(R)-Baclofen [(R)-4-amino-3-(4-chloro­phen­yl)butanoic acid]

Belov, F.; Villinger, A.; von Langermann, J.

doi:10.1107/S2056989021012809

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 78| Part 1| January 2022| Pages 33-35

https://doi.org/10.1107/S2056989021012809

Open

access

(R)-Baclofen [(R)-4-amino-3-(4-chlorophenyl)butanoic acid]

Feodor Belov,^a Alexander Villinger ^b and Jan von Langermann ^a ^*

^aUniversity of Rostock, Institute of Chemistry, Biocatalytic synthesis group, Albert-Einstein-Str. 3A, 18059 Rostock, Germany, and ^bUniversity of Rostock, Institute of Chemistry, X-ray structure analytics, Albert-Einstein-Str. 3A, 18059 Rostock, Germany
^*Correspondence e-mail: jan.langermann@uni-rostock.de

Edited by C. Schulzke, Universität Greifswald, Germany (Received 3 November 2021; accepted 1 December 2021; online 1 January 2022)

This article provides the first single-crystal XRD-based structure of enantiopure (R)-baclofen (form C), C₁₀H₁₂ClNO₂, without any co-crystallized substances. In the enantiopure title compound, the molecules arrange themselves in an orthorhombic crystal structure (space group P2₁2₁2₁). In the crystal, strong hydrogen bonds and C—H⋯Cl bonds interconnect the zwitterionic molecules.

Keywords: crystal structure; (R)-baclofen; enantiopure; hydrogen bonds.

CCDC reference: 2125567

1. Chemical context

(R)-Baclofen, an unnatural β-amino acid and artificial GABA receptor agonist, is a frequently used non-addictive drug to treat muscle spasticity (Dario & Tomei, 2004 ). Although baclofen is conventionally applied as a racemic mixture, only the (R)-enantiomer actually mediates a therapeutic effect (Olpe et al., 1978 ). In addition, baclofen has been recently approved in France as an alternative medication to treat alcohol dependence (Reade, 2021 ). Considering those new developments, the establishment of synthetic routes towards enantiopure (R)-baclofen were discussed recently (Córdova-Villanueva et al., 2018 ; Gendron et al., 2019 ).

2. Structural commentary

The molecular structure of the title compound is shown in Fig. 1. A partial packing diagram is shown in Fig. 2.

Figure 1
The molecular structure of (R)-baclofen with displacement ellipsoids shown at the 50% probability level.

Figure 2
Partial packing diagram of (R)-baclofen form C.

A prediction of crystal forms of the title compound was previously presented by Couvrat et al. (2021 ), which is based on detailed XRPD-studies and Rietveld refinement. Based on the available XRPD-data, three forms, A, B and C, were observed, of which form C is considered to be the most stable form at higher temperatures. The (R)-baclofen crystal analyzed in this work corresponds to the newly predicted polymorphic form C presented by Couvrat et al. (2021).

The molecules crystallize in a zwitterionic configuration, forming an ammonium and a carboxylate residue. The N-bound hydrogen atoms were located and refined freely. Bond lengths and angles fall into the typically observed ranges for organic molecules without any strain.

3. Supramolecular features

In the crystal of enantiopure (R)-baclofen form C, short N—H⋯O hydrogen bonds occur between the carboxylate and the ammonium group of the neighboring baclofen molecule. In parallel, additional hydrogen bonding occurs with neighboring baclofen molecules, resulting in a two-dimensional network parallel to (001), which yields a layered formation of baclofen molecules. Parallel to the hydrogen bonding, T-shaped C—H⋯π interactions occur along the layers of aromatic rings within the molecules [C9—H9 ⋯ Cg1^viii= 2.74 Å; C6—H6 ⋯ Cg1^ix= 3.24 Å; symmetry codes: (viii) −x + 2, y − $[{1\over 2}]$ , −z + $[{3\over 2}]$ ; (ix) −x + 1, y + $[{1\over 2}]$ , −z + $[{3\over 2}]$ ; Cg1 is the centroid of the C5–C10 benzene ring] . The interaction planes both form angles of 67° with the plane of the corresponding benzene ring (C5–C10).

