Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807028267/ez2079sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807028267/ez2079Isup2.hkl |
CCDC reference: 654927
As part of a cocrystal study on theophylline, (I) was obtained from a solution of theophylline in dimethyl sulfoxide to which an equimolar amount of isophthalic acid was added. The solution was allowed to evaporate at room temperature, forming long plate-like crystals.
All non-hydrogen atoms were refined with anisotropic displacement parameters, while the hydrogen atoms were freely refined with an isotropic model.
Theophylline is a pharmaceutically active compound for the treatment of asthma, and is currently known to have two anhydrous and one monohydrate crystal modifications (Sun et al., 2002; Sutor, 1958; Ebisuzaki et al., 1997). A variety of molecular complexes of theophylline have been determined, including with urea (Wiedenfeld & Knoch, 1986), and phenobarbital (Nakao et al., 1977). In addition, a recent co-crystal study on theophylline has also been performed (Trask et al., 2006). In this paper we report the dimethyl sulfoxide solvate of theophylline (I).
(I) has one molecule each of theophylline and dimethyl sulfoxide in the asymmetric unit, with the C—N and C—C bond lengths in (I) ranging from 1.3470 (17) to 1.4702 (16) Å, and 1.3720 (16) to 1.4251 (17) Å, respectively. The packing consists of molecular sheets (Fig 2), lying parallel to the (040) series of lattice planes. Within the molecular sheets each theophylline molecule is hydrogen bonded to one dimethyl sulfoxide molecule through a N—H···O -(2.7658 (15) Å) hydrogen bond (Fig 1). This particular hydrogen bond donor (N7—H1) was found to undergo hydrogen bonding within a variety of theophylline crystal structures, including the anhydrous (Sutor, 1958; Ebisuzaki et al., 1997) and monohydrate (Sun et al., 2002) forms, and in a variety of theophylline cocrystals (Trask et al., 2006).
For related literature, see: Ebisuzaki et al. (1997); Sun et al. (2002); Sutor (1958); Trask et al. (2006); Wiedenfeld & Knoch (1986); Nakao et al. (1977); Spek (2004).
Data collection: CrysAlis CCD (Oxford Diffraction, 2005); cell refinement: CrysAlis RED (Oxford Diffraction, 2005); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and Mercury (Bruno et al., 2002); software used to prepare material for publication: SHELXL97.
C7H8N4O2·C2H6OS | F(000) = 544 |
Mr = 258.30 | Dx = 1.469 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 10.1078 (4) Å | Cell parameters from 7829 reflections |
b = 6.6686 (2) Å | θ = 3.0–30.1° |
c = 17.3716 (6) Å | µ = 0.28 mm−1 |
β = 94.000 (3)° | T = 150 K |
V = 1168.08 (7) Å3 | Plate, colourless |
Z = 4 | 0.30 × 0.20 × 0.10 mm |
Oxford Diffaction Xcalibur System diffractometer | 3389 independent reflections |
Radiation source: Enhance (Mo) X-ray Source | 2954 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.018 |
Detector resolution: 16.2086 pixels mm-1 | θmax = 30.1°, θmin = 3.0° |
321 frames, counting time 10 s. scans | h = −14→13 |
