Single-crystal structure determination of psilocybin after dehydration

Emmett, S.K.; Cameron, L.; Hestermann, M.; Holland, D.; Kessler, S.; McFarlane, L.; Chooi, Y.-H.; Moggach, S.A.

doi:10.1107/S2053229626007692

research papers

STRUCTURAL
CHEMISTRY

ISSN: 2053-2296

Volume 82| Part 9| September 2026|

https://doi.org/10.1107/S2053229626007692

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Single-crystal structure determination of psilocybin after dehydration

Sonya K. Emmett,^a Lee Cameron,^a Mark Hestermann,^b Darren Holland,^a Simon Kessler,^a Luke McFarlane,^b Yit-Heng Chooi ^a and Stephen A. Moggach ^a ^*

^aSchool of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia, and ^bNatural MedTech, Melbourne, VIC 3146, Australia
^*Correspondence e-mail: [email protected]

Edited by I. Oswald, University of Strathclyde, United Kingdom (Received 15 June 2026; accepted 27 July 2026; online 7 August 2026)

The crystal structure of the known low-temperature anhydrous phase of psilocybin {3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate, C₁₂H₁₇N₂O₄P} is reported. While the structure was previously characterized using powder X-ray diffraction, this study describes the first determination via single-crystal X-ray diffraction. High-resolution structural models were obtained both before and after in situ dehydration, allowing for a direct comparison of the lattice response to water loss.

Keywords: crystal structure; psilocybin; phase elucidation; anhydrous; phosphate; psychoactive compound; polymorphs.

CCDC references: 2562278; 2562279

1. Introduction

Found as a natural product in various mushrooms around the world, psilocybin is a phosphorylated tryptamine derivative that undergoes dephosphorylation within the human body to produce the psychoactive compound psilocin (Fig. 1) (Tylš et al., 2014 ). The therapeutic properties of psilocybin have attracted renewed interest in the medical field in the last two decades due to an observed efficacy in the treatment of psychiatric and substance abuse disorders, including post-traumatic stress disorder, treatment resistant depression, anxiety and addiction to nicotine and alcohol (Bogenschutz et al., 2015 ; Johnson et al., 2014 ).

Figure 1
Chemical structure of psilocybin (left) and psilocin (right).

Psilocybin has been reported previously with two anhydrous phases, one trihydrate, six solvates and one cocrystal (Table 1) (Sherwood et al., 2022 ). After the drug's first synthesis in 1958 (Hofmann et al., 1958 ), the anhydrous form of psilocybin was first reported from separately dried trihydrate and methanolate solvates in 1976, and confirmed with IR spectroscopy and differential scanning calorimetry (DSC) (Kuhnert-Brandstätter & Heindl, 1976 ). The hygroscopic nature of psilocybin was also observed in this study, and the authors noted that transitions between the hydrous and anhydrous forms could occur depending on environmental factors such as humidity and temperature.

Table 1
Reported phases of anhydrous psilocybin and precursor solvates, and method of characterization

	SCXRD	PXRD	DSC	IR
Methanol solvate (2:1 v/v)	Weber & Petcher (1974 )	Greenan et al. (2020)	Kuhnert-Brandstätter & Heindl (1976)	Kuhnert-Brandstätter & Heindl (1976)
Trihydrate	Greenan et al. (2020)	Greenan et al. (2020) and Sherwood et al. (2022)	Kuhnert-Brandstätter & Heindl (1976)	Kuhnert-Brandstätter & Heindl (1976)
First anhydrate/Polymorph A′	–	Greenan et al. (2020)†	Kuhnert-Brandstätter & Heindl (1976)	Hofmann et al. (1958) and Kuhnert-Brandstätter & Heindl (1976)
Second anhydrate/Polymorph B	–	Greenan et al. (2020), Londesbrough et al. (2019), Sherwood et al. (2022) and Kargbo et al. (2022)	Greenan et al. (2020)	–

†High-resolution PXRD was used to generate a structure solution.

The first and second anhydrous phases of psilocybin were noted in 2018 under a patent application by Compass Pathways (Londesbrough et al., 2019 ). These were labelled as Polymorph A′ (the first lower-temperature anhydrate) and Polymorph B (a second higher-temperature anhydrate), and were reported using powder X-ray diffraction (PXRD). A third patent was lodged under the label Polymorph A as a `novel isostructural variant'. In 2022, Polymorph A was shown by Sherwood et al. (2022) to be a mixed material of Polymorph A′ and Polymorph B rather than a new phase.

While structure solution with single-crystal X-ray diffraction (SCXRD) has been successfully carried out for many of psilocybin's solvates, poor crystal quality or small crystal size due to mechanical fracturing during dehydration is cited as a significant issue preventing the same being done for anhydrous psilocybin. The structures of Polymorph A′ and Polymorph B were solved at 295 K from high-resolution PXRD patterns in 2022, but SCXRD data of either psilocybin anhydrate phase have been unavailable (Sherwood et al., 2022). In the present study, psilocybin obtained via biosynthetic production using an engineered yeast system was used as the starting material for crystallization and structure analysis, providing access to material suitable for single-crystal analysis. With this in mind, herein we describe the dehydration protocol and first SCXRD structure of the anhydrous Polymorph A′ form of psilocybin. Polymorph A′ is the crystalline anhydrate that first forms during the drying process, and changes in partial trace amounts into Polymorph B upon drying at ambient pressures above 38–40 °C (Kargbo et al., 2022 ; Greenan et al., 2020 ). Polymorph A′ is converted to the higher-temperature phase in totality above 160 °C.

