Acemetacin monohydrate

The structure of the title compound (systematic name: 2-{2-[1-(4-chloro­benzo­yl)-5-meth­oxy-2-methyl-1H-indol-3-yl]acet­oxy}­acetic acid monohydrate, C₂₁H₁₈ClNO₆·H₂O) contains one-dimensional infinite hydrogen-bonded chains. Mol­ecules of acemetacin, a nonsteroidal anti-inflammatory drug, and water are linked by three independent O—H...O bonds. The central unit in each chain consists of a sequence of alternating centrosymmetric R₄⁴(12) and R₄⁴(18) rings, which are edge-fused. Each ring links two acemetacin and two water mol­ecules. A comparison with seven related structures reveals that mol­ecules of acemetacin, indomethacin and their analogues can adopt two principal conformations.

S1. Comment

Acemetacin is a prodrug of indomethacin. It is a nonsteroidal anti-inflammatory drug used for the treatment of osteoarthritis, rheumatoid arthritis, low back pain, and post-operative inflammation and post-operative pain. Yoneda et al. (1981) described four polymorphic forms and two hydrates of acemetacin. Burger & Lettenbichler (1993) investigated five polymorphic forms, one monohydrate and the relatively stable amorphous form of acemetacin, and characterized these phases by means of thermomicroscopy, differential scanning calorimetry, thermogravimetry, IR spectroscopy, X-ray powder diffraction and pycnometry. Crystals of the monohydrate can be obtained from solutions with aqueous solvents. The existence of a second hydrate of acemetacin (Yoneda et al., 1981) was firmly rejected by Burger & Lettenbichler (1993). These authors explained the underlying observations as a consequence of an unusual melting behaviour of the monohydrate. Auer et al. (2003) investigated the FT–Raman spectra of six solid phases of acemetacin, and another account of the monohydrate was given by Kim et al. (1993). To date, no structural information relating to any of the six characterized crystalline phases of acemetacin is available from the Cambridge Structural Database (Version 5.28, November 2006; Allen, 2002).

A comparison of the powder pattern calculated from the structural model of the title compound discussed here with that reported by Burger & Lettenbichler (1993) for their monohydrate confirms that both studies were carried out on the same phase. The structure of the acemetacin molecule is shown in Fig. 1. Bond lengths and angles are unexceptional. The indole unit makes an angle of 69.03 (5)° with the chlorobenzyl fragment and an angle of 69.08 (6)° with the mean plane through the CCOO unit attached to atom C9.

The acemetacin molecule has one potential hydrogen-bond donor and the water molecule has two. These are engaged in three independent O—H···O hydrogen bonds linking the two types of molecule. The OH group of (I) acts as a hydrogen-bond donor to one water molecule (O5—H1O···O7), and two water H atoms are linked to carbonyl atoms O2 and O4 [O7—H2O···O2(x - 1, y, z) and O7—H3O···O4(-x - 1, -y, -z + 1); Table 1]. These acceptor atoms are located in the respective oxyacetic acid units of two different acemetacin molecules. The latter two molecules are related via a centre of inversion. Each water molecule bridges between three acemetacin molecules. In turn, each acemetacin molecule is hydrogen bonded to three water molecules. The described connections generate two fundamentally different centrosymmetric rings. The first ring can be characterized by the graph-set notation (Bernstein et al., 1995) R₄⁴ (12), and the other is an R₄⁴(18) ring. Rings of different types are edge-fused in such a way that C²₂(9) fragments are formed. Thus, infinite chains (Fig. 2) are generated, whose central unit consists of alternating R₄⁴ (12) and R₄⁴(18) rings. These one-dimensional hydrogen-bonded chains are centrosymmetric and propagate parallel to the a axis. The water molecules lie at the centre of each chain and all acemetacin molecules are oriented with their oxyacetic acid units towards the central unit, while their 4-chlorobenzoyl fragments point in the opposite direction. The stacking of the chains in the crystal structure is such that the central unit of a given chain is adjacent to the tail units of four neighbouring chains that are related to the former by a translation along [010], [010], [011], [010] and [011].

