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Acta Crystallogr Sect E Struct Rep Online. 2009 November 1; 65(Pt 11): o2878.
Published online 2009 October 28. doi:  10.1107/S1600536809043980
PMCID: PMC2971410

9-[4-Hydr­oxy-3-(hydroxy­meth­yl)but­yl]guanine monohydrate

Abstract

In the mol­ecular structure of the title compound, also named penciclovir monohydrate, C10H15N5O3·H2O, the 4-hydr­oxy-3-hydroxy­methyl­but-1-yl group is connected to guanine through an N atom of the imidazole ring. Water mol­ecules stabilize the mol­ecular packing by forming O—H(...)O hydrogen bonds. A three-dimensional network is generated via inter­molecular N—H(...)N, N—H(...)O, O—H(...)N and O—H(...)O hydrogen bonding.

Related literature

For the synthesis and biological properies of penciclovir, see: Harnden & Jarvest (1985a [triangle],b [triangle]); Hodge et al.(1989 [triangle]); Boyd et al. (1987 [triangle]). For the medicinal applications of penciclovir, see: Abdel-Hag et al. (2006 [triangle]); Andrei et al. (2004 [triangle]); Schmid-Wendtner & Korting (2004 [triangle]); Smith et al. (2001 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2878-scheme1.jpg

Experimental

Crystal data

  • C10H15N5O3·H2O
  • M r = 271.29
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2878-efi1.jpg
  • a = 8.2020 (16) Å
  • b = 13.889 (3) Å
  • c = 11.001 (2) Å
  • V = 1253.2 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.11 mm−1
  • T = 293 K
  • 0.54 × 0.45 × 0.08 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2001 [triangle]) T min = 0.957, T max = 0.994
  • 6830 measured reflections
  • 1193 independent reflections
  • 1084 reflections with I > 2σ(I)
  • R int = 0.075

Refinement

  • R[F 2 > 2σ(F 2)] = 0.050
  • wR(F 2) = 0.118
  • S = 1.06
  • 1193 reflections
  • 186 parameters
  • 4 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.15 e Å−3
  • Δρmin = −0.31 e Å−3

Data collection: SMART (Bruker, 2001 [triangle]); cell refinement: SAINT-Plus (Bruker, 2001 [triangle]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809043980/ds2005sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809043980/ds2005Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors thank the National Natural Science Foundation of China (No. 20861002), the 973 Plan of China (2009CB526503) and the Open Foundation of the Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China) for financial support.

supplementary crystallographic information

Comment

9-[4-Hydroxy-3-(hydroxymethyl)butyl]guanine (I), known as penciclovir, is very effective for the treatment of herpes simplex virus, varicella zoster virus, Epstein–Barr virus, hepatitis virus and cytomegalovirus (Abdel-Hag et al., 2006; Andrei et al., 2004; Schmid-Wendtner and Korting, 2004; Smith et al., 2001). The crystal lattice is built from molecules of (I) and waters of crystallization (Fig. 1). The guanine ring in (I) is coplanar wherein the C—N bond distances range from 1.312 (4) to 1.395 (5) Å. Three dimensional network is generated via N—H···N, N—H···O (2.816 (3)–2.931 (3) Å,), O—H···N(3.052 (3) Å), and O—H···O(2.719 (3)–2.842 (3) Å) hydrogen bonds from water and penciclovir molecules (Fig.2).

Experimental

0.2 mmol ZnCl2 dissolved in 5 ml ethanol was added into 10 ml water containing 0.3 mmol pencicolvir. The mixture was stirred at room temperature for 5 h. The resulting solution was filtered. The filtrate was allowed to stay at ambient temperature for three weeks. Colourless block crystals were thus obtained. Yeild: 50%.

Refinement

The water H and N(4) bound H were found from a difference Fourier map and refined freely. Other H atoms were treated as riding, with C—H distances of 0.97 and 0.98 Å,N—H distances of 0.86 Å, these hydroxyl O—H distances of 0.82Å and were refined as riding with Uiso(H) = 1.2Ueq (C, N and O). Since the Flack value is 0(2) even after inverting the structure, the title compound is weak anomalous scatterer and therefore, Flack is meaningless.