Absorption correction: multi-scan (ABSPACK; Oxford Diffraction, 2005) | k = −9→4 |
Tmin = 0.909, Tmax = 1.000 | l = −24→23 |
7829 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.039 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.103 | All H-atom parameters refined |
S = 1.14 | w = 1/[σ2(Fo2) + (0.0448P)2 + 0.4489P] where P = (Fo2 + 2Fc2)/3 |
3389 reflections | (Δ/σ)max = 0.001 |
210 parameters | Δρmax = 0.48 e Å−3 |
0 restraints | Δρmin = −0.32 e Å−3 |
C7H8N4O2·C2H6OS | V = 1168.08 (7) Å3 |
Mr = 258.30 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 10.1078 (4) Å | µ = 0.28 mm−1 |
b = 6.6686 (2) Å | T = 150 K |
c = 17.3716 (6) Å | 0.30 × 0.20 × 0.10 mm |
β = 94.000 (3)° |
Oxford Diffaction Xcalibur System diffractometer | 3389 independent reflections |
Absorption correction: multi-scan (ABSPACK; Oxford Diffraction, 2005) | 2954 reflections with I > 2σ(I) |
Tmin = 0.909, Tmax = 1.000 | Rint = 0.018 |
7829 measured reflections |
R[F2 > 2σ(F2)] = 0.039 | 0 restraints |
wR(F2) = 0.103 | All H-atom parameters refined |
S = 1.14 | Δρmax = 0.48 e Å−3 |
3389 reflections | Δρmin = −0.32 e Å−3 |
210 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
S01 | 0.99246 (3) | 0.27513 (6) | 0.39406 (2) | 0.02725 (10) | |
O01 | 0.86611 (10) | 0.21464 (19) | 0.43009 (6) | 0.0339 (3) | |
O13 | 0.80020 (10) | 0.20643 (18) | 0.22207 (6) | 0.0324 (2) | |
C12 | 0.25006 (13) | 0.2289 (3) | 0.17748 (8) | 0.0280 (3) | |
N3 | 0.39458 (10) | 0.21980 (16) | 0.18986 (6) | 0.0185 (2) | |
O11 | 0.41996 (10) | 0.22404 (15) | 0.06081 (5) | 0.0259 (2) | |
N7 | 0.61561 (11) | 0.21610 (16) | 0.35505 (6) | 0.0196 (2) | |
N1 | 0.60823 (11) | 0.21461 (16) | 0.14185 (6) | 0.0197 (2) | |
N9 | 0.39424 (11) | 0.21847 (17) | 0.33061 (6) | 0.0210 (2) | |
C10 | 0.68505 (15) | 0.2138 (2) | 0.07304 (8) | 0.0285 (3) | |
C02 | 1.04433 (15) | 0.0636 (3) | 0.34142 (9) | 0.0341 (3) | |
C4 | 0.45550 (12) | 0.21723 (17) | 0.26335 (7) | 0.0165 (2) | |
C8 | 0.49588 (13) | 0.21820 (19) | 0.38458 (7) | 0.0208 (2) | |
C6 | 0.67877 (13) | 0.21158 (19) | 0.21484 (7) | 0.0206 (2) | |
C5 | 0.59106 (12) | 0.21525 (17) | 0.27559 (6) | 0.0171 (2) | |
C2 | 0.47051 (12) | 0.21983 (18) | 0.12719 (7) | 0.0186 (2) | |
C01 | 1.12025 (16) | 0.2617 (3) | 0.47024 (10) | 0.0364 (4) | |
H2 | 0.4860 (17) | 0.220 (2) | 0.4387 (10) | 0.024 (4)* | |
H6 | 0.6500 (17) | 0.105 (3) | 0.0372 (10) | 0.033 (4)* | |
H1 | 0.694 (2) | 0.220 (3) | 0.3829 (12) | 0.038 (5)* | |
H7 | 0.7726 (19) | 0.191 (3) | 0.0903 (11) | 0.033 (5)* | |
H11 | 1.1159 (19) | 0.130 (3) | 0.4954 (11) | 0.043 (5)* | |
H8 | 0.6760 (18) | 0.344 (3) | 0.0467 (11) | 0.038 (5)* | |
H13 | 1.039 (2) | −0.057 (3) | 0.3756 (12) | 0.050 (6)* | |
H5 | 0.222 (2) | 0.309 (4) | 0.1328 (14) | 0.056 (6)* | |
H12 | 1.134 (2) | 0.086 (3) | 0.3285 (11) | 0.044 (5)* | |
H14 | 0.986 (2) | 0.051 (3) | 0.2967 (12) | 0.049 (6)* | |
H3 | 0.220 (2) | 0.294 (3) | 0.2224 (14) | 0.054 (6)* | |
H9 | 1.106 (2) | 0.364 (3) | 0.5073 (12) | 0.046 (5)* | |
H4 | 0.215 (2) | 0.103 (4) | 0.1702 (14) | 0.065 (7)* | |
