Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine Cocrystals
In this study, the existing set of carbamazepine (CBZ) cocrystals was extended through the successful combination of the drug with the positional isomers of acetamidobenzoic acid. The structural and energetic features of the CBZ cocrystals with 3- and 4-acetamidobenzoic acids were elucidated via sin...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/3/836 |
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| author | Artem O. Surov Anna G. Ramazanova Alexander P. Voronin Ksenia V. Drozd Andrei V. Churakov German L. Perlovich |
| author_facet | Artem O. Surov Anna G. Ramazanova Alexander P. Voronin Ksenia V. Drozd Andrei V. Churakov German L. Perlovich |
| author_sort | Artem O. Surov |
| collection | DOAJ |
| description | In this study, the existing set of carbamazepine (CBZ) cocrystals was extended through the successful combination of the drug with the positional isomers of acetamidobenzoic acid. The structural and energetic features of the CBZ cocrystals with 3- and 4-acetamidobenzoic acids were elucidated via single-crystal X-ray diffraction followed by QTAIMC analysis. The ability of three fundamentally different virtual screening methods to predict the correct cocrystallization outcome for CBZ was assessed based on the new experimental results obtained in this study and data available in the literature. It was found that the hydrogen bond propensity model performed the worst in distinguishing positive and negative results of CBZ cocrystallization experiments with 87 coformers, attaining an accuracy value lower than random guessing. The method that utilizes molecular electrostatic potential maps and the machine learning approach named CCGNet exhibited comparable results in terms of prediction metrics, albeit the latter resulted in superior specificity and overall accuracy while requiring no time-consuming DFT computations. In addition, formation thermodynamic parameters for the newly obtained CBZ cocrystals with 3- and 4-acetamidobenzoic acids were evaluated using temperature dependences of the cocrystallization Gibbs energy. The cocrystallization reactions between CBZ and the selected coformers were found to be enthalpy-driven, with entropy terms being statistically different from zero. The observed difference in dissolution behavior of the cocrystals in aqueous media was thought to be caused by variations in their thermodynamic stability. |
| first_indexed | 2024-03-11T06:02:20Z |
| format | Article |
| id | doaj.art-83d94512f58148ba827e74a1a762085e |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:02:20Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-83d94512f58148ba827e74a1a762085e2023-11-17T13:15:03ZengMDPI AGPharmaceutics1999-49232023-03-0115383610.3390/pharmaceutics15030836Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine CocrystalsArtem O. Surov0Anna G. Ramazanova1Alexander P. Voronin2Ksenia V. Drozd3Andrei V. Churakov4German L. Perlovich5G.A. Krestov Institute of Solution Chemistry RAS, 153045 Ivanovo, RussiaG.A. Krestov Institute of Solution Chemistry RAS, 153045 Ivanovo, RussiaG.A. Krestov Institute of Solution Chemistry RAS, 153045 Ivanovo, RussiaG.A. Krestov Institute of Solution Chemistry RAS, 153045 Ivanovo, RussiaInstitute of General and Inorganic Chemistry RAS, Leninsky Prosp. 31, 119991 Moscow, RussiaG.A. Krestov Institute of Solution Chemistry RAS, 153045 Ivanovo, RussiaIn this study, the existing set of carbamazepine (CBZ) cocrystals was extended through the successful combination of the drug with the positional isomers of acetamidobenzoic acid. The structural and energetic features of the CBZ cocrystals with 3- and 4-acetamidobenzoic acids were elucidated via single-crystal X-ray diffraction followed by QTAIMC analysis. The ability of three fundamentally different virtual screening methods to predict the correct cocrystallization outcome for CBZ was assessed based on the new experimental results obtained in this study and data available in the literature. It was found that the hydrogen bond propensity model performed the worst in distinguishing positive and negative results of CBZ cocrystallization experiments with 87 coformers, attaining an accuracy value lower than random guessing. The method that utilizes molecular electrostatic potential maps and the machine learning approach named CCGNet exhibited comparable results in terms of prediction metrics, albeit the latter resulted in superior specificity and overall accuracy while requiring no time-consuming DFT computations. In addition, formation thermodynamic parameters for the newly obtained CBZ cocrystals with 3- and 4-acetamidobenzoic acids were evaluated using temperature dependences of the cocrystallization Gibbs energy. The cocrystallization reactions between CBZ and the selected coformers were found to be enthalpy-driven, with entropy terms being statistically different from zero. The observed difference in dissolution behavior of the cocrystals in aqueous media was thought to be caused by variations in their thermodynamic stability.https://www.mdpi.com/1999-4923/15/3/836cocrystalcarbamazepinescreeningthermodynamicssolubility |
| spellingShingle | Artem O. Surov Anna G. Ramazanova Alexander P. Voronin Ksenia V. Drozd Andrei V. Churakov German L. Perlovich Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine Cocrystals Pharmaceutics cocrystal carbamazepine screening thermodynamics solubility |
| title | Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine Cocrystals |
| title_full | Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine Cocrystals |
| title_fullStr | Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine Cocrystals |
| title_full_unstemmed | Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine Cocrystals |
| title_short | Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine Cocrystals |
| title_sort | virtual screening structural analysis and formation thermodynamics of carbamazepine cocrystals |
| topic | cocrystal carbamazepine screening thermodynamics solubility |
| url | https://www.mdpi.com/1999-4923/15/3/836 |
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