Preparation of Progesterone Co-Crystals Based on Crystal Engineering Strategies
Abstract
:1. Introduction
2. Results and Discussion
2.1. Preparation of Co-Crystals
2.2. Crystal Structure Analysis
2.2.1. Structure of the PROG-CNA Co-Crystal
2.2.2. Structure of the PROG-DHB Co-Crystal
2.2.3. Structure of the PROG-DOD Co-Crystal
2.3. IR Spectroscopy
2.4. DSC and PXRD Analysis
2.5. In Vitro Dissolution
3. Materials and Methods
3.1. Materials and Reagents
3.2. Synthesis and Crystallization
3.3. Differential Scanning Calorimetry
3.4. IR Spectroscopy
3.5. Powder X-Ray Diffraction
3.6. In Vitro Dissolution
3.7. X-Ray Crystallography
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds of PROG-CNA, PROG-DHB, PROG-DOD are available from the authors. |
Co-Crystal | X-H···Cg | H···Cg (Å) | X-H···Cg (°) | X···Cg (Å) |
---|---|---|---|---|
PROG-CNA | C12-H12A···Cg1 | 2.8276 (8) | 178.9 | 3.797 |
PROG-DHB | C14-H14···Cg1 a | 2.8527 | 171.21 | 3.824 |
C21-C21C···Cg1 b | 3.0350 | 166.4 | 3.975 |
Co-Crystal | Donor-H···Acceptor | D-H (Å) | H···A (Å) | D···A (Å) | D-H···A (°) |
---|---|---|---|---|---|
PROG-CNA | C1-H1B···O4 | 0.970 | 2.964 | 3.767 | 143.0 |
C6-H6B···O1 a | 0.970 | 2.901 | 3.758 | 147.92 | |
C7-H7B···O3 b | 0.970 | 2.909 | 3.669 | 136.0 | |
C7-H7B···O4 b | 0.970 | 3.088 | 3.794 | 130.8 | |
C8-H8···O2 c | 0.980 | 2.799 | 3.769 | 170.30 | |
C14-H14···O3 b | 0.980 | 2.917 | 3.613 | 128.9 | |
C15-H15A···O3 b | 0.970 | 2.845 | 3.554 | 130.6 | |
C18-H18B···N1 c | 0.960 | 3.130 | 3.777 | 126.2 | |
C19-H19H···O2 c | 0.960 | 2.621 | 3.554 | 164.3 | |
C26-H26···O4 d | 0.930 | 2.442 | 3.262 | 147.0 | |
C27-H27···O3 b | 0.930 | 2.516 | 3.353 | 149.8 | |
PROG-DHB | C6-H6B···O4 d | 0.970 | 3.199 | 3.789 | 120.91 |
C11-H11A···O3 e | 0.970 | 2.629 | 3.459 | 143.7 | |
C19-H19C···O5 f | 0.960 | 3.008 | 3.770 | 137.3 | |
C21-H21A···O4 | 0.960 | 2.724 | 3.643 | 160.4 | |
C25-H25···O6 g | 0.930 | 2.488 | 3.281 | 143.3 | |
PROG-DOD | C2-H2B···O3 | 0.970 | 2.697 | 3.592 | 153.6 |
C4-H4···O3A | 0.930 | 3.023 | 3.634 | 124.7 | |
C6-H6A···O1A h | 0.970 | 2.806 | 3.620 | 142.0 | |
C6-H6B···O3A h | 0.970 | 2.903 | 3.661 | 135.7 | |
C21-H21A···O4B i | 0.960 | 2.880 | 3.581 | 130.7 | |
C21-H21B···O2B j | 0.960 | 2.712 | 3.459 | 135.1 | |
C21-H21B···O4 k | 0.960 | 2.978 | 3.565 | 120.7 | |
C6A-H6AB···O1 h | 0.970 | 2.674 | 3.542 | 149.2 | |
C21A-H21D···O4A k | 0.960 | 2.990 | 3.630 | 125.2 | |
C2B-H2BB···O1A | 0.970 | 2.829 | 3.703 | 150.5 | |
C2B-H2BB···O3B | 0.970 | 2.668 | 3.498 | 143.7 | |
C16B-H16E···O4B k | 0.970 | 2.820 | 3.454 | 123.7 | |
C21B-H21G···O4A k | 0.960 | 2.925 | 3.585 | 126.9 | |
C21B-H21H···O2 j | 0.960 | 2.989 | 3.602 | 122.8 | |
C32-H32···O2A l | 0.930 | 2.831 | 3.477 | 127.6 | |
C23A-H23A···O1 | 0.930 | 2.781 | 3.438 | 128.5 | |
C30A-H30A···O2A l | 0.930 | 2.815 | 3.692 | 157.5 | |
C32A-H32A···O2B l | 0.930 | 2.962 | 3.577 | 125.0 | |
C23B-H23B···O1A | 0.930 | 2.795 | 3.444 | 127.8 | |
C32B-H32B···O2 m | 0.930 | 3.170 | 3.751 | 122.4 |
Co-Crystal | Donor-H···Acceptor | D-H (Å) | H···A (Å) | D···A (Å) | D−H···A (°) |
---|---|---|---|---|---|
