Crystal structure of the non-steroidal anti-inflammatory drug (NSAID) tolmetin sodium

Konovalova, I.S.; Kovalenko, S.M.; Kravchenko, D.V.; Chuev, V.P.

doi:10.1107/S2056989021000414

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 77| Part 2| February 2021| Pages 134-137

https://doi.org/10.1107/S2056989021000414

Open

access

Crystal structure of the non-steroidal anti-inflammatory drug (NSAID) tolmetin sodium

Irina S. Konovalova,^a ^* Sergiy M. Kovalenko,^b Dmitry V. Kravchenko ^c and Vladimir P. Chuev ^d,^e

^aSSI Institute for Single Crystals of the National Academy of Sciences of Ukraine, 61001, Kharkov, Ukraine, ^bV.N. Karazin Kharkiv National University, 4 Svobody Aq., Kharkiv, 61077, Ukraine, ^cChemical Diversity Research Institute, 2A Rabochaya St, Khimki, Moscow Region, 141400, Russian Federation, ^dFederal State Autonomous Educational Institution of Higher Education, Belgorod State University, 85, Pobedy St, Belgorod, 308015, Russian Federation, and ^eExperimental Plant for Dental Materials "VladmiVa", 81d, Michurin St, Belgorod, 308015, Russian Federation
^*Correspondence e-mail: ikonovalova0210@gmail.com

Edited by O. Blacque, University of Zürich, Switzerland (Received 10 December 2020; accepted 12 January 2021; online 19 January 2021)

The asymmetric unit of the title compound, sodium 2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetate dihydrate, Na⁺·C₁₅H₁₄NO₃⁻·2H₂O, contains two sodium cations, two organic anions (A and B) and two water molecules. The coordination geometry around the sodium cations corresponds to a distorted octahedron. Each pair of sodium cations (A–A or B–B) is chelated by two bridging anions coordinated by the O atoms of the deprotonated carboxylic groups, and each sodium atom is coordinated by an O atom of a third anion, which connects pairs of sodium atoms, and a water molecule. As a result, a two-dimensional polymer is formed in the crystal. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to analyze the intermolecular contacts present in the crystal.

Keywords: crystal structure; NSAIDs; sodium 2-(1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetate dihydrate; tolmetin sodium.

CCDC reference: 2055407

1. Chemical context

Non-steroidal anti-inflammatory drugs (NSAIDs) are the gold standard for the management of acute or moderate pain associated with inflammatory changes or trauma (Klippel et al., 2010 ). These drugs can suppress inflammation, lower body temperature, and reduce pain. In terms of the scale and frequency of use of NSAIDs, they rank first in the world. The combination of analgesic, anti-inflammatory and antipyretic effects determines the advantage of NSAIDs over other pain relievers. Tolmetin, which is one of the most widely used NSAIDs, belongs to the class of hetarylacetic acids (Moreland, 2004 ; McEvoy, 2007 ). It is commonly used for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and periarticular disorders. Tolmetin sodium (CAS Number 64490-92-2) is the sodium salt form of tolmetin with analgesic, anti-inflammatory and antipyretic activities (Cordrey, 1976 ). In addition, the anticancer activity of Tolmetin has been studied and it was reported that tolmetin has effects on increasing the cytotoxic activity of anti-cancer drugs (Duffy et al., 1998 ). It inhibits the function of β-catenin, so tolmetin can be used to develop new anti-cancer agents (Lu et al., 2005 ).

Recently, work has appeared on the use of this well-known active pharmaceutical compound tolmetin sodium for the development of new dosage forms, for example, novel rectal mucoadhesive hydrogels (Ramadan et al., 2018 ), thermosensitive mucoadhesive liquid suppositories for rectal delivery (Akl et al., 2019 ) and different topical gel formulations (Auda et al., 2015 ).

However, to date, the crystal structure of the substance tolmetin sodium has not been studied and described. Knowledge of the spatial structure of the crystal form of the active pharmaceutical compound is very important to ensure the quality and bioavailability of the drug and, according to the latest pharmacopoeia requirements, X-ray diffraction studies are mandatory for pharmaceutical development. In this work, we carried out an X-ray structural analysis of the crystal form of the substance tolmetin sodium and filled the gap in these studies.

2. Structural commentary

The sodium salt of the C₁₅H₁₄NO₃ organic anion exists in the crystal as a 1:2 hydrate (Fig. 1). The asymmetric unit contains two sodium cations, two organic anions (A and B) and two water molecules. The coordination geometry around the sodium cations corresponds to a distorted octahedron. Each pair of sodium cations (A–A or B–B) is chelated by two bridging anions coordinated by the O atoms of the deprotonated carboxylic groups, and each sodium atom is coordinated by an O atom of a third anion, which connects pairs of sodium atoms, and a water molecule. As a result, a two-dimensional polymer is formed in the crystal (Fig. 2). The Na—O_anion distances are 2.298 (2), 2.416 (2) and 2.441 (2) Å while the Na—O_water distances are on average slightly longer, being in the range 2.364 (2)–2.607 (3) Å. It is worth noting that the terminal atom O2B does not interact with a sodium cation.

Figure 1
The molecular structure of the title compound showing the atom-labeling scheme. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
Two-dimensional polymeric chains in the crystal of the title compound.

The analysis of the molecular structure of the anions showed that the terminal C1—O1 and C1—O2 bonds [1.249 (3) and 1.250 (3) Å in anion A, 1.243 (3) and 1.250 (3) Å in anion B] are very similar to each other and are slightly elongated in comparison with the standard value of 1.210 Å of a carbonyl group (Burgi et al., 1994 ). It is also much shorter than the standard C—O single bond observed for a hydroxyl group (1.362 Å). We can assume that the negative charge is delocalized on both terminal O atoms for each anion.

The toluene substituent is in a synperiplanar conformation with respect to the C5—C6 bond of the pyrrole ring: the C5—C6—C8—C9 torsion angle is 26.9 (4)° in molecule A and −29.0 (4)° in molecule B. The relative orientation of the toluene ring with respect to the pyrrole ring, neither planar nor perpendicular, is given by the the C6—C8—C9—C10 torsion angle: 41.3 (4)° in molecule A and −38.2 (4)° in molecule B. Such an orientation mainly minimizes the intermolecular H⋯H repulsions.

