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Gabapentin [or 1-(amino­meth­yl)cyclo­hexaneacetic acid], C9H17NO2, exists as a zwitterion [1-(ammonio­meth­yl)cyclo­hexaneacetate] in the solid state. The crystal structures and bonding networks of two new monoclinic polymorphs ([beta]-gabapentin and [gamma]-gabapentin) are studied and compared with a previously reported gabapentin polymorph [[alpha]-gabapentin: Ibers (2001). Acta Cryst. C57, 641-643]. All three polymorphs have extensive networks of hydrogen bonds between the NH3+ and COO- groups of neighbouring mol­ecules. In [beta]-gabapentin, there is an additional weak intra­molecular hydrogen bond.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270107066279/tr3031sup1.cif
Contains datablocks global, I, II

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270107066279/tr3031Isup2.hkl
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270107066279/tr3031IIsup3.hkl
Contains datablock II

pdf

Portable Document Format (PDF) file https://doi.org/10.1107/S0108270107066279/tr3031fig7sup4.pdf
Supplementary material

pdf

Portable Document Format (PDF) file https://doi.org/10.1107/S0108270107066279/tr3031fig8sup5.pdf
Supplementary material

CCDC references: 682804; 682805

Comment top

Gabapentin (C9H17NO2) is structurally related to the neurotransmitter γ-aminobutyric acid (GABA), which has been widely studied for its significant inhibitory action in the central nervous system (Bowery, 1993). There have also been studies on the cocrystallization of GABA with various carboxylic acids as a means of possibly improving the effectiveness of GABA (Wenger & Bernstein, 2006).

In recent years, there has been intense interest in the polymorphs of gabapentin and in the synthesis of gabapentin analogues. Gabapentin was originally used as an antiepileptic drug, but its applications have been extended to the treatment of neuropathic pain (Magnus, 1999). One form of gabapentin (α-gabapentin) crystallizes as a zwitterion in space group P21/c [a = 5.8759 (6) Å, b = 6.9189 (7) Å, c = 22.262 (2) Å, β = 90.080 (2)° and V = 905.173 Å3; Ibers, 2001]. Note that α-gabapentin corresponds to form II of Lladó et al. (2003) and to the form of gabapentin found in the commercially available Pfizer pharmaceutical, Neurontin.

The structures of a gabapentin monohydrate (Ibers, 2001), several gabapentin derivatives (Ananda et al., 2003), peptides incorporating gabapentin (Vasudev et al., 2007) and a related 1-(aminomethyl) structure called pregabalin (Venu et al., 2007) have also been reported. The crystal structures of two previously unreported gabapentin polymorphs, β-gabapentin, (I) (Fig. 1), and γ-gabapentin, (II) (Fig. 2), are presented here. X-ray powder diffraction (XRPD) studies show that β-gabapentin corresponds to form III in of Pesachovich et al. (2001) and γ-gabapentin corresponds to form IV of Satyanarayana et al. (2004).

As in the case of α-gabapentin, β- and γ-gabapentin also exist as zwitterions. In all three forms the cyclohexane ring has a chair conformation. However, as shown in Figs. 3–5, each of the three polymorphs has different orientations of the NH3+ and COO- groups. Significantly, in β-gabapentin, the NH3+ group is in an equatorial position and the COO- group in an axial position, while in the α- and γ-gabapentin polymorphs, these groups are in the opposite positions. This difference is further indicated by the torsion angle C3—C1—C5—C7 (Table 2). There is an interesting difference in the rotation of the amine group, which is in an unusual eclipsed conformation for the α form and in a normal staggered conformation for the β and γ forms. These differences are quantified by the torsion angles O1—C2—C3—C1, C2—C3—C1—C4 and C3—C1—C4—N1 (Table 2), showing the different angles and directions in which the NH3+ and COO- groups are twisted (see Figs. 3–5). The torsion angles in Table 2 indicate that the largest conformational difference is due to the twisting of the COO- group.

