Conformational Landscape and Hydrogen Bonding Pattern of Psilocin: Computational Insights

Abstract

Conformational analysis of psilocin, a psychedelic molecule was carried out at B3LYP/cc-pVTZ level of theory. And a global minimum was identified having highest population among all the local conformers along with second stable conformer which is 5.4 kcal/mol higher in energy than global minimum. The global mimimum is stable due to the formation of intramolecular H-bond between ethyl amine nitrogen and indolic hydroxyl group, revealed by AIM (Atoms in molecule) analysis. This is in contradiction to earlier X-ray crystal studies of this molecule reported in literature. Dimers of both stable conformers were studied at same level that is B3LYP/cc-pVTZ and it was observed that the intramolecular H-bond energy dominates over the intermolecular H-bond in the dimers. Other calculations namely NBO (Natural bond orbital), FMO (Frontier molecular orbital), charge analysis, ESP (Electrostatic potential) mapping corroborated the AIM results in a significant manner. The spectroscopic study including UV (Ultraviolet), 1H-NMR (Proton nuclear magnetic resonance) and vibrational modes calculation were found to be in good agreement with the data reported in literature. © 2023 Wiley-VCH GmbH.