Crystal structure of 6,7-dihy­droxy-6,7-di­hydro-3H-imidazo[1,2-a]purin-9(5H)-one

Guo, W.; Li, C.-X.; Lv, J.; Wang, J.

doi:10.1107/S2056989016009087

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 72| Part 8| August 2016| Pages 1147-1149

https://doi.org/10.1107/S2056989016009087

Open

access

Crystal structure of 6,7-dihydroxy-6,7-dihydro-3H-imidazo[1,2-a]purin-9(5H)-one

Wei Guo,^a Cheng-Xun Li,^a Jie Lv ^a and Jing Wang ^a ^*

^aSchool of Pharmacy, Hebei Medical University, Shijiazhuang 050017, People's Republic of China
^*Correspondence e-mail: jingwang@home.ipe.ac.cn

Edited by D.-J. Xu, Zhejiang University (Yuquan Campus), China (Received 4 May 2016; accepted 6 June 2016; online 19 July 2016)

The title purine derivative, C₇H₇N₅O₃, is an adduct of guanine with glyoxal. In the molecule, the dihydroimidazole ring adopts a twisted conformation on the C—C bond, and the two hydroxyl groups lie on opposite sides of the mean plane of the ring. In the crystal, the molecules are linked by N—H⋯O, O—H⋯N and N—H⋯N hydrogen bonds forming a three-dimensional framework. The crystal packing is reinforced by C—H⋯O hydrogen bonds and by offset π–π stacking of the purine ring systems of inversion related molecules [intercentroid distance = 3.4839 (12) Å].

Keywords: crystal structure; purine derivative; hydrogen bonding; framework structure.

CCDC reference: 1469976

1. Chemical context

Purine are essential ingredients of various compounds, for example two of the five bases in nucleic acids, adenine and guanine, are purines. Purine derivatives have been developed as inhibitors of cyclin-dependent kinase (Sausville, 2002 ), and as antiparasitic (Braga et al., 2007 ; Yadav et al., 2004 ), antitumor (Prekupec et al., 2003 ; Trávníček et al., 2001 $[Trávníček, Z., Maloň, M., Šindelář, Z., Doležal, K., Rolč\?ík, J., Kryštof, V., Strnad, M. & Marek, J. (2001). J. Inorg. Biochem. 84, 23-32.]$ ), antiradical (Klanicová et al., 2010 ) and antiviral (Manikowski et al., 2005 ) drugs. The synthesis and the cancerostatic and antiviral activities of the title compound were reported on many years ago (Shapiro et al., 1969 ). Its crystal structure has not been reported to date, and as the conformation of a biologically active molecule is crucial to its activity we undertook the structure analysis of the title compound, which we report on herein.

2. Structural commentary

The molecular structure of title compound is depicted in Fig. 1. The C1—O1 bond length of 1.220 (2) Å shows typical double-bond character, and is coplanar with the purine moiety for their aromatic nature. The non-aromatic five-membered ring (N1/C7/C6/N5/C2) adopts a twisted conformation on the C6—C7 bond. The two hydroxyl groups lie on opposite sides of the ring mean plane with an O2—C7—C6—O3 torsion angle of 114.8 (2)°.

Figure 1
The molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

3. Supramolecular features

In the crystal, molecules are also linked via O—H⋯N and N—H⋯O hydrogen bonds, forming layers lying parallel to the ab plane (Table 1 and Fig. 2). The layers are linked by N—H⋯O hydrogen bonds, forming a three-dimensional framework (Table 1 and Fig. 3). Within the framework there are also C—H⋯O hydrogen bonds present (Table 1), and inversion-related molecules are linked by offset π–π interactions involving the five-membered ring and the six-membered ring of the purine moieties [Cg2⋯Cg3ⁱ = 3.4839 (12) Å, interplanar distance = 3.311 (1) Å, slippage = 1.112 Å; Cg2 and Cg3 are the centroids of the N3/C4/C3/N4/C5 and N1/C1/C4/C3/N2/C2 rings, respectively; symmetry code: (i) −x, −y, −z + 2].