Figures

Fig. 1.
The molecular structure of (I),showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
Three-dimensional structure of (I) along [001] direction. Hydrogen bonds are shown as dashed lines.

Crystal data

C10H15N5O3·H2OF(000) = 576
Mr = 271.29Dx = 1.438 Mg m3
Orthorhombic, Pna21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2nCell parameters from 1193 reflections
a = 8.2020 (16) Åθ = 3.4–25.2°
b = 13.889 (3) ŵ = 0.11 mm1
c = 11.001 (2) ÅT = 293 K
V = 1253.2 (4) Å3Block, colorless
Z = 40.54 × 0.45 × 0.08 mm

Data collection

Bruker SMART CCD area-detector diffractometer1193 independent reflections
Radiation source: fine-focus sealed tube1084 reflections with I > 2σ(I)
graphiteRint = 0.075
ω scansθmax = 25.2°, θmin = 3.4°
Absorption correction: multi-scan (SADABS; Sheldrick, 2001)h = −8→9
Tmin = 0.957, Tmax = 0.994k = −16→16
6830 measured reflectionsl = −11→13

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.050Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.118H atoms treated by a mixture of independent and constrained refinement
S = 1.06w = 1/[σ2(Fo2) + (0.0604P)2 + 0.3P] where P = (Fo2 + 2Fc2)/3
1193 reflections(Δ/σ)max < 0.001
186 parametersΔρmax = 0.15 e Å3
4 restraintsΔρmin = −0.31 e Å3

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 (Å2)

xyzUiso*/Ueq
C10.0269 (5)0.4750 (3)0.0559 (4)0.0321 (9)
C2−0.0398 (5)0.3455 (3)−0.0873 (4)0.0354 (9)
C3−0.0027 (5)0.3211 (3)0.3070 (4)0.0374 (10)
H3−0.00180.30370.38860.045*
C4−0.0242 (5)0.3102 (2)0.1084 (4)0.0311 (9)
C50.0189 (5)−0.0152 (3)0.2010 (4)0.0375 (9)
H5−0.0741−0.01760.14520.045*
C60.0126 (5)0.4027 (3)0.1448 (4)0.0323 (9)
C7−0.0735 (5)0.1556 (3)0.2279 (4)0.0396 (10)
H7A−0.15670.13900.16890.048*
H7B−0.11850.14480.30830.048*
C80.0713 (5)0.0901 (3)0.2102 (5)0.0383 (9)
H8A0.14580.09770.27800.046*
H8B0.12860.10840.13660.046*
C9−0.0360 (6)−0.0601 (3)0.3195 (5)0.0537 (13)
H9A−0.1190−0.01970.35630.064*
H9B−0.0841−0.12260.30320.064*
C100.1551 (5)−0.0729 (3)0.1431 (4)0.0424 (11)