The closest intermolecular C—H···O intra-chain contacts are C17—H17A···O4(x + 1, y, z) and C3—H3 ···O6(x + 1, y, z). The shortest C—H···O contacts between acemetacin molecules belonging to different O—H···O bonded chains are C18—H18A···O2(-x, -y, -z + 1) and C20—H20A···O1(-x + 1, -y + 1, -z + 1).

The Cambridge Structural Database currently holds records for seven structures that contain the indomethacin molecule (α form: Chen et al., 2002; γ form: Cox & Manson, 2003a; MeOH solvate: Stowell et al., 2002; t-ButOH solvate: Cox & Manson, 2003b) or other close analogues of acemetacin (Loll et al., 1996; Trask et al., 2004; Bis & Zaworotko, 2005). The molecular conformations in these structures can be characterized in terms of two torsion angles, T₁ (C—C—N—C) and T₂ (C—C—C—N), which are indicated in Fig. 3 and tabulated in Table 2. The analysis of this list reveals that only two principal conformations exist. Type I and type II are associated with T₁ values of approximately 150 and -30°, respectively, while T₂ is between -30 and -55° for both types. Thus, the main difference between the alternative principal conformations is a rotation by 180° about the C—N bond. As a consequence, the C═O bond and the Me substituent of the indol unit point either in the same direction (type I) or in opposite directions (type II). The conformation adopted by the acemetacin molecule in the title structure is of type I. It is noteworthy that the type I conformation is also adopted by the γ form and the t-BuOH solvate of indomethacin, and also by two of the three independent molecules of the α form, while the conformation of the third molecule in this modification is of type II.

The hydrogen bonding in the MeOH and t-BuOH solvates of indomethacin is such that molecules of different types are linked by hydrogen bonds. The COOH group of indomethacin is employed in these interactions in the same fashion in which the COOH units are engaged in hydrogen bonding between acemetacin and water in Fig. 2. Thus, the indomethacin solvates form a very similar kind of R₄⁴ (12) ring, where the OH group of the solvent replaces water. However, the lack of additional OH donors in the indomethacin molecules prevents further aggregation of these rings via classical hydrogen bonds, so that the hydrogen-bonded structure in these solvates is dimeric.

Related literature

For related literature, see: Allen (2002); Auer et al. (2003); Bernstein et al. (1995); Bis & Zaworotko (2005); Burger & Lettenbichler (1993); Cox & Manson (2003a, 2003b); Kim et al. (1993); Trask et al. (2004); Yoneda et al. (1981).

S2. Experimental

Acemetacin was supplied by Bayer. Colourless prismatic crystals of the title compound were formed by slow evaporation of an acetone/water solution at room temperature.

S3. Refinement

Methyl H atoms were located in difference syntheses, idealized and included as rigid groups allowed to rotate but not tip. Other C-bonded H atoms were positioned geometrically and refined using a riding model with U_iso(H) values of 1.2U_eq(C) for CH and CH₂ or 1.5 U_eq(C) for CH₃ H atoms. The C—H bond lengths were set at 0.95 (aromatic), 0.99 (CH₂) or 0.98 Å (CH₃). H atoms attached to O were refined using geometrical restraints [O—H = 0.82 (s.u. value?) Å and U_iso(H) = 1.2U_eq(O) for OH, and O—H = 0.88 (s.u. value?) Å and U_iso(H) = 1.5U_eq(O) for H₂O].

Computing details

Data collection: COLLECT (Hooft, 1998); cell refinement: DENZO (Otwinowski & Minor, 1997) and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP (Bruker, 1998) and Mercury (Bruno et al., 2002); software used to prepare material for publication: program (reference)?.