The combination of both effects yields the observed structure of form C of (R)-baclofen. In contrast, the cohesion of the apparently less stable form A is ensured by π–π interactions.

Hydrogen-bond geometry data as well as non-classical C—H⋯Cl interaction data are summarized in Table 1.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O2ⁱ	0.91 (3)	1.91 (3)	2.820 (2)	176 (3)
N1—H1B⋯O2ⁱⁱ	0.93 (3)	1.80 (3)	2.7149 (19)	168 (2)
N1—H1C⋯O1ⁱⁱⁱ	0.85 (3)	1.93 (3)	2.775 (2)	174 (3)
N1—H1B⋯Cl1^iv	0.93 (3)	2.95 (2)	3.3192 (14)	105.3 (16)
C4—H4A⋯Cl1^v	0.99	2.73	3.6306 (19)	152
C4—H4B⋯Cl1^vi	0.99	2.81	3.5668 (19)	134
Symmetry codes: (i) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ ; (ii) x, y+1, z; (iii) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ ; (iv) $[-x+{\script{3\over 2}}, -y+1, z-{\script{1\over 2}}]$ ; (v) $[-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (vi) $[-x+2, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

4. Database survey

Using the CSD database (version 5.42 updates 2 and 3; Groom et al., 2016 ), a search for the title compound's structure and names used in this article was conducted with CONQUEST (version 2021.2.0; Bruno et al., 2002 ).

While the crystal structures of (R)- and (S)-baclofenium hydrochloride were reported in the early 1980s (Chang et al., 1981 , 1982 ; refcodes: CRBMZB, CRBMZC10), studies on the phase behavior of pure baclofen have gained attention just recently. This is particularly relevant for the crystal structure of enantiomerically pure (R)-baclofen since X-ray powder diffraction studies were recently described by Couvrat et al. (2021). A total of three polymorphic forms (A, B and C) of (R)-baclofen were analyzed by X-ray powder diffraction, form C being identified as previously unknown. Based on this nomenclature, the crystal structure of form C is reported in this study. For the crystal structure of racemic baclofen, see Maniukiewicz et al. (2016 ; refcode: AQEKUE). A further array of racemic baclofenium co-crystal structures with various carboxylic acids were published by Báthori & Kilinkissa (2015 ; refcodes: LUSXAA, LUSXEE, LUSXII, LUSXUU, LUSXOO, LUSYAB) and Malapile et al. (2021 ; refcodes: LABJIL, LABJOR, LABJUX, LABKAE, LABKEI, LABKIM, LABKOS). Additionally, Gendron et al. (2019; refcode: WONSIE01) presented the crystal structure of (R)-baclofen hydrogenium maleate.

5. Synthesis and crystallization

Crystals of the title compound were grown from a saturated aqueous solution containing enantiopure (R)-baclofen, which was evaporated slowly by a stream of dry argon at 313 K. The purity of the (R)-baclofen was verified via ¹H NMR. Enantiopure (R)-baclofen was purchased from abcr GmbH (Karlsruhe, Germany) under the name (R)-4-amino-3-(4-chlorophenyl)butanoic acid.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The N-bound hydrogen atoms were found in difference syntheses, and refined freely. All C-bound H atoms were positioned geometrically and refined using a riding model, with C—H = 0.99 Å (methylene groups), 1.00 Å (methine groups) or 0.95 Å (aryl CH) and with U_iso(H) = 1.2U_eq(C) (methylene groups, aryl CH, methine groups). The structure was refined as a two-component inversion twin (BASF 0.04470).

