Gabapentin [1-(aminomethyl)cyclohexaneacetic acid, C9H17NO2] is a zwitterion in the solid state. Its crystal structure involves extensive hydrogen bonding between the NH3+ and COO- groups of neighboring molecules. The structure of gabapentin monohydrate [1-(aminomethyl)cyclohexaneacetic acid monohydrate, C9H17NO2·H2O] also involves such hydrogen bonding and, in addition, has a hydrogen-bonding network comprising the water molecules and both the NH3+ and COO- groups.
Supporting information
CCDC references: 164684; 164685
The sample of gabapentin provided by Purepac Pharmaceutical Company contained
crystals suitable for diffraction studies. For the preparation of the
monohydrate, 160 mg of gabapentin was dissolved in 1 ml of water and 3 ml of
2-propanol was added. The resultant solution was placed in a freezer. Four
days later, crystals of gabapentin monohydrate were harvested from the
precipitate, which also contained gabapentin. The two materials differ in
their crystal habits and are readily distinguished from one another.
The positional and isotropic displacement parameters of all H atoms were
refined. The refined C—H distances are in the range 0.95 (2)–1.02 (2) Å for
gabapentin and 0.96 (2)–1.05 (2) Å for gabapentin monohydrate.
For both compounds, data collection: SMART (Bruker, 2000); cell refinement: SMART; data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997a); molecular graphics: SHELXTL/PC (Sheldrick, 1997b); software used to prepare material for publication: SHELXL97.
(I) 1-(aminomethyl)cyclohexaneacetic acid
top
Crystal data top
C9H17NO2 | F(000) = 376 |
Mr = 171.24 | Dx = 1.257 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 5.8759 (6) Å | Cell parameters from 2674 reflections |
b = 6.9198 (7) Å | θ = 6.2–28.1° |
c = 22.262 (2) Å | µ = 0.09 mm−1 |
β = 90.080 (2)° | T = 153 K |
V = 905.18 (16) Å3 | Needle, colourless |
Z = 4 | 0.30 × 0.09 × 0.09 mm |
Data collection top
Bruker SMART 1000 CCD diffractometer | 1572 reflections with I > 2σ(I) |
Radiation source: standard-focus sealed tube | Rint = 0.042 |
Graphite monochromator | θmax = 28.3°, θmin = 1.8° |
ω scans | h = −7→7 |
7951 measured reflections | k = −8→8 |
2147 independent reflections | l = −29→29 |
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) = 0.118 | All H-atom parameters refined |
S = 0.98 | w = 1/[σ2(Fo2) + (0.0752Fo2)2] |
2147 reflections | (Δ/σ)max < 0.001 |
177 parameters | Δρmax = 0.39 e Å−3 |
0 restraints | Δρmin = −0.21 e Å−3 |
Crystal data top
C9H17NO2 | V = 905.18 (16) Å3 |
Mr = 171.24 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 5.8759 (6) Å | µ = 0.09 mm−1 |
b = 6.9198 (7) Å | T = 153 K |
c = 22.262 (2) Å | 0.30 × 0.09 × 0.09 mm |
β = 90.080 (2)° | |
Data collection top
