Abstract
Hydrogen atom transfer (HAT) is the mechanism by which the vast majority of radical-trapping antioxidants (RTAs), such as hindered phenols, inhibit autoxidation. As such, at least one weak O-H bond is the key structural feature which underlies the reactivity of phenolic RTAs. We recently observed that quinone methide dimers (QMDs) synthesized from hindered phenols are significantly more reactive RTAs than the phenols themselves despite lacking O-H bonds. Herein we describe our efforts to elucidate the mechanism by which they inhibit autoxidation. Four possible reaction paths were considered: (1) HAT from the C-H bonds on the carbon atoms which link the quinone methide moieties; (2) tautomerization or hydration of the quinone methide(s) in situ followed by HAT from the resultant phenolic O-H; (3) direct addition of peroxyl radicals to the quinone methide(s), and (4) homolysis of the weak central C-C bond in the QMD followed by combination of the resultant persistent phenoxyl radicals with peroxyl radicals. The insensitivity of the reactivity of the QMDs to substituent effects, solvent effects and a lack of kinetic isotope effects rule out the HAT reactions (mechanisms 1 and 2). Simple (monomeric) quinone methides, to which peroxyl radicals add, were found to be ca. 100-fold less reactive than the QMDs, ruling out mechanism 3. These facts, combined with the poor RTA activity we observe for a QMD with a stronger central C-C bond, support mechanism 4. The lack of solvent effects on the RTA activity of QMDs suggests that they may find application as additives to materials which contain H-bonding accepting moieties that can dramatically suppress the reactivity of conventional RTAs, such as phenols. This reactivity does not extend to biological membranes owing to the increased microviscosity of the phospholipid bilayer, which suppresses QMD dissociation in favour of recombination. Interestingly, the simple QMs were found to be very good RTAs in phospholipid bilayers - besting even the most potent form of vitamin E.
Highlights
The efficient inhibition of autoxidation continues to be a widelypursued objective, given the indispensability of hydrocarbonbased products in day-to-day life and their propensity to undergo autoxidation
We suggested four possible reaction paths that would account for this observation (Fig. 1C): (1) hydrogen atom transfer (HAT) from the C–H bonds on the carbon atoms which link the quinone methide moieties; (2) tautomerization or hydration of the quinone methide(s) followed by HAT from the resultant phenolic O–H; (3) direct addition of peroxyl radicals to the quinone methide to form persistent phenoxyl radicals, and (4) homolysis of the weak central C–C bond in the quinone methide dimers (QMDs) followed by combination of the resultant persistent phenoxyl radicals with peroxyl radicals
Since we have no information on how substituents impact the QMD-phenoxyl radical equilibrium (Fig. 5A), we investigated it by UV-vis spectrophotometry at different temperatures, enabling determination of the C–C BDEs (DHC–C, tabulated in the Electronic supplementary information (ESI)†) from the resultant Van't Hoff plots (e.g. Fig. 5C).[27]
Summary
The efficient inhibition of autoxidation continues to be a widelypursued objective, given the indispensability of hydrocarbonbased products (either petroleum-derived or plant-derived) in day-to-day life and their propensity to undergo autoxidation. BHT and related phenols react with the peroxyl radicals (ROOc) that propagate the autoxidation chain reaction. The mechanism is well understood to involve hydrogen atom transfer (HAT) from the phenolic O–H to a chain-carrying peroxyl radical followed by rapid combination of the resultant phenoxyl radical with a second peroxyl radical (Fig. 1A).[2] A vast literature has established that substituents can have a substantial impact on the rate of the initial H-atom transfer, which is characterized by the inhibition rate constant (kinh).[2,3] Electrondonating groups accelerate the rate as they stabilize the electron-de cient phenoxyl radical[4] and the transition state leading to its formation, whereas electron-withdrawing groups have the opposite effect
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