Figures

	Fig. 1. : The molecular structure of (I), showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. : Part of a hydrogen-bonded chain composed of edge-fused R4^4(12) and R4^4(18) rings.
	Fig. 3. : The common structural unit of the compounds listed in Table 1 and definition of the torsion angles T1 and T2 for acemetacin [R = –CH2C(═O)OCH2COOH and hal = Cl], indomethacin (R = –CH2COOH and hal = Cl), iodoindomethacin (R = –CH2COOH and hal = I) and indomethacin methyl ester (R = –CH2COOMe and hal = Cl).

2-{2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetoxy}acetic acid monohydrate

Crystal data

C21H18ClNO6·H2O	V = 993.44 (6) Å^3
Mr = 433.83	Z = 2
Triclinic, P1	F(000) = 452
a = 7.7257 (3) Å	Dx = 1.450 Mg m^−3
b = 10.2208 (3) Å	Mo Kα radiation, λ = 0.71073 Å
c = 13.4225 (4) Å	µ = 0.24 mm^−1
α = 96.879 (2)°	T = 120 K
β = 96.354 (2)°	Block, colourless
γ = 107.158 (2)°	0.25 × 0.15 × 0.10 mm

Data collection

Bruker–Nonius KappaCCD diffractometer	3877 independent reflections
Radiation source: Bruker-Nonius FR591 rotating anode	3065 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.072
Detector resolution: 9.091 pixels mm^-1	θmax = 26.0°, θmin = 3.1°
ϕ and ω scans	h = −9→9
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −12→12
Tmin = 0.943, Tmax = 0.977	l = −16→16
12459 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.046	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.127	w = 1/[σ^2(Fo^2) + (0.0592P)^2 + 0.1261P] where P = (Fo^2 + 2Fc^2)/3
S = 1.09	(Δ/σ)max < 0.001
3877 reflections	Δρmax = 0.30 e Å^−3
285 parameters	Δρmin = −0.30 e Å^−3
3 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.038 (5)

