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Ganciclovir (GCV; systematic name: 2-amino-9-{[(1,3-di­hydroxy­propan-2-yl)­oxy]meth­yl}-6,9-di­hydro-1H-purin-6-one), C9H13N5O4, an anti­viral drug for treating cytomegalovirus infections, has two known polymorphs (Forms I and II), but only the structure of the metastable Form II has been reported [Kawamura & Hirayama (2009). X-ray Struct. Anal. Online, 25, 51–52]. We describe a successful preparation of GCV Form I and its crystal structure. GCV is an achiral mol­ecule in the sense that its individual conformers, which are generally chiral objects, undergo fast inter­conversion in the liquid state and cannot be isolated. In the crystalline state, GCV exists as two inversion-related conformers in Form I and as a single chiral conformer in Form II. This situation is similar to that observed for glycine, also an achiral mol­ecule, whose α-polymorph contains two inversion-related conformers, while the γ-polymorph contains a single conformer that is chiral. The hydrogen bonds are exclusively inter­molecular in Form I, but both inter- and intra­molecular in Form II, which accounts for the different mol­ecular conformations in the two polymorphs.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229617016059/qp3002sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2053229617016059/qp3002Isup2.hkl
Contains datablock I

pdf

Portable Document Format (PDF) file https://doi.org/10.1107/S2053229617016059/qp3002sup3.pdf
Additional experimental details

CCDC reference: 1584332

Computing details top

Data collection: APEX3 (Bruker, 2015); cell refinement: SAINT-Plus (Bruker, 2015); data reduction: SAINT-Plus (Bruker, 2015); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009) and Gn (Guzei (2013).

2-Amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-1H-purin-6-one top
Crystal data top
C9H13N5O4F(000) = 536
Mr = 255.24Dx = 1.653 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 4.6448 (10) ÅCell parameters from 5037 reflections
b = 15.632 (3) Åθ = 2.9–30.5°
c = 14.130 (3) ŵ = 0.13 mm1
β = 91.632 (10)°T = 100 K
V = 1025.5 (4) Å3Needle, colourless
Z = 40.58 × 0.1 × 0.1 mm
Data collection top
Bruker SMART APEXII area detector
diffractometer
45424 independent reflections
Radiation source: microfocus sealed X-ray tube, Incoatec Iµs38287 reflections with I > 2σ(I)
Mirror optics monochromatorRint = 0.060
Detector resolution: 7.9 pixels mm-1θmax = 30.6°, θmin = 1.9°
0.5° ω and 0.5° φ scansh = 66
Absorption correction: multi-scan
(TWINABS; Bruker, 2012)
k = 2222
Tmin = 0.54, Tmax = 0.99l = 2019
45424 measured reflections
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.054H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.151 w = 1/[σ2(Fo2) + 0.6622P]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max < 0.001
45424 reflectionsΔρmax = 0.45 e Å3
184 parametersΔρmin = 0.29 e Å3
0 restraints
Special details top