2. Experimental

2.1. Sample preparation

A two-step drying process was used to obtain crystals of only Polymorph A′, following the method outlined by Sherwood et al. (2022). A sample of psilocybin was provided by Natural MedTech and recrystallized from water at 60 °C, then dried under vacuum for 24 h at temperatures between 35 and 45 °C. A subsample of these hydrated crystals was removed for analysis, and the remaining crystals were then dried under vacuum for a further 24 h in the temperature range 50–60 °C. PXRD data were collected under ambient temperature conditions on both the hydrated subsample and the dehydrated sample to screen the phase composition of the bulk material. PXRD data were collected on sub- to micron-sized crystals on a Synergy-S diffractometer in transmission geometry, which confirmed the first-step subsample and final two-step product as predominantly psilocybin trihydrate and Polymorph A′, respectively (Fig. 2).

Figure 2
Comparison of the PXRD patterns for psilocybin trihydrate and Polymorph A′. The experimental patterns (green for the trihydrate and blue for Polymorph A′) are shown alongside their respective calculated patterns derived from SCXRD data (red for the trihydrate and grey for Polymorph A′) for structural validation.

2.2. SCXRD structure solution and refinement details

The particle size distribution of the original sample was significant, with sub-to micron-sized crystals, as well as several crystallites of 50 µm and bigger. SCXRD data were collected on these larger crystals from the bulk samples. Data collection was conducted at 100 K on the recrystallized hydrate phase and on a separate crystal from the post heated and dried sample. Relevant crystallographic information is provided in Table 2.

Table 2
Experimental details

For both determionations: orthorhombic, Pbca, Z = 8. Experiments were carried out at 100 K with Cu Kα radiation using a Rigaku XtaLAB Synergy diffractometer with a HyPix detector. Absorption was corrected for by multi-scan methods (CrysAlis PRO; Rigaku OD, 2024 ). H-atom parameters were constrained.

	Dehydrated psilocybin	Psilocybin trihydrate
Crystal data
Chemical formula	C₁₂H₁₇N₂O₄P	C₁₂H₁₇N₂O₄P·3H₂O
M_r	284.24	338.29
a, b, c (Å)	15.920 (3), 9.322 (3), 17.466 (5)	14.3405 (6), 8.2707 (3), 27.098 (1)
V (Å³)	2592.1 (11)	3214.0 (2)
μ (mm⁻¹)	2.02	1.85
Crystal size (mm)	0.23 × 0.15 × 0.11	0.13 × 0.05 × 0.04

Data collection
T_min, T_max	0.210, 1.000	0.615, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	4440, 1013, 486	12268, 3256, 2382
R_int	0.121	0.091
θ_max (°)	45.0	79.3
(sin θ/λ)_max (Å⁻¹)	0.458	0.637

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.082, 0.280, 1.04	0.052, 0.120, 1.04
No. of reflections	1013	3256
No. of parameters	176	211
Δρ_max, Δρ_min (e Å⁻³)	0.32, −0.39	0.36, −0.48
Computer programs: CrysAlis PRO (Rigaku OD, 2024), SHELXT2018 (Sheldrick, 2015a ), SHELXL2019 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

On initial inspection, anhydrous Polymorph A′ appeared subtely different to the reported anhydrous phase of Sherwood et al. (2022) due to a transformation of the unit-cell dimensions. In order to compare with the published structure [Cambridge Structural Database (CSD; Groom et al., 2016 ) refcode TAVZID], we transformed the unit-cell dimensions by applying the following matrix:

$[\left(\matrix{ {\ \ 0} & {\ \ 0} & {1} \cr {-1} & {\ \ 0} & {0} \cr {\ \ 0} & {-1} & {0} \cr } \right)]$

3. Results and discussion

During the first step, psilocybin trihydrate crystallized in the orthorhombic space group Pbca, with water-filled channels parallel to the b axis stabilized by hydrogen bonding to the phosphate moieties (Fig. 3 and Fig. S1 in the supporting information). During the initial stage of dehydration, thermal or vacuum driving forces induce the rapid loss of water molecules occupying the 22.7% void volume (729.7 Å³) within the one-dimensional channels running parallel to the b axis. This loss breaks the critical host–guest hydrogen bonds stabilizing the phosphate moieties, leaving unsupported cylindrical cavities within the lattice. Deprived of solvent support, these channels collapse inward along the transverse crystal directions, causing a large contraction along the c-axis direction [with a reduction from 27.0980 (10) to 17.466 (5) Å]. To optimize space-filling in the absence of channel water, neighbouring stacks of zwitterionic psilocybin molecules undergo a co-operative shear-like sliding motion past one another, closing the macroscopic voids. When water evacuation occurs rapidly at the crystal exterior, localized channel collapse near the surface can seal off interior channels, creating trapped pockets of high-pressure water vapour. The combined localized strain from both side-chain deformation and trapped vapour pressure ultimately leads to micro-cracking and crystal fracturing, explaining the mechanically destructive nature of the dehydration transition. This structural reorganization drives a specific rearrangement of the hydrogen-bonding network. While the phosphate groups remain paired as a dimer and retain a direct hydrogen bond from the protonated dimethylammonium group in both phases, the loss of solvent causes the phosphate group to forfeit two hydrogen bonds with channel water. To compensate, the collapse allows the phosphate group to form a new direct N—H⋯O hydrogen bond with the indole N—H group – a contact that was strictly water-mediated prior to dehydration.

