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The crystal structure of γ-indomethacin, C19H16ClNO4, is supported, not only by O—H...O interactions, but also by C—H...π and π–π interactions.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S160053680301290X/cf6262sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S160053680301290X/cf6262Isup2.hkl
Contains datablock I

CCDC reference: 217467

Key indicators

  • Single-crystal X-ray study
  • T = 120 K
  • Mean [sigma](C-C) = 0.003 Å
  • R factor = 0.044
  • wR factor = 0.105
  • Data-to-parameter ratio = 16.4

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry








Comment top

Room-temperature crystal structures of γ-indomethacin, (I), have been reported previously (Kistenmacher & Marsh, 1972; Galdecki & Glowka, 1976) and the crystal structure of the metastable α form at 203 K is also known (Chen et al., 2002). The compound presents an unusual case in which the more stable γ form is reported to have the lower density. Also, the known dimer formation between the carboxylic acid groups would be difficult to predict in the presence of other donors and acceptors. Only in the metastable α form does the carbonyl atom O1 act as an acceptor, whereby trimers are formed in the space group P21 with Z = 6.

Apart from the previously reported O—H···O interactions, we have now examined other non-covalent interactions between γ-indomethacin molecules. Both crystal structures of γ-indomethacin reported previously used different cell settings, so to avoid confusion, we have used reduced cell dimensions throughout our study.

The molecular structure of (I) is shown in Fig. 1. The dihedral angle between the mean planes of the indole ring system and the chlorophenyl ring is 66.51 (5)°. The geometry of the R22(8) hydrogen bonding between centrosymmetrically related carboxylic acid groups is given in Table 2 and the interaction is shown in Fig. 2.

As well as the classical hydrogen bonding involved in dimer formation, the supramolecular structure is also supported by edge-to-face C—H···π interactions, as listed in Table 3 and shown in Fig. 3. Here the methylene H atoms on C18 and methyl atom H20A interact with the π systems of the indole rings.

Completing the molecular attractions is a ππ interaction between centrosymmetrically related chlorophenyl rings, as shown in Fig. 4 and detailed in Table 4.

Morphological evaluation of γ-indomethacin has also been performed (Slavin et al., 2002).

Experimental top

Indomethacin was purchased from Sigma and was recrystallized from 4-methylpentan-2-one, to produce the γ-polymorph.

Refinement top

The coordinates of the hydroxy H atom were freely refined; the other H atoms were placed in calculated positions and allowed to ride on their parent atoms. For all H atoms, Uiso values were set at 1.2 (non-methyl) or 1.3 (methyl) times Ueq of the parent atom.