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. Refined as a 2-component twin.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.8794 (3)0.29596 (9)0.67663 (10)0.0163 (3)
O20.4005 (3)0.40726 (9)0.25113 (9)0.0144 (3)
O30.2212 (3)0.38278 (9)0.00228 (9)0.0156 (3)
H30.094 (7)0.340 (2)0.007 (2)0.047 (9)*
O40.5480 (3)0.55219 (9)0.16460 (10)0.0158 (3)
H40.617 (6)0.575 (2)0.116 (2)0.042 (9)*
N10.1570 (3)0.49144 (11)0.62555 (12)0.0147 (3)
H1A0.032 (5)0.5186 (17)0.591 (2)0.024 (7)*
H1B0.220 (6)0.5137 (19)0.680 (2)0.029 (7)*
N20.5152 (3)0.39079 (11)0.64408 (12)0.0127 (3)
H20.510 (5)0.4037 (17)0.699 (2)0.024 (7)*
N30.8130 (3)0.24735 (10)0.46481 (11)0.0132 (3)
N40.4703 (3)0.31416 (10)0.37787 (11)0.0126 (3)
N50.2822 (3)0.41260 (10)0.49414 (11)0.0119 (3)
C10.3186 (4)0.43137 (12)0.58517 (13)0.0120 (3)
C20.7116 (4)0.32817 (12)0.61743 (13)0.0126 (3)
C30.6763 (4)0.30842 (12)0.51948 (13)0.0125 (3)
C40.6837 (4)0.25277 (12)0.38132 (13)0.0136 (4)
H4A0.73190.21810.32880.016*
C50.4636 (4)0.34996 (12)0.46676 (12)0.0115 (3)
C60.2863 (4)0.33450 (12)0.29719 (13)0.0138 (4)
H6A0.27730.28540.25300.017*
H6B0.08880.34680.31800.017*
C70.2467 (4)0.42577 (12)0.16349 (13)0.0123 (3)
H70.04100.40810.16910.015*
C80.3819 (4)0.37434 (13)0.08467 (13)0.0156 (4)
H8A0.58150.39450.07580.019*
H8B0.39040.31330.10300.019*
C90.2598 (4)0.52153 (12)0.14811 (13)0.0141 (4)
H9A0.19560.53520.08240.017*
H9B0.12830.55050.19180.017*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0166 (7)0.0192 (7)0.0130 (6)0.0023 (5)0.0019 (5)0.0026 (5)
O20.0176 (7)0.0142 (7)0.0111 (6)0.0036 (5)0.0029 (5)0.0031 (5)
O30.0196 (7)0.0170 (7)0.0102 (6)0.0032 (5)0.0022 (5)0.0006 (5)
O40.0168 (7)0.0174 (7)0.0134 (7)0.0043 (5)0.0001 (5)0.0014 (5)
N10.0148 (8)0.0163 (8)0.0128 (7)0.0023 (6)0.0018 (6)0.0019 (6)
N20.0134 (8)0.0150 (8)0.0096 (7)0.0008 (5)0.0005 (5)0.0008 (6)
N30.0143 (8)0.0126 (7)0.0127 (7)0.0004 (5)0.0025 (5)0.0004 (6)
N40.0147 (8)0.0124 (7)0.0107 (7)0.0007 (5)0.0002 (5)0.0001 (6)
N50.0125 (7)0.0121 (7)0.0111 (7)0.0008 (5)0.0007 (5)0.0000 (6)
C10.0112 (8)0.0125 (8)0.0124 (8)0.0020 (6)0.0000 (6)0.0010 (7)
C20.0126 (8)0.0118 (8)0.0134 (8)0.0015 (6)0.0003 (6)0.0017 (7)
C30.0127 (8)0.0126 (8)0.0121 (8)0.0006 (6)0.0010 (6)0.0008 (7)
C40.0160 (9)0.0113 (8)0.0134 (8)0.0005 (6)0.0023 (6)0.0005 (7)
C50.0129 (8)0.0115 (8)0.0102 (8)0.0028 (6)0.0007 (6)0.0004 (6)
C60.0157 (9)0.0143 (9)0.0114 (8)0.0036 (6)0.0015 (6)0.0014 (7)
C70.0132 (9)0.0132 (8)0.0105 (7)0.0005 (6)0.0019 (6)0.0006 (6)
C80.0186 (9)0.0173 (9)0.0108 (8)0.0035 (7)0.0025 (6)0.0013 (7)
C90.0141 (9)0.0133 (8)0.0148 (8)0.0003 (6)0.0009 (6)0.0002 (7)
Geometric parameters (Å, º) top
O1—C21.234 (2)N4—C51.376 (2)
O2—C61.421 (2)N4—C61.440 (2)
O2—C71.441 (2)N5—C11.326 (2)
O3—H30.89 (3)N5—C51.355 (2)
O3—C81.425 (2)C2—C31.423 (3)