Bruker SMART 1000 CCD diffractometer | 1572 reflections with I > 2σ(I) |
7951 measured reflections | Rint = 0.042 |
2147 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.046 | 0 restraints |
wR(F2) = 0.118 | All H-atom parameters refined |
S = 0.98 | Δρmax = 0.39 e Å−3 |
2147 reflections | Δρmin = −0.21 e Å−3 |
177 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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.32783 (16) | 0.22232 (14) | 0.47786 (5) | 0.0240 (3) | |
O2 | 0.03209 (16) | 0.32934 (15) | 0.42512 (5) | 0.0275 (3) | |
N1 | 0.2248 (2) | 0.83466 (18) | 0.48502 (6) | 0.0204 (3) | |
HN1 | 0.368 (3) | 0.786 (2) | 0.4921 (8) | 0.026 (4)* | |
HN2 | 0.128 (3) | 0.801 (3) | 0.5156 (9) | 0.036 (5)* | |
HN3 | 0.238 (3) | 0.973 (3) | 0.4858 (8) | 0.039 (5)* | |
C1 | 0.2946 (2) | 0.67267 (19) | 0.38403 (6) | 0.0191 (3) | |
C2 | 0.1690 (2) | 0.6198 (2) | 0.32528 (7) | 0.0227 (3) | |
H2A | 0.270 (2) | 0.534 (2) | 0.3024 (7) | 0.020 (4)* | |
H2B | 0.030 (3) | 0.547 (2) | 0.3354 (7) | 0.026 (4)* | |
C3 | 0.1122 (2) | 0.7931 (2) | 0.28509 (7) | 0.0256 (3) | |
H3A | 0.042 (3) | 0.746 (2) | 0.2468 (9) | 0.029 (4)* | |
H3B | −0.002 (3) | 0.877 (2) | 0.3054 (7) | 0.024 (4)* | |
C4 | 0.3237 (2) | 0.9141 (2) | 0.27181 (7) | 0.0262 (3) | |
H4A | 0.438 (2) | 0.836 (2) | 0.2475 (7) | 0.020 (4)* | |
H4B | 0.285 (3) | 1.031 (2) | 0.2465 (8) | 0.028 (4)* | |
C5 | 0.4363 (2) | 0.9798 (2) | 0.33004 (7) | 0.0249 (3) | |
H5A | 0.577 (2) | 1.051 (2) | 0.3221 (7) | 0.026 (4)* | |
H5B | 0.336 (3) | 1.071 (2) | 0.3521 (8) | 0.026 (4)* | |
C6 | 0.4984 (2) | 0.8074 (2) | 0.36947 (7) | 0.0210 (3) | |
H6A | 0.569 (2) | 0.851 (2) | 0.4078 (7) | 0.016 (4)* | |
H6B | 0.618 (2) | 0.730 (2) | 0.3481 (7) | 0.019 (4)* | |
C7 | 0.1240 (2) | 0.7711 (2) | 0.42632 (6) | 0.0209 (3) | |
H7A | 0.061 (2) | 0.886 (2) | 0.4076 (7) | 0.019 (4)* | |
H7B | 0.000 (3) | 0.686 (2) | 0.4339 (7) | 0.022 (4)* | |
C8 | 0.3956 (2) | 0.4900 (2) | 0.41369 (6) | 0.0203 (3) | |
H8A | 0.486 (2) | 0.425 (2) | 0.3827 (7) | 0.022 (4)* | |
H8B | 0.506 (2) | 0.525 (2) | 0.4449 (7) | 0.021 (4)* | |
C9 | 0.2368 (2) | 0.33823 (19) | 0.44058 (6) | 0.0204 (3) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0265 (5) | 0.0210 (5) | 0.0247 (6) | −0.0011 (4) | −0.0029 (4) | 0.0049 (4) |
O2 | 0.0213 (5) | 0.0329 (6) | 0.0282 (6) | −0.0049 (4) | −0.0012 (4) | 0.0085 (5) |
N1 | 0.0202 (6) | 0.0207 (6) | 0.0202 (6) | −0.0004 (4) | 0.0020 (5) | 0.0006 (5) |
C1 | 0.0196 (6) | 0.0194 (7) | 0.0184 (7) | −0.0010 (5) | 0.0012 (5) | 0.0010 (5) |
C2 | 0.0242 (7) | 0.0224 (7) | 0.0215 (8) | −0.0012 (5) | 0.0001 (6) | 0.0004 (6) |
C3 | 0.0266 (7) | 0.0283 (8) | 0.0217 (8) | −0.0008 (6) | −0.0019 (6) | 0.0037 (6) |
C4 | 0.0305 (8) | 0.0258 (8) | 0.0223 (8) | −0.0003 (6) | 0.0021 (6) | 0.0051 (6) |