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯N2ⁱ	0.82	2.03	2.850 (2)	178
O3—H3⋯N2ⁱⁱ	0.82	2.21	2.947 (2)	150
N4—H4⋯O2ⁱⁱⁱ	0.86	1.95	2.791 (2)	167
N5—H5⋯N3^iv	0.86	2.00	2.837 (2)	166
C5—H5A⋯O3^v	0.93	2.50	3.133 (8)	126
C7—H7⋯O1^vi	0.98	2.51	3.449 (2)	161
Symmetry codes: (i) -x+1, -y+1, -z+2; (ii) -x, -y+1, -z+2; (iii) x, y, z+1; (iv) x, y+1, z; (v) -x, -y, -z+2; (vi) -x, -y, -z+1.

Figure 2
A view along the c axis of the crystal packing of the title compound. The hydrogen bonds are shown as dashed lines (see Table 1

Figure 3
A view along the b axis of the crystal packing of the title compound. The hydrogen bonds are shown as dashed lines (see Table 1

4. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.37, update May 2016; Groom et al., 2016 ) for 1,9-dihydro-6H-6-one as substructure, gave 61 hits. Many of these compounds concern guanine and guaninium and some metal complexes, but none involve a fused third ring. The structure of the title compound has not been reported previously.

5. Synthesis and crystallization

The title compound was synthesized according to a literature method (Dey & Garner, 2000 ): An aqueous solution (1 l) of glyoxal monohydrate (8.71 g, 0.18 mol), guanine (1.55g, 0.01 mol) and a small amount of acetic acid was stirred for 24 h at 333 K. Then the excess water was removed by rotary evaporation and 250 ml of THF was added under stirring. The white suspension that formed was suction-filtered and washed with THF. The product was obtained as white powder after drying at 313 K. Colourless block-shaped crystals suitable for X-ray diffraction were obtained by recrystallization of the powder in a DMF/ethanol/water (v/v/v = 1/2/2) medium.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All of the H atoms were positioned with idealized geometry and refined as riding: O—H = 0.82 Å, N—H = 0.86 Å and C—H = 0.93–0.98 Å, with U_iso(H) = 1.2U_eq(C) and 1.5U_eq(O,N).

Table 2
Experimental details

Crystal data
Chemical formula	C₇H₇N₅O₃
M_r	209.18
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	295
a, b, c (Å)	6.8925 (4), 7.6352 (4), 8.0605 (6)
α, β, γ (°)	95.063 (5), 105.135 (6), 107.647 (5)
V (Å³)	383.69 (4)
Z	2
Radiation type	Cu Kα
μ (mm⁻¹)	1.26
Crystal size (mm)	0.20 × 0.18 × 0.16

Data collection
Diffractometer	Agilent Xcalibur, Eos, Gemini
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2012 )
T_min, T_max	0.52, 0.82
No. of measured, independent and observed [I > 2σ(I)] reflections	2506, 1499, 1335
R_int	0.033
(sin θ/λ)_max (Å⁻¹)	0.622

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.057, 0.180, 1.00
No. of reflections	1499
No. of parameters	138
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.67, −0.40
Computer programs: CrysAlis PRO (Agilent, 2012), SHELXS97, SHELXL97 and SHELXTL (Sheldrick, 2008 ) and PLATON (Spek, 2009 ).

Supporting information

CCDC reference: 1469976

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989016009087/xu5887sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989016009087/xu5887Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989016009087/xu5887Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); data reduction: CrysAlis PRO (Agilent, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

6,7-Dihydroxy-6,7-dihydro-3H-imidazo[1,2-a]purin-9(5H)-one top

Crystal data top

C₇H₇N₅O₃	Z = 2
M_r = 209.18	F(000) = 216
Triclinic, P1	D_x = 1.811 Mg m⁻³
Hall symbol: -P 1	Cu Kα radiation, λ = 1.54178 Å
a = 6.8925 (4) Å	Cell parameters from 1705 reflections
b = 7.6352 (4) Å	θ = 7.0–73.5°
c = 8.0605 (6) Å	µ = 1.26 mm⁻¹
α = 95.063 (5)°	T = 295 K
β = 105.135 (6)°	Block, colorless
γ = 107.647 (5)°	0.20 × 0.18 × 0.16 mm
V = 383.69 (4) Å³