Figure 3
(a) The molecular connectivity of psilocybin (taken from the trihydrate crystal structure), with displacement ellipsoids drawn at the 50% probability level. Colour code: C grey, H white, N blue, O red and P orange. Crystal packing of (b) the anhydrous Polymorph A′ and (c) the trihydrate form, both viewed down the b axis. Molecules are shown in stick representation, with the exception of the water O atoms in the trihydrate, which are rendered as red space-filling spheres to highlight their positions within the channels. Note the significant contraction of the unit cell along the c axis upon dehydration, corresponding to the collapse of the lattice into the anhydrous phase.

Comparison of this experimental trihydrate model with the previously reported structure reveals negligible structural disparity. A three-dimensional molecular overlay yields a root-mean-square deviation (RMSD) of 0.0121 Å and a maximum atomic displacement of 0.0280 Å, confirming that the atomic positions and molecular conformation in our structure are virtually identical to the published reference data (Arlin et al., 2021 ).

Psilocybin anhydrate Polymorph A′ crystallized in the orthorhombic space group Pbca, with a unit-cell volume of 2592.1 (11) Å³ [Tables 2 and 3, and Fig. 3(b)]. The anhydrous psilocybin structure outlined herein is structurally analogous to Sherwood's prior solution, however, it has been re-indexed conventionally using the directionality insights provided by SCXRD. The indexing we use also makes it easier to compare the trihydrate and anhydrous Polymorph A′ forms. The unit-cell dimensions we determined are marginally smaller, which is unsurprising considering that the data were collected at 100 K, whereas the original PXRD data were collected at room temperature (298 K).

Table 3
Unit-cell dimensions for Polymorph A′ from published powder (PXRD) and our own single-crystal data (SCXRD), transformed for comparison

	Polymorph A′ (PXRD)	Polymorph A′ (SCXRD)
CCDC refcode	TAVZID	n/a
Temperature (K)	295	100
a (Å)	17.4979 (2)	17.466 (5)
b (Å)	16.0914 (1)	15.920 (3)
c (Å)	9.34815 (7)	9.322 (3)
Volume (Å³)	2632.11 (3)	2592.1 (11)

Data for the anhydrous Polymorph A′ could only be collected to 1 Å resolution without prohibitively long collection times. This is expected, as the loss of water results in a 19.35% reduction in the unit-cell volume. Notably, the successful collection of large intact crystals post-dehydration was a highlight of this study, as the rapid evacuation of water typically causes significant mechanical fracturing.

To quantitatively compare our single-crystal structure of anhydrous Polymorph A′ with the literature, structural overlays were performed using Mercury (Macrae et al., 2020 ). Our experimental SCXRD structure shows outstanding agreement with both the experimental powder structure reported by Sherwood and co-workers (RMSD = 0.082 Å; molecular overlay = 0.042 Å) and a VASP (Vienna Ab initio Simulation Package)-optimized DFT (density functional theory) model (RMSD = 0.090 Å; molecular overlay = 0.039 Å), which was reported in the same article. This remarkably low RMSD confirms that the single-crystal structure determination accurately captures the true anhydrous geometry. The Mogul (Bruno et al., 2004 ) intramolecular geometry check highlights notable conformational differences in the dimethylaminoethyl side chain in the hydrated and anhydrous forms. Notably, in the trihydrate, the C—N—N—C torsion angles adopt expected values of approximately ≈65° and ≈−70°, corresponding to standard low-energy gauche preferences. In contrast, the experimental torsion angle in the anhydrous phase measures 86.8 and −149.7°, and falls directly into the low-frequency local minimum between these two main energy wells, further highlighting the torsional strain accommodated in the anhydrous crystal packing.

4. Conclusion

In summary, this study demonstrates that the dehydration of psilocybin trihydrate can be achieved through a controlled two-step vacuum-drying protocol. Despite the significant 19.35% reduction in unit-cell volume – driven by the collapse of water-filled channels – we have successfully reported the first single-crystal X-ray diffraction structure of an anhydrous psilocybin phase, denoted Polymorph A′. While dehydration is often considered a mechanically destructive process, this work confirms that large intact single crystals can be recovered and analyzed, overcoming previous limitations in structure characterization. These findings provide critical insights into the structural response of psilocybin to water loss and establish a foundation for further investigation into its various solid-state forms.

Supporting information

CCDC references: 2562278; 2562279

Crystal structure: contains datablocks ps1_recryst_dehydrated_100k_auto, ps1_100k_hydrate_recryst_auto, global. DOI: https://doi.org/10.1107/S2053229626007692/vp3057sup1.cif

Structure factors: contains datablock ps1_recryst_dehydrated_100k_auto. DOI: https://doi.org/10.1107/S2053229626007692/vp3057ps1_recryst_dehydrated_100k_autosup2.hkl

Structure factors: contains datablock ps1_100k_hydrate_recryst_auto. DOI: https://doi.org/10.1107/S2053229626007692/vp3057ps1_100k_hydrate_recryst_autosup3.hkl

Single-crystal X-ray diffraction structures of psilocybin showing the dehydrated form alongside the trihydrate phase. DOI: https://doi.org/10.1107/S2053229626007692/vp3057sup4.pdf

Computing details top

3-[2-(Dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate (ps1_recryst_dehydrated_100k_auto) top

Crystal data top

C₁₂H₁₇N₂O₄P	D_x = 1.457 Mg m⁻³
M_r = 284.24	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, Pbca	Cell parameters from 618 reflections
a = 15.920 (3) Å	θ = 5.0–41.9°
b = 9.322 (3) Å	µ = 2.02 mm⁻¹
c = 17.466 (5) Å	T = 100 K
V = 2592.1 (11) Å³	Block, clear light colourless
Z = 8	0.23 × 0.15 × 0.11 mm
F(000) = 1200