C5 | 0.0253 (7) | 0.0217 (7) | 0.0277 (8) | −0.0023 (5) | 0.0031 (6) | 0.0026 (6) |
C6 | 0.0212 (7) | 0.0225 (7) | 0.0192 (7) | −0.0016 (5) | 0.0012 (6) | 0.0009 (6) |
C7 | 0.0194 (6) | 0.0230 (7) | 0.0202 (7) | 0.0006 (5) | 0.0007 (5) | 0.0007 (6) |
C8 | 0.0198 (6) | 0.0209 (7) | 0.0202 (7) | 0.0000 (5) | 0.0008 (6) | 0.0009 (6) |
C9 | 0.0237 (7) | 0.0193 (7) | 0.0181 (7) | 0.0001 (5) | 0.0029 (5) | −0.0016 (5) |
Geometric parameters (Å, º) top
O1—C9 | 1.2717 (17) | C3—H3B | 0.995 (16) |
O2—C9 | 1.2519 (17) | C4—C5 | 1.524 (2) |
N1—C7 | 1.4998 (19) | C4—H4A | 1.018 (16) |
N1—HN1 | 0.918 (18) | C4—H4B | 1.011 (18) |
N1—HN2 | 0.92 (2) | C5—C6 | 1.525 (2) |
N1—HN3 | 0.96 (2) | C5—H5A | 0.978 (15) |
C1—C7 | 1.5353 (19) | C5—H5B | 0.994 (17) |
C1—C2 | 1.544 (2) | C6—H6A | 0.995 (16) |
C1—C8 | 1.5446 (18) | C6—H6B | 1.007 (15) |
C1—C6 | 1.5524 (18) | C7—H7A | 0.973 (16) |
C2—C3 | 1.533 (2) | C7—H7B | 0.954 (16) |
C2—H2A | 0.981 (16) | C8—C9 | 1.5277 (18) |
C2—H2B | 0.987 (16) | C8—H8A | 0.982 (17) |
C3—C4 | 1.528 (2) | C8—H8B | 0.979 (15) |
C3—H3A | 0.999 (19) | | |
| | | |
C7—N1—HN1 | 113.8 (11) | H4A—C4—H4B | 106.1 (13) |
C7—N1—HN2 | 109.1 (12) | C4—C5—C6 | 111.07 (12) |
HN1—N1—HN2 | 110.2 (16) | C4—C5—H5A | 111.2 (9) |
C7—N1—HN3 | 109.9 (11) | C6—C5—H5A | 107.1 (9) |
HN1—N1—HN3 | 106.7 (14) | C4—C5—H5B | 110.5 (9) |
HN2—N1—HN3 | 106.9 (15) | C6—C5—H5B | 110.8 (10) |
C7—C1—C2 | 108.23 (11) | H5A—C5—H5B | 106.0 (13) |
C7—C1—C8 | 110.60 (11) | C5—C6—C1 | 113.95 (11) |
C2—C1—C8 | 110.56 (11) | C5—C6—H6A | 110.9 (9) |
C7—C1—C6 | 111.47 (11) | C1—C6—H6A | 108.8 (9) |
C2—C1—C6 | 109.45 (11) | C5—C6—H6B | 108.2 (9) |
C8—C1—C6 | 106.54 (10) | C1—C6—H6B | 108.5 (8) |
C3—C2—C1 | 114.37 (12) | H6A—C6—H6B | 106.1 (12) |
C3—C2—H2A | 107.5 (9) | N1—C7—C1 | 114.03 (11) |
C1—C2—H2A | 107.2 (9) | N1—C7—H7A | 106.4 (9) |
C3—C2—H2B | 110.7 (9) | C1—C7—H7A | 110.5 (9) |
C1—C2—H2B | 108.9 (10) | N1—C7—H7B | 109.2 (10) |
H2A—C2—H2B | 108.0 (13) | C1—C7—H7B | 109.6 (10) |
C4—C3—C2 | 111.42 (12) | H7A—C7—H7B | 106.8 (13) |
C4—C3—H3A | 110.2 (10) | C9—C8—C1 | 119.68 (11) |
C2—C3—H3A | 109.5 (10) | C9—C8—H8A | 107.1 (9) |
C4—C3—H3B | 108.3 (9) | C1—C8—H8A | 106.4 (9) |
C2—C3—H3B | 109.8 (10) | C9—C8—H8B | 107.2 (9) |
H3A—C3—H3B | 107.4 (13) | C1—C8—H8B | 110.7 (9) |
C5—C4—C3 | 110.54 (12) | H8A—C8—H8B | 104.7 (12) |
C5—C4—H4A | 109.0 (9) | O2—C9—O1 | 123.48 (12) |
C3—C4—H4A | 110.4 (9) | O2—C9—C8 | 120.88 (12) |
C5—C4—H4B | 109.4 (10) | O1—C9—C8 | 115.62 (12) |
C3—C4—H4B | 111.2 (9) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—HN1···O1i | 0.918 (18) | 1.910 (18) | 2.7827 (16) | 158.2 (15) |
N1—HN2···O2ii | 0.92 (2) | 1.85 (2) | 2.7525 (16) | 165.3 (16) |
N1—HN3···O1iii | 0.96 (2) | 1.81 (2) | 2.7547 (16) | 165.8 (16) |
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x, −y+1, −z+1; (iii) x, y+1, z. |
