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Synthesis of dihydroperoxides of linoleic and linolenic acids and studies on their transformation to 4-hydroperoxynonenal

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Lipids

Abstract

The cytotoxic aldehydes 4-hydroxynonenal, 4-hydroperoxynonenal (4-HPNE), and 4-oxononenal are formed during lipid peroxidation via oxidative transformation of the hydroxy or hydroperoxy precursor fatty acids, respectively. The mechanism of the carbon chain cleavage reaction leading to the aldehyde fragments is not known, but Hock-cleavage of a suitable dihydroperoxide derivative was implicated to account for the fragmentation [Schneider, C., Tallman, K.A., Porter, N.A., and Brash, A.R. (2001) Two Distinct Pathways of Formation of 4-Hydroxynonenal. Mechanisms of Nonenzymatic Transformation of the 9- and 13-Hydroperoxides of Linoleic Acid to 4-Hydroxyalkenals, J. Biol. Chem. 275, 20831–20838]. Both 8,13- and 10,13-dihydroperoxyoctadecadienoic acids (diHPODE) could serve as precursors in a Hock-cleavage leading to 4-HPNE via two different pathways. Here, we synthesized diastereomeric 9,12-, 10,12-, and 10,13-diHPODE using singlet oxidation of linoleic acid. 8,13-Dihydroperoxyoctadecatrienoic acid was synthesized by vitamin E-controlled autoxidation of γ-linolenic acid followed by reaction with soybean lipoxygenase. The transformation of these potential precursors to 4-HPNE was studied under conditions of autoxidation, hematin-, and acid-catalysis. In contrast to 9- or 13-HPODE, neither of the dihydroperoxides formed 4-HPNE on autoxidation (lipid film, 37°C), regardless of whether the free acid or the methyl ester derivative was used. Acid treatment of 10,13-diHPODE led to the expected formation of 4-HPNE as a significant product, in accord with a Hock-type cleavage reaction. We conclude that, although the suppression of 4-H(P)NE formation from monohydroperoxides by α-tocopherol indicates peroxyl radical reactions in the major route of carbon chain cleavage, the dihydroperoxides previously implicated are not intermediates in the autoxidative transformation of monohydroperoxy fatty acids to 4-HPNE and related aldehydes.

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Abbreviations

CID:

collision-induced dissociation

HETE:

hydroxyeicosatetraenoic acid

HODE:

hydroxyoctadecadienoic acid

H(P)NE:

4-hydro(pero)xy-2E-nonenal

HPODE:

hydroperoxyoctadecadienoic acid

HPOTE:

hydroperoxyoctadecatrienoic acid

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Authors and Affiliations

  1. Department of Chemistry, Vanderbilt University, 37232, Nashville, Tennessee

    Huiyong Yin, Donald F. Stec & Ned A. Porter

  2. Dept. of Pharmacology, Vanderbilt University, 23rd Ave. at Pierce, 37232-6602, Nashville, TN

    Claus Schneider, William E. Boeglin, Huiyong Yin, David L. Hachey & Alan R. Brash

Authors
  1. Claus Schneider
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  2. William E. Boeglin
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  3. Huiyong Yin
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  4. Donald F. Stec
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  5. David L. Hachey
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  6. Ned A. Porter
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  7. Alan R. Brash
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Correspondence to Alan R. Brash.

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Schneider, C., Boeglin, W.E., Yin, H. et al. Synthesis of dihydroperoxides of linoleic and linolenic acids and studies on their transformation to 4-hydroperoxynonenal. Lipids 40, 1155–1162 (2005). https://doi.org/10.1007/s11745-005-1480-3

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  • DOI: https://doi.org/10.1007/s11745-005-1480-3

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