3. Supramolecular features

In the crystal, O—H⋯O hydrogen bonds (Table 1) are formed between H atoms of the water molecules (donors) and O atoms of the anions (acceptors), forming a two-dimensional network parallel to (001).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1W—H1WA⋯O3A	0.89	2.12	3.002 (3)	169
O1W—H1WB⋯O1Aⁱ	0.89	2.00	2.665 (4)	130
O2W—H2WA⋯O2Bⁱ	0.89	1.88	2.741 (3)	161
O2W—H2WB⋯O2Bⁱⁱ	0.89	2.13	3.019 (3)	172
O3W—H3WA⋯O3Bⁱⁱⁱ	0.89	2.16	2.961 (3)	150
O3W—H3WB⋯O1Bⁱⁱ	0.89	1.84	2.699 (4)	161
O4W—H4WA⋯O1Bⁱⁱ	0.89	2.19	2.894 (3)	136
O4W—H4WB⋯O3Wⁱⁱ	0.89	2.02	2.889 (3)	163
Symmetry codes: (i) x+1, y, z; (ii) ; (iii) .

4. Hirshfeld surface analysis

Crystal Explorer 17.5 (Turner et al., 2017 ) was used to analyze the interactions in the crystal: fingerprint plots mapped over d_norm (Figs. 3 and 4) were generated. The molecular Hirshfeld surfaces were obtained using a standard (high) surface resolution with the three-dimensional d_norm surfaces mapped over a fixed color scale of −0.666 (red) to 1.384 (blue). The areas colored red on the d_norm-mapped Hirshfeld surfaces (Fig. 3) correspond to the contacts which are shorter than van der Waals radii sum of the closest atoms. As can be seen in Fig. 4, short contacts are present at the hydrogen atoms and oxygen lone pair of the water molecules. In addition, the areas of short contacts are located at the oxygen atoms of carbonyl groups (Fig. 3).

Figure 3
The Hirshfeld surface of the title compound mapped over d_norm.

Figure 4
(a) The two-dimensional fingerprint plot for the title compound, and those delineated into (b) H⋯H (48.9%), (c) O⋯H/H⋯O (22.1%), (d) C⋯H/H⋯C (17.9%) and (e) Na⋯O/O⋯Na (5.4%) contacts.

All the intermolecular interactions of the title compound are shown in the two-dimensional fingerprint plot presented in Fig. 4. The contribution of the O⋯H/H⋯O contacts, corresponding to the O—H⋯O interaction, is represented by a pair of long sharp spikes (22.1%). This indicates that O—H⋯O hydrogen bonds are the strongest interactions in the crystal of the title compound (Fig. 4).

5. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.41, update of November 2019; Groom et al., 2016 ) for the 2-(1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetate skeleton yielded only two hits, 2-methoxyphenyl 2-{2-[1-methyl-5-(4-methylbenzoyl)pyrrol-2-yl]acetamido}acetate (CSD refcode MODNID; Lou et al., 2008 ) and bis(dimethylsulfoxide-O)tetrakis[μ₂-1-methyl-5-(p-toluoyl)-1H-pyrrole-2-acetato-O,O′]dicopper(II) (SETBIC; Dendrinou-Samara et al., 1990 ).

6. Crystallization

Crystallization by slow evaporation of an aqueous solution of tolmetin sodium was carried out to provide colorless block-shaped single crystals suitable for a X-ray diffraction analysis (Fig. 5).

Figure 5
Crystals of tolmetin sodium.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were placed in calculated positions (O—H = 0.98 Å, C—H = 0.93–0.96 Å) and refined as riding with U_isoH = 1.2U_eq(C) or 1.5U_eq(O, C-methyl).

Table 2
Experimental details

Crystal data
Chemical formula	2Na⁺·2C₁₅H₁₄NO₃⁻·4H₂O
M_r	630.59
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	293
a, b, c (Å)	8.5404 (8), 9.0144 (9), 21.6217 (19)
α, β, γ (°)	92.922 (8), 98.873 (7), 113.038 (9)
V (Å³)	1502.1 (3)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.13
Crystal size (mm)	0.4 × 0.2 × 0.1

Data collection
Diffractometer	Rigaku Oxford Diffraction Xcalibur, Sapphire3
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction Ltd, Yarnton, England.]$ )
T_min, T_max	0.737, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	11985, 5283, 3288
R_int	0.060
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.064, 0.191, 1.00
No. of reflections	5283
No. of parameters	403
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.38, −0.28
Computer programs: CrysAlis PRO (Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction Ltd, Yarnton, England.]$ ), SHELXT (Sheldrick, 2015a ), SHELXL (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC reference: 2055407

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989021000414/zq2259sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989021000414/zq2259Isup2.hkl

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: ShelXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Sodium 2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetate dihydrate top

Crystal data top

2Na⁺·2C₁₅H₁₄NO₃⁻·4H₂O	Z = 2
M_r = 630.59	F(000) = 664
Triclinic, P1	D_x = 1.394 Mg m⁻³
a = 8.5404 (8) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.0144 (9) Å	Cell parameters from 1420 reflections
c = 21.6217 (19) Å	θ = 3.1–24.2°
α = 92.922 (8)°	µ = 0.13 mm⁻¹
β = 98.873 (7)°	T = 293 K
γ = 113.038 (9)°	Block, colourless
V = 1502.1 (3) Å³	0.4 × 0.2 × 0.1 mm

Data collection top

Rigaku Oxford Diffraction Xcalibur, Sapphire3 diffractometer	5283 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source	3288 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.060
Detector resolution: 16.1827 pixels mm^-1	θ_max = 25.0°, θ_min = 2.9°
phi and ω scans	h = −10→10
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2018)	k = −10→10
T_min = 0.737, T_max = 1.000	l = −25→25
11985 measured reflections

Refinement top

Refinement on F²	Primary atom site location: inferred from neighbouring sites
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F² > 2σ(F²)] = 0.064	H-atom parameters constrained
wR(F²) = 0.191	w = 1/[σ²(F_o²) + (0.0844P)²] where P = (F_o² + 2F_c²)/3
S = 1.00	(Δ/σ)_max < 0.001
5283 reflections	Δρ_max = 0.38 e Å⁻³
403 parameters	Δρ_min = −0.28 e Å⁻³
0 restraints

