Evidence that Criegee intermediates drive autoxidation in unsaturated lipids

Abstract

Autoxidation is an autocatalytic free-radical chain reaction responsible for the oxidative destruction of organic molecules in biological cells, foods, plastics, petrochemicals, fuels, and the environment. In cellular membranes, lipid autoxidation (peroxidation) is linked with oxidative stress, age-related diseases, and cancers. The established mechanism of autoxidation proceeds via H-atom abstraction through a cyclic network of peroxy-hydroperoxide-mediated free-radical chain reactions. For a series of model unsaturated lipids, we present evidence for an autoxidation mechanism, initiated by hydroxyl radical (OH) addition to C=C bonds and propagated by chain reactions involving Criegee intermediates (CIs). This mechanism leads to unexpectedly rapid autoxidation even in the presence of water, implying that as reactive intermediates, CI could play a much more prominent role in chemistries beyond the atmosphere.

Keywords: Criegee intermediate; autoxidation; unsaturated lipids.

Fig. 1.

Two reaction schemes for the OH-initiated autoxidation of unsaturated lipids. (A) The established lipid peroxidation scheme, which is initiated by H abstraction at allylic C-H sites and propagated by peroxy radicals (RO₂) and hydroperoxides (ROOH). (B) CI-driven lipid autoxidation mechanism, which is initiated by the OH addition reactions and propagated by chain reactions involving the CI. The reaction of two RO₂ radicals are common termination steps in both mechanisms. Additional termination reactions of CI include their reactions with aldehydes (RC = O) to produce SOZs, with alcohols (ROH) to produce α-hydroperoxide ethers, and with carboxylic acids (ROOH) to produce hydroperoxide esters.

Fig. 2.

Effective reaction probability (γ_eff) as a function of OH concentration ([OH]). γ_eff of Sqe, AA, LA, OA, Tri, squalane (Sqa), 2-decyl-1-tetradecanol and 2-octyl-1-dodecanol as a function of [OH] at an RH of 30%. The data for Sqa are from ref. . Values of γ_eff ≤ 1 indicate that the reaction is proceeding at or below the OH collision (i.e., initiation) rate. Values larger than 1 are evidence for radical chain reactions and an overall autoxidation rate that exceeds the OH collision frequency.

Fig. 3.

(A and B) VUV-AMS of the OH + Sqe reaction products. (C) Reaction products and (D) effective reaction probability as a function of alcohol mole fraction. (A) Difference mass spectra (unreacted Sqe – reacted Sqe) showing aldehyde products (C₁₇H₂₈O, C₂₂H₃₆O, and C₂₇H₄₄O) and five SOZs. (B) Difference spectra showing product distribution when the CI scavenger (2-decyl-1-tetradecanol) is added to Sqe. Major products are the same three aldehydes, and six α-hydroperoxide ethers (with their structures and fragments in colors). (C) SOZs, aldehydes, and α-hydroperoxide ethers as a function of alcohol mole fraction (2-decyl-1-tetradecanol). (D) γ_eff of Sqe and 2-decyl-1-tetradecanol as a function of alcohol percentage (2-decyl-1-tetradecanol). All experiments are performed at [OH] (∼1.2 × 10⁷ molecules/cm³) and under RH ∼0%.

Fig. 4.

Effective reaction probability (γ_eff) of Sqe, relative fraction of SOZs and aldehydes as a function of % RH in the Sqe + OH reaction. (Left y axis) γ_eff of Sqe and (Right y axis) normalized sum of the five SOZs (C₂₀, C₂₅, C₃₀, C₃₅, C₄₀) and three aldehydes (C₁₇H₂₈O, C₂₂H₃₆O, C₂₇H₄₄O) as a function of RH. All experiments are performed at [OH] ∼1.5 × 10⁷ molecules/cm³. These results indicate that although the product distributions depend upon RH, the autoxidation rate does not.