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.

• Keywords
• dynamics, enantiotropy, entropy, polymorphism, solid-state nuclear magnetic resonance (NMR), transient modulated phase,
• MeSH
• Entropy * MeSH
• Magnetic Resonance Spectroscopy methods   MeSH
• Molecular Conformation * MeSH
• Models, Molecular MeSH
• Cold Temperature MeSH
• Simvastatin chemistry   MeSH
• Hydrogen Bonding MeSH
• Phase Transition * MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Simvastatin MeSH