(II) 1-(aminomethyl)cyclohexaneacetic acid monohydrate
top
Crystal data top
C9H17NO2·H2O | F(000) = 416 |
Mr = 189.25 | Dx = 1.226 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 14.567 (3) Å | Cell parameters from 1958 reflections |
b = 9.2153 (18) Å | θ = 2.6–28.2° |
c = 7.6503 (15) Å | µ = 0.09 mm−1 |
β = 93.375 (3)° | T = 153 K |
V = 1025.2 (3) Å3 | Flat plate, colourless |
Z = 4 | 0.35 × 0.26 × 0.03 mm |
Data collection top
Bruker SMART 1000 CCD diffractometer | 2461 independent reflections |
Radiation source: standard-focus sealed tube | 1550 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.058 |
ω scans | θmax = 28.3°, θmin = 1.4° |
Absorption correction: numerical face indexed | h = −19→18 |
Tmin = 0.972, Tmax = 0.998 | k = −12→12 |
9122 measured reflections | l = −10→10 |
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) = 0.133 | All H-atom parameters refined |
S = 0.97 | w = 1/[σ2(Fo2) + (0.07Fo2)2] |
2461 reflections | (Δ/σ)max < 0.001 |
194 parameters | Δρmax = 0.42 e Å−3 |
0 restraints | Δρmin = −0.22 e Å−3 |
Crystal data top
C9H17NO2·H2O | V = 1025.2 (3) Å3 |
Mr = 189.25 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 14.567 (3) Å | µ = 0.09 mm−1 |
b = 9.2153 (18) Å | T = 153 K |
c = 7.6503 (15) Å | 0.35 × 0.26 × 0.03 mm |
β = 93.375 (3)° | |
Data collection top
Bruker SMART 1000 CCD diffractometer | 2461 independent reflections |
Absorption correction: numerical face indexed | 1550 reflections with I > 2σ(I) |
Tmin = 0.972, Tmax = 0.998 | Rint = 0.058 |
9122 measured reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.057 | 0 restraints |
wR(F2) = 0.133 | All H-atom parameters refined |
S = 0.97 | Δρmax = 0.42 e Å−3 |
2461 reflections | Δρmin = −0.22 e Å−3 |
194 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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.83595 (10) | 0.39302 (13) | 1.10528 (16) | 0.0257 (3) | |
O2 | 0.89054 (10) | 0.61784 (14) | 1.08593 (16) | 0.0295 (4) | |
OW | 0.96959 (10) | 0.84570 (16) | 0.91842 (19) | 0.0283 (4) | |
HWA | 0.9419 (15) | 0.766 (3) | 0.953 (3) | 0.042 (7)* | |
HWB | 0.938 (2) | 0.863 (3) | 0.814 (4) | 0.077 (10)* | |
N1 | 0.84714 (12) | 0.39236 (18) | 0.4660 (2) | 0.0203 (4) | |
HN1 | 0.8344 (14) | 0.294 (2) | 0.499 (3) | 0.033 (6)* | |
HN2 | 0.9057 (15) | 0.411 (2) | 0.508 (3) | 0.028 (6)* | |
HN3 | 0.8494 (15) | 0.394 (2) | 0.333 (3) | 0.038 (6)* | |
C1 | 0.76548 (13) | 0.49637 (19) | 0.7233 (2) | 0.0189 (4) | |
C2 | 0.70261 (13) | 0.3682 (2) | 0.7676 (2) | 0.0222 (4) | |
H2A | 0.7299 (12) | 0.279 (2) | 0.729 (2) | 0.019 (5)* | |
H2B | 0.6992 (13) | 0.362 (2) | 0.899 (3) | 0.025 (5)* | |
C3 | 0.60350 (15) | 0.3842 (2) | 0.6939 (3) | 0.0319 (5) | |
H3A | 0.5693 (14) | 0.300 (2) | 0.735 (3) | 0.035 (6)* | |
