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

Suse S. Bebiano; Joop H. ter Horst; Iain D.H. Oswald

doi:10.1021/acs.cgd.0c00871

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

Suse S. Bebiano, Joop H. ter Horst, Iain D.H. Oswald

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

27 Downloads (Pure)

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). Anisotropic compressions of levetiracetam and etiracetam are observed to 5.26 and 6.29 GPa, respectively. The most compressible direction for both was identified to be perpendicular to the layers of the structure. Raman spectroscopy and an analysis of intermolecular interactions suggest subtle phase transitions in levetiracetam (∼2 GPa) and etiracetam (∼1.5 GPa). The stability of etiracetam increases with respect to levetiracetam on compression; hence, the chiral resolution of this system is unfavorable using pressure. This work contributes to the ongoing efforts in understanding the stability of chiral systems.

Original language	English
Pages (from-to)	6731-6744
Number of pages	14
Journal	Crystal Growth and Design
Volume	20
Issue number	10
Early online date	25 Aug 2020
DOIs	https://doi.org/10.1021/acs.cgd.0c00871
Publication status	Published - 7 Oct 2020

Keywords

chirality
enantiomer
high-pressure
diffraction
CrystalExplorer
racemic

Access to Document

10.1021/acs.cgd.0c00871Licence: CC BY 4.0

Bebiano-etal-CGD-2020-The-effect-of-chirality-on-the-compressionFinal published version, 5.88 MBLicence: CC BY 4.0

Pressure-Induced Nucleation for the Continuous Manufacture of Supramolecular assemblies
Sefcik, J. (Co-investigator), Ter Horst, J. (Co-investigator) & Oswald, I. (Fellow)
EPSRC (Engineering and Physical Sciences Research Council)
1/06/16 → 30/11/22
Project: Research Fellowship
Doctoral Training Partnership (DTP - University of Strathclyde) | Bebiano, Suse Vanessa
Oswald, I. (Principal Investigator), Ter Horst, J. (Co-investigator) & Bebiano, S. V. (Research Co-investigator)
EPSRC (Engineering and Physical Sciences Research Council)
1/10/15 → 7/06/21
Project: Research Studentship - Internally Allocated

Data for: "The effect of chirality on the compression of 2-(2-Oxo-1-pyrrolidinyl) butyramide: A Tale of Two Crystals" article
Bebiano, S. V. (Creator), Oswald, I. (Creator) & Ter Horst, J. (Contributor), University of Strathclyde, 3 Sept 2020
DOI: 10.15129/29ade4d6-6603-4a70-a807-0c8889751f07
Dataset
Data for: "Effect of chirality on the compression of 2-(2-Oxo-1-pyrrolidinyl)butyramide"
Bebiano, S. V. (Creator), Ter Horst, J. (Creator) & Oswald, I. (Creator), University of Strathclyde, 23 Feb 2023
https://doi.org/10.5517%2Fccdc.csd.cc25jlt4 and 17 more links, https://doi.org/10.5517%2Fccdc.csd.cc25jlr2, https://doi.org/10.5517%2Fccdc.csd.cc25jly8, https://doi.org/10.5517%2Fccdc.csd.cc25jm2f, https://doi.org/10.5517%2Fccdc.csd.cc25jm3g, https://doi.org/10.5517%2Fccdc.csd.cc25jm6k, https://doi.org/10.5517%2Fccdc.csd.cc25jm8m, https://doi.org/10.5517%2Fccdc.csd.cc25jls3, https://doi.org/10.5517%2Fccdc.csd.cc25jm1d, https://doi.org/10.5517%2Fccdc.csd.cc25jlp0, https://doi.org/10.5517%2Fccdc.csd.cc25jlv5, https://doi.org/10.5517%2Fccdc.csd.cc25jlz9, https://doi.org/10.5517%2Fccdc.csd.cc25jm4h, https://doi.org/10.5517%2Fccdc.csd.cc25jlx7, https://doi.org/10.5517%2Fccdc.csd.cc25jm7l, https://doi.org/10.5517%2Fccdc.csd.cc25jlq1, https://doi.org/10.5517%2Fccdc.csd.cc25jlmy, https://doi.org/10.5517%2Fccdc.csd.cc25jlnz (show fewer)
Dataset

Pharmaceuticals under high pressure
Oswald, I. (Recipient)
10 Sept 2021
Activity: Public Engagement and Outreach › Media Participation

Cite this

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title = "Effect of chirality on the compression of 2-(2-Oxo-1-pyrrolidinyl)butyramide: a tale of two crystals",

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). Anisotropic compressions of levetiracetam and etiracetam are observed to 5.26 and 6.29 GPa, respectively. The most compressible direction for both was identified to be perpendicular to the layers of the structure. Raman spectroscopy and an analysis of intermolecular interactions suggest subtle phase transitions in levetiracetam (∼2 GPa) and etiracetam (∼1.5 GPa). The stability of etiracetam increases with respect to levetiracetam on compression; hence, the chiral resolution of this system is unfavorable using pressure. This work contributes to the ongoing efforts in understanding the stability of chiral systems.",

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doi = "10.1021/acs.cgd.0c00871",

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T2 - a tale of two crystals

AU - Bebiano, Suse S.

AU - ter Horst, Joop H.

AU - Oswald, Iain D.H.

PY - 2020/10/7

Y1 - 2020/10/7

N2 - 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). Anisotropic compressions of levetiracetam and etiracetam are observed to 5.26 and 6.29 GPa, respectively. The most compressible direction for both was identified to be perpendicular to the layers of the structure. Raman spectroscopy and an analysis of intermolecular interactions suggest subtle phase transitions in levetiracetam (∼2 GPa) and etiracetam (∼1.5 GPa). The stability of etiracetam increases with respect to levetiracetam on compression; hence, the chiral resolution of this system is unfavorable using pressure. This work contributes to the ongoing efforts in understanding the stability of chiral systems.

AB - 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). Anisotropic compressions of levetiracetam and etiracetam are observed to 5.26 and 6.29 GPa, respectively. The most compressible direction for both was identified to be perpendicular to the layers of the structure. Raman spectroscopy and an analysis of intermolecular interactions suggest subtle phase transitions in levetiracetam (∼2 GPa) and etiracetam (∼1.5 GPa). The stability of etiracetam increases with respect to levetiracetam on compression; hence, the chiral resolution of this system is unfavorable using pressure. This work contributes to the ongoing efforts in understanding the stability of chiral systems.

KW - chirality

KW - enantiomer

KW - high-pressure

KW - diffraction

KW - CrystalExplorer

KW - racemic

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DO - 10.1021/acs.cgd.0c00871

M3 - Article

SN - 1528-7483

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EP - 6744

JO - Crystal Growth and Design

JF - Crystal Growth and Design

IS - 10

ER -

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

Abstract

Keywords

Access to Document

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Projects

Pressure-Induced Nucleation for the Continuous Manufacture of Supramolecular assemblies

Doctoral Training Partnership (DTP - University of Strathclyde) | Bebiano, Suse Vanessa

Datasets

Data for: "The effect of chirality on the compression of 2-(2-Oxo-1-pyrrolidinyl) butyramide: A Tale of Two Crystals" article

Data for: "Effect of chirality on the compression of 2-(2-Oxo-1-pyrrolidinyl)butyramide"

Activities

Pharmaceuticals under high pressure

Cite this