OH-Initiated Atmospheric Degradation of Hydroxyalkyl Hydroperoxides: Mechanism, Kinetics, and Structure-Activity Relationship

Hydroxyalkyl hydroperoxides (HHPs), formed in the reactions of Criegee intermediates (CIs) with water vapour, play essential roles in the formation of secondary organic aerosol (SOA) under atmospheric conditions. However, the transformation mechanism for OH-initiated oxidation of HHPs is remain incompletely understood. Herein, the quantum chemical and kinetics modeling methods are applied to insight into the detailed mechanisms of OH-initiated oxidation of distinct HHPs formed form the reactions of CH2OO, anti-CH3CHOO and (CH3)2COO) with water vapor. The calculations show that H-abstraction by OH radical from the -OOH group of distinct HHPs is predominate as the main products peroxyl radicals (RO2), and the barrier of dominant pathway is increased as the number of methyl group is increased. In pristine environments, the self-reaction of RO2 radical initially produces tetroxide intermediate via a head-to-head interaction, then it decomposes into propagation and termination products through the asymmetric two-step O-O bond scission, in which the rate-limiting step is the first O-O bond cleavage. The barrier height of distinct RO2 radicals reactions with HO2 radical is independent on the number of methyl substitution. Compared to the rate coefficient of parent system, it is increased by a factor of 3–5 when one or two methyl groups introduce into the C1-position. The autoxidation of RO2 radicals are unlikely to proceed in the atmosphere due to their dramatically high barriers and strongly endergonic. In urban environments, the rate-limiting step is the hydrogen abstraction by O2 in the processes of HOCH2OO radical reaction with NO, while it becomes the O-O bond scission when one or two methyl substitutions occur at the C1-position of HOCH2OO radical. These new findings are expected to deepen our current understanding for the photochemistry oxidation of hydroperoxides under realistic atmospheric conditions.

7-Dehydrocholesterol is an endogenous suppressor of ferroptosis

Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation exploited by tumours to counteract phospholipid oxidation. Here, we identify a pro-ferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected pro-survival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high levels of 7-DHC are cytotoxic to developing neurons and favour lipid peroxidation, we now demonstrate that 7-DHC accumulation confers a robust pro-survival function in cancer cells. 7-DHC, due to its far superior reactivity towards peroxyl radicals, is shown here to effectively shield (phospho)lipids from autoxidation and subsequent fragmentation. We further demonstrate in a subset of ferroptosis-sensitive Burkitt lymphomas - where DHCR7 mutations have been reported - that the accumulation of 7-DHC is sufficient to suppress the basal sensitivity of cells toward ferroptosis, thereby translating into an unexpected growth advantage. Conclusively, our findings provide compelling evidence of a yet-unrecognised anti-ferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.

A Systematic Study of the Antioxidant Capacity of Humic Substances against Peroxyl Radicals: Relation to Structure

Humic substances (HS) are natural supramolecular systems of high- and low-molecular-weight compounds with distinct immunomodulatory and protective properties. The key beneficial biological activity of HS is their antioxidant activity. However, systematic studies of the antioxidant activity of HS against biologically relevant peroxyl radicals are still scarce. The main objective of this work was to estimate the antioxidant capacity (AOC) of a broad set of HS widely differing in structure using an oxygen radical absorption capacity (ORAC) assay. For this purpose, 25 samples of soil, peat, coal, and aquatic HS and humic-like substances were characterized using elemental analysis and quantitative 13C solution-state NMR. The Folin–Ciocalteu method was used to quantify total phenol (TP) content in HS. The determined AOC values varied in the range of 0.31–2.56 μmol Trolox eqv. mg−1, which is close to the values for ascorbic acid and vitamin E. Forward stepwise regression was used to reveal the four main factors contributing to the AOC value of HS: atomic C/N ratio, content of O-substituted methine and methoxyl groups, and TP. The results obtained clearly demonstrate the dependence of the AOC of HS on both phenolic and non-phenolic moieties in their structure, including carbohydrate fragments.

Uncoupling effect of lipid peroxidation in spinach thylakoids exposed to peroxyl radicals generated by 2,2′-azobis (2-amidinopropane) dihydrochloride