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
Na1A	1.15418 (14)	0.48055 (14)	0.46665 (5)	0.0463 (4)
O1A	0.6328 (3)	0.4448 (3)	0.43538 (9)	0.0463 (5)
O2A	0.8756 (3)	0.4310 (3)	0.41918 (9)	0.0527 (6)
O3A	1.3144 (3)	0.5970 (3)	0.27170 (10)	0.0572 (6)
N1A	0.9595 (3)	0.5322 (3)	0.28684 (10)	0.0370 (6)
C1A	0.7367 (4)	0.4452 (3)	0.40052 (13)	0.0369 (7)
C2A	0.6907 (4)	0.4728 (4)	0.33229 (13)	0.0441 (7)
H2AA	0.568753	0.405386	0.316973	0.053*
H2AB	0.705297	0.584995	0.332112	0.053*
C3A	0.7899 (4)	0.4394 (4)	0.28655 (13)	0.0397 (7)
C4A	0.7319 (4)	0.3165 (4)	0.23764 (14)	0.0445 (7)
H4A	0.620599	0.234969	0.227154	0.053*
C5A	0.8671 (4)	0.3346 (4)	0.20653 (14)	0.0446 (7)
H5A	0.862808	0.267733	0.171513	0.053*
C6A	1.0108 (4)	0.4710 (4)	0.23717 (13)	0.0403 (7)
C7A	1.0633 (4)	0.6845 (3)	0.32769 (13)	0.0453 (7)
H7AA	1.124646	0.663236	0.364871	0.068*
H7AB	0.988702	0.733150	0.339497	0.068*
H7AC	1.144888	0.757182	0.305536	0.068*
C8A	1.1889 (4)	0.5209 (4)	0.22929 (13)	0.0392 (7)
C9A	1.2180 (4)	0.4679 (3)	0.16703 (13)	0.0399 (7)
C10A	1.1169 (4)	0.4703 (4)	0.11027 (14)	0.0457 (7)
H10A	1.026896	0.503734	0.110630	0.055*
C11A	1.1493 (4)	0.4236 (4)	0.05367 (14)	0.0488 (8)
H11A	1.079818	0.425219	0.016307	0.059*
C12A	1.2836 (4)	0.3741 (4)	0.05106 (15)	0.0455 (8)
C13A	1.3832 (4)	0.3726 (4)	0.10725 (15)	0.0508 (8)
H13A	1.472156	0.337798	0.106762	0.061*
C14A	1.3541 (4)	0.4217 (4)	0.16450 (15)	0.0478 (8)
H14A	1.426516	0.423803	0.201665	0.057*
C15A	1.3099 (5)	0.3182 (4)	−0.01169 (16)	0.0620 (9)
H15A	1.253192	0.201892	−0.019774	0.093*
H15B	1.431599	0.351811	−0.011128	0.093*
H15C	1.261676	0.365083	−0.044267	0.093*
Na1B	0.45480 (15)	0.23476 (14)	0.49496 (5)	0.0497 (4)
O1B	0.3539 (3)	0.0551 (3)	0.57285 (10)	0.0520 (6)
O2B	0.1279 (3)	0.0952 (3)	0.59464 (9)	0.0517 (6)
O3B	−0.3202 (3)	−0.0817 (3)	0.73382 (10)	0.0561 (6)
N1B	0.0316 (3)	−0.0303 (3)	0.72107 (10)	0.0392 (6)
C1B	0.2576 (4)	0.0630 (3)	0.60931 (13)	0.0372 (7)
C2B	0.2993 (4)	0.0232 (4)	0.67578 (13)	0.0469 (8)
H2BA	0.277121	−0.091173	0.673239	0.056*
H2BB	0.422204	0.084105	0.691795	0.056*
C3B	0.2033 (4)	0.0571 (4)	0.72214 (13)	0.0405 (7)
C4B	0.2635 (4)	0.1815 (4)	0.77089 (14)	0.0505 (8)
H4B	0.375714	0.261529	0.781418	0.061*
C5B	0.1287 (4)	0.1671 (4)	0.80151 (14)	0.0451 (7)
H5B	0.134436	0.234532	0.836595	0.054*
C6B	−0.0169 (4)	0.0342 (4)	0.77058 (13)	0.0414 (7)
C7B	−0.0783 (4)	−0.1782 (4)	0.67844 (14)	0.0505 (8)
H7BA	−0.140894	−0.151452	0.643088	0.076*
H7BB	−0.158712	−0.252622	0.700442	0.076*
H7BC	−0.007306	−0.227504	0.663767	0.076*
C8B	−0.1949 (4)	−0.0101 (4)	0.77748 (14)	0.0423 (7)
C9B	−0.2254 (4)	0.0398 (4)	0.83992 (13)	0.0396 (7)
C10B	−0.1236 (4)	0.0352 (4)	0.89619 (14)	0.0458 (8)
H10B	−0.034555	0.000647	0.895357	0.055*
C11B	−0.1552 (4)	0.0819 (4)	0.95293 (14)	0.0483 (8)
H11B	−0.086237	0.078848	0.990196	0.058*
C12B	−0.2879 (4)	0.1337 (4)	0.95586 (14)	0.0463 (8)
C13B	−0.3882 (4)	0.1359 (4)	0.89975 (15)	0.0505 (8)
H13B	−0.477015	0.170816	0.900353	0.061*
C14B	−0.3588 (4)	0.0871 (4)	0.84272 (15)	0.0473 (8)
H14B	−0.430573	0.086230	0.805569	0.057*
C15B	−0.3154 (4)	0.1885 (5)	1.01896 (16)	0.0610 (9)
H15D	−0.263611	0.144401	1.051608	0.091*
H15E	−0.437342	0.150939	1.018731	0.091*
H15F	−0.262690	0.304934	1.026643	0.091*
O1W	1.3788 (3)	0.5461 (3)	0.40784 (10)	0.0541 (6)
H1WA	1.363692	0.575550	0.369478	0.081*
H1WB	1.405922	0.460320	0.406558	0.081*
O2W	1.1457 (3)	0.2133 (3)	0.48044 (9)	0.0529 (6)
H2WA	1.128262	0.190038	0.518967	0.079*
H2WB	1.066822	0.127148	0.455027	0.079*
O3W	0.3857 (3)	0.0443 (3)	0.40179 (10)	0.0522 (6)
H3WA	0.383694	0.094075	0.367336	0.078*