Data collection top

XtaLAB Synergy, Single source at home/near, HyPix diffractometer	1013 independent reflections
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Cu) X-ray Source	486 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.121
Detector resolution: 10.0000 pixels mm^-1	θ_max = 45.0°, θ_min = 5.1°
ω scans	h = −14→14
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2024)	k = −8→8
T_min = 0.210, T_max = 1.000	l = −15→15
4440 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.082	w = 1/[σ²(F_o²) + (0.1635P)² + 1.9185P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.280	(Δ/σ)_max < 0.001
S = 1.04	Δρ_max = 0.32 e Å⁻³
1013 reflections	Δρ_min = −0.39 e Å⁻³
176 parameters	Extinction correction: SHELXL2019 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0019 (7)

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Both structures were solved using the SHELXT2018 (Sheldrick, 2015a) solution program using dual space methods and by using OLEX2 (Dolomanov et al., 2009) as the graphical interface. The models were refined with SHELXL (Sheldrick, 2015b) using full-matrix least-squares minimization on F².

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
P1	0.4070 (3)	0.3707 (6)	0.4597 (2)	0.0944 (18)
O5	0.3983 (5)	0.4354 (11)	0.3742 (6)	0.089 (3)
O4	0.3807 (5)	0.5011 (12)	0.5083 (6)	0.097 (3)
H4	0.420908	0.559174	0.511170	0.146*
O2	0.3426 (6)	0.2545 (11)	0.4697 (5)	0.094 (3)
O3	0.4968 (5)	0.3250 (11)	0.4732 (5)	0.099 (3)
N6	0.3064 (10)	0.2954 (15)	0.1345 (7)	0.100 (4)
H6	0.303666	0.259823	0.087938	0.120*
N7	0.1439 (7)	0.4763 (14)	0.4261 (7)	0.092 (4)
H7	0.164342	0.577662	0.427131	0.110*
C15	0.2700 (10)	0.4150 (18)	0.2410 (11)	0.090 (5)
C8	0.4122 (13)	0.3516 (18)	0.3080 (10)	0.090 (5)
C9	0.3518 (11)	0.3522 (19)	0.2509 (10)	0.094 (5)
C17	0.1926 (9)	0.3964 (16)	0.3649 (8)	0.085 (4)
H17A	0.157565	0.316855	0.345110	0.102*
H17B	0.243571	0.353977	0.388161	0.102*
C11	0.4443 (13)	0.1969 (18)	0.1728 (10)	0.099 (5)
H11	0.454001	0.142511	0.127696	0.118*
C14	0.2444 (11)	0.3774 (19)	0.1686 (11)	0.092 (5)
H14	0.192529	0.403512	0.145631	0.110*
C16	0.2182 (9)	0.492 (2)	0.2988 (9)	0.107 (5)
H16A	0.167140	0.530261	0.273680	0.128*
H16B	0.250588	0.574701	0.318927	0.128*
C13	0.4886 (12)	0.2824 (19)	0.2994 (10)	0.095 (5)
H13	0.530983	0.289991	0.337457	0.114*
C18	0.1581 (10)	0.4131 (17)	0.5029 (8)	0.096 (5)
H18A	0.139113	0.313060	0.503053	0.144*
H18B	0.126387	0.467613	0.541220	0.144*
H18C	0.218078	0.416805	0.515245	0.144*
C19	0.0510 (9)	0.4782 (19)	0.4067 (8)	0.106 (6)
H19A	0.043959	0.491989	0.351406	0.160*
H19B	0.023550	0.556948	0.434153	0.160*
H19C	0.025443	0.386856	0.421847	0.160*
C12	0.5018 (10)	0.202 (2)	0.2339 (13)	0.105 (5)
H12	0.552047	0.147444	0.230079	0.126*
C10	0.3728 (12)	0.278 (2)	0.1840 (11)	0.096 (5)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
P1	0.077 (3)	0.111 (4)	0.094 (3)	0.002 (3)	0.005 (2)	−0.002 (3)
O5	0.078 (7)	0.114 (8)	0.074 (7)	−0.005 (6)	0.001 (5)	0.006 (7)
O4	0.071 (7)	0.124 (9)	0.097 (7)	−0.002 (6)	0.009 (6)	0.003 (7)
O2	0.077 (6)	0.116 (8)	0.089 (7)	0.004 (7)	0.004 (5)	0.009 (6)
O3	0.081 (7)	0.122 (9)	0.094 (8)	0.019 (6)	0.005 (6)	0.000 (6)
N6	0.086 (10)	0.124 (12)	0.089 (9)	−0.002 (9)	0.004 (10)	0.005 (9)
N7	0.069 (9)	0.115 (11)	0.091 (9)	0.000 (8)	−0.005 (7)	−0.004 (8)
C15	0.059 (12)	0.107 (14)	0.106 (15)	−0.001 (10)	0.000 (11)	−0.007 (11)
C8	0.097 (14)	0.084 (12)	0.088 (14)	0.000 (11)	0.004 (13)	−0.005 (10)
C9	0.089 (16)	0.121 (14)	0.072 (12)	0.000 (12)	0.001 (12)	−0.006 (11)
C17	0.086 (11)	0.079 (11)	0.090 (11)	0.001 (9)	−0.007 (9)	0.003 (10)
C11	0.096 (13)	0.091 (13)	0.109 (14)	0.002 (11)	0.007 (13)	0.003 (10)
C14	0.076 (11)	0.105 (13)	0.096 (13)	−0.008 (11)	−0.001 (11)	0.004 (11)
C16	0.083 (12)	0.140 (16)	0.097 (12)	0.012 (11)	−0.006 (9)	0.011 (12)
C13	0.092 (14)	0.100 (13)	0.093 (13)	−0.005 (12)	0.008 (10)	−0.005 (11)
C18	0.094 (11)	0.113 (13)	0.081 (10)	−0.010 (10)	0.002 (8)	0.003 (9)
C19	0.067 (11)	0.159 (17)	0.093 (11)	0.010 (11)	0.005 (8)	0.011 (10)
C12	0.076 (12)	0.125 (16)	0.114 (15)	0.016 (11)	0.004 (12)	0.014 (13)
C10	0.080 (13)	0.116 (15)	0.090 (14)	0.006 (12)	0.005 (12)	0.006 (12)