Table 2
Experimental details

Crystal data
Chemical formula	C₁₀H₁₂ClNO₂
M_r	213.66
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	123
a, b, c (Å)	6.8913 (5), 7.6898 (5), 19.7527 (14)
V (Å³)	1046.75 (13)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.34
Crystal size (mm)	0.27 × 0.19 × 0.16

Data collection
Diffractometer	Bruker D8 QUEST diffractometer
Absorption correction	Multi-scan (SADABS2016/2; Krause et al., 2015 )
T_min, T_max	0.662, 0.747
No. of measured, independent and observed [I > 2σ(I)] reflections	23624, 3796, 3447
R_int	0.042
(sin θ/λ)_max (Å⁻¹)	0.756

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.033, 0.082, 1.07
No. of reflections	3796
No. of parameters	140
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.36, −0.30
Absolute structure	Refined as an inversion twin
Absolute structure parameter	0.04 (6)
Computer programs: APEX2 and APEX2 (Bruker, 2003 ), SAINT (Bruker, 2003), SHELXT (Sheldrick, 2015a ), SHELXL2014/7 (Sheldrick, 2015b ) and ORTEP-3 for Windows (Farrugia, 2012 ).

Supporting information

CCDC reference: 2125567

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989021012809/yz2013sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989021012809/yz2013Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989021012809/yz2013Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2003); cell refinement: APEX2 (Bruker, 2003); data reduction: SAINT (Bruker, 2003); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL2014/7 (Sheldrick, 2015b).

(R)-4-amino-3-(4-chlorophenyl)butanoic acid top

Crystal data top

C₁₀H₁₂ClNO₂	D_x = 1.356 Mg m⁻³
M_r = 213.66	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 9871 reflections
a = 6.8913 (5) Å	θ = 2.8–33.0°
b = 7.6898 (5) Å	µ = 0.34 mm⁻¹
c = 19.7527 (14) Å	T = 123 K
V = 1046.75 (13) Å³	Block, colourless
Z = 4	0.27 × 0.19 × 0.16 mm
F(000) = 448

Data collection top

Bruker D8 QUEST diffractometer	3796 independent reflections
Radiation source: microfocus sealed tube	3447 reflections with I > 2σ(I)
Detector resolution: 10.4167 pixels mm^-1	R_int = 0.042
phi and ω scans	θ_max = 32.5°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS2016/2; Krause et al., 2015)	h = −10→10
T_min = 0.662, T_max = 0.747	k = −11→11
23624 measured reflections	l = −29→29

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)] = 0.033	w = 1/[σ²(F_o²) + (0.0372P)² + 0.2629P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.082	(Δ/σ)_max = 0.001
S = 1.07	Δρ_max = 0.36 e Å⁻³
3796 reflections	Δρ_min = −0.30 e Å⁻³
140 parameters	Absolute structure: Refined as an inversion twin
0 restraints	Absolute structure parameter: 0.04 (6)
Primary atom site location: dual

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.

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

3.7985 (0.0046) x + 6.4064 (0.0034) y + 0.9085 (0.0146) z = 5.2962 (0.0108)

* 0.0030 (0.0012) C5 * -0.0067 (0.0012) C6 * 0.0039 (0.0013) C7 * 0.0025 (0.0013) C8 * -0.0062 (0.0014) C9 * 0.0035 (0.0014) C10 2.7365 (0.0020) H9_$8 3.2353 (0.0036) H6_$9

Rms deviation of fitted atoms = 0.0046

3.7985 (0.0045) x - 6.4064 (0.0034) y + 0.9085 (0.0145) z = 0.4604 (0.0136)

Angle to previous plane (with approximate esd) = 67.162 ( 0.045 )

* -0.0030 (0.0012) C5_$8 * 0.0067 (0.0012) C6_$8 * -0.0039 (0.0013) C7_$8 * -0.0025 (0.0014) C8_$8 * 0.0062 (0.0014) C9_$8 * -0.0035 (0.0014) C10_$8

Rms deviation of fitted atoms = 0.0046

3.7985 (0.0045) x + 6.4064 (0.0034) y - 0.9085 (0.0145) z = 7.2622 (0.0039)

Angle to previous plane (with approximate esd) = 66.899 ( 0.045 )

* -0.0030 (0.0012) C5_$6 * 0.0067 (0.0012) C6_$6 * -0.0039 (0.0013) C7_$6 * -0.0025 (0.0013) C8_$6 * 0.0062 (0.0014) C9_$6 * -0.0035 (0.0014) C10_$6

Rms deviation of fitted atoms = 0.0046

Refinement. Refined as a 2-component inversion twin (BASF 0.04470).

