The effect of chirality on the compression of 2-(2-Oxo-1-pyrrolidinyl) butyramide : a tale of two crystals

Bebiano, Suse S. and ter Horst, Joop H. and Oswald, Iain D.H. (2020) The effect of chirality on the compression of 2-(2-Oxo-1-pyrrolidinyl) butyramide : a tale of two crystals. Crystal Growth and Design. ISSN 1528-7483

[img]
Preview
Text (Bebiano-etal-CGD-2020-The-effect-of-chirality-on-the-compression)
Bebiano_etal_CGD_2020_The_effect_of_chirality_on_the_compression.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo

Download (6MB)| Preview

    Abstract

    Understanding polymorphism in chiral systems for drug manufacturing is essential to avoid undesired therapeutic effects. Generally, polymorphism is studied through changes in temperature and solution concentration. A less common approach is the application of pressure. The goal of this work is to investigate the effect of pressure on levetiracetam (pure enantiomer) and etiracetam (racemic compound). An anisotropic compression of levetiracetam and etiracetam is observed to 5.26 and 6.29 GPa, respectively. The most compressible direction for both was identified perpendicular to the layers of the structure. Raman spectroscopy and the analysis of intermolecular interactions suggests subtle phase transitions in levetiracetam (~2 GPa) and etiracetam (~1.5 GPa). The stability of etiracetam increases with respect to levetiracetam on compression hence chiral resolution of this system is unfavorable using pressure. This work contributes to the ongoing efforts in understanding the stability of chiral systems.