Crystal structure of serotonin

Naeem, M.; Chadeayne, A.R.; Golen, J.A.; Manke, D.R.

doi:10.1107/S2056989022002559

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ISSN: 2056-9890

Volume 78| Part 4| April 2022| Pages 365-368

https://doi.org/10.1107/S2056989022002559

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Crystal structure of serotonin

Marilyn Naeem,^a Andrew R. Chadeayne,^b James A. Golen ^a and David R. Manke ^a ^*

^aUniversity of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, MA 02747, USA, and ^bCaaMTech, Inc., 58 East Sunset Way, Suite 209, Issaquah, WA 98027, USA
^*Correspondence e-mail: dmanke@umassd.edu

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 22 February 2022; accepted 5 March 2022; online 10 March 2022)

The title compound, serotonin or 5-hydroxytryptamine (5-HT) [systematic name: 3-(2-aminoethyl)-1H-indol-5-ol], C₁₀H₁₂N₂O, has one molecule in the asymmetric unit. The conformation of the ethylamino side chain is gauche–gauche [C_a—C_a—C_m—C_m and C_a—C_m—C_m—N (a = aromatic, m = methylene) torsion angles = −64.2 (3) and −61.9 (2)°, respectively]. In the crystal, the molecules are linked into a three-dimensional network by N—H⋯O and O—H⋯N hydrogen bonds.

Keywords: crystal structure; serotonin; tryptamine; indole; free base.

CCDC reference: 2156646

1. Chemical context

Serotonin, C₁₀H₁₂N₂O, systematic name 3-(2-aminoethyl)-1H-indol-5-ol, is the primary neurotransmitter in humans, regulating mood, anxiety and happiness (Young & Leyton, 2002 ). While it is best known for its role in the central nervous system, serotonin is found throughout the human body and impacts a wide array of bodily functions. Roughly ninety-five percent of the body's serotonin is actually found in the gastrointestinal tract, where it regulates intestinal movement (Berger et al., 2009 ). Serotonin is produced in the human body through biosynthesis from the essential amino acid tryptophan (Fitzpatrick, 1999 ), and broken down by monoamine oxidase to generate 5-hydroxyindoleacetic acid. As such, monoamine oxidase inhibitors and other compounds that increase serotonin concentration have been used to treat depression (Suchting et al., 2021 ).

Serotonin is not unique to humans, but is found throughout life on Earth including all bilateral animals, where it also functions as a neurotransmitter (Bacqué-Cazenave et al., 2020 ). It is found in plants, notably in seeds, where serotonin stimulates the digestive tract of animals, leading to excretion of the seeds (Akula et al., 2011 ). Serotonin and related tryptamines are well known to be present in a number of fungi (Tyler, 1958 ; Sherwood et al., 2020 ). A variety of related tryptamines found in plants, fungi, and toads, which are active at serotonin receptors, have garnered significant attention as psychedelic drugs to treat mood disorders including anxiety, depression, and addiction (Carhart-Harris & Goodwin, 2017 ). Serotonin was discovered by Vittorio Erspaner in 1935, characterized as 5-hydroxytryptamine (5-HT) in 1949 by Rapport, and synthesized by Upjohn pharmaceutical in 1951 (Whitaker-Azmitia, 1999 ). Despite the simplicity of its structure and universally recognized biological significance, the single-crystal structure of pure free base serotonin has never been reported. Herein, we report this structure to fill in the gap from the scientific record.

2. Structural commentary

Serotonin or 5-hydroxytryptamine (5-HT) is an indolamine with a 5-hydroxy substitution. In the solid state, serotonin crystallizes with one molecule in the asymmetric unit (Fig. 1) in the chiral space group P2₁2₁2₁. The 5-hydroxyindole fused-ring unit is almost planar with the non-hydrogen atoms showing an r.m.s. deviation from planarity of 0.030 Å. The ethylamino arm is turned away from the indole ring, with a C7—C8—C9—C10 torsion angle of −64.2 (3)°. The ethylamino arm itself turns back toward the indole ring with a C8—C9—C10—N2 torsion angle of −61.9 (2)°.

Figure 1
The molecular structure of serotonin free base showing the atomic labeling. Displacement ellipsoids are drawn at the 50% probability level.