Computing details top

Data collection: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998); cell refinement: DENZO and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SIR97 (Altomare et al., 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I). Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. Dimer formation between carboxylic acid groups. Atoms marked with an asterisk (*) are at the symmetry position (−1 − x, 1 − y, −z).
[Figure 3] Fig. 3. The C—H···π hydrogen bonding, shown as double-dashed lines, between molecules related by a centre of symmetry.
[Figure 4] Fig. 4. A crystal packing diagram showing the ππ interactions, as a dashed line, between chlorophenyl rings stacked across a centre of symmetry. The ring centre is indicated by a dot. Dimer formation is also shown.
(I) top
Crystal data top
C19H16ClNO4Z = 2
Mr = 357.78F(000) = 372
Triclinic, P1Dx = 1.401 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 9.236 (5) ÅCell parameters from 4841 reflections
b = 9.620 (5) Åθ = 2.9–27.5°
c = 10.887 (5) ŵ = 0.25 mm1
α = 69.897 (5)°T = 120 K
β = 87.328 (5)°Plate, colourless
γ = 69.501 (5)°0.23 × 0.2 × 0.02 mm
V = 847.9 (7) Å3
Data collection top
Nonius KappaCCD area-detector
diffractometer
2586 reflections with I > 2σ(I)
ϕ and ω scansRint = 0.056
Absorption correction: multi-scan
(SORTAV; Blessing, 1995, 1997)
θmax = 27.5°, θmin = 3.0°
Tmin = 0.956, Tmax = 0.992h = 1111
10585 measured reflectionsk = 1112
3800 independent reflectionsl = 1414
Refinement top
Refinement on F2H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full w = 1/[σ2(Fo2) + (0.0439P)2 + 0.0875P]
where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.044(Δ/σ)max < 0.001
wR(F2) = 0.105Δρmax = 0.27 e Å3
S = 1.01Δρmin = 0.26 e Å3
3800 reflectionsExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
232 parametersExtinction coefficient: 0.012 (2)
0 restraints
Crystal data top
C19H16ClNO4γ = 69.501 (5)°
Mr = 357.78V = 847.9 (7) Å3
Triclinic, P1Z = 2
a = 9.236 (5) ÅMo Kα radiation
b = 9.620 (5) ŵ = 0.25 mm1
c = 10.887 (5) ÅT = 120 K
α = 69.897 (5)°0.23 × 0.2 × 0.02 mm
β = 87.328 (5)°
Data collection top
Nonius KappaCCD area-detector
diffractometer
3800 independent reflections
Absorption correction: multi-scan
(SORTAV; Blessing, 1995, 1997)
2586 reflections with I > 2σ(I)
Tmin = 0.956, Tmax = 0.992Rint = 0.056
10585 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0440 restraints
wR(F2) = 0.105H atoms treated by a mixture of independent and constrained refinement
S = 1.01Δρmax = 0.27 e Å3
3800 reflectionsΔρmin = 0.26 e Å3
232 parameters
Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl10.80746 (6)0.45402 (6)0.57008 (5)0.03666 (18)
O10.03608 (16)0.17070 (16)0.50769 (12)0.0279 (3)
O20.22313 (17)0.42194 (16)0.09306 (13)0.0322 (4)
O30.41729 (18)0.39171 (18)0.11120 (13)0.0349 (4)
H30.490 (3)0.481 (3)0.105 (2)0.042*
O40.38537 (15)0.33417 (15)0.10489 (12)0.0257 (3)
N10.06753 (17)0.04055 (17)0.29426 (14)0.0195 (4)
C20.0734 (2)0.0227 (2)0.23317 (18)0.0198 (4)
C30.0977 (2)0.0896 (2)0.11135 (17)0.0187 (4)