H3B | 0.6032 (15) | 0.377 (2) | 0.557 (3) | 0.034 (6)* | |
C4 | 0.56156 (15) | 0.5276 (3) | 0.7484 (3) | 0.0358 (5) | |
H4A | 0.5583 (15) | 0.529 (2) | 0.883 (3) | 0.039 (6)* | |
H4B | 0.4967 (17) | 0.539 (2) | 0.705 (3) | 0.038 (6)* | |
C5 | 0.62091 (15) | 0.6548 (2) | 0.6957 (3) | 0.0315 (5) | |
H5A | 0.6187 (13) | 0.666 (2) | 0.562 (3) | 0.033 (6)* | |
H5B | 0.5957 (13) | 0.749 (2) | 0.735 (3) | 0.029 (5)* | |
C6 | 0.71894 (14) | 0.6400 (2) | 0.7735 (3) | 0.0237 (4) | |
H6A | 0.7161 (13) | 0.644 (2) | 0.905 (3) | 0.027 (5)* | |
H6B | 0.7582 (13) | 0.723 (2) | 0.742 (3) | 0.026 (5)* | |
C7 | 0.78050 (13) | 0.5022 (2) | 0.5256 (2) | 0.0207 (4) | |
H7A | 0.7209 (13) | 0.4862 (19) | 0.458 (3) | 0.022 (5)* | |
H7B | 0.8059 (12) | 0.603 (2) | 0.496 (2) | 0.014 (4)* | |
C8 | 0.86156 (13) | 0.4847 (2) | 0.8203 (2) | 0.0193 (4) | |
H8A | 0.8909 (13) | 0.392 (2) | 0.802 (2) | 0.017 (5)* | |
H8B | 0.9023 (13) | 0.560 (2) | 0.780 (3) | 0.023 (5)* | |
C9 | 0.86289 (13) | 0.50075 (19) | 1.0188 (2) | 0.0203 (4) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0441 (9) | 0.0240 (7) | 0.0091 (6) | −0.0046 (6) | 0.0023 (5) | 0.0012 (5) |
O2 | 0.0503 (9) | 0.0253 (8) | 0.0127 (7) | −0.0079 (6) | −0.0009 (6) | −0.0027 (5) |
OW | 0.0340 (8) | 0.0310 (8) | 0.0191 (8) | −0.0069 (6) | −0.0044 (6) | 0.0039 (6) |
N1 | 0.0273 (9) | 0.0230 (9) | 0.0104 (8) | −0.0003 (7) | 0.0006 (6) | −0.0001 (6) |
C1 | 0.0254 (9) | 0.0224 (9) | 0.0089 (8) | 0.0000 (7) | 0.0013 (7) | 0.0009 (7) |
C2 | 0.0269 (11) | 0.0255 (11) | 0.0141 (9) | −0.0007 (8) | 0.0014 (8) | 0.0014 (7) |
C3 | 0.0306 (11) | 0.0365 (12) | 0.0284 (12) | −0.0063 (9) | −0.0005 (9) | 0.0044 (9) |
C4 | 0.0256 (12) | 0.0480 (14) | 0.0339 (13) | 0.0045 (10) | 0.0031 (10) | 0.0057 (10) |
C5 | 0.0370 (13) | 0.0340 (12) | 0.0236 (11) | 0.0112 (10) | 0.0034 (9) | 0.0023 (9) |
C6 | 0.0307 (11) | 0.0252 (11) | 0.0154 (10) | 0.0015 (8) | 0.0041 (8) | −0.0010 (8) |
C7 | 0.0273 (10) | 0.0246 (10) | 0.0102 (9) | 0.0040 (8) | 0.0010 (7) | 0.0013 (7) |
C8 | 0.0266 (10) | 0.0231 (10) | 0.0083 (8) | −0.0013 (8) | 0.0012 (7) | 0.0001 (7) |
C9 | 0.0257 (10) | 0.0234 (10) | 0.0117 (9) | 0.0006 (8) | 0.0014 (7) | 0.0000 (7) |
Geometric parameters (Å, º) top
O1—C9 | 1.268 (2) | C3—H3A | 0.98 (2) |
O2—C9 | 1.251 (2) | C3—H3B | 1.05 (2) |
OW—HWA | 0.88 (3) | C4—C5 | 1.525 (3) |
OW—HWB | 0.91 (3) | C4—H4A | 1.03 (2) |
N1—C7 | 1.493 (2) | C4—H4B | 0.99 (2) |
N1—HN1 | 0.96 (2) | C5—C6 | 1.521 (3) |
N1—HN2 | 0.91 (2) | C5—H5A | 1.03 (2) |
N1—HN3 | 1.02 (2) | C5—H5B | 0.99 (2) |
C1—C7 | 1.542 (2) | C6—H6A | 1.01 (2) |
C1—C2 | 1.544 (2) | C6—H6B | 0.99 (2) |
C1—C6 | 1.546 (2) | C7—H7A | 0.99 (2) |
C1—C8 | 1.549 (3) | C7—H7B | 1.033 (18) |
C2—C3 | 1.526 (3) | C8—C9 | 1.525 (2) |
C2—H2A | 0.965 (19) | C8—H8A | 0.969 (19) |