PROG-CNA | N1-H1C···O1 a | 0.869 (3) | 2.109 | 2.952 | 163.6 |
N1-H1D···O2 b | 0.868 | 2.401 | 3.031 | 129.8 | |
PROG-DHB | O3-H3···O4 | 0.820 | 1.893 | 2.612 | 145.76 |
O5-H5···O2 | 0.820 | 1.833 | 2.620 | 160.33 | |
O6-H6···O1 a | 0.820 | 1.972 | 2.774 | 165.9 | |
PROG-DOD | O3-H3···O1B c | 0.820 | 1.862 | 2.649 | 160.3 |
O4-H4C···O2A d | 0.820 | 1.972 | 2.786 | 171.9 | |
O3A-H3A···O1 | 0.820 | 1.936 | 2.747 | 169.9 | |
O4A-H4AA···O2B d | 0.820 | 1.951 | 2.758 | 168.2 | |
O3B-H3B···O1A | 0.820 | 1.893 | 2.706 | 171.2 | |
O4B-H4BA···O2 e | 0.820 | 1.996 | 2.782 | 160.5 |
PROG·CNA | PROG·DHB | PROG·DOD | |
---|---|---|---|
Crystal data | |||
Chemical formula | C21H30O2·C6H5ClN2O2 | C21H30O2·C7H6O4 | C21H30O2·C12H10O2 |
Mr | 487.02 | 468.57 | 500.65 |
Crystal system, space group | Orthorhombic, P212121 | Orthorhombic, P212121 | Monoclinic, P21 |
Temperature (K) | 296 | 296 | 296 |
a, b, c (Å) | 7.721, 11.783, 27.762 | 7.328, 14.173, 23.417 | 17.4955, 10.4030, 22.825 |
α, β, γ (°) | 90, 90, 90 | 90, 90, 90 | 90, 97.252, 90 |
V (Å3) | 2525.8 | 2432.1 | 4121.1 |
Z | 4 | 4 | 6 |
Dx (Mg·m−3) | 1.281 | 1.280 | 1.210 |
Radiation type | Mo Kα | Mo Kα | Mo Kα |
μ (mm−1) | 0.187 | 0.089 | 0.078 |
Crystal size (mm) | 0.05 × 0.04 × 0.03 | 0.06 × 0.05 × 0.04 | 0.07 × 0.06 × 0.05 |
Data collection | |||
Diffractometer | CCD area detector | ||
Absorption correction | Multi-scan (SADABS; Bruker, 2004) | ||
Tmin, Tmax | 0.991, 0.994 | 0.995, 0.996 | 0.995, 0.996 |
No. of measured, independent, and observed [I > 2σ(I)] reflections | 11115, 3736, 3019 | 17382, 5635, 3715 | 80611, 18695, 11453 |
Rint | 0.0385 | 0.0582 | 0.0797 |
(sin θ/λ)max (Å−1) | 0.562 | 0.652 | 0.647 |
Refinement | |||
R[F2 > 2σ(F2)], wR(F2), S(GooF) | 0.0375, 0.0910, 1.029 | 0.0502, 0.1159, 1.007 | 0.0616, 0.1691, 1.008 |
No. of reflections | 3736 | 5635 | 18695 |
No. of parameters | 311 | 313 | 1015 |
No. of restraints | 0 | 0 | 1 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | ||
Δρmax, Δρmin (e Å−3) | 0.117, −0.139 | 0.161, −0.182 | 0.176, −0.254 |
Absolute structure | Flack x determined using 1054 quotients [(I+) − (I−)]/[(I+)+(I−)] | Flack x determined using 1184 quotients [(I+) − (I−)]/[(I+) + (I−)] | Flack x determined using 4022 quotients [(I+) − (I−)]/[(I+) + (I−)] |
Absolute structure parameter | −0.08 | −0.2 | 0.4 |
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Zeng, H.; Xiong, J.; Zhao, Z.; Qiao, J.; Xu, D.; Miao, M.; He, L.; Wu, X. Preparation of Progesterone Co-Crystals Based on Crystal Engineering Strategies. Molecules 2019, 24, 3936. https://doi.org/10.3390/molecules24213936
Zeng H, Xiong J, Zhao Z, Qiao J, Xu D, Miao M, He L, Wu X. Preparation of Progesterone Co-Crystals Based on Crystal Engineering Strategies. Molecules. 2019; 24(21):3936. https://doi.org/10.3390/molecules24213936
Chicago/Turabian StyleZeng, Huahui, Jing Xiong, Zhuang Zhao, Jingyi Qiao, Duanjie Xu, Mingsan Miao, Lan He, and Xiangxiang Wu. 2019. "Preparation of Progesterone Co-Crystals Based on Crystal Engineering Strategies" Molecules 24, no. 21: 3936. https://doi.org/10.3390/molecules24213936