 1,2-isomers. Introduction Hydroquinones (benzene-1,4-diols, I) are naturally occurring compounds, several of which have been isolated from fungi, 1 algae, 2 and sponges, 3,4 but which are most widely found in plants. 5-9 Many such compounds are known or believed to be # Universita ` di Bologna. ² National Institute for Nanotechnology, National Research Council of Canada. § National Research Council of Canada. ‡ Queen’s University. (1) Abdel-Lateff, A. A.; Ko ¨nig, G. M.; Fish, K. M.; Ho ¨ller, U.; Jones, P. G.; Wright, A. D. J. Nat. Prod. 2002, 65, 1605-1611. (2) Aknin, M.; Dayan, T. L.-A.; Rudi, A.; Kashman, Y.; Gaydou, E. M. J. Agric. Food Chem. 1999, 47, 4175-4177. (3) Tziveleka, L.-A.; Abatis, D.; Paulus, K.; Bauer, R.; Vagias, C.; Roussis, V. Chem. BiodiVersity 2005, 2, 901-909. 1830 J. Org. Chem. 2008, 73, 1830-1841 10.1021/jo7024543 CCC: $40.75 © 2008 American Chemical Society Published on Web 02/09/2008