Description of an original molecular ordering process into a disordered crystalline form: the atypical low-temperature transformation of the disordered form III of linezolid

Abstract

Form III of linezolid was prepared by heating the commercial form above 150 °C and subsequently analyzed upon cooling down to −160 °C, by low- and high-frequency Raman spectroscopy, differential scanning calorimetry and powder X-ray diffraction (PXRD). It was observed that form III was preserved down to 0 °C. At lower temperatures a soft mode was clearly detected by low-frequency Raman spectroscopy associated with the detection of additional Raman bands distinctive of additional intermolecular H-bond interactions. Raman spectroscopy investigations performed in a wide frequency range revealed a continuous transformation characterized by both displacive and order–disorder signatures. By contrast, PXRD highlighted the absence of symmetry breaking, Bragg peaks being still indexed in the same unit cell from room temperature down to −160 °C. Additionally, a significant broadening of Bragg peaks was observed with decreasing temperature interpreted as being a consequence of a distribution of frozen molecular conformations.