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Autoxidation of Conjugated Linoleic Acid Methyl Ester in the Presence of α-Tocopherol: The Hydroperoxide Pathway

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Lipids

Abstract

Autoxidation of conjugated linoleic acid (CLA) methyl ester follows at least partly Farmer’s hydroperoxide theory. A mechanism for this hydroperoxide pathway has been proposed based on autoxidation of 9-cis,11-trans-CLA methyl ester. This investigation aims at confirming and further clarifying the mechanism by analyzing the hydroperoxides produced from 10-trans,12-cis-CLA methyl ester and by theoretical calculations. Five methyl hydroxyoctadecadienoates were isolated by HPLC and characterized by UV, GC-MS, and 1D- and 2D-NMR techniques. In addition, an HPLC method for the separation of the intact hydroperoxides was developed. The autoxidation of 10-trans,12-cis-CLA methyl ester in the presence of high amount of α-tocopherol (20%) was diastereoselective in favor of one geometric isomer, namely Me 9-OOH-10t,12c, and produced new positional isomers 10- and 14-hydroperoxides (Me 10-OOH-11t,13t; Me 14-OOH-10t,12c; and Me 14-OOH-10t,12t). Importantly, one of these new isomers, which was characterized as an intact hydroperoxide, had an unusual cis,trans geometry where the cis double bond is adjacent to the hydroperoxyl-bearing methine carbon. Further insight to the mechanism was provided by calculating the relative energies for different conformations of the precursor lipid, the allylic carbon–hydrogen bond dissociation enthalpies, and the spin distributions on the intermediate pentadienyl radicals. As a result, a better understanding of the isomeric distribution of the product hydroperoxides was achieved and a modified mechanism that accounts for these calculations is presented.

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Scheme 1
Fig. 1
Scheme 2
Fig. 2

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Notes

  1. The CLA methyl ester hydroperoxides and their hydroxy derivatives are abbreviated in the following manner: Me 9-(O)OH-10t,12c stands for racemic methyl (hydroperoxy)hydroxyoctadecadienoate where the (hydroperoxyl) hydroxyl group is located at C-9 and the double bonds at C-10 and C-12. The geometry of the double bonds is denoted by c or t that refer to cis and to trans geometry.

Abbreviations

BSTFA:

Bis(trimethylsilyl)-trifluoroacetamide

COSY:

Correlated spectroscopy

C–H BDE:

Carbon–hydrogen bond dissociation enthalpy

DFT:

Density functional theory

gHMBC:

Gradient heteronuclear multiple bond correlation

gHSQC:

Gradient heteronuclear single quantum coherence

LR-COSY:

Long-range COSY

Me 9-OH-10t,12c :

Methyl 9-(R,S)-hydroxy-10-trans,12-cis-octadecadienoate

methyl linoleate:

Methyl 9-cis,12-cis-octadecadienoate

TMCS:

Trimethylchlorosilane

TOCSY:

Total correlation spectroscopy

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Acknowledgments

The authors wish to acknowledge funding support from the Finnish Cultural Foundation, the Emil Aaltonen Foundation, and the Orion Corporation Research Foundation. CSC—The Finnish IT Center for Science is acknowledged for providing computational resources.

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Authors and Affiliations

  1. Department of Chemistry, Laboratory of Organic Chemistry, University of Helsinki, P.O. Box 55, A.I. Virtasen aukio 1, Helsinki, 00014, Finland

    Taina I. Pajunen & Tapio Hase

  2. Lundbeck Foundation Center for Theoretical Chemistry, Aarhus University, 8000, Århus C, Denmark

    Mikael P. Johansson

  3. Department of Chemistry, Laboratory for Instruction in Swedish, University of Helsinki, Helsinki, 00014, Finland

    Mikael P. Johansson

  4. Department of Applied Chemistry and Microbiology, Food Chemistry Division, University of Helsinki, Helsinki, 00014, Finland

    Anu Hopia

  5. Vuoritie 16, 02330, Espoo, Finland

    Taina I. Pajunen

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  1. Taina I. Pajunen
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  4. Anu Hopia
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Correspondence to Taina I. Pajunen.

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Pajunen, T.I., Johansson, M.P., Hase, T. et al. Autoxidation of Conjugated Linoleic Acid Methyl Ester in the Presence of α-Tocopherol: The Hydroperoxide Pathway. Lipids 43, 599–610 (2008). https://doi.org/10.1007/s11745-008-3195-0

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