Conformational Landscape and Hydrogen Bonding Pattern of Psilocin: Computational Insights

Abstract

AbstractConformational 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.