Theophylline–gentisic acid (1/1)

Aitipamula, S.; Chow, P.S.; Tan, R.B.H.

doi:10.1107/S1600536809031031

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 9| September 2009| Pages o2126-o2127

doi:10.1107/S1600536809031031

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Theophylline–gentisic acid (1/1)

Srinivasulu Aitipamula,^a ^* Pui Shan Chow ^a and Reginald B. H. Tan ^a,^b ‡

^aInstitute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road, Jurong Island, 627833 Singapore, and ^bDepartment of Chemical & Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, 117576 Singapore
^*Correspondence e-mail: srinivasulu_aitipamula@ices.a-star.edu.sg

(Received 9 July 2009; accepted 5 August 2009; online 8 August 2009)

In the title 1:1 cocrystal, C₇H₈N₄O₂·C₇H₆O₄, the anti-asthmatic drug theophylline (systematic name: 1,3-dimethyl-7H-purine-2,6-dione) and a non-steroidal anti-inflammatory drug, gentisic acid (systematic name: 2,5-dihydroxybenzoic acid) crystallize together, forming two-dimensional hydrogen-bonded sheets involving N—H⋯O and O—H⋯N hydrogen bonds. The overall crystal packing features π–π stacking interactions [centroid–centroid distance = 3.348 (1) Å]. The cocrystal described herein belongs to the class of pharmaceutical cocrystals involving two active pharmaceutical ingredients which has been relatively unexplored to date.

Related literature

For characterization of the title cocrystal by Fourier Transform Infrared Spectroscopy, see: Childs et al. (2007 ). For a detailed study on theophylline monohydrate see: Khankari & Grant (1995 ). For recent cocrystals of the theophylline, see: Trask et al. (2006 ); Lu et al. (2008 ). For recent cocrystals involving two or more active pharmaceutical ingredients, see: Aitipamula et al. (2009 ); Bhatt et al. (2009 ); Vishweshwar et al. (2005 ); Caira (2007 ); Childs (2007 ); Childs et al. (2007); Fleischman et al. (2003 ); Shan & Zaworotko (2008 ).

Experimental

Crystal data

C₇H₈N₄O₂·C₇H₆O₄
M_r = 334.29
Triclinic, $[P \overline 1]$
a = 7.0989 (14) Å
b = 8.0543 (16) Å
c = 13.034 (3) Å
α = 86.08 (3)°
β = 81.27 (3)°
γ = 74.14 (3)°
V = 708.3 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 110 K
0.24 × 0.22 × 0.13 mm

Data collection

Rigaku Saturn CCD area-deterctor diffractometer
Absorption correction: multi-scan (Blessing, 1995 ) T_min = 0.971, T_max = 0.984
10245 measured reflections
3478 independent reflections
3302 reflections with I > 2σ(I)
R_int = 0.021

Refinement

R[F² > 2σ(F²)] = 0.046
wR(F²) = 0.127
S = 1.08
3478 reflections
235 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.36 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1ⁱ	0.95 (2)	1.85 (2)	2.8000 (16)	177.2 (17)
O6—H6⋯O2	0.92 (2)	1.83 (2)	2.7478 (14)	173.9 (18)
O5—H5⋯O3ⁱⁱ	0.92 (2)	2.24 (2)	2.8503 (16)	122.6 (17)
O5—H5⋯O3	0.92 (2)	1.87 (2)	2.6617 (15)	142.3 (19)
O4—H4A⋯N2ⁱⁱⁱ	0.99 (3)	1.68 (3)	2.6596 (16)	171 (2)
Symmetry codes: (i) -x+1, -y+1, -z+2; (ii) -x, -y+1, -z; (iii) -x, -y+2, -z+1.

