NMR and Computational Studies as Analytical and High-Resolution Structural Tool for Complex Hydroperoxides and Diastereomeric Endo-Hydroperoxides of Fatty Acids in Solution-Exemplified by Methyl Linolenate

Raheel Ahmed; Panayiotis C Varras; Michael G Siskos; Hina Siddiqui; M Iqbal Choudhary; Ioannis P Gerothanassis

doi:10.3390/molecules25214902

NMR and Computational Studies as Analytical and High-Resolution Structural Tool for Complex Hydroperoxides and Diastereomeric Endo-Hydroperoxides of Fatty Acids in Solution-Exemplified by Methyl Linolenate

Molecules. 2020 Oct 23;25(21):4902. doi: 10.3390/molecules25214902.

Authors

Raheel Ahmed¹, Panayiotis C Varras², Michael G Siskos², Hina Siddiqui¹, M Iqbal Choudhary^{1

3}, Ioannis P Gerothanassis^{1

2}

Affiliations

¹ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
² Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, GR-45110 Ioannina, Greece.
³ Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 214412, Saudi Arabia.

Abstract

A combination of selective 1D Total Correlation Spectroscopy (TOCSY) and ¹H-¹³C Heteronuclear Multiple Bond Correlation (HMBC) NMR techniques has been employed for the identification of methyl linolenate primary oxidation products without the need for laborious isolation of the individual compounds. Complex hydroperoxides and diastereomeric endo-hydroperoxides were identified and quantified. Strongly deshielded C-O-O-H ¹H-NMR resonances of diastereomeric endo-hydroperoxides in the region of 8.8 to 9.6 ppm were shown to be due to intramolecular hydrogen bonding interactions of the hydroperoxide proton with an oxygen atom of the five-member endo-peroxide ring. These strongly deshielded resonances were utilized as a new method to derive, for the first time, three-dimensional structures with an assignment of pairs of diastereomers in solution with the combined use of ¹H-NMR chemical shifts, Density Functional Theory (DFT), and Our N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) calculations.

Keywords: 1D TOCSY; 1H-13C HMBC; DFT; NMR; ONIOM; chemical shifts; endo-hydroperoxides; hydrogen bonding; hydroperoxides; polyunsaturated fatty acids.

MeSH terms

Density Functional Theory
Fatty Acids / chemistry*
Hydrogen Peroxide / chemistry*
Linolenic Acids / chemistry*
Magnetic Resonance Spectroscopy*
Models, Molecular
Molecular Conformation
Solutions
Stereoisomerism

Substances

Fatty Acids
Linolenic Acids
Solutions
methyl linolenate
Hydrogen Peroxide