H10A0.1837−0.04350.06600.051*
H10B0.2504−0.06990.19520.051*
N1−0.0334 (4)0.2576 (2)0.2150 (3)0.0352 (8)
N20.0253 (4)0.4092 (2)0.2691 (3)0.0356 (8)
N3−0.0498 (4)0.2759 (2)−0.0038 (3)0.0354 (8)
N4−0.0054 (4)0.4399 (2)−0.0607 (4)0.0359 (8)
N5−0.0645 (5)0.3259 (3)−0.2040 (4)0.0506 (10)
H5A−0.08710.2680−0.22630.061*
H5B−0.05790.3710−0.25730.061*
O10.0604 (4)0.56135 (18)0.0709 (3)0.0396 (7)
O20.1144 (4)−0.17160 (18)0.1226 (3)0.0485 (8)
H20.0219−0.17520.09480.073*
O30.0950 (6)−0.0711 (3)0.4012 (4)0.0760 (12)
H3A0.0878−0.12340.43540.114*
O40.1827 (4)0.1915 (2)0.5157 (4)0.0518 (8)
H4−0.017 (7)0.489 (4)−0.119 (6)0.068 (17)*
H4A0.243 (6)0.234 (3)0.549 (5)0.069 (17)*
H4B0.222 (9)0.1362 (19)0.527 (8)0.14 (3)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.036 (2)0.029 (2)0.031 (2)−0.0005 (16)−0.0003 (17)−0.0003 (17)
C20.045 (2)0.031 (2)0.031 (2)0.0021 (16)0.0000 (18)−0.0032 (19)
C30.050 (2)0.032 (2)0.030 (2)0.0036 (17)0.0007 (19)0.0023 (18)
C40.040 (2)0.0252 (18)0.028 (2)0.0044 (15)−0.0008 (18)−0.0019 (17)
C50.043 (2)0.031 (2)0.039 (3)−0.0014 (16)0.000 (2)0.003 (2)
C60.041 (2)0.0264 (18)0.029 (2)0.0027 (15)−0.0015 (17)−0.0031 (17)
C70.051 (2)0.0270 (19)0.041 (3)−0.0016 (17)0.0036 (19)0.0063 (19)
C80.041 (2)0.0288 (19)0.045 (3)−0.0016 (16)−0.003 (2)0.0041 (19)
C90.059 (3)0.042 (3)0.060 (4)−0.004 (2)0.014 (3)0.006 (2)
C100.050 (2)0.033 (2)0.045 (3)−0.0005 (17)0.008 (2)0.0043 (19)
N10.053 (2)0.0217 (14)0.031 (2)0.0013 (13)0.0017 (18)0.0038 (15)
N20.0508 (19)0.0308 (16)0.025 (2)0.0009 (15)0.0000 (16)−0.0018 (15)
N30.0492 (19)0.0296 (17)0.028 (2)−0.0021 (15)0.0012 (15)−0.0013 (15)
N40.053 (2)0.0274 (17)0.028 (2)−0.0031 (14)0.0004 (16)0.0017 (15)
N50.088 (3)0.0347 (18)0.029 (2)−0.0071 (18)−0.005 (2)−0.0013 (16)
O10.0618 (18)0.0260 (13)0.0311 (18)−0.0097 (13)0.0054 (13)−0.0011 (12)
O20.0553 (17)0.0275 (13)0.063 (2)0.0027 (12)0.0003 (17)−0.0004 (15)
O30.109 (3)0.066 (2)0.053 (3)−0.018 (2)−0.018 (2)0.0180 (19)
O40.0547 (18)0.0418 (17)0.059 (2)0.0001 (16)−0.0074 (17)0.0026 (16)