Data collection top

Agilent Xcalibur, Eos, Gemini diffractometer	1499 independent reflections
Radiation source: Enhance (Cu) X-ray Source	1335 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.033
Detector resolution: 5.3031 pixels mm^-1	θ_max = 73.7°, θ_min = 5.8°
ω scans	h = −8→8
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012)	k = −9→7
T_min = 0.52, T_max = 0.82	l = −10→9
2506 measured reflections

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)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.180	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.1404P)² + 0.079P] where P = (F_o² + 2F_c²)/3
1499 reflections	(Δ/σ)_max < 0.001
138 parameters	Δρ_max = 0.67 e Å⁻³
0 restraints	Δρ_min = −0.40 e Å⁻³

Special details top

Experimental. CrysAlis Pro, Agilent Technologies, Version 1.171.35.21 (release 20-01-2012 CrysAlis171 .NET) (compiled Jan 23 2012,18:06:46) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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
O1	0.1803 (3)	−0.0561 (2)	0.71668 (19)	0.0330 (4)
O2	0.3726 (2)	0.34594 (19)	0.61681 (18)	0.0278 (4)
H2	0.4725	0.4310	0.6862	0.042*
O3	−0.0753 (2)	0.4579 (2)	0.6656 (2)	0.0355 (4)
H3	−0.1043	0.5434	0.7105	0.053*
N1	0.2147 (2)	0.2403 (2)	0.8339 (2)	0.0222 (4)
N2	0.2866 (3)	0.3571 (2)	1.1379 (2)	0.0234 (4)
N3	0.2741 (3)	−0.1191 (2)	1.1004 (2)	0.0267 (4)
N4	0.3297 (3)	0.1187 (2)	1.3093 (2)	0.0254 (4)
H4	0.3563	0.1802	1.4119	0.031*
N5	0.2310 (3)	0.5316 (2)	0.9134 (2)	0.0278 (4)
H5	0.2665	0.6384	0.9789	0.033*
C1	0.2159 (3)	0.0573 (2)	0.8471 (3)	0.0227 (5)
C2	0.2459 (3)	0.3764 (2)	0.9729 (2)	0.0217 (5)
C3	0.2944 (3)	0.1830 (2)	1.1558 (2)	0.0212 (4)
C4	0.2612 (3)	0.0354 (2)	1.0264 (3)	0.0226 (5)
C5	0.3142 (3)	−0.0636 (3)	1.2673 (3)	0.0277 (5)
H5A	0.3306	−0.1402	1.3496	0.033*
C6	0.1474 (3)	0.4966 (3)	0.7242 (3)	0.0245 (5)
H6	0.2227	0.5999	0.6752	0.029*
C7	0.1903 (3)	0.3160 (3)	0.6712 (2)	0.0232 (5)
H7	0.0653	0.2300	0.5793	0.028*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0427 (8)	0.0254 (8)	0.0294 (8)	0.0170 (6)	0.0067 (6)	−0.0085 (6)
O2	0.0276 (7)	0.0275 (7)	0.0277 (7)	0.0082 (6)	0.0123 (6)	−0.0061 (5)
O3	0.0370 (8)	0.0364 (9)	0.0395 (9)	0.0203 (7)	0.0142 (7)	0.0028 (7)
N1	0.0276 (8)	0.0173 (8)	0.0235 (8)	0.0109 (6)	0.0088 (6)	−0.0023 (6)
N2	0.0298 (8)	0.0183 (8)	0.0239 (8)	0.0102 (6)	0.0106 (7)	−0.0020 (6)
N3	0.0307 (8)	0.0173 (8)	0.0331 (9)	0.0099 (6)	0.0106 (7)	0.0008 (6)
N4	0.0315 (8)	0.0225 (8)	0.0242 (8)	0.0107 (7)	0.0112 (6)	0.0002 (6)
N5	0.0421 (10)	0.0175 (8)	0.0264 (8)	0.0148 (7)	0.0109 (7)	−0.0016 (6)
C1	0.0224 (8)	0.0172 (9)	0.0276 (10)	0.0078 (7)	0.0073 (7)	−0.0038 (7)
C2	0.0233 (8)	0.0172 (8)	0.0248 (9)	0.0071 (7)	0.0093 (7)	−0.0027 (7)
C3	0.0213 (8)	0.0160 (9)	0.0269 (9)	0.0069 (6)	0.0095 (7)	−0.0007 (7)
C4	0.0233 (8)	0.0162 (8)	0.0281 (10)	0.0073 (7)	0.0086 (7)	−0.0014 (7)
C5	0.0323 (10)	0.0212 (10)	0.0313 (10)	0.0115 (8)	0.0102 (8)	0.0025 (7)
C6	0.0310 (9)	0.0201 (9)	0.0270 (10)	0.0117 (7)	0.0131 (8)	0.0033 (7)
C7	0.0259 (9)	0.0202 (9)	0.0237 (9)	0.0088 (7)	0.0084 (7)	−0.0018 (7)

