Doxofylline–acrylic acid (1/1)

The title compound, C₁₁H₁₄N₄O₄·C₃H₄O₂, a 1:1 doxofylline–acrylic acid complex, forms via O—H...N and C—H...O hydrogen bonds in the solid state. Dimers of (I) aggregate via meth­yl–acid C—H...O inter­actions about inversion centres, and the three-dimensional structure arises from π–π stacking inter­actions of the purine mol­ecules.

Key indicators

• Single-crystal X-ray study
• T = 273 K
• Mean [sigma](C-C) = 0.004 Å
• Disorder in main residue
• R factor = 0.069
• wR factor = 0.169
• Data-to-parameter ratio = 12.2

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT154_ALERT_1_C The su's on the Cell Angles are Equal  (x 10000)        200 Deg.
PLAT244_ALERT_4_C Low   'Solvent' Ueq as Compared to Neighbors for        C12
PLAT301_ALERT_3_C Main Residue  Disorder .........................       5.00 Perc.
PLAT413_ALERT_2_C Short Inter XH3 .. XHn     H10B   ..  H14A    ..       2.11 Ang.
PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........          2

Alert level G
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          4

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   6 ALERT level C = Check and explain
   2 ALERT level G = General alerts; check

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Doxofylline [7-(1,3-dioxolan-2-ylmethyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione] is a therapeutic agent with anti-asthmatic (Franzone et al., 1989), antiinflammatory activities (Zhao et al., 2001) and a bronchodilating effect on smooth muscle (Franzone et al., 1981; Villani et al., 1997). These studies provide important reference points for futher research into doxofylline. Herein we present the structure of the title compound, (I), a 1:1 complex of doxofylline:acrylic acid.

As shown in Fig. 1, compound (I) is comprised of a doxofylline and acrylic acid molecule. The atoms of acrylic acid molecule are almost coplanar. The angle between the plane of acrylic acid and the plane of the purine ring is 8.2°. The doxofylline molecule in (I) adopts a different conformation from that observed in doxofylline (Chen, Tu, et al., 2007; Chen, Tu & Jin, 2007). In (I), a disordered carbon atom in the dioxolane ring is observed and modelled with site occupancies of 0.759 (17):0.241 (17) for the major and minor sites, respectively.

The geometrical arrangement in the crystal is characterized by formation of the parallel purine rings (Fig. 2). While the O5—H5···N4 hydrogen bond plays an important role in forming the complex, the hydrogen bonds of C5—H5A···O6 and C6—H6A···O1 (Table 2) play roles in dimer formation (forming dimers of (I)) and ultimately a three-dimensional structure is seen via interlocking dioxalane groups and π···π stacking interactions

Related literature

For related literature, see: Chen, Tu & Jin (2007); Chen, Tu et al. (2007); Franzone et al. (1981, 1989); Villani et al. (1997); Zhao & Li (2001).

S2. Experimental

Doxofylline and acrylic acid in 1:1 molar ratio were mixed together in suffient ethanol and heated to afford a clear solution. Crystals of (I) were formed by gradual evaporation of ethanol over a period of one week at 293 K.

S3. Refinement

All H atoms were placed in calculated positions and allowed to ride on their parent atoms at distances of 0.82 (O—H), 0.93 (unsaturated), 0.96 (methyl), 0.97 (methylene) and 0.98 Å (methine), with U_iso(H) = 1.2 or 1.5 U_eq(C) and U_eq(O).

Computing details

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL(Bruker, 2000); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. An ORTEP diagram of the 1:1 complex of (I) with atoms displayed with 30% probability displacement ellipsoids.