H3WB	0.464794	0.002995	0.401246	0.078*
O4W	0.7371 (3)	0.2175 (3)	0.52238 (10)	0.0538 (6)
H4WA	0.769350	0.168269	0.493211	0.081*
H4WB	0.720981	0.138360	0.546861	0.081*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Na1A	0.0365 (7)	0.0608 (8)	0.0418 (7)	0.0197 (6)	0.0075 (5)	0.0091 (6)
O1A	0.0426 (12)	0.0665 (14)	0.0355 (12)	0.0258 (11)	0.0121 (9)	0.0097 (10)
O2A	0.0335 (12)	0.0802 (16)	0.0450 (13)	0.0235 (11)	0.0045 (9)	0.0188 (11)
O3A	0.0405 (13)	0.0796 (17)	0.0398 (13)	0.0148 (12)	0.0031 (10)	−0.0030 (11)
N1A	0.0369 (14)	0.0414 (13)	0.0326 (13)	0.0153 (11)	0.0071 (10)	0.0057 (10)
C1A	0.0346 (16)	0.0406 (16)	0.0358 (16)	0.0154 (13)	0.0062 (13)	0.0090 (13)
C2A	0.0430 (17)	0.0605 (19)	0.0377 (17)	0.0287 (16)	0.0091 (13)	0.0145 (14)
C3A	0.0360 (16)	0.0535 (18)	0.0337 (16)	0.0211 (14)	0.0083 (12)	0.0098 (13)
C4A	0.0381 (17)	0.0456 (18)	0.0409 (17)	0.0093 (14)	0.0030 (13)	0.0040 (14)
C5A	0.0436 (18)	0.0441 (17)	0.0417 (17)	0.0138 (15)	0.0081 (14)	0.0008 (14)
C6A	0.0422 (17)	0.0475 (17)	0.0310 (16)	0.0164 (14)	0.0105 (13)	0.0049 (13)
C7A	0.0509 (19)	0.0416 (16)	0.0377 (17)	0.0149 (15)	0.0046 (14)	−0.0007 (13)
C8A	0.0367 (16)	0.0446 (17)	0.0377 (17)	0.0158 (14)	0.0115 (13)	0.0092 (13)
C9A	0.0382 (17)	0.0432 (17)	0.0344 (16)	0.0121 (14)	0.0090 (12)	0.0016 (13)
C10A	0.0449 (18)	0.0544 (19)	0.0398 (18)	0.0215 (16)	0.0087 (14)	0.0085 (15)
C11A	0.052 (2)	0.0553 (19)	0.0364 (17)	0.0195 (17)	0.0064 (14)	0.0068 (14)
C12A	0.0412 (18)	0.0457 (18)	0.0473 (19)	0.0129 (15)	0.0147 (14)	0.0052 (14)
C13A	0.0431 (18)	0.063 (2)	0.050 (2)	0.0244 (17)	0.0117 (15)	0.0034 (16)
C14A	0.0442 (18)	0.059 (2)	0.0394 (17)	0.0204 (16)	0.0067 (14)	0.0085 (15)
C15A	0.061 (2)	0.067 (2)	0.055 (2)	0.0201 (19)	0.0208 (17)	−0.0028 (17)
Na1B	0.0459 (7)	0.0559 (8)	0.0458 (7)	0.0174 (6)	0.0125 (5)	0.0075 (6)
O1B	0.0549 (14)	0.0749 (16)	0.0407 (12)	0.0366 (12)	0.0200 (10)	0.0163 (11)
O2B	0.0505 (13)	0.0781 (16)	0.0399 (12)	0.0372 (12)	0.0140 (10)	0.0148 (11)
O3B	0.0418 (13)	0.0753 (16)	0.0411 (13)	0.0154 (12)	0.0042 (10)	−0.0022 (11)
N1B	0.0411 (14)	0.0489 (14)	0.0304 (13)	0.0200 (12)	0.0092 (10)	0.0062 (11)
C1B	0.0401 (17)	0.0379 (15)	0.0334 (16)	0.0152 (13)	0.0087 (13)	0.0024 (12)
C2B	0.0497 (19)	0.063 (2)	0.0358 (17)	0.0279 (16)	0.0147 (14)	0.0139 (15)
C3B	0.0379 (17)	0.0560 (19)	0.0327 (16)	0.0228 (15)	0.0081 (12)	0.0129 (14)
C4B	0.0376 (17)	0.061 (2)	0.0451 (19)	0.0123 (16)	0.0061 (14)	0.0113 (16)
C5B	0.0419 (17)	0.0538 (19)	0.0346 (17)	0.0148 (15)	0.0076 (13)	−0.0031 (14)
C6B	0.0379 (17)	0.0523 (18)	0.0322 (16)	0.0162 (15)	0.0061 (12)	0.0073 (13)
C7B	0.056 (2)	0.0468 (18)	0.0443 (19)	0.0197 (16)	0.0020 (15)	−0.0011 (14)
C8B	0.0414 (18)	0.0483 (18)	0.0370 (17)	0.0169 (15)	0.0093 (14)	0.0086 (14)
C9B	0.0345 (16)	0.0461 (17)	0.0373 (17)	0.0137 (14)	0.0104 (12)	0.0083 (13)
C10B	0.0464 (18)	0.0572 (19)	0.0385 (17)	0.0252 (16)	0.0092 (14)	0.0086 (14)
C11B	0.0488 (19)	0.061 (2)	0.0369 (18)	0.0231 (17)	0.0097 (14)	0.0085 (15)
C12B	0.0432 (18)	0.0501 (18)	0.0411 (18)	0.0109 (15)	0.0171 (14)	0.0046 (14)
C13B	0.0414 (18)	0.059 (2)	0.053 (2)	0.0226 (16)	0.0099 (15)	0.0015 (16)
C14B	0.0420 (18)	0.0561 (19)	0.0426 (18)	0.0192 (16)	0.0063 (14)	0.0067 (15)
C15B	0.055 (2)	0.074 (2)	0.052 (2)	0.0217 (19)	0.0174 (16)	−0.0008 (17)
O1W	0.0640 (15)	0.0639 (14)	0.0506 (13)	0.0369 (12)	0.0237 (11)	0.0180 (11)
O2W	0.0596 (14)	0.0589 (14)	0.0377 (12)	0.0211 (12)	0.0085 (10)	0.0093 (10)
O3W	0.0558 (14)	0.0637 (15)	0.0429 (12)	0.0306 (12)	0.0092 (10)	0.0048 (11)
O4W	0.0626 (15)	0.0585 (14)	0.0422 (12)	0.0260 (12)	0.0129 (10)	0.0023 (10)

