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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F22%3A00552594" target="_blank" >RIV/61389013:_____/22:00552594 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22340/22:43924665

Výsledek na webu

<a href="https://www.mdpi.com/1420-3049/27/3/679" target="_blank" >https://www.mdpi.com/1420-3049/27/3/679</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules27030679" target="_blank" >10.3390/molecules27030679</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/LTAUSA18011" target="_blank" >LTAUSA18011: Ab initio studie polymorfismu farmaceuticky aktivních látek podpořená přesnými NMR krystalografickými a kalorimetrickými experimenty</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

1420-3049

Svazek periodika

27

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

679

Kód UT WoS článku

000759813400001

EID výsledku v databázi Scopus

2-s2.0-85123103085