Molecular dynamics of the supercooled pharmaceutical agent posaconazole studied via differential scanning calorimetry and dielectric and mechanical spectroscopies

Mol Pharm. 2013 Oct 7;10(10):3934-45. doi: 10.1021/mp4003915. Epub 2013 Sep 25.


This paper presents comprehensive studies on the molecular dynamics of a pharmaceutically important substance, posaconazole. In order to characterize relaxation dynamics in the supercooled liquid and glassy states, dielectric and mechanical spectroscopies were applied. Dielectric data have indicated multiple relaxation processes that appear above and below the glass transition temperature Tg (τα=100 s) of posaconazole. From the curvature of the dielectric log10(τα) versus inverse of temperature dependence, we determine so-called "fragility", being a very popular parameter for classifying the structural dynamics of supercooled liquids and polymers. From the calculations, we get m=150, which means that is one of the most fragile glass-forming liquids. In this paper, the relaxation dynamics of supercooled posaconazole extracted from the dielectric response function was also confronted with shear-mechanical relaxation. Finally, we have also presented a direct comparison of the fragility and the number of dynamically correlated molecules Nc determined from dynamic calorimetry curves and dielectric and mechanical spectroscopies, showing a clear deviation in the picture of glass-transition dynamics generated by calorimetric and spectroscopic techniques.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning / methods*
  • Molecular Dynamics Simulation*
  • Spectrum Analysis / methods*
  • Triazoles / chemistry*


  • Triazoles
  • posaconazole