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

0552594 - ÚMCH 2023 RIV CH eng J - Journal Article
Brus, Jiří - Czernek, Jiří - Urbanová, Martina - Červinka, C.
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. Roč. 27, č. 3 (2022), č. článku 679. E-ISSN 1420-3049
R&D Projects: GA MŠMT(CZ) LTAUSA18011
Research Infrastructure: e-INFRA CZ - 90140; ELIXIR-CZ - 90047
Institutional support: RVO:61389013
Keywords : polymorphism * enantiotropy * transient modulated phase
OECD category: Physical chemistry
Impact factor: 4.6, year: 2022
Method of publishing: Open access
https://www.mdpi.com/1420-3049/27/3/679

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.
Permanent Link: http://hdl.handle.net/11104/0327801