Doxofylline–acrylic acid (1/1)

Crystal data

C11H14N4O4·C3H4O2	V = 788.70 (15) Å^3
Mr = 338.32	Z = 2
Triclinic, P1	F(000) = 356
Hall symbol: -P 1	Dx = 1.425 Mg m^−3
a = 5.5365 (6) Å	Melting point: 428 K
b = 10.1199 (12) Å	Mo Kα radiation, λ = 0.71073 Å
c = 14.2916 (16) Å	µ = 0.11 mm^−1
α = 87.182 (2)°	T = 273 K
β = 88.023 (2)°	Block, colourless
γ = 80.578 (2)°	0.32 × 0.23 × 0.20 mm

Data collection

Bruker APEX area-detector diffractometer	2785 independent reflections
Radiation source: fine-focus sealed tube	2445 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.014
φ and ω scans	θmax = 25.0°, θmin = 2.0°
Absorption correction: multi-scan (SADABS; Bruker, 2000)	h = −4→6
Tmin = 0.969, Tmax = 0.978	k = −12→12
4155 measured reflections	l = −16→16

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.069	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.169	H-atom parameters constrained
S = 1.15	w = 1/[σ^2(Fo^2) + (0.0731P)^2 + 0.3726P] where P = (Fo^2 + 2Fc^2)/3
2785 reflections	(Δ/σ)max < 0.001
229 parameters	Δρmax = 0.23 e Å^−3
4 restraints	Δρmin = −0.20 e Å^−3

