Structural characterization and comparative analysis of polymorphic forms of psilocin (4-hy-droxy-N,N-di-methyl-tryptamine).
Matthias Zeller, Stephan Parent, Nate Schultheiss
Acta crystallographica. Section E, Crystallographic communications May 1, 2024 DOI: 10.1107/S2056989024004201 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Crystal structure determination Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Crystal structure Psychedelic compounds Variable-temperature diffraction #crystal_structure #polymorphism_crystallography_phases #psychedelics_hallucinogens_entheogens #psilocin_psilocybin_magic_mushrooms |
| Key points | Two anhydrous polymorphs of psilocin were characterized: Form I (space group P21/c) with a trans conformation and no intramolecular hydrogen bonds, and Form II (space group P21/n) with a gauche conformation, an intramolecular O–H⋯N hydrogen bond, and whole-molecule disorder. |
Abstract
The title compound, C12H16N2O, is a hy-droxy-substituted mono-amine 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 redeterm-ination 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 mol-ecules are present in both forms in their phenol-amine tautomeric forms (not resolved in the 1974 report). The mol-ecules in Forms I and II, however, feature different conformations of their N,N-dimethyl ethyl-ene 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 mol-ecule, leading to the formation of a strong intra-molecular O-H⋯N hydrogen bond between the hydroxyl moiety and ethyl-amino-nitro-gen group. In the extended structure of Form II, the mol-ecules 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 mol-ecule. Form II exhibits whole-mol-ecule 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 intra-molecular hydrogen bonds but forms a layered structure through inter-molecular N-H⋯O and O-H⋯N hydrogen bonds.