Special details

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. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cl1	0.82421 (9)	0.97907 (6)	1.19332 (4)	0.0352 (2)
O1	0.7465 (2)	0.71885 (14)	0.70347 (10)	0.0248 (3)
O2	0.02241 (19)	0.11031 (13)	0.42336 (9)	0.0190 (3)
O3	0.02130 (19)	0.32192 (13)	0.48914 (9)	0.0190 (3)
O4	−0.3234 (2)	0.14800 (15)	0.48895 (10)	0.0253 (4)
O5	−0.4141 (2)	0.16934 (15)	0.32904 (11)	0.0251 (4)
H1O	−0.509 (2)	0.1109 (19)	0.3375 (18)	0.030*
O6	−0.2004 (2)	0.39859 (15)	0.85113 (11)	0.0268 (4)
N1	0.4902 (2)	0.56238 (16)	0.73859 (11)	0.0153 (4)
C1	0.7699 (3)	0.8912 (2)	1.06917 (14)	0.0228 (5)
C2	0.7285 (3)	0.7475 (2)	1.05192 (14)	0.0209 (4)
H2	0.7308	0.6978	1.1072	0.020 (5)*
C3	0.6837 (3)	0.6783 (2)	0.95270 (14)	0.0198 (4)
H3	0.6527	0.5801	0.9397	0.018 (5)*
C4	0.6842 (3)	0.75229 (19)	0.87203 (14)	0.0171 (4)
C5	0.7296 (3)	0.8957 (2)	0.89063 (15)	0.0239 (5)
H5	0.7326	0.9460	0.8354	0.029*
C6	0.7706 (3)	0.9660 (2)	0.98975 (16)	0.0275 (5)
H6	0.7987	1.0640	1.0028	0.033*
C7	0.6453 (3)	0.68014 (19)	0.76454 (14)	0.0169 (4)
C8	0.4685 (3)	0.45221 (19)	0.65816 (13)	0.0159 (4)
C9	0.2982 (3)	0.36006 (19)	0.64934 (13)	0.0156 (4)
C10	0.2023 (3)	0.41159 (18)	0.72410 (13)	0.0147 (4)
C11	0.3236 (3)	0.53751 (19)	0.77830 (13)	0.0159 (4)
C12	0.2659 (3)	0.6171 (2)	0.85194 (14)	0.0193 (4)
H12	0.3455	0.7043	0.8864	0.023*
C13	0.0900 (3)	0.5650 (2)	0.87299 (14)	0.0210 (4)
H13	0.0490	0.6170	0.9234	0.025*
C14	−0.0299 (3)	0.4368 (2)	0.82161 (14)	0.0192 (4)
C15	0.0240 (3)	0.3595 (2)	0.74567 (14)	0.0171 (4)
H15	−0.0577	0.2740	0.7095	0.021*
C16	−0.3149 (3)	0.2599 (2)	0.81564 (18)	0.0312 (5)
H16A	−0.4266	0.2425	0.8469	0.047*
H16B	−0.2493	0.1954	0.8339	0.047*
H16C	−0.3476	0.2463	0.7416	0.047*
C17	0.6225 (3)	0.4443 (2)	0.60195 (15)	0.0221 (5)
H17A	0.5927	0.3511	0.5627	0.033*
H17B	0.7349	0.4636	0.6505	0.033*
H17C	0.6410	0.5129	0.5558	0.033*
C18	0.2235 (3)	0.2232 (2)	0.57940 (14)	0.0183 (4)
H18A	0.1696	0.1514	0.6203	0.022*
H18B	0.3281	0.2003	0.5537	0.022*
C19	0.0815 (3)	0.21120 (19)	0.48913 (14)	0.0160 (4)
C20	−0.1183 (3)	0.3084 (2)	0.40441 (14)	0.0193 (4)
H20A	−0.0751	0.2831	0.3403	0.023*
H20B	−0.1412	0.3985	0.4027	0.023*
C21	−0.2938 (3)	0.19914 (19)	0.41263 (14)	0.0183 (4)
O7	−0.7202 (2)	−0.00602 (14)	0.35206 (10)	0.0227 (3)