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	Occ. (<1)
O1	−0.1246 (4)	1.0444 (2)	0.77706 (15)	0.0621 (6)
O2	−0.1415 (5)	0.8294 (3)	0.50445 (15)	0.0777 (7)
O3	0.0059 (3)	0.82622 (19)	0.96331 (14)	0.0521 (5)
O4	0.3894 (3)	0.7265 (2)	0.99833 (15)	0.0604 (6)
O5	0.8511 (4)	0.4874 (3)	0.66161 (16)	0.0743 (7)
H5	0.7459	0.5509	0.6752	0.111*
O6	1.0023 (4)	0.5298 (3)	0.79567 (17)	0.0796 (7)
N1	−0.1292 (4)	0.9348 (2)	0.64116 (16)	0.0507 (6)
N2	0.1766 (5)	0.7543 (2)	0.59918 (15)	0.0526 (6)
N3	0.3591 (4)	0.8519 (2)	0.81369 (15)	0.0450 (5)
N4	0.5041 (4)	0.6996 (2)	0.71012 (16)	0.0518 (6)
C1	−0.0279 (5)	0.9562 (3)	0.72678 (19)	0.0451 (6)
C2	−0.0371 (6)	0.8378 (3)	0.5766 (2)	0.0564 (8)
C3	0.2886 (5)	0.7699 (3)	0.68106 (18)	0.0447 (6)
C4	0.1916 (5)	0.8642 (3)	0.74297 (18)	0.0427 (6)
C5	0.5383 (5)	0.7531 (3)	0.7905 (2)	0.0513 (7)
H5A	0.6741	0.7245	0.8272	0.062*
C6	0.3419 (5)	0.9260 (3)	0.89930 (19)	0.0497 (7)
H6A	0.2372	1.0118	0.8889	0.060*
H6B	0.5034	0.9433	0.9139	0.060*
C7	0.2412 (5)	0.8517 (3)	0.98124 (19)	0.0485 (7)
H7	0.2343	0.9049	1.0370	0.058*
C8	−0.0116 (6)	0.7026 (3)	1.0123 (3)	0.0731 (10)
H8A	−0.1271	0.6565	0.9827	0.088*
H8B	−0.0649	0.7172	1.0768	0.088*
C9	0.2359 (7)	0.6245 (5)	1.0077 (7)	0.065 (2)	0.759 (17)
H9A	0.2707	0.5688	1.0644	0.078*	0.759 (17)
H9B	0.2571	0.5681	0.9542	0.078*	0.759 (17)
C9'	0.2275 (17)	0.664 (2)	1.0606 (12)	0.067 (5)	0.241 (17)
H9'1	0.2199	0.7000	1.1226	0.080*	0.241 (17)
H9'2	0.2765	0.5678	1.0656	0.080*	0.241 (17)
C10	1.3987 (7)	0.3237 (4)	0.7628 (3)	0.0873 (12)
H10A	1.4119	0.3776	0.8127	0.105*
H10B	1.5211	0.2515	0.7509	0.105*
C11	1.2085 (6)	0.3495 (3)	0.7096 (2)	0.0695 (9)
H11	1.1959	0.2954	0.6599	0.083*
C12	1.0133 (5)	0.4639 (3)	0.7279 (2)	0.0539 (7)
C13	0.2871 (7)	0.6508 (3)	0.5350 (2)	0.0693 (9)
H13A	0.4423	0.6706	0.5115	0.104*
H13B	0.1805	0.6493	0.4836	0.104*
H13C	0.3105	0.5649	0.5679	0.104*
C14	−0.3516 (6)	1.0260 (4)	0.6145 (2)	0.0715 (9)
H14A	−0.3993	1.0880	0.6631	0.107*
H14B	−0.4807	0.9754	0.6059	0.107*
H14C	−0.3206	1.0746	0.5572	0.107*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0637 (13)	0.0575 (12)	0.0594 (13)	0.0109 (10)	−0.0033 (10)	−0.0151 (10)
O2	0.0814 (16)	0.0993 (18)	0.0498 (13)	0.0009 (14)	−0.0222 (12)	−0.0146 (12)
O3	0.0338 (10)	0.0583 (12)	0.0626 (13)	−0.0032 (8)	−0.0045 (9)	−0.0001 (10)
O4	0.0349 (10)	0.0802 (15)	0.0636 (13)	−0.0032 (10)	−0.0104 (9)	0.0089 (11)
O5	0.0660 (15)	0.0874 (18)	0.0625 (14)	0.0172 (12)	−0.0082 (12)	−0.0293 (12)
O6	0.0764 (16)	0.0865 (17)	0.0690 (15)	0.0183 (13)	−0.0147 (12)	−0.0305 (13)
N1	0.0496 (14)	0.0566 (14)	0.0439 (13)	−0.0013 (11)	−0.0066 (11)	−0.0020 (11)
N2	0.0608 (15)	0.0570 (14)	0.0385 (13)	−0.0017 (12)	−0.0028 (11)	−0.0113 (11)
N3	0.0425 (12)	0.0520 (13)	0.0405 (12)	−0.0055 (10)	0.0006 (10)	−0.0093 (10)
N4	0.0501 (14)	0.0581 (14)	0.0434 (13)	0.0038 (11)	0.0018 (10)	−0.0085 (11)
C1	0.0459 (15)	0.0450 (15)	0.0434 (15)	−0.0053 (12)	0.0043 (12)	−0.0025 (12)
C2	0.0603 (19)	0.0653 (19)	0.0436 (17)	−0.0085 (15)	−0.0065 (14)	−0.0045 (14)
C3	0.0471 (15)	0.0488 (15)	0.0373 (14)	−0.0042 (12)	0.0004 (11)	−0.0047 (11)
C4	0.0437 (14)	0.0464 (15)	0.0384 (14)	−0.0083 (12)	0.0007 (11)	−0.0046 (11)
C5	0.0437 (15)	0.0624 (18)	0.0449 (16)	0.0017 (13)	−0.0013 (12)	−0.0060 (13)
C6	0.0495 (16)	0.0547 (16)	0.0479 (16)	−0.0133 (13)	−0.0001 (13)	−0.0172 (13)
C7	0.0420 (15)	0.0624 (17)	0.0432 (15)	−0.0100 (13)	−0.0039 (12)	−0.0161 (13)
C8	0.0477 (18)	0.073 (2)	0.099 (3)	−0.0149 (16)	−0.0117 (18)	0.020 (2)
C9	0.047 (2)	0.060 (3)	0.088 (5)	−0.007 (2)	−0.012 (2)	0.006 (3)
C9'	0.073 (10)	0.064 (10)	0.059 (11)	−0.001 (7)	0.000 (8)	−0.009 (8)
C10	0.074 (2)	0.090 (3)	0.088 (3)	0.022 (2)	−0.007 (2)	−0.023 (2)
C11	0.070 (2)	0.066 (2)	0.067 (2)	0.0065 (17)	0.0001 (18)	−0.0171 (17)
C12	0.0528 (17)	0.0547 (17)	0.0524 (17)	−0.0025 (14)	0.0050 (14)	−0.0095 (14)
C13	0.090 (2)	0.069 (2)	0.0462 (18)	0.0015 (18)	0.0000 (16)	−0.0195 (15)
C14	0.063 (2)	0.081 (2)	0.063 (2)	0.0099 (17)	−0.0122 (16)	0.0023 (17)