Data collection: CrystalClear (Rigaku, 2008 ); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001 ); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809031031/pb2002sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809031031/pb2002Isup2.hkl

checkCIF report

Comment top

Theophylline (1,3-dimethyl-7H-purine-2,6-dione) is a drug used in the treatment of respiratory diseases such as asthma. It has been reported that theophylline forms a monohydrate as a function of relative humidity and poses challenges in the formultion stages (Khankari and Grant, 1995). Using the cocrystallization as an aid to improve the physical stability, several theophylline cocrystals with dicarboxylic acids have been prepared and studied for their physical stability (Trask et al., 2006, Childs et al., 2007). Cocrystals which involve two or more active pharmaceutical ingredients (APIs) are relatively unexplored solid forms of APIs which have potential relevance in the context of combination drugs for pharmaceutical drug development (Aitipamula et al., 2009, Bhatt et al., 2009). We have recently reported trimorphs of a pharmaceutical cocrystal involving two APIs, namely ethenzamide (2-ethoxybenzamide), and gentisic acid and shown that the dissolution rate of the cocrystal polymorphs improved by two times when compared to the parent ethenzamide (Aitipamula et al., 2009). In the present paper, we report a 1:1 cocrystal of theophylline with gentisic acid and analyzed the hydrogen bonding.

The crystal structure of the title cocrystal contains each one molecule of theophylline and gentisic acid in the asymmetric unit (Fig. 1). In the structure, two molecules of theophylline which are related by an inversion centre form a dimer involving N—H···O hydrogen bonds (Table 1). Hydroxy atom O5 of the gentisic acid acts as an intramolecular O—H···O hydrogen bond donor to the carbonyl of carboxyl group and also involves in a bifurcated O—H···O hydrogen bond to atom O3 at (-x, -y + 1, -z) (Fig. 2). Hydroxy atom O4 acts as a hydrogen bond donor to atom N2 of the theophylline at (-x, -y + 2, -z + 1), thus generating chains of alternating dimers of theophylline and gentisic acid running parallel to [21–1]. In addition, there is a C—H···O hydrogen bond between C4 of the theophylline and O5 of the gentisic acid. The 5-hydroxyl group (O6) of the gentisic acid acts as a hydrogen bond donor to atom O2 of the theophylline at (1 + x, -1 + y, 1 + z), thus generating a hydrogen bonded sheet parallel to the (21–1) plane (Fig. 2). The crystal structure is further stabilized by a π-π interaction involving pyrimidine ring of theophylline and phenyl ring of gentisic acid: Cg1···Cg2 (x, y, z) = 3.348 (1) Å, where Cg1 and Cg2 denote the centroids of N3/C2/N4/C1/C5/C3 of the theophylline and C8—C13 of the gentisic acid, respectively (Fig. 3).

Zaworotko and co-workers distinguished between two types of hydrogen bonding possibilities in cocrystal structures depending on whether the interacting complementary functional groups are the same or different (Fleischman et al., 2003). In type I, an API forms hydrogen bonds like in pure structure, e.g. dimers, catemers, etc. (homosynthons) and such units are connected by cocrystal former spacer, and in type II, both the API and cocrystal former involve in heterosynthon formation. The title cocrystal belongs to type I, in which both the theophylline and gentisic acid molecules form dimers involving homosynthons, and such dimers are connected via O—H···O hydrogen bonds (Fig. 2).

Related literature top

For characterization of the title cocrystal by Fourier Transform Infrared Spectroscopy, see: Childs et al. (2007). For a detailed study on the theophylline monohydrate see: Khankari & Grant (1995). For recent cocrystals of the theophylline, see: Trask et al. (2006); Lu et al. (2008). For recent cocrystals involving two or more active pharmaceutical ingredients, see: Aitipamula et al. (2009); Bhatt et al. (2009); Vishweshwar et al. (2005); Caira (2007); Childs (2007); Childs et al. (2007); Fleischman et al. (2003); Shan & Zaworotko (2008).

Experimental top

Equimolar quantities of theophylline and gentisic acid (purchased from Aldrich) were dissolved in methanol upon heating. The solution was set aside to crystallize providing crystals that belong to a 1:1 cocrystal. Crystal suitable for single-crystal X-ray diffraction were selected directly from the sample as prepared.