Geometric parameters (Å, º) top

O1—C1	1.221 (2)	N4—C3	1.361 (3)
O2—C7	1.398 (2)	N4—C5	1.367 (2)
O2—H2	0.8200	N4—H4	0.8600
O3—C6	1.410 (2)	N5—C2	1.339 (3)
O3—H3	0.8200	N5—C6	1.450 (2)
N1—C2	1.384 (2)	N5—H5	0.8600
N1—C1	1.413 (2)	C1—C4	1.433 (3)
N1—C7	1.470 (2)	C3—C4	1.386 (2)
N2—C2	1.316 (2)	C5—H5A	0.9300
N2—C3	1.365 (2)	C6—C7	1.543 (2)
N3—C5	1.304 (3)	C6—H6	0.9800
N3—C4	1.384 (2)	C7—H7	0.9800

C7—O2—H2	109.5	N4—C3—C4	106.17 (16)
C6—O3—H3	109.5	N2—C3—C4	128.41 (18)
C2—N1—C1	125.05 (16)	N3—C4—C3	109.67 (17)
C2—N1—C7	110.23 (15)	N3—C4—C1	130.23 (17)
C1—N1—C7	124.65 (15)	C3—C4—C1	120.08 (17)
C2—N2—C3	111.14 (15)	N3—C5—N4	113.27 (18)
C5—N3—C4	104.69 (16)	N3—C5—H5A	123.4
C3—N4—C5	106.20 (16)	N4—C5—H5A	123.4
C3—N4—H4	126.9	O3—C6—N5	112.28 (16)
C5—N4—H4	126.9	O3—C6—C7	107.73 (15)
C2—N5—C6	111.39 (14)	N5—C6—C7	102.64 (14)
C2—N5—H5	124.3	O3—C6—H6	111.3
C6—N5—H5	124.3	N5—C6—H6	111.3
O1—C1—N1	120.75 (18)	C7—C6—H6	111.3
O1—C1—C4	129.30 (18)	O2—C7—N1	111.34 (15)
N1—C1—C4	109.95 (15)	O2—C7—C6	114.01 (15)
N2—C2—N5	125.43 (16)	N1—C7—C6	101.82 (14)
N2—C2—N1	125.33 (17)	O2—C7—H7	109.8
N5—C2—N1	109.23 (16)	N1—C7—H7	109.8
N4—C3—N2	125.38 (16)	C6—C7—H7	109.8