3. Supramolecular features

In the crystal, the serotonin molecules are linked by a series of hydrogen bonds that produce a three-dimensional network in the solid state. The hydroxy groups form hydrogen bonds to the amine N atoms on an adjacent serotonin molecules forming O1—H1⋯N2 hydrogen bonds. The indole N atoms form hydrogen bonds to the hydroxy groups of adjacent serotonin molecules through N1—H1A⋯O1 hydrogen bonds. Half of the amine H atoms link to the hydroxy groups of nearby molecules through N2—H2B⋯O1 hydrogen bonds. There are no observed π–π stacking interactions. Fig. 2 outlines the hydrogen bonds, which are detailed in Table 1. The crystal packing of serotonin is shown in Fig. 3.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯N2ⁱ	0.88 (1)	1.77 (1)	2.636 (2)	170 (3)
N1—H1A⋯O1ⁱⁱ	0.88 (1)	2.10 (1)	2.967 (2)	169 (2)
N2—H2B⋯O1ⁱⁱⁱ	0.91 (1)	2.19 (1)	3.092 (3)	168 (2)
Symmetry codes: (i) $[-x+{\script{3\over 2}}, -y+1, z-{\script{1\over 2}}]$ ; (ii) $[-x+{\script{3\over 2}}, -y, z+{\script{1\over 2}}]$ ; (iii) $[-x+2, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Figure 2
The different hydrogen-bonding interactions between the serotonin molecules. Hydrogen atoms not involved in hydrogen bonding are omitted for clarity. Symmetry codes: (i) $[{3\over 2}]$ − x, 1 − y, $[{1\over 2}]$ + z (ii) 2 − x, − $[{1\over 2}]$ + y, $[{1\over 2}]$ − z (iii) 3/2 − x, −y, − $[{1\over 2}]$ + z.

Figure 3
The crystal packing of serotonin free base viewed along the a-axis. Hydrogen bonds are shown as dashed lines. Hydrogen atoms not involved in hydrogen bonds are omitted for clarity.

4. Database survey

The previous structural reports of serotonin are all complex mixtures containing serotonin in its C₁₀H₁₃N₂O⁺ cationic form. These include the creatine sulfate monohydrate (Karle et al., 1965 : Cambridge Structural Database refcode HTRCRS), the hydrogen oxalate salt (Amit et al., 1978 : SERHOX), the hydroadipate salt (Rychkov et al., 2013 : VIKWIX), the picrate monohydrate (Thewalt & Bugg, 1972 : SERPIC) and two compounds where it is co-crystallized with 1,3,6,8-tetrasulfonatopyrene (Feng et al., 2017 : RAWDIF, RAWDOL). The two most closely reported free-base structures to serotonin are the natural product bufotenine, 5-hydroxy-N,N-dimethyltryptamine (Falkenberg, 1972 : BUFTEN) and 5-methoxytryptamine (Quarles et al., 1974 : MXTRYP). 5-Methoxytryptamine has also been reported as its picrate (Nagata et al., 1995 : ZILMIQ) and chloride (Pham et al., 2021 : CCDC 2106050) salts. The free base reported here shows the ethylamino arm turned away from the indole plane. The majority of the cationic tryptamine structures show ethylamino arms that are nearly in-plane with the indole ring. Only the picrate salt has a structure similar to that of the title compound, showing an ethylamino arm turned similarly away from the indole ring. The torsion angles associated with the ethylamino arms of the different structures are summarized in Table 2.

Table 2
Torsion angles of the ethylamino arms of different serotonin structures (our atom-numbering scheme)

	Space group	C7—C8—C9—C10	C8—C9—C10—N2	Reference
5-HT free base	P2₁2₁2₁	−64.2 (3)	−61.9 (2)	This work
HTRCRS	C2/c	166.7	172.6	Karle et al. (1965)
SERHOX	P2₁/n	171.7	179.7	Amit et al. (1978)
SERPIC	P2₁/c	67.5	66.6	Thewalt & Bugg (1972)
VIKWIX	P $[\overline{1}]$	178.7	177.2	Rychkov et al. (2013)
RAWDIF	Pca2₁	177.8	177.6	Feng et al. (2017)
RAWDOL^a	Cc	178.7	175.1	Feng et al. (2017)
RAWDOL^b	Cc	102	43	Feng et al. (2017)
Notes: (a, b) RAWDOL contains two molecules in the asymmetric unit. The b molecule is probably disordered and the geometrical data are less certain.