C2—H2B | 1.01 (2) | C8—H8B | 0.98 (2) |
C3—C4 | 1.524 (3) | | |
| | | |
HWA—OW—HWB | 101 (2) | C5—C4—H4B | 111.8 (12) |
C7—N1—HN1 | 114.8 (12) | H4A—C4—H4B | 103.4 (18) |
C7—N1—HN2 | 112.2 (13) | C6—C5—C4 | 111.17 (17) |
HN1—N1—HN2 | 106.3 (17) | C6—C5—H5A | 111.9 (11) |
C7—N1—HN3 | 110.9 (12) | C4—C5—H5A | 110.6 (11) |
HN1—N1—HN3 | 106.9 (17) | C6—C5—H5B | 108.5 (12) |
HN2—N1—HN3 | 105.2 (18) | C4—C5—H5B | 111.5 (11) |
C7—C1—C2 | 111.23 (15) | H5A—C5—H5B | 102.9 (15) |
C7—C1—C6 | 107.67 (15) | C5—C6—C1 | 113.28 (16) |
C2—C1—C6 | 109.01 (15) | C5—C6—H6A | 107.1 (11) |
C7—C1—C8 | 107.22 (15) | C1—C6—H6A | 108.8 (11) |
C2—C1—C8 | 111.88 (15) | C5—C6—H6B | 112.1 (11) |
C6—C1—C8 | 109.73 (15) | C1—C6—H6B | 109.2 (11) |
C3—C2—C1 | 113.95 (16) | H6A—C6—H6B | 106.0 (15) |
C3—C2—H2A | 111.5 (11) | N1—C7—C1 | 114.11 (15) |
C1—C2—H2A | 108.9 (11) | N1—C7—H7A | 107.7 (11) |
C3—C2—H2B | 105.8 (11) | C1—C7—H7A | 109.4 (11) |
C1—C2—H2B | 108.9 (11) | N1—C7—H7B | 107.3 (10) |
H2A—C2—H2B | 107.5 (15) | C1—C7—H7B | 108.6 (10) |
C4—C3—C2 | 111.62 (18) | H7A—C7—H7B | 109.6 (14) |
C4—C3—H3A | 112.2 (12) | C9—C8—C1 | 115.38 (15) |
C2—C3—H3A | 107.0 (12) | C9—C8—H8A | 104.6 (11) |
C4—C3—H3B | 110.6 (11) | C1—C8—H8A | 112.6 (11) |
C2—C3—H3B | 108.1 (12) | C9—C8—H8B | 105.7 (12) |
H3A—C3—H3B | 107.1 (16) | C1—C8—H8B | 110.4 (11) |
C3—C4—C5 | 110.60 (18) | H8A—C8—H8B | 107.6 (16) |
C3—C4—H4A | 109.1 (12) | O2—C9—O1 | 124.28 (17) |
C5—C4—H4A | 108.2 (13) | O2—C9—C8 | 118.50 (16) |
C3—C4—H4B | 113.3 (13) | O1—C9—C8 | 117.22 (16) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
OW—HWA···O2 | 0.88 (3) | 1.89 (3) | 2.748 (2) | 165 (2) |
OW—HWB···O2i | 0.91 (3) | 1.85 (3) | 2.7503 (19) | 170 (3) |
N1—HN1···O1ii | 0.96 (2) | 1.91 (2) | 2.846 (2) | 165.1 (18) |
N1—HN2···OWiii | 0.91 (2) | 1.97 (2) | 2.796 (2) | 151.0 (18) |
N1—HN3···O1iv | 1.02 (2) | 1.74 (2) | 2.755 (2) | 171.7 (19) |
Symmetry codes: (i) x, −y+3/2, z−1/2; (ii) x, −y+1/2, z−1/2; (iii) −x+2, y−1/2, −z+3/2; (iv) x, y, z−1. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C9H17NO2 | C9H17NO2·H2O |
Mr | 171.24 | 189.25 |
Crystal system, space group | Monoclinic, P21/c | Monoclinic, P21/c |
Temperature (K) | 153 | 153 |
a, b, c (Å) | 5.8759 (6), 6.9198 (7), 22.262 (2) | 14.567 (3), 9.2153 (18), 7.6503 (15) |
β (°) | 90.080 (2) | 93.375 (3) |
V (Å3) | 905.18 (16) | 1025.2 (3) |
Z | 4 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.09 | 0.09 |
Crystal size (mm) | 0.30 × 0.09 × 0.09 | 0.35 × 0.26 × 0.03 |
|
Data collection |
Diffractometer | Bruker SMART 1000 CCD diffractometer | Bruker SMART 1000 CCD diffractometer |
Absorption correction | – | Numerical face indexed |
Tmin, Tmax | – | 0.972, 0.998 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7951, 2147, 1572 | 9122, 2461, 1550 |