H10 | 1.204 (3) | 0.280 (3) | 0.4482 (16) | 0.064 (7)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S01 | 0.01938 (16) | 0.03553 (19) | 0.02636 (17) | 0.00271 (12) | −0.00191 (12) | 0.00318 (13) |
O01 | 0.0160 (4) | 0.0631 (7) | 0.0226 (5) | 0.0054 (4) | 0.0019 (3) | −0.0009 (5) |
O13 | 0.0174 (5) | 0.0550 (7) | 0.0245 (5) | −0.0004 (4) | 0.0007 (4) | 0.0054 (4) |
C12 | 0.0171 (6) | 0.0443 (8) | 0.0218 (6) | −0.0008 (5) | −0.0038 (5) | 0.0000 (6) |
N3 | 0.0163 (5) | 0.0248 (5) | 0.0141 (4) | −0.0004 (4) | −0.0021 (3) | −0.0002 (4) |
O11 | 0.0256 (5) | 0.0369 (5) | 0.0145 (4) | −0.0007 (4) | −0.0025 (3) | −0.0007 (4) |
N7 | 0.0196 (5) | 0.0238 (5) | 0.0149 (4) | −0.0004 (4) | −0.0027 (4) | 0.0005 (4) |
N1 | 0.0196 (5) | 0.0253 (5) | 0.0143 (4) | −0.0003 (4) | 0.0015 (4) | 0.0001 (4) |
N9 | 0.0197 (5) | 0.0278 (5) | 0.0154 (4) | 0.0001 (4) | 0.0011 (4) | −0.0003 (4) |
C10 | 0.0245 (7) | 0.0431 (8) | 0.0185 (6) | −0.0004 (6) | 0.0062 (5) | −0.0018 (5) |
C02 | 0.0215 (7) | 0.0530 (10) | 0.0281 (7) | 0.0041 (6) | 0.0030 (5) | −0.0064 (7) |
C4 | 0.0183 (5) | 0.0163 (5) | 0.0146 (5) | −0.0004 (4) | −0.0013 (4) | −0.0001 (4) |
C8 | 0.0229 (6) | 0.0245 (6) | 0.0149 (5) | 0.0005 (5) | 0.0000 (4) | 0.0000 (4) |
C6 | 0.0193 (6) | 0.0241 (6) | 0.0180 (5) | −0.0009 (4) | −0.0010 (4) | 0.0017 (4) |
C5 | 0.0177 (5) | 0.0191 (5) | 0.0143 (5) | −0.0004 (4) | −0.0016 (4) | 0.0008 (4) |
C2 | 0.0214 (6) | 0.0184 (5) | 0.0156 (5) | −0.0004 (4) | −0.0007 (4) | −0.0005 (4) |
C01 | 0.0254 (7) | 0.0438 (9) | 0.0382 (8) | 0.0013 (6) | −0.0106 (6) | −0.0062 (7) |
S01—O01 | 1.5156 (11) | N1—C10 | 1.4702 (16) |
S01—C02 | 1.7797 (17) | N9—C8 | 1.3417 (16) |
S01—C01 | 1.7859 (16) | N9—C4 | 1.3601 (15) |
O13—C6 | 1.2256 (16) | C10—H6 | 1.003 (18) |
C12—N3 | 1.4628 (16) | C10—H7 | 0.927 (19) |
C12—H5 | 0.97 (2) | C10—H8 | 0.98 (2) |
C12—H3 | 0.96 (2) | C02—H13 | 1.01 (2) |
C12—H4 | 0.91 (3) | C02—H12 | 0.96 (2) |
N3—C2 | 1.3751 (16) | C02—H14 | 0.94 (2) |
N3—C4 | 1.3781 (14) | C4—C5 | 1.3720 (16) |
O11—C2 | 1.2286 (15) | C8—H2 | 0.952 (17) |
N7—C8 | 1.3470 (17) | C6—C5 | 1.4251 (17) |
N7—C5 | 1.3854 (15) | C01—H11 | 0.98 (2) |
N7—H1 | 0.90 (2) | C01—H9 | 0.96 (2) |
N1—C2 | 1.3980 (16) | C01—H10 | 0.96 (3) |
N1—C6 | 1.4108 (15) | ||
O01—S01—C02 | 106.75 (7) | S01—C02—H12 | 108.2 (12) |
O01—S01—C01 | 105.50 (8) | H13—C02—H12 | 110.5 (17) |
C02—S01—C01 | 96.73 (8) | S01—C02—H14 | 107.5 (13) |
N3—C12—H5 | 112.3 (13) | H13—C02—H14 | 111.2 (17) |
N3—C12—H3 | 105.7 (14) | H12—C02—H14 | 111.4 (17) |
H5—C12—H3 | 107.8 (19) | N9—C4—C5 | 112.12 (10) |
N3—C12—H4 | 110.7 (15) | N9—C4—N3 | 126.50 (11) |
H5—C12—H4 | 107.8 (19) | C5—C4—N3 | 121.37 (11) |
H3—C12—H4 | 112.6 (19) | N9—C8—N7 | 113.49 (11) |
C2—N3—C4 | 119.69 (10) | N9—C8—H2 | 124.2 (11) |
C2—N3—C12 | 119.36 (10) | N7—C8—H2 | 122.3 (11) |
C4—N3—C12 | 120.92 (11) | O13—C6—N1 | 122.16 (12) |
C8—N7—C5 | 106.03 (10) | O13—C6—C5 | 126.50 (12) |
C8—N7—H1 | 125.1 (13) | N1—C6—C5 | 111.33 (11) |
C5—N7—H1 | 128.8 (13) | C4—C5—N7 | 105.19 (10) |
C2—N1—C6 | 126.76 (10) | C4—C5—C6 | 123.47 (11) |
C2—N1—C10 | 115.32 (10) | N7—C5—C6 | 131.34 (11) |
C6—N1—C10 | 117.92 (11) | O11—C2—N3 | 121.64 (12) |
