The Unusual Reaction of Semiquinone Radicals with Molecular Oxygen

Abstract

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 O2, provide many important insights. They show that the reaction of O2 with 2,5-di-tert-butyl-1,4-semiquinone radical (used as model compound) has a rate constant of 2.4 +/- 0.9 x 10(5) M-1 s-1 in acetonitrile and as high as 2.0 +/- 0.9 x 10(6) M-1 s-1 in chlorobenzene, i.e., similar to that previously reported in water at pH approximately 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 O2 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.

Antioxidant Effect of Berberine and its Phenolic Derivatives Against Human Fibrosarcoma Cells

“…That is the reason why catechol, containing two hydroxyl groups in ortho position, is classified as the most active antioxidant compounds due to the ability to trap two peroxyl radicals (Valgimigli et al, 2008). More phenolic groups were believed to produce more antioxidant activity as found in the previous report (Bors et al, 1996).…”

Antioxidants in Chemistry and Biology

“…57 Alternatively, the value of k inh and the time course of changes in reactants/products can be obtained by computational methods, by simulating the oxygen-uptake trace in accordance with (6)-(11) (or (12-18 and 21, 22)). 58,59 It should be noted that the stoichiometric factor cannot be obtained from plots C and D, and it has to be assumed as 2 or determined using a substrate with a much lower k p . It should be pointed out that, in plot C, although the rate of oxygen uptake changes during the autoxidation, the intersection of the linear regressions corresponding to the apparent inhibited and uninhibited portions of the autoxidation does not represent τ .…”

“…160 The lower O-H BDE in catechols as compared to hydroquinones is the result of a strengthening in the intramolecular H bond as one of the H atoms is removed and the semiquinone radical is formed. Consequently, catechols and hydroquinones have very large inhibition rate constants, for example, 2.0 × 10 6 M −1 s −1 for 60 and 1.6 × 10 6 M −1 s −1 for 61 in chlorobenzene at 30 • C. 58 Resorcinols, on the other hand, are not documented to be very effective antioxidants.…”

“…This is the result of the competing reaction of the intermediate p-semiquinone radical with O 2 . 58 This reaction, which has been shown to proceed with a rate constant of 2 × 10 6 M −1 s −1 at 298 K in chlorobenzene for the semiquinone radical derived from 61, is believed Table 4 Representative self-reaction rate constants for selected phenoxyl radicals. Data from Ref.…”

A new efficient domino approach for the synthesis of pyrazolyl-phthalazine-diones. Antiradical activity of novel phenolic products

“…19 Resonance and electron donating effects of these groups increase the stability of the formed phenoxy radical. This stabilisation effect is the most pronounced in catechol-like compounds, where the hydroxy group contributes to the homolytic cleavage of the neighbouring O-H bond, and has the ability to form a hydrogen bond with formed phenoxy radical.…”