Rint | 0.042 | 0.058 |
(sin θ/λ)max (Å−1) | 0.667 | 0.667 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.046, 0.118, 0.98 | 0.057, 0.133, 0.97 |
No. of reflections | 2147 | 2461 |
No. of parameters | 177 | 194 |
H-atom treatment | All H-atom parameters refined | All H-atom parameters refined |
Δρmax, Δρmin (e Å−3) | 0.39, −0.21 | 0.42, −0.22 |
Selected geometric parameters (Å, º) for (I) topO1—C9 | 1.2717 (17) | C1—C6 | 1.5524 (18) |
O2—C9 | 1.2519 (17) | C2—C3 | 1.533 (2) |
N1—C7 | 1.4998 (19) | C3—C4 | 1.528 (2) |
C1—C7 | 1.5353 (19) | C4—C5 | 1.524 (2) |
C1—C2 | 1.544 (2) | C5—C6 | 1.525 (2) |
C1—C8 | 1.5446 (18) | C8—C9 | 1.5277 (18) |
| | | |
C7—C1—C2 | 108.23 (11) | C5—C4—C3 | 110.54 (12) |
C7—C1—C8 | 110.60 (11) | C4—C5—C6 | 111.07 (12) |
C2—C1—C8 | 110.56 (11) | C5—C6—C1 | 113.95 (11) |
C7—C1—C6 | 111.47 (11) | N1—C7—C1 | 114.03 (11) |
C2—C1—C6 | 109.45 (11) | C9—C8—C1 | 119.68 (11) |
C8—C1—C6 | 106.54 (10) | O2—C9—O1 | 123.48 (12) |
C3—C2—C1 | 114.37 (12) | O2—C9—C8 | 120.88 (12) |
C4—C3—C2 | 111.42 (12) | O1—C9—C8 | 115.62 (12) |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—HN1···O1i | 0.918 (18) | 1.910 (18) | 2.7827 (16) | 158.2 (15) |
N1—HN2···O2ii | 0.92 (2) | 1.85 (2) | 2.7525 (16) | 165.3 (16) |
N1—HN3···O1iii | 0.96 (2) | 1.81 (2) | 2.7547 (16) | 165.8 (16) |
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x, −y+1, −z+1; (iii) x, y+1, z. |
Selected geometric parameters (Å, º) for (II) topO1—C9 | 1.268 (2) | C1—C8 | 1.549 (3) |
O2—C9 | 1.251 (2) | C2—C3 | 1.526 (3) |
N1—C7 | 1.493 (2) | C3—C4 | 1.524 (3) |
C1—C7 | 1.542 (2) | C4—C5 | 1.525 (3) |
C1—C2 | 1.544 (2) | C5—C6 | 1.521 (3) |
C1—C6 | 1.546 (2) | C8—C9 | 1.525 (2) |
| | | |
C7—C1—C2 | 111.23 (15) | C3—C4—C5 | 110.60 (18) |
C7—C1—C6 | 107.67 (15) | C6—C5—C4 | 111.17 (17) |
C2—C1—C6 | 109.01 (15) | C5—C6—C1 | 113.28 (16) |
C7—C1—C8 | 107.22 (15) | N1—C7—C1 | 114.11 (15) |
C2—C1—C8 | 111.88 (15) | C9—C8—C1 | 115.38 (15) |
C6—C1—C8 | 109.73 (15) | O2—C9—O1 | 124.28 (17) |
C3—C2—C1 | 113.95 (16) | O2—C9—C8 | 118.50 (16) |
C4—C3—C2 | 111.62 (18) | O1—C9—C8 | 117.22 (16) |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
OW—HWA···O2 | 0.88 (3) | 1.89 (3) | 2.748 (2) | 165 (2) |
OW—HWB···O2i | 0.91 (3) | 1.85 (3) | 2.7503 (19) | 170 (3) |
N1—HN1···O1ii | 0.96 (2) | 1.91 (2) | 2.846 (2) | 165.1 (18) |
N1—HN2···OWiii | 0.91 (2) | 1.97 (2) | 2.796 (2) | 151.0 (18) |
N1—HN3···O1iv | 1.02 (2) | 1.74 (2) | 2.755 (2) | 171.7 (19) |
Symmetry codes: (i) x, −y+3/2, z−1/2; (ii) x, −y+1/2, z−1/2; (iii) −x+2, y−1/2, −z+3/2; (iv) x, y, z−1. |