C8—N9—C4 | 103.18 (10) | O11—C2—N1 | 121.01 (11) |
N1—C10—H6 | 108.9 (10) | N3—C2—N1 | 117.35 (10) |
N1—C10—H7 | 106.5 (12) | S01—C01—H11 | 108.8 (12) |
H6—C10—H7 | 111.7 (15) | S01—C01—H9 | 109.1 (12) |
N1—C10—H8 | 109.7 (11) | H11—C01—H9 | 108.9 (18) |
H6—C10—H8 | 109.4 (15) | S01—C01—H10 | 108.1 (16) |
H7—C10—H8 | 110.6 (16) | H11—C01—H10 | 111.0 (18) |
S01—C02—H13 | 107.8 (12) | H9—C01—H10 | 110.9 (19) |
D—H···A | D—H | H···A | D···A | D—H···A |
N7—H1···O01 | 0.90 (2) | 1.87 (2) | 2.7658 (15) | 172.8 (19) |
Experimental details
Crystal data | |
Chemical formula | C7H8N4O2·C2H6OS |
Mr | 258.30 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 150 |
a, b, c (Å) | 10.1078 (4), 6.6686 (2), 17.3716 (6) |
β (°) | 94.000 (3) |
V (Å3) | 1168.08 (7) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.28 |
Crystal size (mm) | 0.30 × 0.20 × 0.10 |
Data collection | |
Diffractometer | Oxford Diffaction Xcalibur System |
Absorption correction | Multi-scan (ABSPACK; Oxford Diffraction, 2005) |
Tmin, Tmax | 0.909, 1.000 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7829, 3389, 2954 |
Rint | 0.018 |
(sin θ/λ)max (Å−1) | 0.706 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.039, 0.103, 1.14 |
No. of reflections | 3389 |
No. of parameters | 210 |
H-atom treatment | All H-atom parameters refined |
Δρmax, Δρmin (e Å−3) | 0.48, −0.32 |
Computer programs: CrysAlis CCD (Oxford Diffraction, 2005), CrysAlis RED (Oxford Diffraction, 2005), CrysAlis RED, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEPIII (Burnett & Johnson, 1996) and Mercury (Bruno et al., 2002), SHELXL97.
D—H···A | D—H | H···A | D···A | D—H···A |
N7—H1···O01 | 0.90 (2) | 1.87 (2) | 2.7658 (15) | 172.8 (19) |
Theophylline is a pharmaceutically active compound for the treatment of asthma, and is currently known to have two anhydrous and one monohydrate crystal modifications (Sun et al., 2002; Sutor, 1958; Ebisuzaki et al., 1997). A variety of molecular complexes of theophylline have been determined, including with urea (Wiedenfeld & Knoch, 1986), and phenobarbital (Nakao et al., 1977). In addition, a recent co-crystal study on theophylline has also been performed (Trask et al., 2006). In this paper we report the dimethyl sulfoxide solvate of theophylline (I).
(I) has one molecule each of theophylline and dimethyl sulfoxide in the asymmetric unit, with the C—N and C—C bond lengths in (I) ranging from 1.3470 (17) to 1.4702 (16) Å, and 1.3720 (16) to 1.4251 (17) Å, respectively. The packing consists of molecular sheets (Fig 2), lying parallel to the (040) series of lattice planes. Within the molecular sheets each theophylline molecule is hydrogen bonded to one dimethyl sulfoxide molecule through a N—H···O -(2.7658 (15) Å) hydrogen bond (Fig 1). This particular hydrogen bond donor (N7—H1) was found to undergo hydrogen bonding within a variety of theophylline crystal structures, including the anhydrous (Sutor, 1958; Ebisuzaki et al., 1997) and monohydrate (Sun et al., 2002) forms, and in a variety of theophylline cocrystals (Trask et al., 2006).