Geometric parameters (Å, º)

O1—C1	1.216 (3)	C6—C7	1.501 (4)
O2—C2	1.213 (4)	C6—H6A	0.9700
O3—C7	1.403 (3)	C6—H6B	0.9700
O3—C8	1.418 (4)	C7—H7	0.9800
O4—C7	1.407 (3)	C8—C9	1.467 (5)
O4—C9'	1.437 (9)	C8—C9'	1.499 (9)
O4—C9	1.440 (5)	C8—H8A	0.9700
O5—C12	1.315 (4)	C8—H8B	0.9700
O5—H5	0.8200	C9—H9A	0.9700
O6—C12	1.197 (4)	C9—H9B	0.9700
N1—C2	1.403 (4)	C9'—H9'1	0.9700
N1—C1	1.404 (3)	C9'—H9'2	0.9700
N1—C14	1.462 (4)	C10—C11	1.304 (5)
N2—C3	1.371 (3)	C10—H10A	0.9300
N2—C2	1.375 (4)	C10—H10B	0.9300
N2—C13	1.469 (4)	C11—C12	1.476 (4)
N3—C5	1.334 (4)	C11—H11	0.9300
N3—C4	1.383 (3)	C13—H13A	0.9600
N3—C6	1.458 (3)	C13—H13B	0.9600
N4—C5	1.327 (4)	C13—H13C	0.9600
N4—C3	1.353 (4)	C14—H14A	0.9600
C1—C4	1.424 (4)	C14—H14B	0.9600
C3—C4	1.365 (4)	C14—H14C	0.9600
C5—H5A	0.9300
C7—O3—C8	105.0 (2)	O3—C8—C9'	104.9 (6)
C7—O4—C9'	99.5 (7)	O3—C8—H8A	110.7
C7—O4—C9	108.9 (2)	C9—C8—H8A	110.7
C12—O5—H5	109.5	C9'—C8—H8A	136.8
C2—N1—C1	127.3 (2)	O3—C8—H8B	110.7
C2—N1—C14	116.0 (2)	C9—C8—H8B	110.7
C1—N1—C14	116.7 (2)	C9'—C8—H8B	79.6
C3—N2—C2	119.6 (2)	H8A—C8—H8B	108.8
C3—N2—C13	120.2 (3)	O4—C9—C8	102.9 (3)
C2—N2—C13	120.2 (2)	O4—C9—H9A	111.2
C5—N3—C4	106.2 (2)	C8—C9—H9A	111.2
C5—N3—C6	125.9 (2)	O4—C9—H9B	111.2
C4—N3—C6	127.8 (2)	C8—C9—H9B	111.2
C5—N4—C3	103.6 (2)	H9A—C9—H9B	109.1
O1—C1—N1	121.4 (3)	O4—C9'—C8	101.4 (6)
O1—C1—C4	127.5 (3)	O4—C9'—H9'1	111.5
N1—C1—C4	111.2 (2)	C8—C9'—H9'1	111.5
O2—C2—N2	122.2 (3)	O4—C9'—H9'2	111.5
O2—C2—N1	121.2 (3)	C8—C9'—H9'2	111.5
N2—C2—N1	116.7 (2)	H9'1—C9'—H9'2	109.3
N4—C3—C4	111.8 (2)	C11—C10—H10A	120.0
N4—C3—N2	126.0 (2)	C11—C10—H10B	120.0
C4—C3—N2	122.2 (2)	H10A—C10—H10B	120.0
C3—C4—N3	104.9 (2)	C10—C11—C12	120.4 (3)
C3—C4—C1	123.1 (2)	C10—C11—H11	119.8
N3—C4—C1	131.8 (2)	C12—C11—H11	119.8
N4—C5—N3	113.5 (3)	O6—C12—O5	122.8 (3)
N4—C5—H5A	123.3	O6—C12—C11	124.1 (3)