C40.0257 (2)0.1515 (2)0.09355 (17)0.0181 (4)
C50.0524 (2)0.2719 (2)0.01188 (18)0.0200 (4)
H50.01660.32680.08920.024*
C60.1818 (2)0.3074 (2)0.00067 (18)0.0228 (4)
C70.2815 (2)0.2272 (2)0.11648 (19)0.0268 (5)
H70.36950.25450.12320.032*
C80.2551 (2)0.1095 (2)0.22104 (19)0.0245 (4)
H80.32240.05730.29940.029*
C90.1272 (2)0.0705 (2)0.20744 (17)0.0184 (4)
C100.1238 (2)0.1381 (2)0.42508 (18)0.0206 (4)
C110.2954 (2)0.2061 (2)0.45484 (17)0.0194 (4)
C120.3937 (2)0.2635 (2)0.36842 (18)0.0227 (4)
H120.3520.25020.28530.027*
C130.5518 (2)0.3399 (2)0.40265 (18)0.0252 (5)
H130.61880.38110.34470.03*
C140.6100 (2)0.3547 (2)0.52357 (19)0.0239 (4)
C150.5142 (2)0.2964 (2)0.60978 (18)0.0246 (4)
H150.55650.30610.69140.03*
C160.3566 (2)0.2242 (2)0.57606 (18)0.0231 (4)
H160.28960.18660.63580.028*
C170.1655 (2)0.1244 (2)0.29603 (19)0.0273 (5)
H17A0.24080.11450.23010.035*
H17B0.22050.09070.36590.035*
H17C0.09580.23510.33350.035*
C180.2287 (2)0.1459 (2)0.01031 (18)0.0212 (4)
H18A0.27690.06430.0290.025*
H18B0.18780.15950.0770.025*
C190.3506 (2)0.3000 (2)0.00690 (18)0.0200 (4)
C200.1179 (2)0.5202 (2)0.20739 (18)0.0282 (5)
H20A0.0150.56860.18080.037*
H20B0.11120.45570.25820.037*
H20C0.15540.60350.26140.037*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0219 (3)0.0375 (3)0.0394 (3)0.0077 (2)0.0060 (2)0.0018 (2)
O10.0272 (8)0.0292 (8)0.0209 (7)0.0083 (7)0.0048 (6)0.0034 (6)
O20.0329 (8)0.0307 (8)0.0275 (8)0.0181 (7)0.0013 (6)0.0036 (6)
O30.0355 (9)0.0301 (8)0.0200 (7)0.0117 (7)0.0045 (6)0.0091 (7)
O40.0257 (8)0.0253 (7)0.0195 (7)0.0005 (6)0.0007 (6)0.0087 (6)
N10.0187 (8)0.0185 (8)0.0168 (8)0.0053 (7)0.0013 (6)0.0018 (6)
C20.0168 (10)0.0191 (10)0.0227 (10)0.0038 (8)0.0019 (8)0.0090 (8)
C30.0164 (9)0.0172 (9)0.0203 (10)0.0023 (8)0.0003 (8)0.0077 (8)
C40.0186 (10)0.0168 (9)0.0176 (9)0.0031 (8)0.0010 (8)0.0079 (8)
C50.0211 (10)0.0172 (9)0.0169 (9)0.0022 (8)0.0011 (8)0.0045 (8)
C60.0261 (11)0.0192 (10)0.0208 (10)0.0090 (9)0.0032 (8)0.0035 (8)
C70.0226 (11)0.0312 (11)0.0293 (11)0.0143 (9)0.0000 (9)0.0088 (9)
C80.0230 (11)0.0230 (10)0.0226 (10)0.0059 (9)0.0047 (8)0.0038 (9)
C90.0189 (10)0.0152 (9)0.0184 (9)0.0040 (8)0.0024 (8)0.0047 (8)
C100.0249 (11)0.0156 (9)0.0192 (10)0.0052 (8)0.0015 (8)0.0052 (8)
C110.0235 (10)0.0149 (9)0.0164 (9)0.0057 (8)0.0004 (8)0.0023 (7)
C120.0267 (11)0.0221 (10)0.0153 (9)0.0050 (9)0.0028 (8)0.0051 (8)
C130.0256 (11)0.0247 (11)0.0218 (10)0.0061 (9)0.0013 (9)0.0067 (9)
C140.0187 (10)0.0192 (10)0.0270 (11)0.0066 (8)0.0036 (8)0.0005 (8)
C150.0289 (11)0.0274 (11)0.0171 (10)0.0128 (9)0.0034 (8)0.0036 (8)
C160.0293 (11)0.0207 (10)0.0177 (10)0.0088 (9)0.0027 (8)0.0052 (8)
C170.0266 (11)0.0269 (11)0.0281 (11)0.0118 (9)0.0025 (9)0.0070 (9)
C180.0196 (10)0.0192 (10)0.0224 (10)0.0042 (8)0.0012 (8)0.0069 (8)
C190.0168 (10)0.0229 (10)0.0190 (10)0.0063 (8)0.0003 (8)0.0063 (8)
C200.0338 (12)0.0255 (11)0.0222 (10)0.0122 (9)0.0030 (9)0.0034 (9)
Geometric parameters (Å, º) top
Cl1—C141.740 (2)C8—H80.95
O1—C101.216 (2)C10—C111.490 (3)
O2—C61.373 (2)C11—C161.391 (3)
O2—C201.431 (2)C11—C121.393 (3)
O3—C191.313 (2)C12—C131.386 (3)
O3—H30.91 (2)C12—H120.95
