On the conformational varieties of 5-methoxy-N,N-dimethyltryptamine and serotonin in crystalline environment

Conformational energy maps obtained from quantum-mechanical computations for two indolalkylamines (5-methylbufotenine and serotonin) indicate preferred conformers which do not correspond to those observed in some crystals containing these molecules. Moreover, two different conformations are observed for serotonin in two different mixed crystals [serotonin creatinine sulphate (hydrated) and serotonin picrate]. These facts suggest an influence of the crystalline environment upon intramolecular conformation. The intermolecular lattice energy has been computed for the experimental crystals and a number of hypothetical ones, obtained by varying the conformation of the indolalkylamine molecule. The results obtained establish complete agreement with the experimental observations: for the three crystals considered, the lattice energy is much lower when use is made of the corresponding observed conformation and these differences between the lattice energies largely overcompensate the variations of the intramolecular conformational energy, thus explaining the role of the lattice energy in the determination of the conformations observed in the crystals.