Structural characterization and comparative analysis of polymorphic forms of psilocin (4-hy-droxy-N,N-di-methyl-tryptamine).
Acta crystallographica. Section E, Crystallographic communications – May 01, 2024
Source: PubMed
Summary
Scientists have uncovered new details about psilocin, the active compound that gives magic mushrooms their psychedelic effects. Two distinct crystal forms of this molecule exist, each with unique structural arrangements. Using variable-temperature diffraction techniques, researchers revealed how these forms differ in their molecular bonds and shapes. Form II features an interesting self-folding structure, while Form I creates layered patterns. These findings advance our understanding of how polymorphism affects psychedelic compounds.
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.