5. Synthesis and crystallization

Single crystals suitable for X-ray diffraction studies were grown from the slow evaporation of a tetrahydrofuran solution of a commercial sample of serotonin free base (Chem-Impex).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. Hydrogen atoms H1, H1A, H2A and H2B were found from a difference-Fourier map and were refined isotropically, using DFIX restraints with an N—H(indole) distance of 0.87 (1) Å, N—H(amine) distances of 0.90 (1) Å, and an O—H distance of 0.86 (1) Å. Isotropic displacement parameters were set to 1.2 U_eq of the parent nitrogen atoms and 1.5 U_eq of the parent oxygen atom. All other hydrogen atoms were placed in calculated positions with C—H = 0.93 Å (sp²) or 0.97 Å (sp³). Isotropic displacement parameters were set to 1.2 U_eq of the parent carbon atoms. The absolute structure of the crystal chosen for data collection was indeterminate in the present refinement.

Table 3
Experimental details

Crystal data
Chemical formula	C₁₀H₁₂N₂O
M_r	176.22
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	297
a, b, c (Å)	8.2248 (6), 8.7542 (6), 13.0712 (10)
V (Å³)	941.15 (12)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.08
Crystal size (mm)	0.18 × 0.10 × 0.02

Data collection
Diffractometer	Bruker D8 Venture CMOS
Absorption correction	Multi-scan (SADABS; Bruker, 2018 )
T_min, T_max	0.711, 0.745
No. of measured, independent and observed [I > 2σ(I)] reflections	25138, 1783, 1590
R_int	0.052
(sin θ/λ)_max (Å⁻¹)	0.610

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.030, 0.073, 1.05
No. of reflections	1783
No. of parameters	134
No. of restraints	4
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.13, −0.13
Absolute structure	Flack x determined using 609 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013 )
Absolute structure parameter	−1.2 (6)
Computer programs: APEX3 (Bruker, 2018), SAINT (Bruker, 2018), SHELXT2014 (Sheldrick, 2015a ), SHELXL2018 (Sheldrick, 2015b ), OLEX2 (Dolomanov et al., 2009 ), publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 2156646

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989022002559/hb8014sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989022002559/hb8014Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989022002559/hb8014Isup3.cml

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2018); cell refinement: SAINT (Bruker, 2018); data reduction: SAINT (Bruker, 2018); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

3-(2-Aminoethyl)-1H-indol-5-ol top

Crystal data top

C₁₀H₁₂N₂O	D_x = 1.244 Mg m⁻³
M_r = 176.22	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 6263 reflections
a = 8.2248 (6) Å	θ = 3.1–25.4°
b = 8.7542 (6) Å	µ = 0.08 mm⁻¹
c = 13.0712 (10) Å	T = 297 K
V = 941.15 (12) Å³	Block, colourless
Z = 4	0.18 × 0.10 × 0.02 mm
F(000) = 376

Data collection top

Bruker D8 Venture CMOS diffractometer	1590 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.052
Absorption correction: multi-scan (SADABS; Bruker, 2018)	θ_max = 25.7°, θ_min = 2.8°
T_min = 0.711, T_max = 0.745	h = −10→10
25138 measured reflections	k = −10→10
1783 independent reflections	l = −15→15

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.030	w = 1/[σ²(F_o²) + (0.0372P)² + 0.1115P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.073	(Δ/σ)_max < 0.001
S = 1.05	Δρ_max = 0.13 e Å⁻³
1783 reflections	Δρ_min = −0.13 e Å⁻³
134 parameters	Absolute structure: Flack x determined using 609 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
4 restraints	Absolute structure parameter: −1.2 (6)