Computing details top

Data collection: CrystalClear (Rigaku, 2008); cell refinement: CrystalClear (Rigaku, 2008); data reduction: CrystalClear (Rigaku, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top

	Fig. 1. The molecular structures of theophylline and gentisic acid, with atom labels and 50% probability displacement ellipsoids for non-H atoms.
	Fig. 2. Part of the crystal structure of the title cocrystal, showing formation of a hydrogen bonded sheet in the (21–1) plane.
	Fig. 3. Part of the crystal structure of the title cocrystal, showing the π-π stacking interaction between two layers.

Theophylline–gentisic acid (1/1) top

Crystal data top

C₇H₈N₄O₂·C₇H₆O₄	Z = 2
M_r = 334.29	F(000) = 348
Triclinic, P1	D_x = 1.567 Mg m⁻³
Hall symbol: -P 1	Melting point: 513 K
a = 7.0989 (14) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.0543 (16) Å	Cell parameters from 2156 reflections
c = 13.034 (3) Å	θ = 2.6–31.0°
α = 86.08 (3)°	µ = 0.13 mm⁻¹
β = 81.27 (3)°	T = 110 K
γ = 74.14 (3)°	Needle, yellow
V = 708.3 (3) Å³	0.24 × 0.22 × 0.13 mm

Data collection top

Rigaku Saturn CCD area-deterctor diffractometer	3478 independent reflections
Radiation source: fine-focus sealed tube	3302 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.021
ω scans	θ_max = 28.3°, θ_min = 2.6°
Absorption correction: multi-scan (Blessing, 1995)	h = −9→7
T_min = 0.971, T_max = 0.984	k = −10→10
10245 measured reflections	l = −17→17

Refinement top

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)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.127	H atoms treated by a mixture of independent and constrained refinement
S = 1.08	w = 1/[σ²(F_o²) + (0.0749P)² + 0.2093P] where P = (F_o² + 2F_c²)/3
3478 reflections	(Δ/σ)_max < 0.001
235 parameters	Δρ_max = 0.36 e Å⁻³
0 restraints	Δρ_min = −0.33 e Å⁻³
0 constraints

Crystal data top

C₇H₈N₄O₂·C₇H₆O₄	γ = 74.14 (3)°
M_r = 334.29	V = 708.3 (3) Å³
Triclinic, P1	Z = 2
a = 7.0989 (14) Å	Mo Kα radiation
b = 8.0543 (16) Å	µ = 0.13 mm⁻¹
c = 13.034 (3) Å	T = 110 K
α = 86.08 (3)°	0.24 × 0.22 × 0.13 mm
β = 81.27 (3)°

Data collection top

Rigaku Saturn CCD area-deterctor diffractometer	3478 independent reflections
Absorption correction: multi-scan (Blessing, 1995)	3302 reflections with I > 2σ(I)
T_min = 0.971, T_max = 0.984	R_int = 0.021
10245 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.046	0 restraints
wR(F²) = 0.127	H atoms treated by a mixture of independent and constrained refinement
S = 1.08	Δρ_max = 0.36 e Å⁻³
3478 reflections	Δρ_min = −0.33 e Å⁻³
235 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.