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

	x	y	z	U_iso*/U_eq
Cl1	0.90826 (7)	0.16066 (7)	0.88304 (2)	0.02370 (11)
N1	0.5842 (2)	0.60260 (18)	0.52352 (7)	0.0134 (2)
O1	0.76064 (19)	0.02092 (17)	0.54492 (7)	0.0194 (3)
O2	0.45342 (19)	−0.06602 (16)	0.53636 (7)	0.0178 (3)
C1	0.5825 (3)	0.0466 (2)	0.54937 (7)	0.0123 (3)
C2	0.5085 (2)	0.2255 (2)	0.57066 (9)	0.0147 (3)
H2A	0.4081	0.2098	0.6060	0.018*
H2B	0.4454	0.2809	0.5311	0.018*
C3	0.6643 (2)	0.3497 (2)	0.59801 (8)	0.0124 (3)
H3	0.7818	0.3378	0.5687	0.015*
C4	0.5966 (3)	0.5388 (2)	0.59429 (8)	0.0139 (3)
H4A	0.4674	0.5490	0.6159	0.017*
H4B	0.6882	0.6130	0.6199	0.017*
C5	0.7231 (2)	0.3034 (2)	0.67012 (8)	0.0134 (3)
C6	0.6148 (2)	0.3582 (2)	0.72594 (8)	0.0160 (3)
H6	0.5005	0.4248	0.7190	0.019*
C7	0.6719 (3)	0.3166 (2)	0.79192 (8)	0.0173 (3)
H7	0.5986	0.3560	0.8297	0.021*
C8	0.8370 (3)	0.2172 (2)	0.80119 (8)	0.0176 (3)
C9	0.9459 (3)	0.1590 (3)	0.74684 (9)	0.0223 (4)
H9	1.0580	0.0896	0.7540	0.027*
C10	0.8886 (3)	0.2037 (2)	0.68165 (8)	0.0200 (3)
H10	0.9639	0.1655	0.6442	0.024*
H1A	0.701 (5)	0.586 (4)	0.5031 (16)	0.044 (8)*
H1B	0.555 (4)	0.721 (3)	0.5245 (11)	0.022 (6)*
H1C	0.490 (4)	0.557 (4)	0.5021 (14)	0.029 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.02181 (19)	0.0335 (2)	0.01578 (16)	0.0041 (2)	−0.00328 (16)	0.00057 (16)
N1	0.0134 (6)	0.0094 (6)	0.0174 (6)	0.0003 (5)	−0.0012 (5)	0.0000 (4)
O1	0.0152 (6)	0.0173 (6)	0.0258 (6)	0.0016 (5)	0.0031 (5)	−0.0055 (5)
O2	0.0167 (6)	0.0096 (5)	0.0272 (6)	−0.0011 (4)	−0.0027 (5)	−0.0011 (5)
C1	0.0156 (7)	0.0097 (6)	0.0117 (6)	0.0006 (6)	0.0003 (6)	0.0009 (5)
C2	0.0147 (7)	0.0091 (6)	0.0202 (7)	0.0006 (6)	−0.0025 (6)	−0.0018 (6)
C3	0.0130 (6)	0.0099 (6)	0.0144 (6)	0.0013 (6)	−0.0013 (5)	−0.0010 (5)
C4	0.0159 (7)	0.0104 (6)	0.0155 (6)	0.0015 (6)	−0.0012 (6)	−0.0012 (5)
C5	0.0133 (7)	0.0100 (7)	0.0169 (7)	0.0006 (5)	−0.0013 (5)	−0.0010 (5)
C6	0.0146 (7)	0.0146 (7)	0.0187 (7)	0.0028 (6)	0.0015 (5)	0.0012 (6)
C7	0.0186 (7)	0.0171 (8)	0.0163 (7)	0.0010 (7)	0.0029 (6)	0.0004 (6)
C8	0.0188 (8)	0.0188 (8)	0.0151 (7)	0.0001 (6)	−0.0025 (6)	0.0002 (6)
C9	0.0200 (9)	0.0276 (9)	0.0194 (7)	0.0115 (8)	−0.0034 (6)	0.0002 (7)
C10	0.0188 (8)	0.0243 (9)	0.0169 (7)	0.0090 (7)	−0.0015 (6)	−0.0030 (6)