Special details top

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

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

	x	y	z	U_iso*/U_eq
O1	0.91964 (18)	0.18734 (16)	0.08462 (10)	0.0398 (4)
H1	0.868 (3)	0.263 (2)	0.054 (2)	0.078 (9)*
N1	0.6390 (2)	0.0903 (2)	0.45983 (14)	0.0445 (5)
H1A	0.633 (3)	0.012 (2)	0.5016 (15)	0.051 (7)*
N2	0.7279 (2)	0.6020 (2)	0.47447 (15)	0.0458 (5)
H2A	0.725 (3)	0.5092 (18)	0.5030 (18)	0.050 (7)*
H2B	0.8312 (19)	0.638 (3)	0.465 (2)	0.072 (9)*
C1	0.5533 (3)	0.2238 (2)	0.47087 (16)	0.0433 (5)
H1B	0.487070	0.246998	0.526412	0.052*
C2	0.7237 (2)	0.0960 (2)	0.36910 (15)	0.0343 (4)
C3	0.8303 (2)	−0.0077 (2)	0.32446 (16)	0.0388 (5)
H3	0.856712	−0.098830	0.357097	0.047*
C4	0.8956 (2)	0.0283 (2)	0.23057 (16)	0.0375 (5)
H4	0.967797	−0.039127	0.199600	0.045*
C5	0.8552 (2)	0.1654 (2)	0.18068 (14)	0.0316 (4)
C6	0.7543 (2)	0.27075 (19)	0.22632 (14)	0.0304 (4)
H6	0.731045	0.362796	0.193965	0.036*
C7	0.6874 (2)	0.2373 (2)	0.32214 (14)	0.0300 (4)
C8	0.5785 (2)	0.3173 (2)	0.38953 (14)	0.0349 (4)
C9	0.5130 (2)	0.4756 (2)	0.37352 (17)	0.0391 (5)
H9A	0.434413	0.497950	0.426806	0.047*
H9B	0.456668	0.479381	0.308368	0.047*
C10	0.6446 (3)	0.5971 (2)	0.37477 (16)	0.0412 (5)
H10A	0.723268	0.575700	0.321372	0.049*
H10B	0.596386	0.696063	0.360712	0.049*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0473 (8)	0.0370 (8)	0.0351 (7)	0.0049 (7)	0.0058 (6)	−0.0021 (6)
N1	0.0536 (11)	0.0411 (10)	0.0390 (10)	0.0009 (9)	0.0040 (9)	0.0125 (8)
N2	0.0465 (11)	0.0406 (10)	0.0502 (12)	0.0012 (9)	−0.0064 (9)	−0.0055 (9)
C1	0.0441 (11)	0.0456 (13)	0.0402 (11)	0.0009 (10)	0.0064 (9)	0.0025 (9)
C2	0.0378 (10)	0.0309 (9)	0.0342 (10)	−0.0019 (8)	−0.0068 (9)	0.0044 (8)
C3	0.0434 (11)	0.0268 (9)	0.0461 (11)	0.0031 (8)	−0.0094 (10)	0.0058 (8)
C4	0.0366 (10)	0.0325 (10)	0.0435 (11)	0.0061 (8)	−0.0055 (9)	−0.0036 (9)
C5	0.0322 (9)	0.0299 (9)	0.0328 (9)	−0.0033 (7)	−0.0037 (8)	−0.0034 (8)
C6	0.0360 (9)	0.0230 (8)	0.0323 (9)	−0.0004 (8)	−0.0052 (8)	0.0010 (7)
C7	0.0304 (9)	0.0282 (9)	0.0315 (9)	−0.0012 (7)	−0.0060 (7)	0.0001 (7)
C8	0.0348 (9)	0.0347 (10)	0.0353 (10)	0.0004 (8)	−0.0024 (9)	−0.0004 (8)
C9	0.0377 (10)	0.0390 (11)	0.0406 (11)	0.0078 (9)	−0.0006 (9)	−0.0009 (9)
C10	0.0493 (12)	0.0340 (10)	0.0404 (11)	0.0045 (9)	−0.0001 (10)	−0.0030 (9)

Geometric parameters (Å, º) top

O1—H1	0.878 (13)	C3—C4	1.376 (3)
O1—C5	1.376 (2)	C4—H4	0.9300
N1—H1A	0.879 (12)	C4—C5	1.406 (3)
N1—C1	1.373 (3)	C5—C6	1.376 (3)
N1—C2	1.376 (3)	C6—H6	0.9300
N2—H2A	0.894 (12)	C6—C7	1.399 (3)
N2—H2B	0.914 (13)	C7—C8	1.438 (3)
N2—C10	1.473 (3)	C8—C9	1.501 (3)
C1—H1B	0.9300	C9—H9A	0.9700
C1—C8	1.358 (3)	C9—H9B	0.9700
C2—C3	1.391 (3)	C9—C10	1.518 (3)
C2—C7	1.412 (3)	C10—H10A	0.9700
C3—H3	0.9300	C10—H10B	0.9700