In β- and γ-gabapentin, there is extensive hydrogen bonding between the NH3+ and COO- groups of neighbouring molecules. The NH3+ group hydrogen bonds to three COO- groups, each from a different neighbouring molecule. The geometry of hydrogen-bonding interactions for the three polymorphs of gabapentin are compared in Table 3. There is a significant difference in the hydrogen-bonding networks of α- and β-gabapentin, and this is primarily due to the presence of an intramolecular hydrogen bond in β-gabapentin [N1(H15)···O1 = 2.940 (2) Å]. Atom O1 acts as a trifurcated hydrogen-bond acceptor in β-gabapentin as opposed to the bifurcated acceptor in α-gabapentin. There is a corresponding lengthening of the N1(H15)···O1i hydrogen bond between two neighbouring molecules [i.e. N1(H15)···O1i = 2.783 (2) and 3.024 (2) Å for α- and β-gabapentin, respectively; symmetry codes: (i) -x + 1, -y + 1, -z + 1; -x, -y, -z + 1, respectively].

As with α-gabapentin, there is no intramolecular hydrogen bond in γ-gabapentin. The N···O hydrogen-bond distances are very similar in α- and γ-gabapentin [average N1···O = 2.763 and 2.771 Å for α- and γ-gabapentin, respectively]. In both the α and γ polymorphs, atom O1 acts as a bifurcated hydrogen-bond acceptor. The differences in the packing of gabapentin in the three polymorphs is evident from Fig. 6, which shows their hydrogen-bonding networks and the graph sets (Bernstein et al., 1995) of these networks. The hydrogen-bonded chains and rings are shown along the b axis of the α polymorph (Fig. 6a) and along the c axes of the β and γ polymorphs (Figs. 6b and 6c). There are four graph sets common to each polymorph, i.e. two unitary-level graph sets, C11(7) and R22(14), and two secondary-level graph sets, C22(14) and C22(6). The centrosymmetric hydrogen-bonded dimers shown in Figs. 3–5 all have the R22(14) graph set. Only the γ polymorph has the unitary-level S(7) graph set for the intramolecular interaction.

A comparison of the densities (1.257, 1.247 and 1.216 kg m-3) and packing efficiencies (71.3, 70.5 and 68.7%) for the three gabapentin polymorphs shows that the molecules are most efficiently packed in α-gabapentin and suggests, as shown by preliminary differential scanning calorimetry (DSC) sudies, that it is the thermodynamically most stable form. Hot stage microscopy and DSC (see supplementary material, Figs. 7 and 8) were used to measure the melting points of the three polymorphs, which occur over a broad temperature range. The melting points (peak positions and range) are 434.0 (428–439), 439.28 (428–441) and 436.80 (423–441) K for the α-, β- and γ-gabapentin forms, respectively. However, DSC studies also show that possible phase transitions occur at temperatures between 358 and 368 K in both the β (small endotherm) and the γ polymorphs (small exotherm), implying that the final melting points refer to only one thermodynamically stable polymorph. Further investigations of these phase transformations are currently being undertaken (Levendis & Reece, 2007). A fourth polymorph has been reported in the patent literature, referred to as form I by Lladó et al. (2003). However single crystals of this polymorph have not yet been isolated.

Related literature top

For related literature, see: Ananda et al. (2003); Bowery (1993); Ibers (2001); Levendis & Reece (2007); Lladó et al. (2003); Magnus (1999); Pesachovich et al. (2001); Satyanarayana et al. (2004); Vasudev et al. (2007); Venu et al. (2007); Wenger & Bernstein (2006).