O4—H40.85 (3)C3—C51.382 (2)
O4—C91.435 (2)C4—H4A0.9500
N1—H1A0.86 (3)C6—H6A0.9900
N1—H1B0.88 (3)C6—H6B0.9900
N1—C11.340 (2)C7—H71.0000
N2—H20.80 (3)C7—C81.523 (3)
N2—C11.373 (2)C7—C91.514 (3)
N2—C21.397 (2)C8—H8A0.9900
N3—C31.393 (2)C8—H8B0.9900
N3—C41.311 (2)C9—H9A0.9900
N4—C41.380 (2)C9—H9B0.9900
C6—O2—C7111.84 (13)N5—C5—N4125.76 (16)
C8—O3—H3109 (2)N5—C5—C3128.77 (17)
C9—O4—H4112 (2)O2—C6—N4108.58 (14)
H1A—N1—H1B120 (3)O2—C6—H6A110.0
C1—N1—H1A118.8 (19)O2—C6—H6B110.0
C1—N1—H1B117.9 (18)N4—C6—H6A110.0
C1—N2—H2115.7 (19)N4—C6—H6B110.0
C1—N2—C2126.04 (16)H6A—C6—H6B108.4
C2—N2—H2118.3 (19)O2—C7—H7109.1
C4—N3—C3104.51 (15)O2—C7—C8108.53 (15)
C4—N4—C6126.23 (16)O2—C7—C9107.51 (14)
C5—N4—C4106.57 (15)C8—C7—H7109.1
C5—N4—C6127.18 (16)C9—C7—H7109.1
C1—N5—C5111.93 (15)C9—C7—C8113.43 (16)
N1—C1—N2115.89 (16)O3—C8—C7111.39 (15)
N5—C1—N1120.71 (17)O3—C8—H8A109.4
N5—C1—N2123.39 (17)O3—C8—H8B109.4
O1—C2—N2120.52 (17)C7—C8—H8A109.4
O1—C2—C3128.58 (18)C7—C8—H8B109.4
N2—C2—C3110.86 (16)H8A—C8—H8B108.0
N3—C3—C2130.29 (17)O4—C9—C7110.37 (15)
C5—C3—N3110.68 (16)O4—C9—H9A109.6
C5—C3—C2118.89 (17)O4—C9—H9B109.6
N3—C4—N4112.77 (17)C7—C9—H9A109.6
N3—C4—H4A123.6C7—C9—H9B109.6
N4—C4—H4A123.6H9A—C9—H9B108.1
N4—C5—C3105.47 (16)
O1—C2—C3—N31.7 (3)C4—N3—C3—C2175.54 (19)
O1—C2—C3—C5176.87 (18)C4—N3—C3—C50.1 (2)
O2—C7—C8—O3173.90 (14)C4—N4—C5—N5179.39 (17)
O2—C7—C9—O446.58 (19)C4—N4—C5—C30.39 (19)
N2—C2—C3—N3176.04 (18)C4—N4—C6—O298.1 (2)
N2—C2—C3—C50.9 (2)C5—N4—C4—N30.4 (2)
N3—C3—C5—N40.3 (2)C5—N4—C6—O283.8 (2)
N3—C3—C5—N5179.48 (17)C5—N5—C1—N1179.50 (17)
C1—N2—C2—O1179.91 (17)C5—N5—C1—N20.8 (2)
C1—N2—C2—C32.1 (3)C6—O2—C7—C887.48 (18)
C1—N5—C5—N4177.25 (17)C6—O2—C7—C9149.46 (15)
C1—N5—C5—C32.5 (3)C6—N4—C4—N3178.82 (17)
C2—N2—C1—N1178.02 (17)C6—N4—C5—N51.0 (3)
C2—N2—C1—N53.2 (3)C6—N4—C5—C3178.81 (17)
C2—C3—C5—N4176.35 (16)C7—O2—C6—N4173.40 (14)
C2—C3—C5—N53.4 (3)C8—C7—C9—O473.42 (19)
C3—N3—C4—N40.2 (2)C9—C7—C8—O366.7 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···N3i0.89 (3)1.93 (3)2.811 (2)172 (3)
O4—H4···O3ii0.85 (3)1.91 (4)2.754 (2)176 (3)
N1—H1A···N5iii0.86 (3)2.15 (3)3.012 (2)179 (3)
N1—H1B···O2iv0.88 (3)2.34 (3)3.093 (2)143 (2)
N2—H2···O4iv0.80 (3)2.07 (3)2.869 (2)172 (3)
Symmetry codes: (i) x1, y+1/2, z1/2; (ii) x+1, y+1, z; (iii) x, y+1, z+1; (iv) x+1, y+1, z+1.
Summary of the GCV crystallization experiments performed in this work top
TrialSolventForm
GCV-1Water, methanol, dimethylformamide (DMF)I
GCV-AWater, acetonitrileIV
GCV-BWater, methanol, dimethyl sulfoxideI
GCV-CWater, methanol, 1-propanolIII
GCV-DWater, methanol, ethyl acetateIII
GCV-EWater, methanol, tetrahydrofuran (THF)V
GCV-FWater, methanol, 1,4-dioxaneIII
GCV-GWater, 1,4-dioxane, THFIII
GCV-HWater, DMF, THFI
 

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