C5—O1—H1	109.1 (19)	C5—C6—H6	120.5
C1—N1—H1A	124.8 (16)	C5—C6—C7	119.01 (16)
C1—N1—C2	108.64 (16)	C7—C6—H6	120.5
C2—N1—H1A	126.4 (16)	C2—C7—C8	107.00 (17)
H2A—N2—H2B	113 (2)	C6—C7—C2	119.27 (17)
C10—N2—H2A	109.3 (16)	C6—C7—C8	133.72 (17)
C10—N2—H2B	108.5 (18)	C1—C8—C7	106.30 (17)
N1—C1—H1B	124.7	C1—C8—C9	127.65 (19)
C8—C1—N1	110.65 (19)	C7—C8—C9	126.01 (17)
C8—C1—H1B	124.7	C8—C9—H9A	109.0
N1—C2—C3	131.04 (18)	C8—C9—H9B	109.0
N1—C2—C7	107.41 (16)	C8—C9—C10	112.92 (16)
C3—C2—C7	121.54 (18)	H9A—C9—H9B	107.8
C2—C3—H3	121.0	C10—C9—H9A	109.0
C4—C3—C2	118.04 (17)	C10—C9—H9B	109.0
C4—C3—H3	121.0	N2—C10—C9	111.17 (17)
C3—C4—H4	119.4	N2—C10—H10A	109.4
C3—C4—C5	121.14 (18)	N2—C10—H10B	109.4
C5—C4—H4	119.4	C9—C10—H10A	109.4
O1—C5—C4	116.80 (17)	C9—C10—H10B	109.4
C6—C5—O1	122.29 (17)	H10A—C10—H10B	108.0
C6—C5—C4	120.90 (17)

O1—C5—C6—C7	177.03 (16)	C3—C2—C7—C6	2.9 (3)
N1—C1—C8—C7	0.2 (2)	C3—C2—C7—C8	−178.28 (17)
N1—C1—C8—C9	−177.44 (19)	C3—C4—C5—O1	−176.50 (17)
N1—C2—C3—C4	178.8 (2)	C3—C4—C5—C6	2.8 (3)
N1—C2—C7—C6	−178.03 (16)	C4—C5—C6—C7	−2.3 (3)
N1—C2—C7—C8	0.8 (2)	C5—C6—C7—C2	−0.5 (2)
C1—N1—C2—C3	178.3 (2)	C5—C6—C7—C8	−178.96 (18)
C1—N1—C2—C7	−0.7 (2)	C6—C7—C8—C1	178.0 (2)
C1—C8—C9—C10	113.0 (2)	C6—C7—C8—C9	−4.4 (3)
C2—N1—C1—C8	0.3 (3)	C7—C2—C3—C4	−2.4 (3)
C2—C3—C4—C5	−0.5 (3)	C7—C8—C9—C10	−64.2 (3)
C2—C7—C8—C1	−0.6 (2)	C8—C9—C10—N2	−61.9 (2)
C2—C7—C8—C9	177.08 (18)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N2ⁱ	0.88 (1)	1.77 (1)	2.636 (2)	170 (3)
N1—H1A···O1ⁱⁱ	0.88 (1)	2.10 (1)	2.967 (2)	169 (2)
N2—H2B···O1ⁱⁱⁱ	0.91 (1)	2.19 (1)	3.092 (3)	168 (2)

Symmetry codes: (i) −x+3/2, −y+1, z−1/2; (ii) −x+3/2, −y, z+1/2; (iii) −x+2, y+1/2, −z+1/2.

Torsion angles of the ethylamino arms of different serotonin structures (our atom-numbering scheme) top

	Space group	C7—C8—C9—C10	C8—C9—C10—N2	Reference
5-HT free base	P2₁2₁2₁	-64.2 (3)	-61.9 (2)	This work
HTRCRS	C2/c	166.7	172.6	Karle et al. (1965)
SERHOX	P2₁/n	171.7	179.7	Amit et al. (1978)
SERPIC	P2₁/c	67.5	66.6	Thewalt & Bugg (1972)
VIKWIX	P1	178.7	177.2	Rychkov et al. (2013)
RAWDIF	Pca2₁	177.8	177.6	Feng et al. (2017)
RAWDOL^a	Cc	178.7	175.1	Feng et al. (2017)
RAWDOL^b	Cc	102	43	Feng et al. (2017)

Notes: (a, b) RAWDOL contains two molecules in the asymmetric unit. The b molecule is probably disordered and the geometrical data are less certain.