Geometric parameters (Å, º) top

Na1A—Na1Aⁱ	3.314 (2)	Na1B—O1Wⁱ	2.607 (3)
Na1A—O1Aⁱ	2.441 (2)	Na1B—O2Wⁱⁱⁱ	2.538 (2)
Na1A—O2A	2.298 (2)	Na1B—O3W	2.417 (2)
Na1A—O2Aⁱ	2.636 (2)	Na1B—O4W	2.460 (2)
Na1A—C1Aⁱ	2.838 (3)	O1B—C1B	1.243 (3)
Na1A—Na1Bⁱⁱ	3.9976 (16)	O2B—C1B	1.250 (3)
Na1A—Na1Bⁱ	3.2629 (17)	O3B—C8B	1.241 (4)
Na1A—O1W	2.364 (2)	N1B—C3B	1.362 (4)
Na1A—O2W	2.417 (2)	N1B—C6B	1.385 (4)
Na1A—O4Wⁱ	2.493 (2)	N1B—C7B	1.461 (4)
O1A—C1A	1.249 (3)	C1B—C2B	1.522 (4)
O1A—Na1B	2.481 (2)	C2B—H2BA	0.9700
O2A—C1A	1.250 (3)	C2B—H2BB	0.9700
O3A—C8A	1.232 (3)	C2B—C3B	1.479 (4)
N1A—C3A	1.359 (4)	C3B—C4B	1.376 (4)
N1A—C6A	1.387 (3)	C4B—H4B	0.9300
N1A—C7A	1.461 (4)	C4B—C5B	1.382 (4)
C1A—C2A	1.526 (4)	C5B—H5B	0.9300
C2A—H2AA	0.9700	C5B—C6B	1.387 (4)
C2A—H2AB	0.9700	C6B—C8B	1.446 (4)
C2A—C3A	1.488 (4)	C7B—H7BA	0.9600
C3A—C4A	1.371 (4)	C7B—H7BB	0.9600
C4A—H4A	0.9300	C7B—H7BC	0.9600
C4A—C5A	1.384 (4)	C8B—C9B	1.494 (4)
C5A—H5A	0.9300	C9B—C10B	1.395 (4)
C5A—C6A	1.394 (4)	C9B—C14B	1.371 (4)
C6A—C8A	1.448 (4)	C10B—H10B	0.9300
C7A—H7AA	0.9600	C10B—C11B	1.376 (4)
C7A—H7AB	0.9600	C11B—H11B	0.9300
C7A—H7AC	0.9600	C11B—C12B	1.393 (4)
C8A—C9A	1.494 (4)	C12B—C13B	1.379 (4)
C9A—C10A	1.394 (4)	C12B—C15B	1.510 (4)
C9A—C14A	1.387 (4)	C13B—H13B	0.9300
C10A—H10A	0.9300	C13B—C14B	1.380 (4)
C10A—C11A	1.376 (4)	C14B—H14B	0.9300
C11A—H11A	0.9300	C15B—H15D	0.9600
C11A—C12A	1.391 (4)	C15B—H15E	0.9600
C12A—C13A	1.375 (4)	C15B—H15F	0.9600
C12A—C15A	1.503 (4)	O1W—H1WA	0.8897
C13A—H13A	0.9300	O1W—H1WB	0.8899
C13A—C14A	1.384 (4)	O2W—H2WA	0.8899
C14A—H14A	0.9300	O2W—H2WB	0.8899
C15A—H15A	0.9600	O3W—H3WA	0.8905
C15A—H15B	0.9600	O3W—H3WB	0.8905
C15A—H15C	0.9600	O4W—H4WA	0.8897
Na1B—O1B	2.416 (2)	O4W—H4WB	0.8902