Experimental top

Gabapentin purchased from Sigma–Aldrich was found by XRPD to correspond to the α polymorph. The β-gabapentin was prepared by dissolving the commercially available gabapentin (Sigma–Aldrich) in 96% ethanol until the solution was saturated. The solution was then heated at 333 K for 48 h. Needle-like crystals of β-gabapentin were grown from the solution at 333 K. In the preparation of γ-gabapentin, α-gabapentin was dissolved in 96% ethanol at 333 K. The solution was then cooled to room temperature. Plate-like crystals of γ-gabapentin formed after 3 d of slow evaporation (see supplementary material for photographs of the β and γ crystals; Fig. 7). In each case, crystals suitable for single-crystal X-ray diffraction were selected directly from the samples. A comparison of the experimental and calculated XRPD of each of the bulk samples confirmed that the bulk solid was, in fact, a pure form of the polymorph studied by single-crystal X-ray diffraction.

Refinement top

H atoms were positioned geometrically and allowed to ride on their respective parent atoms.

Computing details top

For both compounds, data collection: APEX2 (Bruker, 2005); cell refinement: SAINT-NT (Bruker, 2005); data reduction: SAINT-NT (Bruker, 2005); program(s) used to solve structure: SHELXTL (Bruker, 1999); program(s) used to refine structure: SHELXTL (Bruker, 1999); molecular graphics: SHELXTL (Bruker, 1999) and DIAMOND (Brandenburg, 2004); software used to prepare material for publication: SHELXTL (Bruker, 1999), ORTEP-3 (Farrugia, 1997) and PLATON (Spek, 2003).