Geometric parameters (Å, º) top

P1—O5	1.616 (10)	C17—H17A	0.9900
P1—O4	1.541 (10)	C17—H17B	0.9900
P1—O2	1.501 (10)	C17—C16	1.516 (19)
P1—O3	1.510 (9)	C11—H11	0.9500
O5—C8	1.413 (17)	C11—C12	1.41 (2)
O4—H4	0.8400	C11—C10	1.38 (2)
N6—H6	0.8800	C14—H14	0.9500
N6—C14	1.382 (17)	C16—H16A	0.9900
N6—C10	1.376 (17)	C16—H16B	0.9900
N7—H7	1.0000	C13—H13	0.9500
N7—C17	1.516 (16)	C13—C12	1.38 (2)
N7—C18	1.482 (15)	C18—H18A	0.9800
N7—C19	1.518 (16)	C18—H18B	0.9800
C15—C9	1.44 (2)	C18—H18C	0.9800
C15—C14	1.375 (18)	C19—H19A	0.9800
C15—C16	1.49 (2)	C19—H19B	0.9800
C8—C9	1.39 (2)	C19—H19C	0.9800
C8—C13	1.386 (19)	C12—H12	0.9500
C9—C10	1.40 (2)

O4—P1—O5	101.1 (6)	C10—C11—H11	122.8
O2—P1—O5	108.6 (5)	C10—C11—C12	114.3 (17)
O2—P1—O4	108.6 (6)	N6—C14—H14	125.5
O2—P1—O3	115.1 (6)	C15—C14—N6	109.0 (14)
O3—P1—O5	109.3 (5)	C15—C14—H14	125.5
O3—P1—O4	113.2 (6)	C15—C16—C17	112.4 (14)
C8—O5—P1	122.4 (10)	C15—C16—H16A	109.1
P1—O4—H4	109.5	C15—C16—H16B	109.1
C14—N6—H6	124.9	C17—C16—H16A	109.1
C10—N6—H6	124.9	C17—C16—H16B	109.1
C10—N6—C14	110.2 (14)	H16A—C16—H16B	107.9
C17—N7—H7	108.1	C8—C13—H13	120.8
C17—N7—C19	110.3 (11)	C12—C13—C8	118.4 (16)
C18—N7—H7	108.1	C12—C13—H13	120.8
C18—N7—C17	111.4 (11)	N7—C18—H18A	109.5
C18—N7—C19	110.8 (11)	N7—C18—H18B	109.5
C19—N7—H7	108.1	N7—C18—H18C	109.5
C9—C15—C16	128.1 (17)	H18A—C18—H18B	109.5
C14—C15—C9	106.0 (15)	H18A—C18—H18C	109.5
C14—C15—C16	125.7 (17)	H18B—C18—H18C	109.5
C9—C8—O5	118.6 (18)	N7—C19—H19A	109.5
C9—C8—C13	122.2 (16)	N7—C19—H19B	109.5
C13—C8—O5	119.0 (16)	N7—C19—H19C	109.5
C8—C9—C15	135.8 (19)	H19A—C19—H19B	109.5
C8—C9—C10	115.6 (18)	H19A—C19—H19C	109.5
C10—C9—C15	108.6 (16)	H19B—C19—H19C	109.5
N7—C17—H17A	109.1	C11—C12—H12	118.4
N7—C17—H17B	109.1	C13—C12—C11	123.1 (16)
N7—C17—C16	112.7 (12)	C13—C12—H12	118.4
H17A—C17—H17B	107.8	N6—C10—C9	106.2 (17)
C16—C17—H17A	109.1	N6—C10—C11	127.8 (19)
C16—C17—H17B	109.1	C11—C10—C9	125.9 (18)
C12—C11—H11	122.8

P1—O5—C8—C9	129.3 (13)	C14—N6—C10—C9	−0.5 (17)
P1—O5—C8—C13	−56.5 (17)	C14—N6—C10—C11	176.4 (15)
O5—C8—C9—C15	−4 (3)	C14—C15—C9—C8	177.8 (18)
O5—C8—C9—C10	174.3 (13)	C14—C15—C9—C10	−0.3 (18)
O5—C8—C13—C12	−179.3 (13)	C14—C15—C16—C17	109.3 (17)
O4—P1—O5—C8	−176.8 (11)	C16—C15—C9—C8	−8 (3)
O2—P1—O5—C8	−62.6 (12)	C16—C15—C9—C10	173.7 (16)
O3—P1—O5—C8	63.7 (12)	C16—C15—C14—N6	−174.3 (15)
N7—C17—C16—C15	176.8 (12)	C13—C8—C9—C15	−177.7 (17)
C15—C9—C10—N6	0.5 (18)	C13—C8—C9—C10	0 (2)
C15—C9—C10—C11	−176.4 (15)	C18—N7—C17—C16	−149.7 (12)
C8—C9—C10—N6	−178.0 (13)	C19—N7—C17—C16	86.8 (14)
C8—C9—C10—C11	5 (2)	C12—C11—C10—N6	179.0 (15)
C8—C13—C12—C11	6 (2)	C12—C11—C10—C9	−5 (2)
C9—C15—C14—N6	0.0 (17)	C10—N6—C14—C15	0.4 (17)
C9—C15—C16—C17	−64 (2)	C10—C11—C12—C13	−1 (2)
C9—C8—C13—C12	−5 (2)