C2—N1—C1—O1	177.72 (17)	N2—C3—C4—N3	−177.14 (17)
C7—N1—C1—O1	−5.4 (3)	N4—C3—C4—C1	179.03 (16)
C2—N1—C1—C4	−1.9 (2)	N2—C3—C4—C1	1.3 (3)
C7—N1—C1—C4	175.00 (15)	O1—C1—C4—N3	−1.0 (3)
C3—N2—C2—N5	−179.08 (18)	N1—C1—C4—N3	178.54 (17)
C3—N2—C2—N1	−0.1 (3)	O1—C1—C4—C3	−179.13 (19)
C6—N5—C2—N2	−169.71 (17)	N1—C1—C4—C3	0.4 (2)
C6—N5—C2—N1	11.1 (2)	C4—N3—C5—N4	−0.3 (2)
C1—N1—C2—N2	1.8 (3)	C3—N4—C5—N3	0.6 (2)
C7—N1—C2—N2	−175.41 (17)	C2—N5—C6—O3	95.18 (19)
C1—N1—C2—N5	−179.00 (16)	C2—N5—C6—C7	−20.2 (2)
C7—N1—C2—N5	3.7 (2)	C2—N1—C7—O2	106.35 (17)
C5—N4—C3—N2	177.11 (17)	C1—N1—C7—O2	−70.9 (2)
C5—N4—C3—C4	−0.7 (2)	C2—N1—C7—C6	−15.51 (18)
C2—N2—C3—N4	−178.80 (17)	C1—N1—C7—C6	167.22 (16)
C2—N2—C3—C4	−1.5 (3)	O3—C6—C7—O2	141.81 (16)
C5—N3—C4—C3	−0.2 (2)	N5—C6—C7—O2	−99.53 (18)
C5—N3—C4—C1	−178.47 (19)	O3—C6—C7—N1	−98.19 (17)
N4—C3—C4—N3	0.6 (2)	N5—C6—C7—N1	20.48 (18)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···N2ⁱ	0.82	2.03	2.850 (2)	178
O3—H3···N2ⁱⁱ	0.82	2.21	2.947 (2)	150
N4—H4···O2ⁱⁱⁱ	0.86	1.95	2.791 (2)	167
N5—H5···N3^iv	0.86	2.00	2.837 (2)	166
C5—H5A···O3^v	0.93	2.50	3.133 (8)	126
C7—H7···O1^vi	0.98	2.51	3.449 (2)	161

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

Acknowledgements

The authors gratefully acknowledge financial support from the Natural Science Foundation of Hebei Province of China (B2015206500) and the Science and Technology Research Project of Higher Education of Hebei Province (QN2014073).

References

Agilent (2012). CrysAlis PRO. Agilent Technologies Ltd., Yarnton, England. Google Scholar
Braga, F. G., Coimbra, E. S., de Oliveira Matos, M., Lino Carmo, A. M., Cancio, M. D. & da Silva, A. D. (2007). Eur. J. Med. Chem. 42, 530–537. CrossRef PubMed CAS Google Scholar
Dey, S. & Garner, P. (2000). J. Org. Chem. 65, 7697–7699. Web of Science CrossRef PubMed CAS Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CSD CrossRef IUCr Journals Google Scholar
Klanicová, A., Trávníček, Z., Vančo, J., Popa, I. & Šindelář, Z. (2010). Polyhedron, 29, 2582–2589. Google Scholar
Manikowski, A., Verri, A., Lossani, A., Gebhardt, B. M., Gambino, J., Focher, F., Spadari, S. & Wright, G. E. (2005). J. Med. Chem. 48, 3919–3929. CrossRef PubMed CAS Google Scholar
Prekupec, S., Svedružić, D., Gazivoda, T., Mrvoš-Sermek, D., Nagl, A., Grdiša, M., Pavelić, K., Balzarini, J., De Clercq, E., Folkers, G., Scapozza, L., Mintas, M. & Raić-Malić, S. (2003). J. Med. Chem. 46, 5763–5772. CSD CrossRef PubMed CAS Google Scholar
Sausville, E. A. (2002). Trends Mol. Med. 8, S32–S37. CrossRef PubMed CAS Google Scholar
Shapiro, R., Cohen, B. I., Shiuey, S. J. & Maurer, H. (1969). Biochemistry, 8, 238–245. CrossRef CAS PubMed Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Trávníček, Z., Maloň, M., Šindelář, Z., Doležal, K., Rolč\?ík, J., Kryštof, V., Strnad, M. & Marek, J. (2001). J. Inorg. Biochem. 84, 23–32. Google Scholar
Yadav, V., Chu, C. K., Rais, R. H., Al Safarjalani, O. N., Guarcello, V., Naguib, F. N. M. & el Kouni, M. H. (2004). J. Med. Chem. 47, 1987–1996. Web of Science CrossRef PubMed CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.