Figures top
[Figure 1] Fig. 1. The atomic numbering scheme of β-gabapentin. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. The atomic numbering scheme of γ-gabapentin. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 3] Fig. 3. A view of the R22(14) centrosymmetric hydrogen-bonded dimer in α-gabapentin.
[Figure 4] Fig. 4. A view of the R22(14) centrosymmetric hydrogen-bonded dimer in β-gabapentin.
[Figure 5] Fig. 5. A view of the R22(14) centrosymmetric hydrogen-bonded dimer in γ-gabapentin.
[Figure 6] Fig. 6. The hydrogen-bonding networks and associated unitary- and secondary-level graph sets for α-, β- and γ-gabapentin. The α-form (left) is viewed down the a axis. The β (centre) and γ (right) forms are viewed down the b axis.
(I) 1-(ammoniomethyl)cycloheaxaneacetate top
Crystal data top
C9H17NO2F(000) = 376
Mr = 171.24Dx = 1.247 Mg m3
Monoclinic, P21/cMelting point: 439 K
Hall symbol: -P 2ybcMo Kα radiation, λ = 0.71073 Å
a = 14.5376 (16) ÅCell parameters from 868 reflections
b = 6.6329 (6) Åθ = 2.9–23.7°
c = 9.8343 (9) ŵ = 0.09 mm1
β = 105.922 (5)°T = 173 K
V = 911.91 (15) Å3Needle, colourless
Z = 40.58 × 0.10 × 0.02 mm
Data collection top
Bruker APEXII CCD detector
diffractometer
1168 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.084
Graphite monochromatorθmax = 28.0°, θmin = 1.5°
ω scansh = 1819
5118 measured reflectionsk = 88
2195 independent reflectionsl = 128
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.046Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.101H-atom parameters constrained
S = 0.87 w = 1/[σ2(Fo2) + (0.0322P)2]
where P = (Fo2 + 2Fc2)/3
2195 reflections(Δ/σ)max < 0.001
109 parametersΔρmax = 0.20 e Å3
0 restraintsΔρmin = 0.28 e Å3
Crystal data top
C9H17NO2V = 911.91 (15) Å3
Mr = 171.24Z = 4
Monoclinic, P21/cMo Kα radiation
a = 14.5376 (16) ŵ = 0.09 mm1
b = 6.6329 (6) ÅT = 173 K
c = 9.8343 (9) Å0.58 × 0.10 × 0.02 mm
β = 105.922 (5)°
Data collection top
Bruker APEXII CCD detector
diffractometer
1168 reflections with I > 2σ(I)
5118 measured reflectionsRint = 0.084
2195 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0460 restraints
wR(F2) = 0.101H-atom parameters constrained
S = 0.87Δρmax = 0.20 e Å3
2195 reflectionsΔρmin = 0.28 e Å3
109 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
xyzUiso*/Ueq
C20.10437 (13)0.2698 (3)0.47078 (19)0.0237 (4)
C30.17104 (12)0.1189 (3)0.56450 (18)0.0210 (4)
H10.13290.02300.60390.025*
H20.21480.19120.64460.025*
C40.16677 (12)0.0743 (3)0.34216 (18)0.0233 (4)
H30.14560.04350.27960.028*
H40.20530.16150.29710.028*
C10.23067 (12)0.0001 (3)0.48329 (18)0.0191 (4)
C50.28098 (12)0.1785 (3)0.57268 (18)0.0227 (4)
H70.23250.26320.59900.027*
H80.31240.26210.51500.027*
C70.35531 (13)0.1127 (3)0.70615 (19)0.0276 (5)
H90.32370.03690.76750.033*
H100.38610.23310.75880.033*
C80.43075 (13)0.0192 (3)0.6708 (2)0.0365 (5)