3-[2-(Dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate trihydrate (ps1_100k_hydrate_recryst_auto) top

Crystal data top

C₁₂H₁₇N₂O₄P·3H₂O	D_x = 1.398 Mg m⁻³
M_r = 338.29	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, Pbca	Cell parameters from 2310 reflections
a = 14.3405 (6) Å	θ = 3.3–73.3°
b = 8.2707 (3) Å	µ = 1.85 mm⁻¹
c = 27.098 (1) Å	T = 100 K
V = 3214.0 (2) Å³	Block, clear light colourless
Z = 8	0.13 × 0.05 × 0.04 mm
F(000) = 1440

Data collection top

XtaLAB Synergy, Single source at home/near, HyPix diffractometer	3256 independent reflections
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Cu) X-ray Source	2382 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.091
Detector resolution: 10.0000 pixels mm^-1	θ_max = 79.3°, θ_min = 3.3°
ω scans	h = −15→18
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2024)	k = −6→10
T_min = 0.615, T_max = 1.000	l = −34→34
12268 measured reflections

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.052	H-atom parameters constrained
wR(F²) = 0.120	w = 1/[σ²(F_o²) + (0.0178P)² + 3.4248P] where P = (F_o² + 2F_c²)/3
S = 1.04	(Δ/σ)_max = 0.001
3256 reflections	Δρ_max = 0.36 e Å⁻³
211 parameters	Δρ_min = −0.48 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
P1	0.92494 (5)	0.36117 (8)	0.55230 (2)	0.01156 (16)
O5	0.90092 (13)	0.4647 (2)	0.60101 (6)	0.0128 (4)
O2	0.88834 (15)	0.1936 (2)	0.55872 (7)	0.0159 (4)
O4	1.03363 (13)	0.3565 (2)	0.54911 (7)	0.0170 (4)
H4	1.051771	0.419918	0.526881	0.025*
O3	0.88452 (14)	0.4585 (2)	0.51054 (7)	0.0168 (4)
O7	0.71249 (15)	0.1728 (3)	0.40288 (7)	0.0212 (4)
H7A	0.655669	0.177781	0.414046	0.032*
H7B	0.745799	0.145864	0.428469	0.032*
O6	0.79746 (16)	0.0341 (3)	0.48255 (7)	0.0246 (5)
H6A	0.818913	0.099334	0.505045	0.037*
H6B	0.745419	−0.002182	0.494787	0.037*
O8	0.77588 (19)	0.4082 (3)	0.33838 (8)	0.0305 (6)
H8A	0.758593	0.334819	0.359436	0.046*
H8B	0.779033	0.496851	0.355568	0.046*
N7	0.53409 (16)	0.4368 (3)	0.60186 (8)	0.0131 (5)
H7	0.565556	0.537578	0.590092	0.016*
N6	0.79851 (17)	0.1754 (3)	0.73888 (8)	0.0154 (5)
H6	0.795486	0.123080	0.767115	0.019*
C10	0.8761 (2)	0.2495 (3)	0.71985 (10)	0.0143 (6)
C17	0.59537 (19)	0.3618 (3)	0.63999 (9)	0.0147 (5)
H17A	0.568600	0.256214	0.649719	0.018*
H17B	0.595896	0.431933	0.669608	0.018*
C11	0.9655 (2)	0.2661 (3)	0.74049 (10)	0.0177 (6)
H11	0.980436	0.219930	0.771597	0.021*
C8	0.9215 (2)	0.3970 (3)	0.64722 (9)	0.0131 (5)
C14	0.7266 (2)	0.1968 (3)	0.70634 (9)	0.0147 (5)
H14	0.664951	0.158289	0.711478	0.018*
C16	0.6951 (2)	0.3361 (3)	0.62286 (9)	0.0149 (5)
H16A	0.696455	0.253806	0.596333	0.018*
H16B	0.720295	0.438359	0.609346	0.018*
C15	0.7548 (2)	0.2806 (3)	0.66548 (9)	0.0125 (5)
C9	0.8520 (2)	0.3144 (3)	0.67336 (9)	0.0119 (5)
C13	1.0091 (2)	0.4174 (3)	0.66692 (10)	0.0169 (6)
H13	1.055240	0.475451	0.649032	0.020*
C18	0.5192 (2)	0.3308 (3)	0.55809 (10)	0.0195 (6)
H18A	0.579514	0.304628	0.543093	0.029*
H18B	0.480071	0.387163	0.533947	0.029*
H18C	0.488182	0.230795	0.568466	0.029*
C12	1.0306 (2)	0.3518 (4)	0.71395 (10)	0.0183 (6)
H12	1.091200	0.367327	0.727354	0.022*
C19	0.4430 (2)	0.4847 (4)	0.62373 (11)	0.0201 (6)
H19A	0.410567	0.388208	0.635864	0.030*
H19B	0.404701	0.537776	0.598526	0.030*
H19C	0.453626	0.559512	0.651189	0.030*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
P1	0.0136 (3)	0.0101 (3)	0.0110 (3)	0.0003 (3)	0.0000 (2)	0.0022 (2)
O5	0.0163 (9)	0.0099 (9)	0.0123 (8)	0.0019 (7)	0.0011 (7)	0.0031 (7)
O2	0.0244 (10)	0.0094 (9)	0.0140 (9)	−0.0014 (8)	−0.0017 (8)	0.0018 (7)
O4	0.0170 (9)	0.0196 (10)	0.0144 (8)	0.0006 (8)	0.0023 (8)	0.0069 (8)
O3	0.0160 (9)	0.0188 (10)	0.0156 (9)	0.0011 (8)	−0.0014 (8)	0.0047 (8)
O7	0.0223 (10)	0.0233 (11)	0.0181 (9)	0.0019 (9)	0.0035 (8)	−0.0001 (8)
O6	0.0227 (11)	0.0324 (13)	0.0186 (10)	−0.0100 (10)	0.0011 (9)	−0.0028 (9)
O8	0.0466 (15)	0.0281 (12)	0.0167 (10)	−0.0144 (11)	0.0107 (10)	−0.0068 (9)
N7	0.0181 (11)	0.0090 (11)	0.0122 (10)	−0.0001 (9)	−0.0014 (9)	0.0002 (8)
N6	0.0212 (12)	0.0134 (12)	0.0118 (10)	0.0015 (10)	0.0006 (9)	0.0028 (8)
C10	0.0218 (15)	0.0089 (12)	0.0123 (12)	0.0002 (11)	0.0014 (10)	−0.0019 (9)
C17	0.0182 (14)	0.0120 (13)	0.0137 (11)	0.0014 (11)	0.0000 (10)	0.0016 (10)
C11	0.0266 (16)	0.0153 (14)	0.0112 (11)	−0.0003 (12)	−0.0028 (11)	−0.0011 (10)
C8	0.0201 (13)	0.0090 (13)	0.0103 (11)	0.0018 (11)	0.0019 (10)	−0.0003 (9)
C14	0.0165 (13)	0.0142 (14)	0.0134 (11)	−0.0011 (11)	0.0029 (10)	−0.0009 (10)
C16	0.0173 (13)	0.0137 (14)	0.0136 (11)	−0.0034 (11)	−0.0016 (10)	0.0001 (10)
C15	0.0175 (13)	0.0080 (13)	0.0119 (11)	0.0010 (10)	0.0015 (10)	0.0000 (9)
C9	0.0170 (13)	0.0070 (12)	0.0116 (11)	0.0021 (10)	−0.0003 (10)	−0.0027 (9)
C13	0.0214 (14)	0.0126 (14)	0.0166 (12)	−0.0020 (11)	−0.0010 (11)	−0.0023 (10)
C18	0.0252 (15)	0.0153 (14)	0.0178 (13)	0.0033 (12)	−0.0060 (11)	−0.0037 (11)
C12	0.0188 (13)	0.0172 (14)	0.0190 (12)	0.0004 (12)	−0.0060 (11)	−0.0033 (11)
C19	0.0183 (14)	0.0161 (15)	0.0260 (14)	0.0037 (12)	0.0003 (11)	−0.0005 (12)

