Enantiotropy of Simvastatin as a Result of Weakened Interactions in the Crystal Lattice: Entropy-Driven Double Transitions and the Transient Modulated Phase as Seen by Solid-State NMR Spectroscopy

Autor: Jiri Brus, Jiri Czernek, Martina Urbanova, Ctirad Červinka
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecules, Vol 27, Iss 3, p 679 (2022)
Druh dokumentu: article
ISSN: 27030679
1420-3049
DOI: 10.3390/molecules27030679
Popis: In crystalline molecular solids, in the absence of strong intermolecular interactions, entropy-driven processes play a key role in the formation of dynamically modulated transient phases. Specifically, in crystalline simvastatin, the observed fully reversible enantiotropic behavior is associated with multiple order–disorder transitions: upon cooling, the dynamically disordered high-temperature polymorphic Form I is transformed to the completely ordered low-temperature polymorphic Form III via the intermediate (transient) modulated phase II. This behavior is associated with a significant reduction in the kinetic energy of the rotating and flipping ester substituents, as well as a decrease in structural ordering into two distinct positions. In transient phase II, the conventional three-dimensional structure is modulated by periodic distortions caused by cooperative conformation exchange of the ester substituent between the two states, which is enabled by weakened hydrogen bonding. Based on solid-state NMR data analysis, the mechanism of the enantiotropic phase transition and the presence of the transient modulated phase are documented.
Databáze: Directory of Open Access Journals
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