Structural characterization and comparative analysis of polymorphic forms of psilocin (4-hydroxy-N,N-dimethyltryptamine)

Abstract

The title compound, C12H16N2O, is a hydroxy-substituted monoamine alkaloid, and the primary metabolite of the naturally occurring psychedelic compound psilocybin. Crystalline forms of psilocin are known, but their characterization by single-crystal structure analysis is limited. Herein, two anhydrous polymorphic forms (I and II) of psilocin are described. The crystal structure of polymorphic Form I, in space group P21/c, was first reported in 1974. Along with the redetermination to modern standards and unambiguous location of the acidic H atom and variable-temperature single-crystal unit-cell determinations for Form I, the Form II polymorph of the title compound, which crystallizes in the monoclinic space group P21/n, is described for the first time. The psilocin molecules are present in both forms in their phenol–amine tautomeric forms (not resolved in the 1974 report). The molecules in Forms I and II, however, feature different conformations of their N,N-dimethyl ethylene substituent, with the N—C—C—C link in Form I being trans and in Form II being gauche, allowing the latter to bend back to the hydroxyl group of the same molecule, leading to the formation of a strong intramolecular O—H...N hydrogen bond between the hydroxyl moiety and ethylamino-nitrogen group. In the extended structure of Form II, the molecules form one-dimensional strands through N—H...O hydrogen bonds from the indole group to the oxygen atom of the hydroxyl moiety of an adjacent molecule. Form II exhibits whole-molecule disorder due to a pseudo-mirror operation, with an occupancy ratio of 0.689 (5):0.311 (5) for the two components. In contrast, Form I does not feature intramolecular hydrogen bonds but forms a layered structure through intermolecular N—H...O and O—H...N hydrogen bonds.