Geometric parameters (Å, º) top

P1—O5	1.6107 (19)	C17—H17B	0.9900
P1—O2	1.492 (2)	C17—C16	1.519 (4)
P1—O4	1.562 (2)	C11—H11	0.9500
P1—O3	1.5047 (19)	C11—C12	1.375 (4)
O5—C8	1.403 (3)	C8—C9	1.401 (4)
O4—H4	0.8400	C8—C13	1.376 (4)
O7—H7A	0.8702	C14—H14	0.9500
O7—H7B	0.8709	C14—C15	1.368 (4)
O6—H6A	0.8700	C16—H16A	0.9900
O6—H6B	0.8701	C16—H16B	0.9900
O8—H8A	0.8694	C16—C15	1.509 (4)
O8—H8B	0.8695	C15—C9	1.437 (4)
N7—H7	1.0000	C13—H13	0.9500
N7—C17	1.492 (3)	C13—C12	1.419 (4)
N7—C18	1.490 (3)	C18—H18A	0.9800
N7—C19	1.488 (4)	C18—H18B	0.9800
N6—H6	0.8800	C18—H18C	0.9800
N6—C10	1.371 (4)	C12—H12	0.9500
N6—C14	1.368 (4)	C19—H19A	0.9800
C10—C11	1.406 (4)	C19—H19B	0.9800
C10—C9	1.412 (4)	C19—H19C	0.9800
C17—H17A	0.9900