H110.46780.06200.61980.044*
H120.47550.06850.75950.044*
C90.38609 (12)0.1983 (3)0.5799 (2)0.0318 (5)
H130.43650.27200.55010.038*
H140.35850.29150.63690.038*
C60.30796 (12)0.1340 (3)0.44909 (19)0.0256 (4)
H50.33770.05960.38480.031*
H60.27710.25610.39870.031*
N10.08083 (10)0.1887 (2)0.35151 (15)0.0231 (4)
H150.04380.10900.39040.035*
H160.09940.29980.40650.035*
H170.04670.22740.26330.035*
O10.01899 (8)0.21326 (19)0.41666 (13)0.0272 (3)
O20.13809 (10)0.4345 (2)0.44863 (17)0.0460 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C20.0269 (10)0.0189 (11)0.0256 (10)0.0027 (9)0.0076 (9)0.0044 (9)
C30.0203 (9)0.0222 (10)0.0199 (9)0.0010 (8)0.0042 (8)0.0024 (8)
C40.0236 (9)0.0254 (11)0.0221 (10)0.0021 (8)0.0080 (9)0.0004 (9)
C10.0204 (9)0.0184 (10)0.0187 (9)0.0006 (8)0.0056 (8)0.0014 (8)
C50.0228 (9)0.0210 (11)0.0250 (10)0.0011 (8)0.0075 (8)0.0027 (9)
C70.0232 (9)0.0288 (12)0.0285 (11)0.0020 (8)0.0030 (9)0.0054 (9)
C80.0238 (10)0.0419 (14)0.0393 (13)0.0034 (10)0.0010 (10)0.0051 (11)
C90.0261 (10)0.0347 (13)0.0341 (11)0.0093 (9)0.0071 (10)0.0037 (10)
C60.0241 (10)0.0275 (11)0.0266 (10)0.0017 (8)0.0093 (9)0.0034 (9)
N10.0223 (8)0.0224 (9)0.0238 (8)0.0001 (7)0.0048 (7)0.0028 (7)
O10.0211 (6)0.0296 (8)0.0282 (7)0.0020 (6)0.0023 (6)0.0032 (6)
O20.0380 (8)0.0197 (8)0.0761 (12)0.0020 (7)0.0085 (8)0.0084 (8)
Geometric parameters (Å, º) top
C2—O21.241 (2)C7—C81.516 (2)
C2—O11.266 (2)C7—H90.9900
C2—C31.517 (2)C7—H100.9900
C3—C11.546 (2)C8—C91.521 (3)
C3—H10.9900C8—H110.9900
C3—H20.9900C8—H120.9900
C4—N11.486 (2)C9—C61.525 (2)
C4—C11.525 (2)C9—H130.9900
C4—H30.9900C9—H140.9900
C4—H40.9900C6—H50.9900
C1—C51.536 (2)C6—H60.9900
C1—C61.540 (2)N1—H150.9100
C5—C71.518 (2)N1—H160.9100
C5—H70.9900N1—H170.9100
C5—H80.9900
O2—C2—O1125.16 (17)C5—C7—H9109.5
O2—C2—C3118.05 (16)C8—C7—H10109.5
O1—C2—C3116.72 (16)C5—C7—H10109.5
C2—C3—C1112.20 (14)H9—C7—H10108.1
C2—C3—H1109.2C7—C8—C9111.49 (15)
C1—C3—H1109.2C7—C8—H11109.3
C2—C3—H2109.2C9—C8—H11109.3
C1—C3—H2109.2C7—C8—H12109.3
H1—C3—H2107.9C9—C8—H12109.3
N1—C4—C1114.93 (13)H11—C8—H12108.0
N1—C4—H3108.5C8—C9—C6112.13 (16)
C1—C4—H3108.5C8—C9—H13109.2
N1—C4—H4108.5C6—C9—H13109.2
C1—C4—H4108.5C8—C9—H14109.2
H3—C4—H4107.5C6—C9—H14109.2
C4—C1—C5110.30 (15)H13—C9—H14107.9
C4—C1—C6106.66 (13)C9—C6—C1113.34 (15)
C5—C1—C6107.97 (14)C9—C6—H5108.9
C4—C1—C3110.32 (14)C1—C6—H5108.9
C5—C1—C3110.13 (14)C9—C6—H6108.9
C6—C1—C3111.38 (15)C1—C6—H6108.9
C7—C5—C1112.80 (15)H5—C6—H6107.7
C7—C5—H7109.0C4—N1—H15109.5
C1—C5—H7109.0C4—N1—H16109.5
C7—C5—H8109.0H15—N1—H16109.5
C1—C5—H8109.0C4—N1—H17109.5
H7—C5—H8107.8H15—N1—H17109.5
C8—C7—C5110.86 (15)H16—N1—H17109.5
C8—C7—H9109.5
O2—C2—C3—C181.3 (2)C6—C1—C5—C756.37 (18)
O1—C2—C3—C195.97 (18)C3—C1—C5—C765.44 (18)
N1—C4—C1—C569.42 (18)C1—C5—C7—C858.3 (2)
N1—C4—C1—C6173.57 (14)C5—C7—C8—C954.7 (2)
N1—C4—C1—C352.5 (2)C7—C8—C9—C652.5 (2)
C2—C3—C1—C446.4 (2)C8—C9—C6—C153.3 (2)