Geometric parameters (Å, °)

C1—O11.241 (5)C7—C81.508 (6)
C1—N41.397 (6)C7—H7A0.9700
C1—C61.407 (6)C7—H7B0.9700
C2—N51.329 (6)C8—H8A0.9700
C2—N31.336 (5)C8—H8B0.9700
C2—N41.372 (5)C9—O31.410 (6)
C3—N21.312 (5)C9—H9A0.9700
C3—N11.366 (6)C9—H9B0.9700
C3—H30.9300C10—O21.429 (5)
C4—N31.340 (5)C10—H10A0.9700
C4—C61.379 (5)C10—H10B0.9700
C4—N11.383 (5)N4—H40.94 (6)
C5—C91.514 (7)N5—H5A0.8600
C5—C101.515 (6)N5—H5B0.8600
C5—C81.528 (5)O2—H20.8200
C5—H50.9800O3—H3A0.8200
C6—N21.375 (5)O4—H4A0.85 (5)
C7—N11.461 (5)O4—H4B0.84 (2)
O1—C1—N4120.1 (4)C7—C8—H8B109.3
O1—C1—C6128.0 (4)C5—C8—H8B109.3
N4—C1—C6111.9 (3)H8A—C8—H8B108.0
N5—C2—N3120.4 (4)O3—C9—C5111.5 (4)
N5—C2—N4115.7 (4)O3—C9—H9A109.3
N3—C2—N4123.9 (4)C5—C9—H9A109.3
N2—C3—N1113.5 (4)O3—C9—H9B109.3
N2—C3—H3123.2C5—C9—H9B109.3
N1—C3—H3123.2H9A—C9—H9B108.0
N3—C4—C6129.3 (4)O2—C10—C5113.7 (3)
N3—C4—N1125.8 (3)O2—C10—H10A108.8
C6—C4—N1104.9 (4)C5—C10—H10A108.8
C9—C5—C10111.3 (3)O2—C10—H10B108.8
C9—C5—C8114.9 (4)C5—C10—H10B108.8
C10—C5—C8109.1 (3)H10A—C10—H10B107.7
C9—C5—H5107.0C3—N1—C4106.1 (3)
C10—C5—H5107.0C3—N1—C7126.6 (4)
C8—C5—H5107.0C4—N1—C7127.3 (4)
N2—C6—C4111.5 (4)C3—N2—C6104.0 (4)
N2—C6—C1129.7 (4)C2—N3—C4111.5 (3)
C4—C6—C1118.8 (4)C2—N4—C1124.6 (4)
N1—C7—C8113.3 (3)C2—N4—H4122 (4)
N1—C7—H7A108.9C1—N4—H4113 (4)
C8—C7—H7A108.9C2—N5—H5A120.0
N1—C7—H7B108.9C2—N5—H5B120.0
C8—C7—H7B108.9H5A—N5—H5B120.0
H7A—C7—H7B107.7C10—O2—H2109.5
C7—C8—C5111.4 (3)C9—O3—H3A109.5
C7—C8—H8A109.3H4A—O4—H4B110 (3)
C5—C8—H8A109.3
N3—C4—C6—N2178.4 (4)N3—C4—N1—C3−178.5 (4)
N1—C4—C6—N2−0.4 (4)C6—C4—N1—C30.3 (4)
N3—C4—C6—C10.1 (6)N3—C4—N1—C7−0.5 (6)
N1—C4—C6—C1−178.6 (3)C6—C4—N1—C7178.3 (3)
O1—C1—C6—N22.8 (7)C8—C7—N1—C3−98.2 (5)
N4—C1—C6—N2−175.9 (4)C8—C7—N1—C484.2 (5)
O1—C1—C6—C4−179.3 (4)N1—C3—N2—C6−0.2 (5)
N4—C1—C6—C42.0 (5)C4—C6—N2—C30.3 (5)
N1—C7—C8—C5−169.4 (4)C1—C6—N2—C3178.4 (4)
C9—C5—C8—C7−72.7 (5)N5—C2—N3—C4−178.8 (4)
C10—C5—C8—C7161.5 (4)N4—C2—N3—C40.8 (5)
C10—C5—C9—O356.0 (5)C6—C4—N3—C2−1.6 (6)
C8—C5—C9—O3−68.6 (5)N1—C4—N3—C2176.9 (4)
C9—C5—C10—O256.1 (5)N5—C2—N4—C1−178.9 (4)
C8—C5—C10—O2−176.0 (4)N3—C2—N4—C11.4 (6)
N2—C3—N1—C4−0.1 (4)O1—C1—N4—C2178.4 (4)
N2—C3—N1—C7−178.1 (3)C6—C1—N4—C2−2.8 (5)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O2—H2···O4i0.821.902.719 (3)175
O3—H3A···N3ii0.822.243.052 (3)169
N4—H4···N2iii0.96 (3)1.86 (3)2.816 (3)176 (3)
O4—H4A···O2iv0.86 (3)1.93 (3)2.787 (3)178 (3)
O4—H4B···O1v0.84 (3)2.11 (5)2.842 (3)146 (3)
N5—H5A···O2i0.862.152.898 (3)146
N5—H5B···O1iii0.862.112.931 (3)159

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: DS2005).

References

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  • Bruker (2001). SAINT-Plus and SMART Bruker AXS Inc., Madison, Wisconsin, USA.
  • Harnden, M. R. & Jarvest, R. L. (1985a). Tetrahedron Lett 26, 4265–4268.
  • Harnden, M. R. & Jarvest, R. L. (1985b). Eur. Patent 0141927A.
  • Hodge, R. A. V., Sutton, D., Boyd, M., Harnden, M. R. & Jarvest, R. L. (1989). Antimicrob. Agents Chemother 33, 1765–1773. [PMC free article] [PubMed]
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  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Smith, R. L., Morroni, J. & Wilcox, C. L. (2001). Antiviral Res.52, 19–24. [PubMed]

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