H2O	−0.801 (3)	0.036 (2)	0.3628 (18)	0.034*
H3O	−0.707 (4)	−0.049 (2)	0.4037 (13)	0.034*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0458 (4)	0.0342 (3)	0.0170 (3)	0.0038 (3)	0.0023 (2)	−0.0052 (2)
O1	0.0243 (8)	0.0249 (8)	0.0205 (7)	−0.0001 (6)	0.0068 (6)	0.0027 (6)
O2	0.0213 (8)	0.0175 (7)	0.0153 (7)	0.0034 (6)	0.0020 (5)	−0.0011 (5)
O3	0.0199 (7)	0.0167 (7)	0.0183 (7)	0.0053 (6)	−0.0017 (6)	0.0008 (5)
O4	0.0256 (8)	0.0307 (8)	0.0213 (7)	0.0085 (7)	0.0059 (6)	0.0089 (6)
O5	0.0183 (8)	0.0283 (8)	0.0244 (7)	0.0012 (6)	−0.0012 (6)	0.0072 (6)
O6	0.0183 (8)	0.0253 (8)	0.0348 (8)	0.0036 (6)	0.0115 (6)	−0.0016 (6)
N1	0.0146 (8)	0.0148 (8)	0.0147 (8)	0.0026 (7)	0.0024 (6)	0.0001 (6)
C1	0.0202 (11)	0.0271 (11)	0.0167 (9)	0.0036 (9)	0.0006 (8)	−0.0017 (8)
C2	0.0199 (11)	0.0255 (11)	0.0190 (10)	0.0079 (9)	0.0033 (8)	0.0076 (8)
C3	0.0169 (10)	0.0201 (10)	0.0218 (10)	0.0052 (8)	0.0021 (8)	0.0032 (8)
C4	0.0132 (10)	0.0181 (10)	0.0170 (9)	0.0016 (8)	0.0014 (7)	0.0005 (7)
C5	0.0285 (12)	0.0204 (10)	0.0197 (10)	0.0029 (9)	0.0011 (9)	0.0063 (8)
C6	0.0354 (13)	0.0176 (10)	0.0251 (11)	0.0029 (10)	0.0037 (9)	0.0011 (8)
C7	0.0174 (10)	0.0179 (9)	0.0162 (9)	0.0062 (8)	0.0023 (8)	0.0036 (7)
C8	0.0180 (10)	0.0176 (9)	0.0121 (8)	0.0067 (8)	0.0009 (7)	0.0012 (7)
C9	0.0166 (10)	0.0165 (9)	0.0133 (8)	0.0056 (8)	0.0004 (7)	0.0020 (7)
C10	0.0180 (10)	0.0137 (9)	0.0121 (8)	0.0054 (8)	0.0000 (7)	0.0023 (7)
C11	0.0145 (10)	0.0180 (9)	0.0153 (9)	0.0051 (8)	0.0010 (7)	0.0043 (7)
C12	0.0186 (10)	0.0187 (10)	0.0183 (9)	0.0041 (8)	0.0009 (8)	−0.0003 (8)
C13	0.0229 (11)	0.0223 (10)	0.0183 (9)	0.0090 (9)	0.0048 (8)	−0.0014 (8)
C14	0.0162 (10)	0.0222 (10)	0.0206 (10)	0.0075 (9)	0.0040 (8)	0.0038 (8)
C15	0.0172 (10)	0.0163 (9)	0.0180 (9)	0.0056 (8)	0.0011 (8)	0.0042 (7)
C16	0.0261 (12)	0.0244 (11)	0.0415 (13)	0.0028 (10)	0.0150 (10)	0.0032 (10)
C17	0.0218 (11)	0.0221 (10)	0.0210 (10)	0.0049 (9)	0.0066 (8)	0.0002 (8)
C18	0.0209 (11)	0.0169 (9)	0.0167 (9)	0.0071 (8)	0.0009 (8)	−0.0002 (8)
C19	0.0163 (10)	0.0155 (9)	0.0165 (9)	0.0038 (8)	0.0062 (8)	0.0031 (8)
C20	0.0189 (11)	0.0202 (10)	0.0174 (9)	0.0043 (8)	−0.0004 (8)	0.0058 (8)
C21	0.0210 (11)	0.0187 (10)	0.0188 (9)	0.0120 (9)	0.0042 (8)	0.0011 (8)
O7	0.0229 (8)	0.0239 (8)	0.0228 (7)	0.0101 (6)	0.0025 (6)	0.0037 (6)