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 (Å²) top

	x	y	z	U_iso*/U_eq
O5	0.17595 (15)	0.25838 (12)	0.08234 (7)	0.0256 (2)
O3	0.01074 (15)	0.59680 (12)	0.09419 (7)	0.0271 (2)
O4	0.00547 (15)	0.72663 (12)	0.24149 (7)	0.0271 (2)
O6	0.30321 (16)	0.26347 (12)	0.48941 (7)	0.0294 (2)
C8	0.14294 (17)	0.42610 (14)	0.23596 (9)	0.0181 (2)
C13	0.17542 (18)	0.42529 (15)	0.33978 (9)	0.0199 (2)
H13	0.1353	0.5278	0.3757	0.024*
C14	0.04741 (18)	0.58978 (15)	0.18344 (9)	0.0202 (2)
C10	0.29140 (18)	0.11806 (15)	0.23356 (10)	0.0217 (3)
H10	0.3297	0.0145	0.1988	0.026*
C11	0.32413 (19)	0.11938 (15)	0.33503 (10)	0.0220 (3)
H11	0.3851	0.0169	0.3679	0.026*
C9	0.20119 (18)	0.27073 (15)	0.18233 (9)	0.0195 (2)
C12	0.26646 (19)	0.27340 (15)	0.38900 (9)	0.0213 (2)
O2	0.28704 (13)	0.57656 (11)	0.56702 (7)	0.0221 (2)
O1	0.50287 (14)	0.39024 (11)	0.87972 (7)	0.0244 (2)
N3	0.23273 (15)	0.78018 (12)	0.68830 (8)	0.0181 (2)
N4	0.39267 (15)	0.48739 (12)	0.72414 (8)	0.0187 (2)
N2	0.19067 (16)	0.97032 (13)	0.83320 (8)	0.0207 (2)
C1	0.41682 (17)	0.51168 (15)	0.82663 (9)	0.0186 (2)
C2	0.30251 (17)	0.61332 (15)	0.65492 (9)	0.0176 (2)
C5	0.33462 (17)	0.68618 (15)	0.85505 (9)	0.0183 (2)
C3	0.24950 (17)	0.81358 (15)	0.78778 (9)	0.0177 (2)
N1	0.32986 (16)	0.76825 (13)	0.94525 (8)	0.0206 (2)
C6	0.1586 (2)	0.91951 (15)	0.61444 (9)	0.0232 (3)
H6A	0.0502	1.0050	0.6495	0.035*
H6B	0.1146	0.8733	0.5593	0.035*
H6C	0.2626	0.9716	0.5862	0.035*
C7	0.4852 (2)	0.31464 (15)	0.68265 (10)	0.0251 (3)
H7A	0.3879	0.2508	0.6880	0.038*
H7B	0.5893	0.2551	0.7217	0.038*
H7C	0.5391	0.3250	0.6111	0.038*
C4	0.24348 (19)	0.93614 (15)	0.92880 (9)	0.0225 (3)
H4	0.2224	1.0198	0.9781	0.027*
H5	0.111 (3)	0.366 (3)	0.0573 (16)	0.048 (6)*
H6	0.289 (3)	0.372 (3)	0.5139 (16)	0.046 (5)*
H4A	−0.063 (4)	0.834 (3)	0.2064 (19)	0.069 (7)*
H1	0.383 (3)	0.714 (3)	1.0054 (15)	0.040 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O5	0.0382 (5)	0.0190 (4)	0.0179 (4)	−0.0011 (4)	−0.0094 (4)	−0.0033 (3)
O3	0.0373 (5)	0.0208 (4)	0.0222 (4)	−0.0018 (4)	−0.0123 (4)	−0.0001 (3)
O4	0.0395 (5)	0.0152 (4)	0.0233 (4)	0.0025 (4)	−0.0105 (4)	−0.0035 (3)
O6	0.0512 (6)	0.0186 (4)	0.0205 (5)	−0.0070 (4)	−0.0162 (4)	0.0000 (3)
C8	0.0198 (5)	0.0149 (5)	0.0192 (5)	−0.0026 (4)	−0.0049 (4)	−0.0002 (4)
C13	0.0244 (6)	0.0155 (5)	0.0195 (5)	−0.0034 (4)	−0.0053 (4)	−0.0021 (4)
C14	0.0229 (5)	0.0157 (5)	0.0212 (5)	−0.0024 (4)	−0.0045 (4)	−0.0017 (4)
C10	0.0277 (6)	0.0142 (5)	0.0221 (6)	−0.0019 (4)	−0.0052 (5)	−0.0035 (4)
C11	0.0278 (6)	0.0157 (5)	0.0218 (6)	−0.0030 (4)	−0.0071 (5)	0.0006 (4)
C9	0.0222 (5)	0.0190 (5)	0.0171 (5)	−0.0037 (4)	−0.0047 (4)	−0.0028 (4)
C12	0.0285 (6)	0.0189 (5)	0.0181 (5)	−0.0066 (5)	−0.0073 (4)	−0.0006 (4)
O2	0.0307 (5)	0.0190 (4)	0.0158 (4)	−0.0032 (3)	−0.0069 (3)	−0.0023 (3)
O1	0.0324 (5)	0.0177 (4)	0.0206 (4)	−0.0001 (3)	−0.0089 (4)	0.0008 (3)
N3	0.0235 (5)	0.0142 (4)	0.0157 (5)	−0.0018 (4)	−0.0061 (4)	−0.0003 (3)
N4	0.0251 (5)	0.0134 (4)	0.0163 (5)	−0.0011 (4)	−0.0061 (4)	−0.0016 (4)
N2	0.0265 (5)	0.0158 (5)	0.0185 (5)	−0.0018 (4)	−0.0055 (4)	−0.0027 (4)
C1	0.0216 (5)	0.0174 (5)	0.0164 (5)	−0.0041 (4)	−0.0033 (4)	−0.0007 (4)
C2	0.0204 (5)	0.0156 (5)	0.0160 (5)	−0.0027 (4)	−0.0034 (4)	−0.0008 (4)
C5	0.0224 (5)	0.0168 (5)	0.0150 (5)	−0.0029 (4)	−0.0047 (4)	−0.0013 (4)
C3	0.0206 (5)	0.0160 (5)	0.0163 (5)	−0.0034 (4)	−0.0039 (4)	−0.0016 (4)
N1	0.0282 (5)	0.0170 (5)	0.0152 (5)	−0.0016 (4)	−0.0060 (4)	−0.0018 (4)
C6	0.0318 (6)	0.0166 (5)	0.0203 (5)	−0.0023 (5)	−0.0092 (5)	0.0020 (4)
C7	0.0359 (7)	0.0131 (5)	0.0236 (6)	0.0010 (5)	−0.0083 (5)	−0.0040 (4)
C4	0.0288 (6)	0.0171 (5)	0.0196 (6)	−0.0010 (4)	−0.0054 (5)	−0.0039 (4)