In this study, we characterized how lipid peroxidation alters the functionality of spinach thylakoids exposed to peroxyl radicals generated by the azo compound 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH). Incubation of thylakoids in presence of different concentrations (0 to 200 mM) of AAPH inhibited the formation of ΔpH (IC50 ≈ 1.5 mM) estimated by the quenching of 9-aminoacridine fluorescence (Q9-AA). The Q9-AA inhibition was correlated (R2=0.98) to the extent of lipid peroxidation determined by the accumulation of thiobarbituric acid reactive substances (TBARS). Much higher AAPH concentrations were required to inhibit the maximum (Fv/Fm) and effective (ΔF/Fm’) photochemical efficiencies of photosystem II (IC50 ≈ 120 mM and 50 mM respectively), indicating that moderate lipid peroxidation caused the uncoupling of spinach thylakoids. This was confirmed by the 62 % stimulation of the O2 uptake rates measured without the artificial uncoupler NH4Cl when the AAPH concentrations increased from 0 to at 20 mM, reaching similar values to the rates measured in presence of NH4Cl. Above 20 mM AAPH, the O2 uptake rates measured with and without NH4Cl declined similarly to the decrease of ΔF/Fm’. These results suggest that the increased H+-leakiness of thylakoid membranes could be one of the primary effects of oxidative stress.

Terpenoids and Polyphenols as Natural Antioxidant Agents in Food Preservation

Synthetic antioxidant food additives, such as BHA, BHT and TBHQ, are going through a difficult time, since these products generate a negative perception in consumers. This has generated an increased pressure on food manufacturers to search for safer natural alternatives like phytochemicals (such as polyphenols, including flavonoids, and essential oils rich in terpenoids, including carotenoids). These plant bioactive compounds have antioxidant activities widely proven in in vitro tests and in diverse food matrices (meat, fish, oil and vegetables). As tons of food are wasted every year due to aesthetic reasons (lipid oxidation) and premature damage caused by inappropriate packaging, there is an urgent need for natural antioxidants capable of replacing the synthetic ones to meet consumer demands. This review summarizes industrially interesting antioxidant bioactivities associated with terpenoids and polyphenols with respect to the prevention of lipid oxidation in high fat containing foods, such as meat (rich in saturated fat), fish (rich in polyunsaturated fat), oil and vegetable products, while avoiding the generation of rancid flavors and negative visual deterioration (such as color changes due to oxidized lipids). Terpenoids (like monoterpenes and carotenoids) and polyphenols (like quercetin and other flavonoids) are important phytochemicals with a broad range of antioxidant effects. These phytochemicals are widely distributed in fruits and vegetables, including agricultural waste, and are remarkably useful in food preservation, as they show bioactivity as plant antioxidants, able to scavenge reactive oxygen and nitrogen species, such as superoxide, hydroxyl or peroxyl radicals in meat and other products, contributing to the prevention of lipid oxidation processes in food matrices.

Measurement report: Nitrogen isotopes (<i>δ</i>¹⁵N) and first quantification of oxygen isotope anomalies (<i>Δ</i>¹⁷O, <i>δ</i>¹⁸O) in atmospheric nitrogen dioxide

The isotopic composition of nitrogen and oxygen in nitrogen dioxide (NO2) potentially carries a wealth of information about the dynamics of the nitrogen oxides (NOx = nitric oxide (NO) + NO2) chemistry in the atmosphere. While nitrogen isotopes of NO2 are subtle indicators of NOx emissions and chemistry, oxygen isotopes are believed to reflect only the O3 / NOx / VOC chemical regime in different atmospheric environments. In order to access this potential tracer of the tropospheric chemistry, we have developed an efficient active method to trap atmospheric NO2 on denuder tubes and measured, for the first time, its multi-isotopic composition (δ15N, δ18O, and Δ17O). The Δ17O values of NO2 trapped at our site in Grenoble, France, show a large diurnal cycle peaking in late morning at (39.2 ± 0.3) ‰ and decreasing at night until (20.5 ± 0.3) ‰. On top of this diurnal cycle, Δ17O also exhibits substantial daytime variability (from 29.7 ‰ to 39.2 ‰), certainly driven by changes in the O3 to peroxyl radicals (RO2) ratio. The nighttime decay of Δ17O(NO2) appears to be driven by NO2 slow removal, mostly from conversion into N2O5, and its formation from the reaction between O3 and freshly emitted NO. As expected from a nighttime Δ17O(NO2) expression, our Δ17O(NO2) measured towards the end of the night is quantitatively consistent with typical values of Δ17O(O3). Daytime N isotope fractionation is estimated using a general expression linking it to Δ17O(NO2). An expression is also derived for the nighttime N isotope fractionation. In contrast to Δ17O(NO2), δ15N(NO2) measurements exhibit little diurnal variability (−11.8 ‰ to −4.9 ‰) with negligible isotope fractionations between NO and NO2, mainly due to high NO2 / NOx ratios, excepted during the morning rush hours. The main NOx emission sources are estimated using a Bayesian isotope mixing model, indicating the predominance of traffic emissions in this area. These preliminary results are very promising for using the combination of Δ17O and δ15N of NO2 as a probe of the NOx sources and fate and for interpreting nitrate isotopic composition records.