Relative Stability of Pyrazinamide Polymorphs Revisited: A Computational Study of Bending and Brittle Forms Phase Transitions in a Broad Temperature Range
Pyrazinamide may exist in at least four known polymorphic forms, which were obtained experimentally. One of these polymorphs, (α), shows outstanding mechanical properties, demonstrating a significant anisotropic plasticity in a three-point bending test, while the δ form was brittle. Despite a δ → α...
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MDPI AG
2023-04-01
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| Series: | Crystals |
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| Online Access: | https://www.mdpi.com/2073-4352/13/4/617 |
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| author | Aleksandr S. Dubok Denis A. Rychkov |
| author_facet | Aleksandr S. Dubok Denis A. Rychkov |
| author_sort | Aleksandr S. Dubok |
| collection | DOAJ |
| description | Pyrazinamide may exist in at least four known polymorphic forms, which were obtained experimentally. One of these polymorphs, (α), shows outstanding mechanical properties, demonstrating a significant anisotropic plasticity in a three-point bending test, while the δ form was brittle. Despite a δ → α transition as well as β and γ behavior being experimentally studied, the relative stability of pyrazinamide polymorphs remains unclear and even controversial. In this work we provide a pure computational study of the thermodynamic relationships between all four polymorphs as a function of temperature using periodic DFT calculations. It was shown that the β but not the δ form is the most stable at low temperatures. Moreover, the relative stability of the δ form in comparison to α is questioned, showing that the “brittle to bending” δ → α transition was kinetically hindered in the experiments. We show that α and γ polymorphs were stabilized at higher temperatures due to an entropy term. Finally, the calculated stability of the bending α form of pyrazinamide at room temperature was in perfect agreement with previous experiments, which showed a transformation of all other forms to α during six month storage or grinding. |
| first_indexed | 2024-03-11T05:06:53Z |
| format | Article |
| id | doaj.art-4e02a498e1824e50835587e01a3c5264 |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-03-11T05:06:53Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
| series | Crystals |
| spelling | doaj.art-4e02a498e1824e50835587e01a3c52642023-11-17T18:51:06ZengMDPI AGCrystals2073-43522023-04-0113461710.3390/cryst13040617Relative Stability of Pyrazinamide Polymorphs Revisited: A Computational Study of Bending and Brittle Forms Phase Transitions in a Broad Temperature RangeAleksandr S. Dubok0Denis A. Rychkov1Institute of Solid State Chemistry and Mechanochemistry, SB RAS, 18 Kutateladze Str., 630090 Novosibirsk, RussiaInstitute of Solid State Chemistry and Mechanochemistry, SB RAS, 18 Kutateladze Str., 630090 Novosibirsk, RussiaPyrazinamide may exist in at least four known polymorphic forms, which were obtained experimentally. One of these polymorphs, (α), shows outstanding mechanical properties, demonstrating a significant anisotropic plasticity in a three-point bending test, while the δ form was brittle. Despite a δ → α transition as well as β and γ behavior being experimentally studied, the relative stability of pyrazinamide polymorphs remains unclear and even controversial. In this work we provide a pure computational study of the thermodynamic relationships between all four polymorphs as a function of temperature using periodic DFT calculations. It was shown that the β but not the δ form is the most stable at low temperatures. Moreover, the relative stability of the δ form in comparison to α is questioned, showing that the “brittle to bending” δ → α transition was kinetically hindered in the experiments. We show that α and γ polymorphs were stabilized at higher temperatures due to an entropy term. Finally, the calculated stability of the bending α form of pyrazinamide at room temperature was in perfect agreement with previous experiments, which showed a transformation of all other forms to α during six month storage or grinding.https://www.mdpi.com/2073-4352/13/4/617pyrazinamidepolymorphismrelative stabilitydrug stabilitycomputational studyDFT |
| spellingShingle | Aleksandr S. Dubok Denis A. Rychkov Relative Stability of Pyrazinamide Polymorphs Revisited: A Computational Study of Bending and Brittle Forms Phase Transitions in a Broad Temperature Range Crystals pyrazinamide polymorphism relative stability drug stability computational study DFT |
| title | Relative Stability of Pyrazinamide Polymorphs Revisited: A Computational Study of Bending and Brittle Forms Phase Transitions in a Broad Temperature Range |
| title_full | Relative Stability of Pyrazinamide Polymorphs Revisited: A Computational Study of Bending and Brittle Forms Phase Transitions in a Broad Temperature Range |
| title_fullStr | Relative Stability of Pyrazinamide Polymorphs Revisited: A Computational Study of Bending and Brittle Forms Phase Transitions in a Broad Temperature Range |
| title_full_unstemmed | Relative Stability of Pyrazinamide Polymorphs Revisited: A Computational Study of Bending and Brittle Forms Phase Transitions in a Broad Temperature Range |
| title_short | Relative Stability of Pyrazinamide Polymorphs Revisited: A Computational Study of Bending and Brittle Forms Phase Transitions in a Broad Temperature Range |
| title_sort | relative stability of pyrazinamide polymorphs revisited a computational study of bending and brittle forms phase transitions in a broad temperature range |
| topic | pyrazinamide polymorphism relative stability drug stability computational study DFT |
| url | https://www.mdpi.com/2073-4352/13/4/617 |
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