Scientists Solve Another Crystal Structure of the Psilocybin Analog Miprocin, 4-HO-MiPT

This is the second crystal structure of this compound, providing additional options for developing psychedelics into therapeutic drug formulations.

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In the April 2020 issue of Acta Crystallographica, researchers from CaaMTech and the University of Massachusetts Dartmouth published the crystal structure of the psilocybin analog miprocin, also known as 4-HO-MiPT, or 4-hydroxy-N-methyl-N-isopropyltryptamine.1 This publication is the latest in a recent series of papers from this team of researchers describing the crystal structures of psilocybin analogs.2–6

Building on Previous Knowledge

This is the second crystal structure of 4-HO-MiPT published by this research team. In 2019, they reported on the crystal structure of the hydrofumarate monohydrate salt form of 4-HO-MiPT.4 In the current paper, the researchers reacted this salt with lead(II) acetate. This formed the 4-hydroxy-N-methyl-N-isopropyltryptamine/fumarate compound in a 2:1 ratio, namely bis(4-hydroxy-N-isopropyl-N-methyltryptammonium) fumarate. The current paper reports on the crystal structure of this compound.

The paper describes the crystal structure as,

…a singly protonated tryptammonium cation and one half of a fumarate dianion in the asymmetric unit.

The images below detail the crystal structure of the compound and show how the individual molecules pack themselves together.

The molecular structure of bis(4-hydroxy-N-isopropyl-N-methyltryptammonium) fumarate.1 The labels on the atoms are C = carbon, O = oxygen, and N = nitrogen. The dashed lines are hydrogen bonds between the atoms.

This image illustrates the lattice structure that is created when the 4-HO-MiPT crystals pack themselves together.1 The dashed lines represent hydrogen bonds between the atoms.

Learning About the Chemistry of 4-HO-MiPT

Prior to the two studies by Chadeayne et al., virtually nothing was known about 4-HO-MiPT. There was no research interest in it, and this compounded by the fact that it is difficult to synthesize in the lab. Nevertheless, solving its crystal structure (and that of other bioactive tryptamine molecules) is a pioneering step because it defines the physical identity of 4-HO-MiPT. Characterizing this fundamental structure is essential for all downstream research, such as structure-activity relationships that define the biological and clinical properties of the molecule. Understanding these relationships is key to developing effective drugs.

Why Solve the Crystal Structures of Compounds?

Small changes at the molecular level can translate into significant changes in effect when it comes to drugs. Therefore, working with compounds at the molecular level is essential for unraveling the mysteries of how drugs work and how other compounds affect them. The new crystalline forms of 4-HO-MiPT could be used to modulate the effects of each compound in a drug formulation (the entourage effect). In addition, determining the crystal structures of compounds is critical for understanding their physical properties and for probing their activity at receptors in modeling studies, for example.

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    References
  1. Chadeayne AR, Pham DNK, Golen JA, Manke DR. Bis(4-hy­droxy-N-isopropyl-N-methyl­trypt­ammo­nium) fumarate: a new crystalline form of miprocin. Acta Cryst E. 2020;76(4):514-517. doi:10.1107/S2056989020002923
  2. Chadeayne AR, Golen JA, Manke DR. The Crystal Structure of 4-AcO-DMT Fumarate. 2019. https://psychedelicreview.com/wp-content/uploads/2019/03/The-Crystal-Structure-of-4-AcO-DMT-Fumarate.pdf.
  3. Chadeayne AR, Golen JA, Manke DR. Bis(4-acetoxy-N,N -dimethyltryptammonium) fumarate: a new crystalline form of psilacetin, an alternative to psilocybin as a psilocin prodrug. Acta Crystallographica Section E Crystallographic Communications. 2019;75(6):900-902. doi:10.1107/S2056989019007370
  4. Chadeayne AR, Pham DNK, Golen JA, Manke DR. The fumarate salts of the N-isopropyl-N-methyl derivatives of DMT and psilocin. Acta Crystallographica Section E Crystallographic Communications. 2019;75(9):1316-1320. doi:10.1107/S2056989019011253
  5. Chadeayne AR, Pham DNK, Golen JA, Manke DR. Bis(4-hy­droxy-N,N-di-n-propyl­tryptammonium) fumarate tetrahydrate. IUCrData. 2019;4(11):x191469. doi:10.1107/S241431461901469X
  6. Chadeayne AR, Golen JA, Manke DR. N-Methyl-N-propyl­tryptamine (MPT). IUCrData. 2019;4(7):x190962. doi:10.1107/S2414314619009623