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

Molecules

卷:27

Martina Urbanova¹  Jiri Czernek¹  Jiri Brus¹  Ctirad Červinka² 

[1] Department of NMR Spectroscopy, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky Sq. 2, 162 06 Prague, Czech Republic;

[2] Department of Physical Chemistry, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic;

关键词: polymorphism;    enantiotropy;    transient modulated phase;    dynamics;    entropy;    solid-state nuclear magnetic resonance (NMR);   

DOI  :  10.3390/molecules27030679

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown