research papers
The crystal structure of a new cocrystal of carbamazepine (systematic name: 5H-dibenzo[b,f]azepine-5-carboxamide, C15H12N2O) and DL-tartaric acid (C4H6O6), obtained by liquid-assisted grinding, was solved by powder X-ray diffraction (PXRD). The high-resolution PXRD pattern of this new phase was recorded at room temperature thanks to synchrotron experiments at the European Synchrotron Radiation Facility (Grenoble, France). The starting structural model was generated by a Monte-Carlo simulated annealing method. The final structure was obtained through Rietveld refinement and an energy minimization simulation was used to estimate the H-atom positions. The stability of the proposed structure as a function of temperature was also assessed from molecular dynamics simulations. The symmetry is monoclinic (space group P21/c) and contains eight molecules per unit cell, namely, four DL-tartaric acid and four carbamazepine molecules.
Keywords: powder diffraction; cocrystal; carbamazepine; DL-tartaric acid; synchrotron; powder X-ray diffraction.
Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229620000868/yo3068sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S2053229620000868/yo3068Isup2.hkl | |
Rietveld powder data file (CIF format) https://doi.org/10.1107/S2053229620000868/yo3068Isup3.rtv |
CCDC reference: 1979490
Computing details top
Data collection: WinPlotr (Roisnel & Rodriguez-Carvajal, 2002); cell refinement: DICVOL (Boultif & Louër, 2004); program(s) used to solve structure: DASH (David et al., 2006); program(s) used to refine structure: MAUD (Luterotti, 2010) and JANA2006 (Petříček et al., 2014); molecular graphics: Mercury (Macrae et al., 2020).
5H-Dibenzo[b,f]azepine-5-carboxamide–DL-tartaric
acid (1/1) top
Crystal data top
C15H12N2O·C4H6O6 | β = 92.959 (2)° |
Mr = 386.4 | V = 1761.03 (10) Å3 |
Monoclinic, P21/c | Z = 4 |
Hall symbol: -P 2ycb | F(000) = 808 |
a = 4.96273 (12) Å | Dx = 1.457 Mg m−3 |
b = 9.3760 (3) Å | Synchrotron radiation |
c = 37.8971 (13) Å | T = 293 K |
Refinement top
Rp = 0.121 | 77 restraints |
Rwp = 0.173 | 87 constraints |
Rexp = 0.073 | H atoms treated by a mixture of independent and constrained refinement |
R(F) = 0.175 | Weighting scheme based on measured s.u.'s |
9666 data points | (Δ/σ)max = 0.035 |
Excluded region(s): from 1.68 to 1.710, from 2.27 to 2.300, from 2.58 to 2.590, from 5.05 to 5.070, from 5.58 to 5.590, from 8.36 to 8.380, from 8.99 to 9.000, from 9.37 to 9.380 | Background function: Manual background |
Profile function: Pseudo-Voigt | Preferred orientation correction: none |
106 parameters |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
x | y | z | Uiso*/Ueq | ||
O1b | −0.143 (2) | 0.9642 (10) | 0.38043 (18) | 0.0314 (16)* | |
N1b | −0.3043 (11) | 0.7706 (8) | 0.34986 (9) | 0.0314 (16)* | |
N2b | −0.0655 (19) | 0.7444 (12) | 0.40339 (14) | 0.0314 (16)* | |
H1b | −0.1320 | 0.6424 | 0.4042 | 0.0314 (16)* | |
H2b | 0.0375 | 0.7870 | 0.4249 | 0.0314 (16)* | |
C1b | −0.663 (2) | 1.0317 (10) | 0.2906 (3) | 0.0314 (16)* | |
H3b | −0.803729 | 1.096852 | 0.291436 | 0.0314 (16)* | |
C2b | −0.5924 (16) | 0.9497 (9) | 0.3199 (2) | 0.0314 (16)* | |
H4b | −0.685971 | 0.959894 | 0.340344 | 0.0314 (16)* | |
C3b | −0.3835 (14) | 0.8524 (8) | 0.31894 (13) | 0.0314 (16)* | |
C4b | −0.3377 (13) | 0.6191 (8) | 0.34740 (11) | 0.0314 (16)* | |
C5b | −0.1763 (16) | 0.5405 (7) | 0.32527 (16) | 0.0314 (16)* | |
C6b | −0.209 (2) | 0.3926 (7) | 0.3251 (2) | 0.0314 (16)* | |
H5b | −0.1042 | 0.337458 | 0.310701 | 0.0314 (16)* | |
C7b | −0.391 (3) | 0.3260 (9) | 0.3458 (3) | 0.0314 (16)* | |
H6b | −0.408616 | 0.227235 | 0.345189 | 0.0314 (16)* | |
C8b | −0.525 (3) | 1.0171 (10) | 0.2602 (3) | 0.0314 (16)* | |
H7b | −0.572564 | 1.072333 | 0.240475 | 0.0314 (16)* | |
C9b | −0.318 (3) | 0.9207 (10) | 0.25918 (18) | 0.0314 (16)* | |
H8b | −0.226043 | 0.911516 | 0.238529 | 0.0314 (16)* | |
C10b | −0.2409 (18) | 0.8357 (8) | 0.28832 (13) | 0.0314 (16)* | |
C11b | −0.1717 (14) | 0.8339 (10) | 0.37852 (13) | 0.0314 (16)* | |
C12b | −0.5215 (16) | 0.5517 (11) | 0.36822 (17) | 0.0314 (16)* | |
H9b | −0.627402 | 0.605453 | 0.382786 | 0.0314 (16)* | |
C13b | −0.548 (2) | 0.4052 (12) | 0.3674 (2) | 0.0314 (16)* | |
H10b | −0.670758 | 0.360192 | 0.381321 | 0.0314 (16)* | |
C14b | 0.0098 (16) | 0.6071 (9) | 0.30167 (17) | 0.0314 (16)* | |
H11b | 0.165985 | 0.556459 | 0.297398 | 0.0314 (16)* | |
C15b | −0.0209 (17) | 0.7332 (9) | 0.28555 (14) | 0.0314 (16)* | |
H12b | 0.114542 | 0.759078 | 0.270722 | 0.0314 (16)* | |
C1a | 0.3917 (16) | 0.4532 (9) | 0.93122 (15) | 0.0314 (16)* | |
O1a | 0.379 (3) | 0.5801 (9) | 0.9456 (3) | 0.0314 (16)* | |
H1a | 0.0967 | 0.4799 | 0.9008 | 0.0314 (16)* | |
O2a | 0.248 (2) | 0.4111 (14) | 0.9064 (3) | 0.0314 (16)* | |
C2a | 0.6180 (14) | 0.3639 (8) | 0.94855 (18) | 0.0314 (16)* | |
H2a | 0.729927 | 0.332257 | 0.931232 | 0.0314 (16)* | |
O3a | 0.785 (2) | 0.4441 (10) | 0.9722 (4) | 0.0314 (16)* | |
H3a | 0.6839 | 0.5341 | 0.9754 | 0.0314 (16)* | |
C3a | 0.4937 (15) | 0.2330 (6) | 0.9665 (2) | 0.0314 (16)* | |
H4a | 0.362039 | 0.194586 | 0.950947 | 0.0314 (16)* | |
O4a | 0.374 (2) | 0.2691 (11) | 0.9979 (3) | 0.0314 (16)* | |
H5a | 0.5221 | 0.2985 | 1.0168 | 0.0314 (16)* | |
C4a | 0.7217 (19) | 0.1295 (8) | 0.9760 (2) | 0.0314 (16)* | |
O5a | 0.849 (3) | 0.0676 (14) | 0.9540 (3) | 0.0314 (16)* | |
O6a | 0.760 (2) | 0.1141 (14) | 1.0102 (3) | 0.0314 (16)* | |
H6a | 0.9185 | 0.0573 | 1.017 | 0.0314 (16)* |
Geometric parameters (Å, º) top
O1b—C11b | 1.232 (13) | C8b—C9b | 1.372 (16) |
N1b—C3b | 1.438 (8) | C9b—H8b | 0.93 |
N1b—C4b | 1.433 (11) | C9b—C10b | 1.399 (10) |
N1b—C11b | 1.375 (8) | C10b—C15b | 1.463 (12) |
N2b—H1b | 0.86 | C12b—H9b | 0.93 |
N2b—H2b | 0.86 | C12b—C13b | 1.380 (8) |
N2b—C11b | 1.349 (11) | C13b—H10b | 0.93 |
C1b—H3b | 0.93 | C14b—H11b | 0.93 |
C1b—C2b | 1.379 (10) | C14b—C15b | 1.337 (11) |
C1b—C8b | 1.376 (11) | C15b—H12b | 0.93 |
C2b—H4b | 0.93 | C1a—O1a | 1.312 (9) |
C2b—C3b | 1.383 (11) | C1a—O2a | 1.215 (13) |
C3b—C10b | 1.399 (9) | C1a—C2a | 1.523 (10) |
C4b—C5b | 1.399 (9) | C2a—H2a | 0.93 |
C4b—C12b | 1.389 (10) | C2a—O3a | 1.408 (13) |
C5b—C6b | 1.396 (10) | C2a—C3a | 1.546 (10) |
C5b—C14b | 1.459 (10) | C3a—H4a | 0.93 |
C6b—H5b | 0.93 | C3a—O4a | 1.401 (14) |
C6b—C7b | 1.378 (9) | C3a—C4a | 1.520 (11) |
C7b—H6b | 0.93 | C4a—O5a | 1.219 (16) |
C7b—C13b | 1.373 (8) | C4a—O6a | 1.308 (13) |
C8b—H7b | 0.93 | ||
C3b—N1b—C4b | 116.7 (5) | C9b—C10b—C15b | 119.5 (7) |
C3b—N1b—C11b | 120.9 (7) | O1b—C11b—N1b | 121.6 (7) |
C4b—N1b—C11b | 121.9 (6) | O1b—C11b—N2b | 122.4 (7) |
H1b—N2b—H2b | 120 | N1b—C11b—N2b | 115.9 (8) |
H1b—N2b—C11b | 120 | C4b—C12b—H9b | 119.9 |
H2b—N2b—C11b | 120 | C4b—C12b—C13b | 120.2 (8) |
H3b—C1b—C2b | 119.97 | H9b—C12b—C13b | 119.89 |
H3b—C1b—C8b | 119.97 | C7b—C13b—C12b | 119.8 (9) |
C2b—C1b—C8b | 120.1 (10) | C7b—C13b—H10b | 120.09 |
C1b—C2b—H4b | 119.76 | C12b—C13b—H10b | 120.09 |
C1b—C2b—C3b | 120.5 (8) | C5b—C14b—H11b | 116.63 |
H4b—C2b—C3b | 119.76 | C5b—C14b—C15b | 126.7 (7) |
N1b—C3b—C2b | 120.3 (6) | H11b—C14b—C15b | 116.63 |
N1b—C3b—C10b | 119.2 (6) | C10b—C15b—C14b | 128.1 (7) |
C2b—C3b—C10b | 120.4 (6) | C10b—C15b—H12b | 115.96 |
N1b—C4b—C5b | 119.6 (6) | C14b—C15b—H12b | 115.96 |
N1b—C4b—C12b | 119.4 (6) | O1a—C1a—O2a | 125.3 (10) |
C5b—C4b—C12b | 120.9 (8) | O1a—C1a—C2a | 111.8 (7) |
C4b—C5b—C6b | 117.1 (7) | O2a—C1a—C2a | 123.0 (9) |
C4b—C5b—C14b | 122.8 (6) | C1a—C2a—H2a | 108.98 |
C6b—C5b—C14b | 120.0 (7) | C1a—C2a—O3a | 112.2 (7) |
C5b—C6b—H5b | 119.09 | C1a—C2a—C3a | 108.9 (6) |
C5b—C6b—C7b | 121.8 (8) | H2a—C2a—O3a | 105.39 |
H5b—C6b—C7b | 119.09 | H2a—C2a—C3a | 108.91 |
C6b—C7b—H6b | 119.95 | O3a—C2a—C3a | 112.3 (7) |
C6b—C7b—C13b | 120.1 (8) | C2a—C3a—H4a | 108.17 |
H6b—C7b—C13b | 119.95 | C2a—C3a—O4a | 112.3 (6) |
C1b—C8b—H7b | 120.17 | C2a—C3a—C4a | 107.6 (6) |
C1b—C8b—C9b | 119.7 (9) | H4a—C3a—O4a | 108.45 |
H7b—C8b—C9b | 120.17 | H4a—C3a—C4a | 113.12 |
C8b—C9b—H8b | 119.08 | O4a—C3a—C4a | 107.3 (8) |
C8b—C9b—C10b | 121.8 (8) | C3a—C4a—O5a | 123.3 (9) |
H8b—C9b—C10b | 119.08 | C3a—C4a—O6a | 112.0 (9) |
C3b—C10b—C9b | 117.5 (8) | O5a—C4a—O6a | 124.8 (10) |
C3b—C10b—C15b | 123.0 (6) |
Lattice unit-cell parameters comparisons between carbamazepine phase III,
the cocrystal obtained after solvent evaporation (MOXWIG; Childs et al.,
2009)
and the new cocrystal obtained by liquid-assisted grinding (LAG cocrystal) top
Crystal data | |
Chemical formula | C19H18N2O7 |
Mr | 386.4 |
Cell setting, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 4.96273 (12), 9.3760 (3), 37.8971 (13) |
β (°) | 92.959 (2) |
V (Å3) | 1761.03 (10) |
Z | 4 |
F(000) | 808 |
µ (mm-1) | 0.043 |
Specimen shape, size (mm) | Cylinder, 0.5 |
2θ range (°) | 0.5–27.9 |
Data collection | |
Beamline | ID22 (ESRF) |
Specimen mounting | 0.5 mm diameter Lindemann capillary |
Data collection mode | Transmission (Debye–Scherrer geometry) |
Scan method | Continuous scan |
Radiation type | Synchrotron 31 KeV, λ = 0.39997 Å |
Binning size (2θ, °) | 0.0015 |
Refinement | |
R factors and goodness of fit | R = 0.1207, Rwpnb = 0.1725, Rexp = 0.0732 |
No. of refined parameters | 108 |
Crystallographic data, profile and structural parameters for
CBZ/DL-TA cocrystal obtained after Rietveld refinements top
Structure | a (Å) | b (Å) | c (Å) | β (°) | V (Å3) | Symmetry | Reference |
CBZ Phase III | 7.5500 | 11.186 | 13.954 | 92.938 | 1176.9 | Monoclinic P21/n | Eccles et al. (2011) |
MOXWIG | 10.3006 | 26.972 | 5.0718 | 104.235 | 1365.82 | Monoclinic P21/c | Childs et al. (2009) |
LAG cocrystal | 4.96273 | 9.3760 | 37.8971 | 92.959 | 1761.03 | Monoclinic P21/c | This work |