N3—C5—H5A	123.3	O5—C12—C11	113.1 (3)
N3—C6—C7	112.4 (2)	N2—C13—H13A	109.5
N3—C6—H6A	109.1	N2—C13—H13B	109.5
C7—C6—H6A	109.1	H13A—C13—H13B	109.5
N3—C6—H6B	109.1	N2—C13—H13C	109.5
C7—C6—H6B	109.1	H13A—C13—H13C	109.5
H6A—C6—H6B	107.9	H13B—C13—H13C	109.5
O3—C7—O4	106.9 (2)	N1—C14—H14A	109.5
O3—C7—C6	110.9 (2)	N1—C14—H14B	109.5
O4—C7—C6	110.6 (2)	H14A—C14—H14B	109.5
O3—C7—H7	109.5	N1—C14—H14C	109.5
O4—C7—H7	109.5	H14A—C14—H14C	109.5
C6—C7—H7	109.5	H14B—C14—H14C	109.5
O3—C8—C9	105.4 (3)
C2—N1—C1—O1	179.7 (3)	O1—C1—C4—C3	−178.6 (3)
C14—N1—C1—O1	1.7 (4)	N1—C1—C4—C3	1.0 (4)
C2—N1—C1—C4	0.0 (4)	O1—C1—C4—N3	−3.8 (5)
C14—N1—C1—C4	−178.0 (3)	N1—C1—C4—N3	175.9 (3)
C3—N2—C2—O2	179.0 (3)	C3—N4—C5—N3	0.0 (3)
C13—N2—C2—O2	0.3 (5)	C4—N3—C5—N4	0.4 (3)
C3—N2—C2—N1	−0.7 (4)	C6—N3—C5—N4	177.6 (2)
C13—N2—C2—N1	−179.4 (3)	C5—N3—C6—C7	−81.2 (3)
C1—N1—C2—O2	−179.8 (3)	C4—N3—C6—C7	95.5 (3)
C14—N1—C2—O2	−1.9 (4)	C8—O3—C7—O4	27.3 (3)
C1—N1—C2—N2	−0.1 (4)	C8—O3—C7—C6	147.9 (3)
C14—N1—C2—N2	177.8 (3)	C9'—O4—C7—O3	−45.4 (9)
C5—N4—C3—C4	−0.5 (3)	C9—O4—C7—O3	−10.3 (5)
C5—N4—C3—N2	178.2 (3)	C9'—O4—C7—C6	−166.3 (9)
C2—N2—C3—N4	−176.8 (3)	C9—O4—C7—C6	−131.2 (5)
C13—N2—C3—N4	1.9 (4)	N3—C6—C7—O3	−59.6 (3)
C2—N2—C3—C4	1.8 (4)	N3—C6—C7—O4	58.9 (3)
C13—N2—C3—C4	−179.6 (3)	C7—O3—C8—C9	−33.7 (5)
N4—C3—C4—N3	0.7 (3)	C7—O3—C8—C9'	1.7 (10)
N2—C3—C4—N3	−178.0 (2)	C7—O4—C9—C8	−10.1 (7)
N4—C3—C4—C1	176.7 (2)	O3—C8—C9—O4	26.7 (6)
N2—C3—C4—C1	−2.0 (4)	C7—O4—C9'—C8	43.9 (14)
C5—N3—C4—C3	−0.6 (3)	O3—C8—C9'—O4	−28.8 (15)
C6—N3—C4—C3	−177.8 (2)	C10—C11—C12—O6	−8.0 (6)
C5—N3—C4—C1	−176.2 (3)	C10—C11—C12—O5	171.6 (4)
C6—N3—C4—C1	6.6 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···N4	0.82	1.92	2.736 (3)	178
C5—H5A···O6	0.93	2.50	3.131 (4)	125
C6—H6A···O1	0.97	2.58	3.202 (3)	122
C13—H13B···O5^i	0.96	2.58	3.365 (4)	140

Symmetry code: (i) −x+1, −y+1, −z+1.