O4—C191.218 (2)C13—C141.388 (3)
N1—C101.410 (2)C13—H130.95
N1—C91.417 (2)C14—C151.384 (3)
N1—C21.418 (2)C15—C161.379 (3)
C2—C31.360 (3)C15—H150.95
C2—C171.489 (3)C16—H160.95
C3—C41.437 (3)C17—H17A0.98
C3—C181.491 (3)C17—H17B0.98
C4—C91.399 (3)C17—H17C0.98
C4—C51.407 (3)C18—C191.505 (3)
C5—C61.378 (3)C18—H18A0.99
C5—H50.95C18—H18B0.99
C6—C71.405 (3)C20—H20A0.98
C7—C81.385 (3)C20—H20B0.98
C7—H70.95C20—H20C0.98
C8—C91.387 (3)
C6—O2—C20117.68 (16)C13—C12—H12119.7
C19—O3—H3108.1 (13)C11—C12—H12119.7
C10—N1—C9127.18 (16)C12—C13—C14118.46 (18)
C10—N1—C2124.39 (15)C12—C13—H13120.8
C9—N1—C2107.94 (14)C14—C13—H13120.8
C3—C2—N1108.62 (16)C15—C14—C13121.63 (18)
C3—C2—C17128.94 (17)C15—C14—Cl1119.12 (15)
N1—C2—C17122.28 (16)C13—C14—Cl1119.22 (16)
C2—C3—C4108.40 (16)C16—C15—C14119.40 (18)
C2—C3—C18127.92 (17)C16—C15—H15120.3
C4—C3—C18123.67 (16)C14—C15—H15120.3
C9—C4—C5121.07 (17)C15—C16—C11120.15 (18)
C9—C4—C3107.74 (16)C15—C16—H16119.9
C5—C4—C3131.18 (17)C11—C16—H16119.9
C6—C5—C4117.85 (17)C2—C17—H17A109.5
C6—C5—H5121.1C2—C17—H17B109.5
C4—C5—H5121.1H17A—C17—H17B109.5
O2—C6—C5124.72 (17)C2—C17—H17C109.5
O2—C6—C7114.70 (17)H17A—C17—H17C109.5
C5—C6—C7120.57 (17)H17B—C17—H17C109.5
C8—C7—C6121.85 (18)C3—C18—C19112.44 (15)
C8—C7—H7119.1C3—C18—H18A109.1
C6—C7—H7119.1C19—C18—H18A109.1
C7—C8—C9117.74 (18)C3—C18—H18B109.1
C7—C8—H8121.1C19—C18—H18B109.1
C9—C8—H8121.1H18A—C18—H18B107.8
C8—C9—C4120.89 (17)O4—C19—O3123.67 (17)
C8—C9—N1131.83 (17)O4—C19—C18122.95 (17)
C4—C9—N1107.23 (16)O3—C19—C18113.37 (16)
O1—C10—N1121.16 (18)O2—C20—H20A109.5
O1—C10—C11121.94 (17)O2—C20—H20B109.5
N1—C10—C11116.81 (16)H20A—C20—H20B109.5
C16—C11—C12119.72 (18)O2—C20—H20C109.5
C16—C11—C10118.87 (17)H20A—C20—H20C109.5
C12—C11—C10121.19 (16)H20B—C20—H20C109.5
C13—C12—C11120.61 (17)
C10—N1—C2—C3175.00 (16)C10—N1—C9—C83.4 (3)
C9—N1—C2—C32.49 (19)C2—N1—C9—C8175.65 (19)
C10—N1—C2—C179.2 (3)C10—N1—C9—C4173.88 (16)
C9—N1—C2—C17178.34 (16)C2—N1—C9—C41.65 (19)
N1—C2—C3—C42.3 (2)C9—N1—C10—O1145.19 (18)
C17—C2—C3—C4177.82 (18)C2—N1—C10—O125.9 (3)
N1—C2—C3—C18178.70 (16)C9—N1—C10—C1138.2 (2)
C17—C2—C3—C183.2 (3)C2—N1—C10—C11150.80 (16)
C2—C3—C4—C91.3 (2)O1—C10—C11—C1638.7 (3)
C18—C3—C4—C9179.67 (16)N1—C10—C11—C16144.67 (17)
C2—C3—C4—C5177.67 (18)O1—C10—C11—C12135.90 (19)
C18—C3—C4—C51.4 (3)N1—C10—C11—C1240.7 (2)
C9—C4—C5—C60.0 (3)C16—C11—C12—C130.6 (3)
C3—C4—C5—C6178.87 (18)C10—C11—C12—C13173.92 (17)
C20—O2—C6—C55.4 (3)C11—C12—C13—C141.3 (3)
C20—O2—C6—C7173.24 (17)C12—C13—C14—C150.5 (3)
C4—C5—C6—O2179.68 (17)C12—C13—C14—Cl1178.57 (15)
C4—C5—C6—C71.1 (3)C13—C14—C15—C161.1 (3)
O2—C6—C7—C8179.31 (18)Cl1—C14—C15—C16176.97 (14)
C5—C6—C7—C80.6 (3)C14—C15—C16—C111.9 (3)
C6—C7—C8—C91.0 (3)C12—C11—C16—C151.0 (3)
C7—C8—C9—C42.2 (3)C10—C11—C16—C15175.67 (17)
C7—C8—C9—N1179.16 (18)C2—C3—C18—C19100.1 (2)
C5—C4—C9—C81.7 (3)C4—C3—C18—C1978.7 (2)
C3—C4—C9—C8177.40 (17)C3—C18—C19—O435.0 (3)
C5—C4—C9—N1179.35 (16)C3—C18—C19—O3146.26 (17)
C3—C4—C9—N10.25 (19)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O4i0.91 (3)1.75 (3)2.651 (3)173 (3)
Symmetry code: (i) x1, y+1, z.