Geometric parameters (Å, º) top

O5—C9	1.3561 (14)	N3—C2	1.3754 (15)
O5—H5	0.92 (2)	N3—C6	1.4649 (15)
O3—C14	1.2245 (15)	N4—C2	1.3957 (15)
O4—C14	1.3199 (15)	N4—C1	1.4055 (14)
O4—H4A	0.99 (3)	N4—C7	1.4682 (15)
O6—C12	1.3658 (14)	N2—C4	1.3444 (15)
O6—H6	0.92 (2)	N2—C3	1.3629 (15)
C8—C9	1.4052 (16)	C1—C5	1.4179 (16)
C8—C13	1.4060 (16)	C5—C3	1.3733 (16)
C8—C14	1.4817 (17)	C5—N1	1.3792 (14)
C13—C12	1.3828 (17)	N1—C4	1.3408 (16)
C13—H13	0.9300	N1—H1	0.95 (2)
C10—C11	1.3783 (16)	C6—H6A	0.9600
C10—C9	1.3983 (17)	C6—H6B	0.9600
C10—H10	0.9300	C6—H6C	0.9600
C11—C12	1.3984 (17)	C7—H7A	0.9600
C11—H11	0.9300	C7—H7B	0.9600
O2—C2	1.2306 (14)	C7—H7C	0.9600
O1—C1	1.2321 (15)	C4—H4	0.9300
N3—C3	1.3710 (14)

