Structural characterization and comparative analysis of polymorphic forms of psilocin...

Area of Science:

• Crystallography
• Solid-state chemistry
• Pharmacology

Background:

• Psilocin is a hydroxy-substituted monoamine alkaloid and the primary metabolite of psilocybin.
• Crystalline forms of psilocin are known, but detailed structural characterization is limited.
• Polymorphism in psilocin can influence its physical and potentially pharmacological properties.

Purpose of the Study:

• To characterize two anhydrous polymorphic forms of psilocin (Form I and Form II).
• To elucidate the crystal structures, including tautomeric forms and hydrogen bonding interactions.
• To compare the solid-state structures of psilocin polymorphs.

Main Methods:

• Single-crystal X-ray diffraction analysis was performed on both psilocin polymorphs.
• Variable-temperature single-crystal unit-cell determinations were conducted for Form I.
• Crystal structures were analyzed to identify tautomeric forms, conformations, and hydrogen bonding networks.

Main Results:

• Two anhydrous polymorphic forms of psilocin, Form I (space group P2₁/c) and Form II (space group P2₁/n), were described.
• Psilocin molecules exist in their phenol-amine tautomeric forms in both polymorphs.
• Form I exhibits a trans conformation and intermolecular hydrogen bonds forming a layered structure, while Form II shows a gauche conformation with an intramolecular O-H⋯N bond and 1D strands via intermolecular N-H⋯O bonds. Form II also displays whole-molecule disorder.

Conclusions:

• The study provides the first detailed structural description of psilocin Form II, alongside a modern redetermination of Form I.
• Differences in molecular conformation and hydrogen bonding significantly distinguish the two psilocin polymorphs.
• Understanding these distinct solid-state structures is crucial for psilocin's chemical and pharmacological characterization.