DFT Calculations of 1H- and 13C-NMR Chemical Shifts of Geometric Isomers of Conjugated Linoleic Acid (18:2 ω-7) and Model Compounds in Solution

Abstract

A density functional theory (DFT) study of the ¹H- and ¹³C-NMR chemical shifts of the geometric isomers of 18:2 ω-7 conjugated linoleic acid (CLA) and nine model compounds is presented, using five functionals and two basis sets. The results are compared with available experimental data from solution high resolution nuclear magnetic resonance (NMR). The experimental ¹H chemical shifts exhibit highly diagnostic resonances due to the olefinic protons of the conjugated double bonds. The "inside" olefinic protons of the conjugated double bonds are deshielded than those of the "outside" protons. Furthermore, in the cis/trans isomers, the signals of the cis bonds are more deshielded than those of the trans bonds. These regularities of the experimental ¹H chemical shifts of the olefinic protons of the conjugated double bonds are reproduced very accurately for the lowest energy DFT optimized single conformer, for all functionals and basis sets used. The other low energy conformers have negligible effects on the computational ¹H-NMR chemical shifts. We conclude that proton NMR chemical shifts are more discriminating than carbon, and DFT calculations can provide a valuable tool for (i) the accurate prediction of ¹H-NMR chemical shifts even with less demanding functionals and basis sets; (ii) the unequivocal identification of geometric isomerism of CLAs that occur in nature, and (iii) to derive high resolution structures in solution.

Keywords: CLA; DFT; GIAO; NMR; chemical shifts.

Figure 1

Chemical structures of the four geometric isomers of the 18:2 ω-7 conjugated linoleic acid (rumenic acid) and the model compounds investigated in the present work.

Figure 1

Chemical structures of the four geometric isomers of the 18:2 ω-7 conjugated linoleic acid (rumenic acid) and the model compounds investigated in the present work.

Figure 2

(A) Calculated, δ_calc, ¹H-NMR chemical shifts (at the GIAO/B3LYP/6-311+G(2d,p) level of theory with CPCM in CHCl₃/CH₃CN) vs. experimental, δ_exp, chemical shifts with energy minimization using various functionals and basis sets for (Z)-1,3-pentadiene, (E)-1,3-pentadiene, (E,Z)-2.4-hexadiene, (E,E)-2,4-nonediene, (Z,Z)-2,4-nonediene, (E,Z)- 2,4-nonediene, and (Z,E)-2,4-nonediene (Figure 1). (Β) Calculated, δ_calc, ¹H-NMR chemical shifts of the olefinic protons vs. experimental, δ_exp, chemical shifts of the data of Figure 2A.

Figure 3

(A) Calculated, δ_calc, of the olefinic protons (at the GIAO/B3LYP/6-311+G(2d,p) level of theory with CPCM in CH₃CN) of (E,E)-2,4-nonediene vs. experimental, δ_exp, olefinic protons in CD₃CN of (E,E)-2,4-nonediene with energy minimization using the B3LYP/6-31+G(d), B3LYP/6-311++G(d,p), APFD/6-31+G(d), APFD/6-311G++(d,p), PBE0/6-31+G(d), and PBE0/6-311++G(d,p) methods. (B) Calculated, δ_calc, of the olefinic protons (at the GIAO/B3LYP/6-311+G(2d,p) level of theory with CPCM in CH₃CN) of (E,E)-2,4-nonediene vs. experimental, δ_exp, olefinic protons in CD₃CN of (E,Z)-2,4-nonediene with energy minimization using the same basis sets and functionals as in (A).

Figure 4

Effect of variation of the C₁C₂C₃C₄ torsion angle of (E)-1,3-pentadiene (A) on the electronic energy ΔΕ (kcal·mol⁻¹) (B), and olefinic ¹H-NMR chemical shifts (C) with energy minimization at the B3LYP/6-31+G(d) level. The Gibbs energy difference, ΔG, of the two low energy conformers is also indicated.

Figure 5

Effect of variation of the C₂C₃C₄C₅ torsion angle of (E,E)-2,4-nonediene (A) on the electronic energy ΔΕ(kcal·mol⁻¹) (B), and the ¹H-NMR chemical shifts (C) with energy minimization at the B3LYP/6-31+G(d) level. The Gibbs energy difference, ΔG, of the two low energy conformers is also indicated.

Figure 6

Effect of variation of the C₄C₅C₆C₇ torsion angle of (E,E)-2,4-nonediene (A) on the electronic energy ΔΕ(kcal·mol⁻¹) (B), and the ¹H-NMR chemical shifts (C) with energy minimization at the B3LYP/6-31+G(d) level. The Gibbs energy difference, ΔG, of the two low energy conformers is also indicated.

Figure 7

Effect of variation of the C₆C₇C₈C₉ torsion angle of (E,E)-2,4-nonediene (A) on the electronic energy ΔΕ(kcal·mol⁻¹) (B), and the ¹H-NMR chemical shifts (C) with energy minimization at the B3LYP/6-31+G(d) level. The Gibbs energy difference, ΔG, of the two low energy conformers is also indicated.

Figure 8

(A) NBO bond order of the olefinic C–H bonds of the model compounds of Figure 1 vs. calculated, δ_calc, ¹H-NMR chemical shifts with energy minimization at the B3LYP/6-31+G(d) level. (B) AIM bond order of the olefinic C–H bonds of the model compounds (Z)-1,3-pentadiene, (E)-1,3 pentadiene, (E,Z)-2,4 hexadiene, (E,E)-2,4 nonadiene vs. calculated, δ_calc, ¹H-NMR chemical shifts with energy minimization at the B3LYP/6-31+G(d) level.