Na1Aⁱ—Na1A—Na1Bⁱⁱ	135.58 (5)	H15A—C15A—H15C	109.5
O1Aⁱ—Na1A—Na1Aⁱ	94.89 (7)	H15B—C15A—H15C	109.5
O1Aⁱ—Na1A—O2Aⁱ	51.31 (6)	Na1Aⁱ—Na1B—Na1Aⁱⁱⁱ	103.67 (4)
O1Aⁱ—Na1A—C1Aⁱ	26.00 (7)	O1A—Na1B—Na1Aⁱ	47.95 (5)
O1Aⁱ—Na1A—Na1Bⁱ	49.01 (5)	O1A—Na1B—Na1Aⁱⁱⁱ	81.27 (6)
O1Aⁱ—Na1A—Na1Bⁱⁱ	61.96 (6)	O1A—Na1B—O1Wⁱ	83.94 (8)
O1Aⁱ—Na1A—O4Wⁱ	78.93 (8)	O1A—Na1B—O2Wⁱⁱⁱ	111.77 (8)
O2Aⁱ—Na1A—Na1Aⁱ	43.62 (5)	O1B—Na1B—Na1Aⁱ	116.87 (7)
O2A—Na1A—Na1Aⁱ	52.29 (6)	O1B—Na1B—Na1Aⁱⁱⁱ	107.75 (6)
O2A—Na1A—O1Aⁱ	147.11 (9)	O1B—Na1B—O1A	164.64 (8)
O2A—Na1A—O2Aⁱ	95.91 (8)	O1B—Na1B—O1Wⁱ	84.57 (8)
O2Aⁱ—Na1A—C1Aⁱ	26.07 (7)	O1B—Na1B—O2Wⁱⁱⁱ	81.05 (7)
O2A—Na1A—C1Aⁱ	121.17 (9)	O1B—Na1B—O3W	101.75 (9)
O2Aⁱ—Na1A—Na1Bⁱⁱ	104.45 (6)	O1B—Na1B—O4W	88.42 (8)
O2A—Na1A—Na1Bⁱ	142.94 (8)	O1Wⁱ—Na1B—Na1Aⁱ	45.82 (5)
O2Aⁱ—Na1A—Na1Bⁱ	84.23 (6)	O1Wⁱ—Na1B—Na1Aⁱⁱⁱ	84.57 (6)
O2A—Na1A—Na1Bⁱⁱ	138.04 (8)	O2Wⁱⁱⁱ—Na1B—Na1Aⁱⁱⁱ	35.20 (5)
O2A—Na1A—O1W	121.00 (9)	O2Wⁱⁱⁱ—Na1B—Na1Aⁱ	137.63 (7)
O2A—Na1A—O2W	103.90 (9)	O2Wⁱⁱⁱ—Na1B—O1Wⁱ	104.60 (8)
O2A—Na1A—O4Wⁱ	95.91 (8)	O3W—Na1B—Na1Aⁱⁱⁱ	107.78 (6)
C1Aⁱ—Na1A—Na1Aⁱ	69.18 (7)	O3W—Na1B—Na1Aⁱ	118.49 (7)
C1Aⁱ—Na1A—Na1Bⁱⁱ	80.46 (6)	O3W—Na1B—O1A	86.73 (8)
C1Aⁱ—Na1A—Na1Bⁱ	68.45 (6)	O3W—Na1B—O1Wⁱ	163.22 (8)
Na1Bⁱ—Na1A—Na1Aⁱ	118.26 (6)	O3W—Na1B—O2Wⁱⁱⁱ	91.80 (8)
Na1Bⁱ—Na1A—Na1Bⁱⁱ	76.33 (4)	O3W—Na1B—O4W	89.29 (8)
O1W—Na1A—Na1Aⁱ	158.68 (9)	O4W—Na1B—Na1Aⁱⁱⁱ	152.90 (7)
O1W—Na1A—O1Aⁱ	90.21 (8)	O4W—Na1B—Na1Aⁱ	49.23 (6)
O1W—Na1A—O2Aⁱ	136.23 (9)	O4W—Na1B—O1A	78.81 (8)
O1W—Na1A—C1Aⁱ	115.58 (9)	O4W—Na1B—O1Wⁱ	75.24 (8)
O1W—Na1A—Na1Bⁱ	52.29 (6)	O4W—Na1B—O2Wⁱⁱⁱ	169.41 (8)
O1W—Na1A—Na1Bⁱⁱ	64.50 (6)	C1B—O1B—Na1B	126.86 (19)
O1W—Na1A—O2W	93.84 (8)	C3B—N1B—C6B	109.0 (2)
O1W—Na1A—O4Wⁱ	79.14 (8)	C3B—N1B—C7B	125.0 (2)
O2W—Na1A—Na1Aⁱ	107.35 (7)	C6B—N1B—C7B	125.7 (2)
O2W—Na1A—O1Aⁱ	82.17 (8)	O1B—C1B—O2B	125.0 (3)
O2W—Na1A—O2Aⁱ	99.52 (8)	O1B—C1B—C2B	116.3 (3)
O2W—Na1A—C1Aⁱ	86.62 (8)	O2B—C1B—C2B	118.7 (2)
O2W—Na1A—Na1Bⁱ	112.65 (7)	C1B—C2B—H2BA	108.2
O2W—Na1A—Na1Bⁱⁱ	37.26 (6)	C1B—C2B—H2BB	108.2
O2W—Na1A—O4Wⁱ	159.77 (8)	H2BA—C2B—H2BB	107.3
O4Wⁱ—Na1A—Na1Aⁱ	81.55 (7)	C3B—C2B—C1B	116.5 (2)
O4Wⁱ—Na1A—O2Aⁱ	74.06 (8)	C3B—C2B—H2BA	108.2
O4Wⁱ—Na1A—C1Aⁱ	79.57 (8)	C3B—C2B—H2BB	108.2
O4Wⁱ—Na1A—Na1Bⁱ	48.35 (6)	N1B—C3B—C2B	123.9 (3)
O4Wⁱ—Na1A—Na1Bⁱⁱ	124.68 (6)	N1B—C3B—C4B	107.9 (2)
Na1Aⁱ—O1A—Na1B	83.04 (7)	C4B—C3B—C2B	128.1 (3)
C1A—O1A—Na1Aⁱ	95.05 (17)	C3B—C4B—H4B	125.9
C1A—O1A—Na1B	132.45 (19)	C3B—C4B—C5B	108.2 (3)
Na1A—O2A—Na1Aⁱ	84.09 (8)	C5B—C4B—H4B	125.9
C1A—O2A—Na1Aⁱ	86.05 (17)	C4B—C5B—H5B	126.1
C1A—O2A—Na1A	163.4 (2)	C4B—C5B—C6B	107.8 (3)
C3A—N1A—C6A	109.3 (2)	C6B—C5B—H5B	126.1
C3A—N1A—C7A	124.8 (2)	N1B—C6B—C5B	107.0 (3)
C6A—N1A—C7A	125.4 (2)	N1B—C6B—C8B	123.9 (3)
O1A—C1A—Na1Aⁱ	58.95 (14)	C5B—C6B—C8B	127.8 (3)
O1A—C1A—O2A	123.8 (3)	N1B—C7B—H7BA	109.5
O1A—C1A—C2A	116.3 (2)	N1B—C7B—H7BB	109.5
O2A—C1A—Na1Aⁱ	67.89 (15)	N1B—C7B—H7BC	109.5
O2A—C1A—C2A	119.8 (2)	H7BA—C7B—H7BB	109.5
C2A—C1A—Na1Aⁱ	158.3 (2)	H7BA—C7B—H7BC	109.5
C1A—C2A—H2AA	107.9	H7BB—C7B—H7BC	109.5
C1A—C2A—H2AB	107.9	O3B—C8B—C6B	123.2 (3)
H2AA—C2A—H2AB	107.2	O3B—C8B—C9B	119.5 (3)
C3A—C2A—C1A	117.4 (2)	C6B—C8B—C9B	117.3 (3)
C3A—C2A—H2AA	107.9	C10B—C9B—C8B	121.3 (3)
C3A—C2A—H2AB	107.9	C14B—C9B—C8B	120.0 (3)
N1A—C3A—C2A	123.8 (3)	C14B—C9B—C10B	118.7 (3)
N1A—C3A—C4A	108.1 (2)	C9B—C10B—H10B	120.1
C4A—C3A—C2A	128.1 (3)	C11B—C10B—C9B	119.9 (3)
C3A—C4A—H4A	125.8	C11B—C10B—H10B	120.1
C3A—C4A—C5A	108.4 (3)	C10B—C11B—H11B	119.2
C5A—C4A—H4A	125.8	C10B—C11B—C12B	121.5 (3)
C4A—C5A—H5A	126.2	C12B—C11B—H11B	119.2
C4A—C5A—C6A	107.6 (3)	C11B—C12B—C15B	120.0 (3)
C6A—C5A—H5A	126.2	C13B—C12B—C11B	117.7 (3)
N1A—C6A—C5A	106.6 (3)	C13B—C12B—C15B	122.3 (3)
N1A—C6A—C8A	124.4 (3)	C12B—C13B—H13B	119.5
C5A—C6A—C8A	127.6 (3)	C12B—C13B—C14B	121.1 (3)
N1A—C7A—H7AA	109.5	C14B—C13B—H13B	119.5
N1A—C7A—H7AB	109.5	C9B—C14B—C13B	121.1 (3)
N1A—C7A—H7AC	109.5	C9B—C14B—H14B	119.5
H7AA—C7A—H7AB	109.5	C13B—C14B—H14B	119.5
H7AA—C7A—H7AC	109.5	C12B—C15B—H15D	109.5
H7AB—C7A—H7AC	109.5	C12B—C15B—H15E	109.5
O3A—C8A—C6A	123.4 (3)	C12B—C15B—H15F	109.5
O3A—C8A—C9A	119.5 (3)	H15D—C15B—H15E	109.5
C6A—C8A—C9A	117.0 (3)	H15D—C15B—H15F	109.5
C10A—C9A—C8A	122.0 (3)	H15E—C15B—H15F	109.5
C14A—C9A—C8A	119.9 (3)	Na1A—O1W—Na1Bⁱ	81.89 (7)
C14A—C9A—C10A	118.0 (3)	Na1A—O1W—H1WA	120.2
C9A—C10A—H10A	119.7	Na1A—O1W—H1WB	105.3
C11A—C10A—C9A	120.5 (3)	Na1Bⁱ—O1W—H1WA	120.3
C11A—C10A—H10A	119.7	Na1Bⁱ—O1W—H1WB	115.2
C10A—C11A—H11A	119.2	H1WA—O1W—H1WB	110.6
C10A—C11A—C12A	121.5 (3)	Na1A—O2W—Na1Bⁱⁱ	107.54 (9)
C12A—C11A—H11A	119.2	Na1A—O2W—H2WA	110.1
C11A—C12A—C15A	119.7 (3)	Na1A—O2W—H2WB	119.8
C13A—C12A—C11A	117.6 (3)	Na1Bⁱⁱ—O2W—H2WA	97.1
C13A—C12A—C15A	122.7 (3)	Na1Bⁱⁱ—O2W—H2WB	115.5
C12A—C13A—H13A	119.2	H2WA—O2W—H2WB	104.2
C12A—C13A—C14A	121.5 (3)	Na1B—O3W—H3WA	110.1
C14A—C13A—H13A	119.2	Na1B—O3W—H3WB	111.9
C9A—C14A—H14A	119.7	H3WA—O3W—H3WB	106.7
C13A—C14A—C9A	120.7 (3)	Na1Aⁱ—O4W—H4WA	118.6
C13A—C14A—H14A	119.7	Na1Aⁱ—O4W—H4WB	139.0
C12A—C15A—H15A	109.5	Na1B—O4W—Na1Aⁱ	82.42 (7)
C12A—C15A—H15B	109.5	Na1B—O4W—H4WA	117.6
C12A—C15A—H15C	109.5	Na1B—O4W—H4WB	105.9
H15A—C15A—H15B	109.5	H4WA—O4W—H4WB	93.5