Geometric parameters (Å, º)

Cl1—C1	1.7389 (19)	C9—C10	1.450 (3)
O1—C7	1.215 (2)	C9—C18	1.504 (3)
O2—C19	1.211 (2)	C10—C15	1.399 (3)
O3—C19	1.345 (2)	C10—C11	1.406 (3)
O3—C20	1.442 (2)	C11—C12	1.398 (3)
O4—C21	1.218 (2)	C12—C13	1.380 (3)
O5—C21	1.317 (2)	C12—H12	0.9500
O5—H1O	0.828 (10)	C13—C14	1.406 (3)
O6—C14	1.376 (2)	C13—H13	0.9500
O6—C16	1.423 (3)	C14—C15	1.390 (3)
N1—C7	1.401 (3)	C15—H15	0.9500
N1—C11	1.413 (2)	C16—H16A	0.9800
N1—C8	1.421 (2)	C16—H16B	0.9800
C1—C6	1.384 (3)	C16—H16C	0.9800
C1—C2	1.392 (3)	C17—H17A	0.9800
C2—C3	1.386 (3)	C17—H17B	0.9800
C2—H2	0.9500	C17—H17C	0.9800
C3—C4	1.393 (3)	C18—C19	1.509 (3)
C3—H3	0.9500	C18—H18A	0.9900
C4—C5	1.387 (3)	C18—H18B	0.9900
C4—C7	1.495 (2)	C20—C21	1.506 (3)
C5—C6	1.389 (3)	C20—H20A	0.9900
C5—H5	0.9500	C20—H20B	0.9900
C6—H6	0.9500	O7—H2O	0.872 (10)
C8—C9	1.356 (3)	O7—H3O	0.875 (10)
C8—C17	1.494 (3)
C19—O3—C20	113.79 (14)	C11—C12—H12	121.0
C21—O5—H1O	108.8 (17)	C12—C13—C14	121.61 (17)
C14—O6—C16	117.09 (15)	C12—C13—H13	119.2
C7—N1—C11	127.42 (15)	C14—C13—H13	119.2
C7—N1—C8	124.35 (16)	O6—C14—C15	124.37 (18)
C11—N1—C8	107.93 (15)	O6—C14—C13	114.87 (16)
C6—C1—C2	121.52 (18)	C15—C14—C13	120.75 (19)
C6—C1—Cl1	119.18 (16)	C14—C15—C10	117.92 (18)
C2—C1—Cl1	119.30 (16)	C14—C15—H15	121.0
C3—C2—C1	118.88 (18)	C10—C15—H15	121.0
C3—C2—H2	120.6	O6—C16—H16A	109.5
C1—C2—H2	120.6	O6—C16—H16B	109.5
C2—C3—C4	120.20 (18)	H16A—C16—H16B	109.5
C2—C3—H3	119.9	O6—C16—H16C	109.5
C4—C3—H3	119.9	H16A—C16—H16C	109.5
C5—C4—C3	120.11 (17)	H16B—C16—H16C	109.5
C5—C4—C7	118.86 (17)	C8—C17—H17A	109.5
C3—C4—C7	120.95 (17)	C8—C17—H17B	109.5
C6—C5—C4	120.22 (19)	H17A—C17—H17B	109.5
C6—C5—H5	119.9	C8—C17—H17C	109.5
C4—C5—H5	119.9	H17A—C17—H17C	109.5
C1—C6—C5	119.05 (19)	H17B—C17—H17C	109.5
C1—C6—H6	120.5	C9—C18—C19	117.85 (15)
C5—C6—H6	120.5	C9—C18—H18A	107.8
O1—C7—N1	121.53 (17)	C19—C18—H18A	107.8
O1—C7—C4	121.71 (18)	C9—C18—H18B	107.8
N1—C7—C4	116.72 (17)	C19—C18—H18B	107.8
C9—C8—N1	109.04 (16)	H18A—C18—H18B	107.2
C9—C8—C17	129.21 (17)	O2—C19—O3	122.27 (16)
N1—C8—C17	121.62 (17)	O2—C19—C18	123.77 (16)
C8—C9—C10	108.25 (16)	O3—C19—C18	113.94 (15)
C8—C9—C18	126.56 (17)	O3—C20—C21	110.87 (15)
C10—C9—C18	125.08 (18)	O3—C20—H20A	109.5
C15—C10—C11	120.99 (17)	C21—C20—H20A	109.5
C15—C10—C9	131.78 (17)	O3—C20—H20B	109.5
C11—C10—C9	107.22 (17)	C21—C20—H20B	109.5
C12—C11—C10	120.64 (18)	H20A—C20—H20B	108.1
C12—C11—N1	131.70 (18)	O4—C21—O5	124.0 (2)
C10—C11—N1	107.54 (15)	O4—C21—C20	123.89 (17)
C13—C12—C11	118.01 (18)	O5—C21—C20	112.08 (16)
C13—C12—H12	121.0	H2O—O7—H3O	107 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H1O···O7	0.83 (1)	1.76 (1)	2.587 (2)	176 (2)
O7—H2O···O2^i	0.87 (1)	1.95 (1)	2.7980 (19)	164 (2)
O7—H3O···O4^ii	0.88 (1)	1.89 (1)	2.7649 (19)	177 (2)
C20—H20A···O1^iii	0.99	2.67	3.424 (3)	133
C18—H18A···O2^iv	0.99	2.61	3.371 (2)	134
C17—H17A···O4^v	0.98	2.48	3.381 (2)	153
C3—H3···O6^v	0.95	2.67	3.417 (2)	136

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