C2—C3—C1—C5168.37 (14)C4—C1—C6—C9172.22 (15)
C2—C3—C1—C671.87 (18)C5—C1—C6—C953.7 (2)
C4—C1—C5—C7172.56 (13)C3—C1—C6—C967.35 (19)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H15···O10.912.192.9398 (19)139
N1—H15···O1i0.912.423.0242 (18)124
N1—H16···O2ii0.911.862.723 (2)157
N1—H17···O1iii0.911.812.7174 (19)176
Symmetry codes: (i) x, y, z+1; (ii) x, y1, z; (iii) x, y1/2, z+1/2.
(II) 1-(ammoniomethyl)cycloheaxaneacetate top
Crystal data top
C9H17NO2F(000) = 752
Mr = 171.24Dx = 1.216 Mg m3
Monoclinic, C2/cMelting point: 437 K
Hall symbol: -C 2ycMo Kα radiation, λ = 0.71073 Å
a = 30.5452 (11) ÅCell parameters from 2596 reflections
b = 5.9268 (2) Åθ = 2.8–27.9°
c = 10.8841 (4) ŵ = 0.09 mm1
β = 108.316 (2)°T = 173 K
V = 1870.58 (12) Å3Plate, colourless
Z = 80.58 × 0.49 × 0.11 mm
Data collection top
Bruker APEXII CCD detector
diffractometer
1608 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.031
Graphite monochromatorθmax = 27.0°, θmin = 1.4°
ω scansh = 3837
7746 measured reflectionsk = 77
2042 independent reflectionsl = 1313
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.046Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.125H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.0542P)2 + 1.349P]
where P = (Fo2 + 2Fc2)/3
2042 reflections(Δ/σ)max = 0.002
110 parametersΔρmax = 0.24 e Å3
0 restraintsΔρmin = 0.17 e Å3
Crystal data top
C9H17NO2V = 1870.58 (12) Å3
Mr = 171.24Z = 8
Monoclinic, C2/cMo Kα radiation
a = 30.5452 (11) ŵ = 0.09 mm1
b = 5.9268 (2) ÅT = 173 K
c = 10.8841 (4) Å0.58 × 0.49 × 0.11 mm
β = 108.316 (2)°
Data collection top
Bruker APEXII CCD detector
diffractometer
1608 reflections with I > 2σ(I)
7746 measured reflectionsRint = 0.031
2042 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0460 restraints
wR(F2) = 0.125H-atom parameters constrained
S = 1.06Δρmax = 0.24 e Å3
2042 reflectionsΔρmin = 0.17 e Å3
110 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
xyzUiso*/Ueq
C10.36190 (5)0.2176 (3)0.72157 (14)0.0310 (3)
C20.30226 (5)0.2639 (3)0.48949 (14)0.0311 (3)
C30.32851 (6)0.1096 (3)0.59961 (14)0.0334 (4)
H30.34630.00140.56480.040*
H40.30560.02100.62650.040*
C40.33683 (5)0.3708 (3)0.79133 (15)0.0331 (4)
H10.35870.41230.87670.040*
H20.32790.51150.74060.040*
C50.39772 (6)0.3621 (3)0.68455 (18)0.0433 (4)
H50.41010.27360.62570.052*
H60.38210.49660.63650.052*
C60.38743 (6)0.0247 (3)0.81054 (16)0.0389 (4)
H130.36510.05730.84320.047*
H140.39910.08270.75860.047*
C70.43791 (7)0.4397 (4)0.8004 (2)0.0576 (5)
H70.46040.52300.76910.069*
H80.42630.54390.85420.069*
C80.46176 (7)0.2409 (4)0.8823 (2)0.0649 (6)
H90.47630.14510.83140.078*
H100.48640.29680.95920.078*
C90.42760 (7)0.1015 (4)0.92549 (18)0.0530 (5)
H110.41570.19250.98450.064*
H120.44350.03220.97390.064*
N10.29507 (4)0.2717 (2)0.81185 (12)0.0332 (3)
H150.27110.27930.73690.050*
H160.28790.35010.87480.050*
