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Low-frequency Raman signatures of transient polyamorphic situation in linezolid: A competition between conformational
Mehrnaz Khalaji1,2, Laurent Paccou2, Yannick Guinet2
1Centre of Molecular and Macromolecular Studies of Polish Academy of Sciences, Sienkiewicza 112, Lodz 90-363, Poland.
The Journal of Chemical Physics
|February 18, 2025
Summary
This study reveals unusual polyamorphism and polymorphic transitions in linezolid, involving transient amorphous and liquid states. These transformations, crucial for understanding pharmaceutical solid-state behavior, were detected using advanced Raman spectroscopy.
Area of Science:
- Solid-state chemistry
- Pharmaceutical science
- Materials science
Background:
- Linezolid exhibits complex solid-state transformations.
- Understanding these transitions is critical for drug formulation and stability.
Purpose of the Study:
- To investigate bimodal first-order transformations in disordered linezolid form III.
- To identify and characterize transient amorphous and liquid states during heating.
- To explore the implications of polyamorphism and polymorphic transitions in pharmaceutical ingredients.
Main Methods:
- Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) for thermal analysis.
- Low-frequency Raman spectroscopy for probing molecular organization.
- Kinetic analysis of thermally activated conformational motions.
Main Results:
- Identification of a transient, apparently amorphous state distinct from glass during slow heating.
- Observation of polyamorphism in a pharmaceutical active ingredient, a rare phenomenon in molecular materials.
- Detection of bimodal polymorphic transformation of crystalline form II to form III via a transient liquid state during rapid heating.
- Confirmation that high energy barriers between conformational polymorphs can kinetically hinder transformations.
Conclusions:
- The study highlights unusual polyamorphic and polymorphic transformations in linezolid.
- These transformations are facilitated by thermally activated conformational motions but can be kinetically hindered.
- Rapid acquisition low-frequency Raman spectroscopy is essential for detecting these short-lifetime states and understanding molecular organization.
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