Molecular Mechanism of Conformational Crossover of Mefenamic Acid Molecules in scCO2

Abstract

In this work, we studied conformational equilibria of molecules of mefenamic acid in its diluted solution in scCO2 under isochoric heating conditions in the temperature range of 140–210 °С along the isochore corresponding to the scCO2 density of 1.1 of its critical value. This phase diagram range totally covers the region of conformational transitions of molecules of mefenamic acid in its saturated solution in scCO2. We found that in the considered phase diagram region, the equilibrium of two conformers is realized in this solution. In the temperature range of 140–180 °C, conformer I related to the first, most stable polymorph of mefenamic acid prevails. In the temperature range of 200–210 °C, conformer II, which is related to the second metastable polymorph becomes dominant. Based on the results of quantum chemical calculations and experimental IR spectroscopy data on the mefenamic acid conformer populations, we classified this temperature-induced conformational crossover as an entropy-driven phenomenon.

Prediction of Drug-like Compounds Solubility in Supercritical Carbon Dioxide: A Comparative Study between Classical Density Functional Theory and Machine Learning Approaches

“…Supercritical carbon dioxide (scCO 2 ) has demonstrated significant efficacy in various fields including extraction of essential oil, − seed oil, − nanoparticle formation, − impregnation, − control of polymorphic forms, − polymer synthesis, etc.…”