O2—P1—O5	108.85 (11)	C13—C8—C9	120.9 (2)
O2—P1—O4	109.55 (12)	N6—C14—H14	124.3
O2—P1—O3	116.67 (11)	C15—C14—N6	111.4 (3)
O4—P1—O5	105.78 (11)	C15—C14—H14	124.3
O3—P1—O5	104.46 (10)	C17—C16—H16A	109.6
O3—P1—O4	110.86 (11)	C17—C16—H16B	109.6
C8—O5—P1	118.29 (16)	H16A—C16—H16B	108.2
P1—O4—H4	109.5	C15—C16—C17	110.1 (2)
H7A—O7—H7B	104.4	C15—C16—H16A	109.6
H6A—O6—H6B	104.5	C15—C16—H16B	109.6
H8A—O8—H8B	104.6	C14—C15—C16	127.3 (3)
C17—N7—H7	107.5	C14—C15—C9	105.4 (2)
C18—N7—H7	107.5	C9—C15—C16	127.2 (2)
C18—N7—C17	113.0 (2)	C10—C9—C15	107.2 (2)
C19—N7—H7	107.5	C8—C9—C10	117.5 (3)
C19—N7—C17	110.6 (2)	C8—C9—C15	135.2 (2)
C19—N7—C18	110.3 (2)	C8—C13—H13	120.0
C10—N6—H6	125.9	C8—C13—C12	120.0 (3)
C14—N6—H6	125.9	C12—C13—H13	120.0
C14—N6—C10	108.1 (2)	N7—C18—H18A	109.5
N6—C10—C11	129.4 (2)	N7—C18—H18B	109.5
N6—C10—C9	107.9 (2)	N7—C18—H18C	109.5
C11—C10—C9	122.7 (3)	H18A—C18—H18B	109.5
N7—C17—H17A	108.8	H18A—C18—H18C	109.5
N7—C17—H17B	108.8	H18B—C18—H18C	109.5
N7—C17—C16	113.7 (2)	C11—C12—C13	121.3 (3)
H17A—C17—H17B	107.7	C11—C12—H12	119.4
C16—C17—H17A	108.8	C13—C12—H12	119.4
C16—C17—H17B	108.8	N7—C19—H19A	109.5
C10—C11—H11	121.2	N7—C19—H19B	109.5
C12—C11—C10	117.5 (2)	N7—C19—H19C	109.5
C12—C11—H11	121.2	H19A—C19—H19B	109.5
C9—C8—O5	119.8 (2)	H19A—C19—H19C	109.5
C13—C8—O5	119.3 (2)	H19B—C19—H19C	109.5

P1—O5—C8—C9	−95.4 (3)	C17—C16—C15—C9	−147.8 (3)
P1—O5—C8—C13	86.7 (3)	C11—C10—C9—C8	0.6 (4)
O5—C8—C9—C10	−179.5 (2)	C11—C10—C9—C15	−177.4 (2)
O5—C8—C9—C15	−2.3 (5)	C8—C13—C12—C11	0.5 (4)
O5—C8—C13—C12	179.0 (2)	C14—N6—C10—C11	177.2 (3)
O2—P1—O5—C8	48.3 (2)	C14—N6—C10—C9	−1.9 (3)
O4—P1—O5—C8	−69.3 (2)	C14—C15—C9—C10	−1.0 (3)
O3—P1—O5—C8	173.60 (19)	C14—C15—C9—C8	−178.4 (3)
N7—C17—C16—C15	172.6 (2)	C16—C15—C9—C10	175.2 (3)
N6—C10—C11—C12	−177.9 (3)	C16—C15—C9—C8	−2.3 (5)
N6—C10—C9—C8	179.7 (2)	C9—C10—C11—C12	1.0 (4)
N6—C10—C9—C15	1.8 (3)	C9—C8—C13—C12	1.2 (4)
N6—C14—C15—C16	−176.3 (2)	C13—C8—C9—C10	−1.7 (4)
N6—C14—C15—C9	−0.2 (3)	C13—C8—C9—C15	175.5 (3)
C10—N6—C14—C15	1.3 (3)	C18—N7—C17—C16	65.6 (3)
C10—C11—C12—C13	−1.6 (4)	C19—N7—C17—C16	−170.1 (2)
C17—C16—C15—C14	27.5 (4)

Reported phases of anhydrous psilocybin and precursor solvates, and method of characterization top

	SCXRD	PXRD	DSC	IR
Methanol solvate (2:1)	Weber & Petcher (1974)	Greenan et al. (2020)	Kuhnert-Brandstätter & Heindl (1976)	Kuhnert-Brandstätter & Heindl (1976)
Trihydrate	Greenan et al. (2020)	Greenan et al. (2020) and Sherwood et al. (2022)	Kuhnert-Brandstätter & Heindl (1976)	Kuhnert-Brandstätter & Heindl (1976)
First anhydrate/(Polymorph A')	–	Greenan et al. (2020)*	Kuhnert-Brandstätter & Heindl (1976)	Hofmann et al. (1958) and Kuhnert-Brandstätter & Heindl (1976)
Second anhydrate/(Polymorph B)	–	Greenan et al. (2020), Londesbrough et al. (2019), Sherwood et al. (2022) and Kargbo et al. (2022)	Greenan et al. (2020)	–

* High resolution PXRD was used to generate a structure solution.

Unit-cell dimensions of the Polymorph A' psilocybin anhydrate atomic structures. Unit-cell dimensions for Polymorph A' from published powder (PXRD) and our own single-crystal data (SCXRD), transformed for comparison, are shown top

	Polymorph A' (PXRD)	Polymorph A' (SCXRD)
CCDC refcode	TAVZID	n/a
Temperature (K)	295	100
a (Å)	17.4979 (2)	17.466 (5)
b (Å)	16.0914 (1)	15.920 (3)
c (Å)	9.34815 (7)	9.322 (3)
Volume (Å³)	2632.11 (3)	2592.1 (11)

Acknowledgements

The authors thank the UWA XRD Facility for access to equipment and facilities.

Conflict of interest

LM and MH are employees of Natural MedTech.

Funding information

The following funding is acknowledged: Australian Research Council (Mid-Career Industry Fellowship IM230100154 to Yit-Heng Chooi).

References

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