C9—O5—H5	109.4 (13)	O1—C1—N4	120.78 (11)
C14—O4—H4A	113.1 (14)	O1—C1—C5	127.75 (11)
C12—O6—H6	111.2 (13)	N4—C1—C5	111.46 (10)
C9—C8—C13	119.63 (11)	O2—C2—N3	121.22 (11)
C9—C8—C14	120.17 (11)	O2—C2—N4	121.22 (10)
C13—C8—C14	120.20 (11)	N3—C2—N4	117.56 (10)
C12—C13—C8	120.56 (11)	C3—C5—N1	105.65 (10)
C12—C13—H13	119.7	C3—C5—C1	122.98 (10)
C8—C13—H13	119.7	N1—C5—C1	131.26 (11)
O3—C14—O4	123.21 (11)	N2—C3—N3	126.79 (11)
O3—C14—C8	122.79 (11)	N2—C3—C5	110.99 (10)
O4—C14—C8	114.00 (10)	N3—C3—C5	122.21 (11)
C11—C10—C9	120.70 (11)	C4—N1—C5	106.66 (10)
C11—C10—H10	119.7	C4—N1—H1	128.1 (12)
C9—C10—H10	119.7	C5—N1—H1	125.2 (12)
C10—C11—C12	120.60 (11)	N3—C6—H6A	109.5
C10—C11—H11	119.7	N3—C6—H6B	109.5
C12—C11—H11	119.7	H6A—C6—H6B	109.5
O5—C9—C10	116.96 (10)	N3—C6—H6C	109.5
O5—C9—C8	123.97 (11)	H6A—C6—H6C	109.5
C10—C9—C8	119.07 (11)	H6B—C6—H6C	109.5
O6—C12—C13	123.61 (11)	N4—C7—H7A	109.5
O6—C12—C11	116.95 (11)	N4—C7—H7B	109.5
C13—C12—C11	119.44 (11)	H7A—C7—H7B	109.5
C3—N3—C2	118.91 (10)	N4—C7—H7C	109.5
C3—N3—C6	121.52 (10)	H7A—C7—H7C	109.5
C2—N3—C6	119.35 (10)	H7B—C7—H7C	109.5
C2—N4—C1	126.83 (10)	N1—C4—N2	112.63 (11)
C2—N4—C7	116.29 (10)	N1—C4—H4	123.7
C1—N4—C7	116.70 (10)	N2—C4—H4	123.7
C4—N2—C3	104.07 (10)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1ⁱ	0.95 (2)	1.85 (2)	2.8000 (16)	177.2 (17)
O6—H6···O2	0.92 (2)	1.83 (2)	2.7478 (14)	173.9 (18)
O5—H5···O3ⁱⁱ	0.92 (2)	2.24 (2)	2.8503 (16)	122.6 (17)
O5—H5···O3	0.92 (2)	1.87 (2)	2.6617 (15)	142.3 (19)
O4—H4A···N2ⁱⁱⁱ	0.99 (3)	1.68 (3)	2.6596 (16)	171 (2)

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

Experimental details

Crystal data
Chemical formula	C₇H₈N₄O₂·C₇H₆O₄
M_r	334.29
Crystal system, space group	Triclinic, P1
Temperature (K)	110
a, b, c (Å)	7.0989 (14), 8.0543 (16), 13.034 (3)
α, β, γ (°)	86.08 (3), 81.27 (3), 74.14 (3)
V (Å³)	708.3 (3)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.13
Crystal size (mm)	0.24 × 0.22 × 0.13

Data collection
Diffractometer	Rigaku Saturn CCD area-deterctor diffractometer
Absorption correction	Multi-scan (Blessing, 1995)
T_min, T_max	0.971, 0.984
No. of measured, independent and observed [I > 2σ(I)] reflections	10245, 3478, 3302
R_int	0.021
(sin θ/λ)_max (Å⁻¹)	0.667

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.127, 1.08
No. of reflections	3478
No. of parameters	235
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.36, −0.33

Computer programs: CrystalClear (Rigaku, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), X-SEED (Barbour, 2001), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1ⁱ	0.95 (2)	1.85 (2)	2.8000 (16)	177.2 (17)
O6—H6···O2	0.92 (2)	1.83 (2)	2.7478 (14)	173.9 (18)
O5—H5···O3ⁱⁱ	0.92 (2)	2.24 (2)	2.8503 (16)	122.6 (17)
O5—H5···O3	0.92 (2)	1.87 (2)	2.6617 (15)	142.3 (19)
O4—H4A···N2ⁱⁱⁱ	0.99 (3)	1.68 (3)	2.6596 (16)	171 (2)

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

Footnotes

‡Additional contact author, e-mail: reginald_tan@ices.a-star.edu.sg.

Acknowledgements

This work was supported by the Institute of Chemical and Engineering Sciences of A*STAR (Agency for Science, Technology and Research), Singapore.

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