Na1Aⁱ—O1A—C1A—O2A	21.2 (3)	C15A—C12A—C13A—C14A	−178.7 (3)
Na1Aⁱ—O1A—C1A—C2A	−155.9 (2)	Na1B—O1A—C1A—Na1Aⁱ	−85.19 (19)
Na1A—O2A—C1A—Na1Aⁱ	−53.7 (6)	Na1B—O1A—C1A—O2A	−64.0 (4)
Na1Aⁱ—O2A—C1A—O1A	−19.5 (3)	Na1B—O1A—C1A—C2A	119.0 (2)
Na1A—O2A—C1A—O1A	−73.2 (8)	Na1B—O1B—C1B—O2B	40.8 (4)
Na1Aⁱ—O2A—C1A—C2A	157.4 (2)	Na1B—O1B—C1B—C2B	−141.7 (2)
Na1A—O2A—C1A—C2A	103.7 (7)	O1B—C1B—C2B—C3B	170.7 (3)
Na1Aⁱ—C1A—C2A—C3A	120.9 (5)	O2B—C1B—C2B—C3B	−11.7 (4)
O1A—C1A—C2A—C3A	−167.4 (3)	O3B—C8B—C9B—C10B	144.1 (3)
O2A—C1A—C2A—C3A	15.5 (4)	O3B—C8B—C9B—C14B	−34.1 (4)
O3A—C8A—C9A—C10A	−142.0 (3)	N1B—C3B—C4B—C5B	2.0 (3)
O3A—C8A—C9A—C14A	34.9 (4)	N1B—C6B—C8B—O3B	−16.1 (5)
N1A—C3A—C4A—C5A	−0.8 (3)	N1B—C6B—C8B—C9B	166.3 (3)
N1A—C6A—C8A—O3A	15.4 (5)	C1B—C2B—C3B—N1B	71.0 (4)
N1A—C6A—C8A—C9A	−168.0 (3)	C1B—C2B—C3B—C4B	−105.8 (3)
C1A—C2A—C3A—N1A	−70.1 (4)	C2B—C3B—C4B—C5B	179.2 (3)
C1A—C2A—C3A—C4A	110.7 (3)	C3B—N1B—C6B—C5B	1.6 (3)
C2A—C3A—C4A—C5A	178.5 (3)	C3B—N1B—C6B—C8B	169.0 (3)
C3A—N1A—C6A—C5A	−1.0 (3)	C3B—C4B—C5B—C6B	−1.1 (4)
C3A—N1A—C6A—C8A	−168.7 (3)	C4B—C5B—C6B—N1B	−0.3 (3)
C3A—C4A—C5A—C6A	0.2 (3)	C4B—C5B—C6B—C8B	−167.0 (3)
C4A—C5A—C6A—N1A	0.5 (3)	C5B—C6B—C8B—O3B	148.6 (3)
C4A—C5A—C6A—C8A	167.7 (3)	C5B—C6B—C8B—C9B	−29.0 (4)
C5A—C6A—C8A—O3A	−149.7 (3)	C6B—N1B—C3B—C2B	−179.5 (3)
C5A—C6A—C8A—C9A	26.9 (4)	C6B—N1B—C3B—C4B	−2.2 (3)
C6A—N1A—C3A—C2A	−178.3 (2)	C6B—C8B—C9B—C10B	−38.2 (4)
C6A—N1A—C3A—C4A	1.1 (3)	C6B—C8B—C9B—C14B	143.6 (3)
C6A—C8A—C9A—C10A	41.3 (4)	C7B—N1B—C3B—C2B	6.3 (4)
C6A—C8A—C9A—C14A	−141.8 (3)	C7B—N1B—C3B—C4B	−176.4 (3)
C7A—N1A—C3A—C2A	−6.0 (4)	C7B—N1B—C6B—C5B	175.7 (3)
C7A—N1A—C3A—C4A	173.4 (2)	C7B—N1B—C6B—C8B	−16.9 (4)
C7A—N1A—C6A—C5A	−173.2 (2)	C8B—C9B—C10B—C11B	−180.0 (3)
C7A—N1A—C6A—C8A	19.0 (4)	C8B—C9B—C14B—C13B	−179.1 (3)
C8A—C9A—C10A—C11A	178.7 (3)	C9B—C10B—C11B—C12B	0.3 (5)
C8A—C9A—C14A—C13A	−179.9 (3)	C10B—C9B—C14B—C13B	2.7 (5)
C9A—C10A—C11A—C12A	−0.5 (5)	C10B—C11B—C12B—C13B	0.3 (5)
C10A—C9A—C14A—C13A	−2.8 (5)	C10B—C11B—C12B—C15B	−178.3 (3)
C10A—C11A—C12A—C13A	0.3 (5)	C11B—C12B—C13B—C14B	0.6 (5)
C10A—C11A—C12A—C15A	177.7 (3)	C12B—C13B—C14B—C9B	−2.1 (5)
C11A—C12A—C13A—C14A	−1.3 (5)	C14B—C9B—C10B—C11B	−1.8 (5)
C12A—C13A—C14A—C9A	2.7 (5)	C15B—C12B—C13B—C14B	179.1 (3)
C14A—C9A—C10A—C11A	1.8 (4)

