Theoretical NMR and IR spectroscopic analyses of the preferred conformers of the neurotransmitter anandamide

Abstract

AbstractAnandamide, an endogenous fatty acid, displays a wide conformational space due to the nature of its chemical structure, particularly its polyunsaturated aliphatic chain component (omega‐6 fatty acid). Six main minima are considered after a conformational search based on the MM+ method, namely, extended shape, U‐shape, and hairpin shape with either an open or a closed conformation of the ethanolamide (EA) ring. For these six conformers, DFT calculations were performed to theoretically characterize their structural stability, NMR and IR spectroscopic, and electronic properties using the BP86/cc‐pVTZ level of theory with the solute‐implicit solvent model PCM. DLPNO‐CCSD(T) level of theory was used for comparison with DFT results. Our results indicate that the conformers with closed EA ring are more stable than their corresponding open ring counterparts. With the NMR and IR spectroscopies was characterized the formation of the intramolecular hydrogen bond in the closed conformers of the EA ring. The electronic properties investigated include the calculation of the frontier molecular orbitals (FMO), the molecular electrostatic potential (MEP), and the natural bond orbitals (NBO). Additionally, the multiscale ONIOM QM1/QM2 model was used to simulate a solute‐explicit solvent system and molecular dynamics simulations were used to simulate the anandamide systems embedded in a hydrated symmetric POPC membrane and in aqueous solution. The results suggest that alkyl‐middle and EA groups in anandamide may play an important role in the ligand‐receptor interaction.