H170.30060.12490.83640.050*
O10.29105 (4)0.1805 (2)0.37705 (10)0.0381 (3)
O20.29272 (4)0.4596 (2)0.51366 (11)0.0418 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0362 (8)0.0254 (7)0.0307 (7)0.0041 (6)0.0093 (6)0.0027 (6)
C20.0329 (8)0.0308 (8)0.0302 (7)0.0003 (6)0.0108 (6)0.0034 (6)
C30.0449 (9)0.0270 (8)0.0289 (8)0.0046 (6)0.0122 (7)0.0005 (6)
C40.0383 (8)0.0261 (8)0.0332 (8)0.0011 (6)0.0087 (6)0.0032 (6)
C50.0442 (9)0.0379 (9)0.0499 (10)0.0016 (7)0.0180 (8)0.0069 (8)
C60.0438 (9)0.0322 (8)0.0385 (9)0.0086 (7)0.0099 (7)0.0056 (7)
C70.0399 (10)0.0500 (12)0.0771 (14)0.0055 (9)0.0102 (9)0.0043 (11)
C80.0391 (10)0.0626 (14)0.0783 (15)0.0056 (9)0.0026 (10)0.0015 (12)
C90.0513 (11)0.0503 (11)0.0461 (11)0.0142 (9)0.0006 (8)0.0079 (9)
N10.0364 (7)0.0308 (7)0.0295 (6)0.0048 (5)0.0061 (5)0.0038 (5)
O10.0444 (7)0.0380 (6)0.0287 (6)0.0000 (5)0.0071 (5)0.0001 (5)
O20.0570 (7)0.0319 (6)0.0369 (6)0.0118 (5)0.0154 (5)0.0056 (5)
Geometric parameters (Å, º) top
C1—C41.534 (2)C6—C91.521 (2)
C1—C31.537 (2)C6—H130.9900
C1—C51.539 (2)C6—H140.9900
C1—C61.542 (2)C7—C81.518 (3)
C2—O21.2440 (19)C7—H70.9900
C2—O11.2632 (19)C7—H80.9900
C2—C31.520 (2)C8—C91.517 (3)
C3—H30.9900C8—H90.9900
C3—H40.9900C8—H100.9900
C4—N11.484 (2)C9—H110.9900
C4—H10.9900C9—H120.9900
C4—H20.9900N1—H150.9100
C5—C71.528 (3)N1—H160.9100
C5—H50.9900N1—H170.9100
C5—H60.9900
C4—C1—C3112.05 (12)C1—C6—H13108.7
C4—C1—C5107.87 (13)C9—C6—H14108.7
C3—C1—C5109.82 (13)C1—C6—H14108.7
C4—C1—C6111.14 (13)H13—C6—H14107.6
C3—C1—C6107.51 (13)C8—C7—C5111.32 (17)
C5—C1—C6108.42 (13)C8—C7—H7109.4
O2—C2—O1124.01 (14)C5—C7—H7109.4
O2—C2—C3119.65 (13)C8—C7—H8109.4
O1—C2—C3116.34 (13)C5—C7—H8109.4
C2—C3—C1118.21 (13)H7—C7—H8108.0
C2—C3—H3107.8C9—C8—C7110.78 (16)
C1—C3—H3107.8C9—C8—H9109.5
C2—C3—H4107.8C7—C8—H9109.5
C1—C3—H4107.8C9—C8—H10109.5
H3—C3—H4107.1C7—C8—H10109.5
N1—C4—C1115.27 (13)H9—C8—H10108.1
N1—C4—H1108.5C8—C9—C6111.33 (16)
C1—C4—H1108.5C8—C9—H11109.4
N1—C4—H2108.5C6—C9—H11109.4
C1—C4—H2108.5C8—C9—H12109.4
H1—C4—H2107.5C6—C9—H12109.4
C7—C5—C1113.85 (15)H11—C9—H12108.0
C7—C5—H5108.8C4—N1—H15109.5
C1—C5—H5108.8C4—N1—H16109.5
C7—C5—H6108.8H15—N1—H16109.5
C1—C5—H6108.8C4—N1—H17109.5
H5—C5—H6107.7H15—N1—H17109.5
C9—C6—C1114.37 (14)H16—N1—H17109.5
C9—C6—H13108.7
O2—C2—C3—C129.1 (2)C3—C1—C5—C7168.79 (15)
O1—C2—C3—C1151.56 (14)C6—C1—C5—C751.60 (19)
C4—C1—C3—C263.47 (18)C4—C1—C6—C966.85 (19)
C5—C1—C3—C256.38 (18)C3—C1—C6—C9170.20 (14)
C6—C1—C3—C2174.14 (14)C5—C1—C6—C951.54 (19)
C3—C1—C4—N147.74 (17)C1—C5—C7—C855.5 (2)
C5—C1—C4—N1168.72 (13)C5—C7—C8—C955.8 (3)
C6—C1—C4—N172.56 (17)C7—C8—C9—C655.4 (2)
C4—C1—C5—C768.85 (18)C1—C6—C9—C855.0 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H15···O1i0.911.932.7980 (16)159
N1—H16···O2ii0.911.852.7324 (17)161
N1—H17···O1iii0.911.912.7851 (18)161
Symmetry codes: (i) x+1/2, y+1/2, z+1; (ii) x, y+1, z+1/2; (iii) x, y, z+1/2.