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

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1W—H1WA···O3A	0.89	2.12	3.002 (3)	169
O1W—H1WB···O1Aⁱⁱ	0.89	2.00	2.665 (4)	130
O2W—H2WA···O2Bⁱⁱ	0.89	1.88	2.741 (3)	161
O2W—H2WB···O2B^iv	0.89	2.13	3.019 (3)	172
O3W—H3WA···O3B^v	0.89	2.16	2.961 (3)	150
O3W—H3WB···O1B^iv	0.89	1.84	2.699 (4)	161
O4W—H4WA···O1B^iv	0.89	2.19	2.894 (3)	136
O4W—H4WB···O3W^iv	0.89	2.02	2.889 (3)	163

Symmetry codes: (ii) x+1, y, z; (iv) −x+1, −y, −z+1; (v) −x, −y, −z+1.

References

Akl, M. A., Ismael, H. R., Abd Allah, F. I., Kassem, A. A. & Samy, A. M. (2019). Drug Dev. Ind. Pharm. 45, 252–264. CrossRef CAS PubMed Google Scholar
Auda, S. H., El-Rasoul, S. A., Ahmed, M. M., Osman, S. K. & El-Badry, M. (2015). J. Pharm. Investig. 45, 311–317. CrossRef CAS Google Scholar
Burgi, H.-B. & Dunitz, J. D. (1994). Structure Correlation, vol. 2, pp. 741–784. Weinheim: VCH. Google Scholar
Cordrey, L. J. (1976). J. Am. Geriatr. Soc. 24, 440–446. CrossRef CAS PubMed Google Scholar
Dendrinou-Samara, C., Kessissoglou, D. P., Manoussakis, G. E., Mentzafos, D. & Terzis, A. (1990). J. Chem. Soc. Dalton Trans. pp. 959–965. 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
Duffy, C. P., Elliott, C. J., O'Connor, R. A., Heenan, M. M., Coyle, S., Cleary, I. M., Kavanagh, K., Verhaegen, S., O'Loughlin, C. M., NicAmhlaoibh, R. & Clynes, M. (1998). Eur. J. Cancer, 34, 1250–1259. Web of Science CrossRef CAS PubMed 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
Klippel, J. H., Stone, J. H., Crofford, L. J. & White, P. H. (2010). Nonsteroidal Anti-Inflammatory Drugs. In The Pocket Primer on the Rheumatic Diseases. London: Springer. Google Scholar
Lou, B.-Y., Guo, X. & Lin, Q. (2008). Acta Cryst. E64, o1439. CSD CrossRef IUCr Journals Google Scholar
Lu, D., Cottam, H. B., Corr, M. & Carson, D. A. (2005). Proc. Natl Acad. Sci. USA, 102, 18567–18571. CrossRef PubMed CAS Google Scholar
McEvoy, G. K. (2007). Editor. AHFS Drug Information, pp. 2118–2122. Bethesda, MD: American Society of Health-System Pharmacists. Google Scholar
Moreland, L. W. (2004). Tolmetin. Rheumatology and Immunology Therapy. Berlin, Heidelberg: Springer. Google Scholar
Ramadan, A. A., Elbakry, A. M., Esmaeil, A. H. & Khaleel, S. A. (2018). J. Pharm. Investig. 48, 673–683. CrossRef CAS PubMed Google Scholar
Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction Ltd, Yarnton, England. 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
Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). Crystal Explorer 17. University of Western Australia. https://hirshfeldsurface.net. 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 77| Part 2| February 2021| Pages 134-137

https://doi.org/10.1107/S2056989021000414

Open

access

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text
		Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text
		Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Crystal structure of the non-steroidal anti-inflammatory drug (NSAID) tolmetin sodium

1. Chemical context

2. Structural commentary

3. Supra­molecular features

4. Hirshfeld surface analysis

5. Database survey

6. Crystallization

7. Refinement

Supporting information

References

research communications

3. Supramolecular features