Experimental details

Crystal data
Chemical formulaC19H16ClNO4
Mr357.78
Crystal system, space groupTriclinic, P1
Temperature (K)120
a, b, c (Å)9.236 (5), 9.620 (5), 10.887 (5)
α, β, γ (°)69.897 (5), 87.328 (5), 69.501 (5)
V3)847.9 (7)
Z2
Radiation typeMo Kα
µ (mm1)0.25
Crystal size (mm)0.23 × 0.2 × 0.02
Data collection
DiffractometerNonius KappaCCD area-detector
diffractometer
Absorption correctionMulti-scan
(SORTAV; Blessing, 1995, 1997)
Tmin, Tmax0.956, 0.992
No. of measured, independent and
observed [I > 2σ(I)] reflections
10585, 3800, 2586
Rint0.056
(sin θ/λ)max1)0.650
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.044, 0.105, 1.01
No. of reflections3800
No. of parameters232
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.27, 0.26

Computer programs: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998), DENZO and COLLECT, SIR97 (Altomare et al., 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Selected geometric parameters (Å, º) top
Cl1—C141.740 (2)O4—C191.218 (2)
O1—C101.216 (2)C18—C191.505 (3)
O3—C191.313 (2)
C9—C4—C3107.74 (16)C8—C9—N1131.83 (17)
C5—C4—C3131.18 (17)C4—C9—N1107.23 (16)
C10—N1—C2—C179.2 (3)C2—N1—C10—O125.9 (3)
C17—C2—C3—C183.2 (3)O1—C10—C11—C12135.90 (19)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O4i0.91 (3)1.75 (3)2.651 (3)173 (3)
Symmetry code: (i) x1, y+1, z.
C—H···π interactions (Å, °) top
C—HCgISymmetry codeH···CgIC—H···CgIC···CgI
C18—H18A2-x, −y, −z3.121183.687 (3)
C18—H18B1-x, −y, −z2.721663.692 (3)
C20—H20A2-x, 1 − y, −z2.681423.511 (3)
Cg is the centre of gravity of rings in the indole system: Cg1 five-membered ring and Cg2 six-membered ring. The symmetry applies to the CgI position.
ππ interactions (Å, °) top
CgICgJSymmetry codeCg···Cgdihedral_angleinterplanaroffset
331 − x, −1 − y, 1 − z3.922 (2)0.03.411 (2)1.942
Cg3 is the centre of gravity of the chlorophenyl ring. The symmetry applies to the CgJ position.
 

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