Gabapentin is a new-generation antiepileptic drug that is used as add-on therapy (Placidi et al., 2000), as well as monotherapy (Chadwick et al., 1998) in patients with partial seizures (Lima, 2000; Morton & Pellock, 2000). With the introduction of gabapentin and other promising new antiepileptic drugs, safe and effective seizure control may become a reality for an increasing number of adults with epilepsy (Mattson, 1998). The mechanism of action of gabapentin remains unclear, although it is apparently dissimilar to that of other antiepileptic agents (Gee et al., 1996). Earlier data suggest that an effect of gabapentin on the formation of γ-aminobutyric acid (gaba), a non-protein amino acid that functions as a neurotransmitter, might be involved in its mechanism of action (Loescher et al., 1991). A later study in which a [3H]gabapentin-binding protein was isolated and characterized indicates that [3H]gabapentin interacts with the α2δ subunit of a voltage-dependent Ca2+ channel (Gee et al., 1996).
Despite intense interest in gabapentin and its polymorphs (Pesachovich et al., 1998), its crystal structure is unknown, as is that of its monohydrate. The structures of these two compounds, (I) and (II), respectively, are presented here.
Gabapentin is a zwitterion in the solid state, as shown in Fig. 1. Metrical data for the non-H atoms are given in Table 1. These data are in good agreement with those found in the low-temperature determination of the structure of γ-aminobutyric acid (gaba; Craven & Weber, 1983; Weber et al., 1983). Gaba is also a zwitterion.
The structure of gabapentin monohydrate, (II), is shown in Fig. 2. It too is a zwitterion. Metrical data for the non-H atoms are given in Table 3 and again agree well with those in gaba as well as in anhydrous gabapentin.
In gabapentin, as in gaba, there is extensive hydrogen bonding between the NH3+ and COO- groups of neighboring molecules. These hydrogen-bonding interactions are detailed in Table 2. In the monohydrate, in addition to the direct hydrogen bonding between the NH3+ and COO- groups of neighboring molecules, the O atom (OW) of the water molecule is hydrogen bonded to both groups. The hydrogen-bonding interactions are detailed in Table 4.
In gaba, the difference [0.019 (6) Å] in carboxylate C—O bond lengths was ascribed to hydrogen bonding, with the longer bond involving an O atom that forms two N—H···O bonds and the shorter bond involving the other O atom which forms only one N—H···O bond. In gabapentin, the carboxylate C—O bonds differ by 0.020 (2) Å and again the long bond involves an O atom that forms two N—H···O bonds and the short bond involves an O atom that forms only one N—H···O bond. In the monohydrate, the C—O bond lengths differ by 0.017 (3) Å, with the long bond involving an O atom that forms two N—H···O bonds and the short bond involving an O atom that forms two OW—H···O bonds. In all three compounds, the hydrogen bonds are strong.