Experimental details

(I)(II)
Crystal data
Chemical formulaC9H17NO2C9H17NO2
Mr171.24171.24
Crystal system, space groupMonoclinic, P21/cMonoclinic, C2/c
Temperature (K)173173
a, b, c (Å)14.5376 (16), 6.6329 (6), 9.8343 (9)30.5452 (11), 5.9268 (2), 10.8841 (4)
β (°) 105.922 (5) 108.316 (2)
V3)911.91 (15)1870.58 (12)
Z48
Radiation typeMo KαMo Kα
µ (mm1)0.090.09
Crystal size (mm)0.58 × 0.10 × 0.020.58 × 0.49 × 0.11
Data collection
DiffractometerBruker APEXII CCD detector
diffractometer
Bruker APEXII CCD detector
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
5118, 2195, 1168 7746, 2042, 1608
Rint0.0840.031
(sin θ/λ)max1)0.6600.639
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.046, 0.101, 0.87 0.046, 0.125, 1.06
No. of reflections21952042
No. of parameters109110
H-atom treatmentH-atom parameters constrainedH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.20, 0.280.24, 0.17

Computer programs: APEX2 (Bruker, 2005), SAINT-NT (Bruker, 2005), SHELXTL (Bruker, 1999) and DIAMOND (Brandenburg, 2004), SHELXTL (Bruker, 1999), ORTEP-3 (Farrugia, 1997) and PLATON (Spek, 2003).

Table 2: Selected torsion angles(°) for the α-, β- and γ-polymorphs of gabapentin top
Torsionαaβγ
C3-C1-C5-C7-166.22-65.44 (18)-168.79 (15)
O1-C2-C3-C1-161.3695.97 (18)151.56 (14)
C2-C3-C1-C451.21-46.4 (2)63.47 (18)
C3-C1-C4-N160.07-52.5 (2)47.74 (17)
C2-C3-C1-C5-68.63-168.37 (14)-56.38 (18)
C2-C3-C1-C6172.5271.87 (18)-174.14 (14)
N1-C4-C1-C6-58.28-173.57 (14)-72.56 (17)
N1-C4-C1-C5-178.7169.42 (18)168.72 (13)
Notes: (a) Parameters extracted from Ibers, (2001).
Table 3: Hydrogen bonding parameters (Å) for the α-,β- and γ-polymorphs of gabapentin top
D-H—AD-HH—AD—AD-H—A
α-gabapentin
N1-H15—O1i,a0.9181.9102.7827 (16)158.2
N1-H16—O2ii,a0.921.852.7525 (16)165.3
N1-H17—O1iii,a0.961.812.7547 (18)165.8
β-gabapentin
N1-H15—O10.912.192.9398 (19)138.7
N1-H15—O1i,b0.912.423.0242 (18)123.8
N1-H16—O2ii,b0.911.862.723 (2)157.0
N1-H17—O1iii,b0.911.812.7174 (19)175.8
γ-gabapentin
N1-H15—O1i,c0.911.932.7980 (16)159.2
N1-H16—O2ii,c0.911.852.7324 (17)161.5
N1-H17—O1iii,c0.911.912.7851 (18)161.3
Notes: 1.) Symmetry codes: a. (i) -x+1, -y+1, -z+1; (ii) -x, -y+1, -z+1; (iii) x, y+1, z; b. (i) -x, -y, -z+1; (ii) x, y-1, z; (iii) -x, y-1/2, -z+1/2; c. (i) -x+1/2, -y+1/2, -z+1; (ii) x, -y+1, z+1/2; (iii) x, -y, z+1/2.

2.) α-gabapentin parameters extracted from Ibers, (2001).
 

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