Geometric parameters (Å, º) top

Cl1—C8	1.7445 (17)	C3—H3	1.0000
N1—C4	1.484 (2)	C4—H4A	0.9900
N1—H1A	0.91 (3)	C4—H4B	0.9900
N1—H1B	0.93 (3)	C5—C10	1.394 (2)
N1—H1C	0.85 (3)	C5—C6	1.396 (2)
O1—C1	1.247 (2)	C6—C7	1.398 (2)
O2—C1	1.268 (2)	C6—H6	0.9500
C1—C2	1.526 (2)	C7—C8	1.383 (3)
C2—C3	1.535 (2)	C7—H7	0.9500
C2—H2A	0.9900	C8—C9	1.384 (2)
C2—H2B	0.9900	C9—C10	1.390 (2)
C3—C5	1.523 (2)	C9—H9	0.9500
C3—C4	1.529 (2)	C10—H10	0.9500

C4—N1—H1A	109 (2)	C3—C4—H4A	109.2
C4—N1—H1B	108.4 (14)	N1—C4—H4B	109.2
H1A—N1—H1B	110 (3)	C3—C4—H4B	109.2
C4—N1—H1C	112.1 (19)	H4A—C4—H4B	107.9
H1A—N1—H1C	114 (2)	C10—C5—C6	118.31 (15)
H1B—N1—H1C	104 (2)	C10—C5—C3	119.94 (14)
O1—C1—O2	124.61 (16)	C6—C5—C3	121.76 (14)
O1—C1—C2	119.43 (15)	C5—C6—C7	121.13 (15)
O2—C1—C2	115.95 (15)	C5—C6—H6	119.4
C1—C2—C3	115.09 (14)	C7—C6—H6	119.4
C1—C2—H2A	108.5	C8—C7—C6	118.76 (15)
C3—C2—H2A	108.5	C8—C7—H7	120.6
C1—C2—H2B	108.5	C6—C7—H7	120.6
C3—C2—H2B	108.5	C7—C8—C9	121.46 (16)
H2A—C2—H2B	107.5	C7—C8—Cl1	119.47 (13)
C5—C3—C4	110.37 (13)	C9—C8—Cl1	119.07 (14)
C5—C3—C2	111.71 (14)	C8—C9—C10	119.01 (16)
C4—C3—C2	111.18 (13)	C8—C9—H9	120.5
C5—C3—H3	107.8	C10—C9—H9	120.5
C4—C3—H3	107.8	C9—C10—C5	121.32 (16)
C2—C3—H3	107.8	C9—C10—H10	119.3
N1—C4—C3	112.15 (12)	C5—C10—H10	119.3
N1—C4—H4A	109.2

