Analytical and Structural Tools of Lipid Hydroperoxides: Present State and Future Perspectives

Abstract

Mono- and polyunsaturated lipids are particularly susceptible to peroxidation, which results in the formation of lipid hydroperoxides (LOOHs) as primary nonradical-reaction products. LOOHs may undergo degradation to various products that have been implicated in vital biological reactions, and thus in the pathogenesis of various diseases. The structure elucidation and qualitative and quantitative analysis of lipid hydroperoxides are therefore of great importance. The objectives of the present review are to provide a critical analysis of various methods that have been widely applied, and more specifically on volumetric methods, applications of UV-visible, infrared, Raman/surface-enhanced Raman, fluorescence and chemiluminescence spectroscopies, chromatographic methods, hyphenated MS techniques, NMR and chromatographic methods, NMR spectroscopy in mixture analysis, structural investigations based on quantum chemical calculations of NMR parameters, applications in living cells, and metabolomics. Emphasis will be given to analytical and structural methods that can contribute significantly to the molecular basis of the chemical process involved in the formation of lipid hydroperoxides without the need for the isolation of the individual components. Furthermore, future developments in the field will be discussed.

Density functional theory calculations of δ(13C) and δ(1H) chemical shifts and 3J(13COO1H) coupling constants as structural and analytical tools in hydroperoxides: Prospects and limitations of 1H13C heteronuclear multiple bond correlation experiments

“…On the contrary, the methine CH OOH proton chemical shifts of the trans isomer are in the region of 4.24-4.41 ppm and, thus, significantly shielded by 0.62-0.70 ppm than those of the cis geometric isomer (4.93-5.05 ppm). The computational results are in very good agreement with literature experimental 1 H chemical shifts [10,31,32] (Figure 6). Thus, the experimental chemical shift difference Δδ( 1 Η) cis/trans ≈ 0.45 ppm is in very good agreement with the computational chemical shift differences of 0.62-0.70 ppm for all functionals and basis sets used.…”

“…This shows that the Boltzmann contribution of, for example, conformer A2 is negligible, in excellent agreement with computational ΔG values (Table S1). Despite the significant chemical shift differences of the two olefinic protons, the chemical shift differences between the cis and trans geometric isomers are very small, in agreement with experimental chemical shift differences ≤ 0.06 ppm, [10,31,32] and, thus, unimportant in stereochemical analysis.…”

“…[29] Recently, very sharp resonances of the hydroperoxide protons (Δν 1/2 < 3 Hz) were obtained in CDCl 3 with the use of methyl ester derivatives of fatty acids. [30][31][32] This was attributed to the absence of the carboxylic proton that accelerates intermolecular proton transfer, thus, resulting in linewidth broadening. This allows the application of the combined use of 1 H 13 C heteronuclear multiple bond correlation (HMBC) [30][31][32] and 1D TOCSY [31,32] for the identification of the hydroperoxide protons of methyl oleate, methyl linoleate, and methyl linolenate primary oxidation products without the need of laborious isolation of the individual compounds.…”

“…[30][31][32] This was attributed to the absence of the carboxylic proton that accelerates intermolecular proton transfer, thus, resulting in linewidth broadening. This allows the application of the combined use of 1 H 13 C heteronuclear multiple bond correlation (HMBC) [30][31][32] and 1D TOCSY [31,32] for the identification of the hydroperoxide protons of methyl oleate, methyl linoleate, and methyl linolenate primary oxidation products without the need of laborious isolation of the individual compounds. A wide range of chemical shifts of sharp resonances of the hydroperoxide protons (7.5 to 9.6 ppm) was observed in CDCl 3 .…”

NMR and computational studies reveal novel aspects in molecular recognition of unsaturated fatty acids with non‐labelled serum albumin

“…Further NMR, computational and ITC studies are currently in progress to investigate the interaction of EPA (20 : 5 cis 5,8,11,14,17), DHA (22 : 6 cis 4,7,10, 13,16,19), nitro-FFAs [56,57] and primary and secondary oxidation products of polyunsaturated fatty acids [58,59] with serum albumin.…”