Acknowledgements

Financial statements and conflict of interest: This study was funded by CaaMTech, Inc. ARC reports an ownership interest in CaaMTech, Inc., which owns US and worldwide patent applications, covering new tryptamine compounds, compositions, formulations, novel crystalline forms, and methods of making and using the same.

Funding information

Funding for this research was provided by: National Science Foundation, Directorate for Mathematical and Physical Sciences (grant No. CHE-1429086).

References

Akula, R., Giridhar, P. & Ravishankar, G. A. (2011). Plant Signal. Behav. 6, 800–809. CrossRef PubMed Google Scholar
Amit, A., Mester, L., Klewe, B. & Furberg, S. (1978). Acta Chem. Scand. 32a, 267–270. CSD CrossRef Web of Science Google Scholar
Bacqué-Cazenave, J., Bharatiya, R., Barrière, G., Delbecque, J.-P., Bouguiyoud, N., Di Giovanni, G., Cattaert, D. & De Deurwaerdère, P. (2020). Int. J. Mol. Sci. 21, 1649. Google Scholar
Berger, M., Gray, J. A. & Roth, B. L. (2009). Annu. Rev. Med. 60, 355–366. Web of Science CrossRef PubMed CAS Google Scholar
Bruker (2018). APEX3, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Carhart-Harris, R. L. & Goodwin, G. M. (2017). Neuropsychopharmacol, 42, 2105–2113. CAS Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Falkenberg, G. (1972). Acta Cryst. B28, 3219–3228. CSD CrossRef IUCr Journals Web of Science Google Scholar
Feng, W.-X., van der Lee, A., Legrand, Y.-M., Petit, E., Su, C.-Y. & Barboiu, M. (2017). Chem. Eur. J. 23, 4037–4041. Web of Science CSD CrossRef CAS PubMed Google Scholar
Fitzpatrick, P. F. (1999). Annu. Rev. Biochem. 68, 355–381. Web of Science CrossRef PubMed CAS Google Scholar
Karle, I. L., Dragonette, K. S. & Brenner, S. A. (1965). Acta Cryst. 19, 713–716. CSD CrossRef CAS IUCr Journals Web of Science Google Scholar
Nagata, H., In, Y., Doi, M., Ishida, T. & Wakahara, A. (1995). Acta Cryst. B51, 1051–1058. CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Pham, D. N. K., Belanger, Z. S., Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2021). Acta Cryst. C77, 615–620. Web of Science CSD CrossRef IUCr Journals Google Scholar
Quarles, W. G., Templeton, D. H. & Zalkin, A. (1974). Acta Cryst. B30, 95–98. CSD CrossRef IUCr Journals Web of Science Google Scholar
Rychkov, D., Boldyreva, E. V. & Tumanov, N. A. (2013). Acta Cryst. C69, 1055–1061. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sherwood, A. M., Halberstadt, A. L., Klein, A. K., McCorvy, J. D., Kaylo, K. W., Kargbo, R. B. & Meisenheimer, P. (2020). J. Nat. Prod. 83, 461–467. Web of Science CrossRef CAS PubMed Google Scholar
Suchting, R., Tirumalaraju, V., Gareeb, R., Bockmann, T., de Dios, C., Aickareth, J., Pinjari, O., Soares, J. C., Cowen, P. J. & Selvaraj, S. (2021). J. Affect. Disord. 282, 1153–1160. Web of Science CrossRef CAS PubMed Google Scholar
Thewalt, U. & Bugg, C. E. (1972). Acta Cryst. B28, 82–92. CSD CrossRef CAS IUCr Journals Web of Science Google Scholar
Tyler, V. E. (1958). Science, 128, 718. CrossRef PubMed Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
Whitaker-Azmitia, P. M. (1999). Neuropsychopharmacology, 21, 2S8S. Google Scholar
Young, S. N. & Leyton, M. (2002). Pharmacol. Biochem. Behav. 71, 857–865. Web of Science CrossRef PubMed CAS Google Scholar