O1—C1—C2—C3	−11.2 (2)	C10—C5—C6—C7	0.9 (3)
O2—C1—C2—C3	169.78 (14)	C3—C5—C6—C7	−179.16 (16)
C1—C2—C3—C5	−76.36 (17)	C5—C6—C7—C8	−1.0 (3)
C1—C2—C3—C4	159.86 (13)	C6—C7—C8—C9	0.1 (3)
C5—C3—C4—N1	165.95 (14)	C6—C7—C8—Cl1	−178.86 (14)
C2—C3—C4—N1	−69.51 (18)	C7—C8—C9—C10	0.8 (3)
C4—C3—C5—C10	−138.39 (16)	Cl1—C8—C9—C10	179.81 (16)
C2—C3—C5—C10	97.37 (19)	C8—C9—C10—C5	−0.9 (3)
C4—C3—C5—C6	41.7 (2)	C6—C5—C10—C9	0.0 (3)
C2—C3—C5—C6	−82.53 (19)	C3—C5—C10—C9	−179.86 (18)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O2ⁱ	0.91 (3)	1.91 (3)	2.820 (2)	176 (3)
N1—H1B···O2ⁱⁱ	0.93 (3)	1.80 (3)	2.7149 (19)	168 (2)
N1—H1C···O1ⁱⁱⁱ	0.85 (3)	1.93 (3)	2.775 (2)	174 (3)
N1—H1B···Cl1^iv	0.93 (3)	2.95 (2)	3.3192 (14)	105.3 (16)
C4—H4A···Cl1^v	0.99	2.73	3.6306 (19)	152
C4—H4B···Cl1^vi	0.99	2.81	3.5668 (19)	134

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

Acknowledgements

Funding by the Central SME Innovation Programme (ZIM, project No. ZF4402103CR9) is gratefully acknowledged. The authors thank Isabel Schicht and Sandra Diederich for experimental and technical support.

Funding information

Funding for this research was provided by: Bundesministerium für Wirtschaft und Energie (grant No. ZF4402103CR9 to Dr Jan von Langermann).

References

Báthori, N. B. & Kilinkissa, O. E. Y. (2015). CrystEngComm, 17, 8264–8272. Google Scholar
Bruker (2003). Apex, V7, 51A SADABS, SAINT, SHELXTL and SMART. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruno, I. J., Cole, J. C., Edgington, P. R., Kessler, M., Macrae, C. F., McCabe, P., Pearson, J. & Taylor, R. (2002). Acta Cryst. B58, 389–397. Web of Science CrossRef CAS IUCr Journals Google Scholar
Chang, C.-H., Yang, D. S. C., Yoo, C. S., Wang, B.-c., Pletcher, J. & Sax, M. (1981). Acta Cryst. A37, C71. CrossRef IUCr Journals Google Scholar
Chang, C.-H., Yang, D. S. C., Yoo, C. S., Wang, B.-C., Pletcher, J., Sax, M. & Terrence, C. F. (1982). Acta Cryst. B38, 2065–2067. CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
Córdova-Villanueva, E. N., Rodríguez-Ruiz, C., Sánchez-Guadarrama, O., Rivera-Islas, J., Herrera-Ruiz, D., Morales-Rojas, H. & Höpfl, H. (2018). Cryst. Growth Des. 18, 7356–7367. Google Scholar
Couvrat, N., Sanselme, M., Poupard, M., Bensakoun, C., Drouin, S. H., Schneider, J.-M. & Coquerel, G. (2021). J. Pharm. Sci. 110, 3457–3463. Web of Science CrossRef CAS PubMed Google Scholar
Dario, A. & Tomei, G. (2004). Drug Saf. 27, 799–818. Web of Science CrossRef PubMed CAS Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Gendron, F.-X., Mahieux, J., Sanselme, M. & Coquerel, G. (2019). Cryst. Growth Des. 19, 4793–4801. Web of Science CSD CrossRef CAS Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Malapile, R. J., Nyamayaro, K., Nassimbeni, L. R. & Báthori, N. B. (2021). CrystEngComm, 23, 91–99. Web of Science CSD CrossRef CAS Google Scholar
Maniukiewicz, W., Oracz, M. & Sieroń, L. (2016). J. Mol. Struct. 1123, 271–275. Web of Science CSD CrossRef CAS Google Scholar
Olpe, H.-R., Demiéville, H., Baltzer, V., Bencze, W. L., Koella, W. P., Wolf, P. & Haas, H. L. (1978). Eur. J. Pharmacol. 52, 133–136. CrossRef CAS PubMed Web of Science Google Scholar
Reade, M. C. (2021). JAMA, 325, 727–729. Web of Science CrossRef CAS PubMed 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

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 78| Part 1| January 2022| Pages 33-35

https://doi.org/10.1107/S2056989021012809

Open

access