From solvation to sorption: a comprehensive molecular dynamics study of mefenamic acid conformer behavior in pure scCO2 and scCO2/cellobiose systems

Journal of Molecular Liquids. 2026. Vol. 448. Article 129401.

Gurina D., Fashchevsky K. A., Budkov Y., Kiselev M. G.

Classical and ab initio molecular dynamics (MD) simulations were employed to investigate the solvation and sorption behavior of mefenamic acid (MFA) molecules in supercritical CO2 (scCO2) and scCO2/cellobiose systems. Using classical MD with alchemical transformation, the Gibbs free energy of solvation (ΔGsolv) for four stable MFA conformers in scCO2 was calculated along the isochores ρ = 1.1ρc and ρ = 1.69ρc over a temperature range of 333–483 K. The solvation capacity and conformational selectivity of the medium were found to be maximal at high density and low temperature, with the C2a conformer exhibiting the highest thermodynamic stability. For the first time, ab initio MD simulations were performed to gain insight into the conformational preferences, local structure and vibrational density of states spectra of MFA in ternary MFA/scCO2/cellobiose systems (using cellobiose as a model cellulose fragment), compared to binary MFA/scCO2 systems. The ab initio simulations successfully captured transitions between the type-a and type-b MFA conformers via rotation of the aromatic fragment, providing a direct molecular rationale for why these conformations remain indistinguishable in NMR and IR experiments. The presence of cellobiose stabilizes type-b conformers, restricts the rotational freedom of MFA, and induces the formation of directed hydrogen bonds, primarily via the carboxylic acid group. A direct correlation was established between the hydrogen bonds formation and the red shift of O–H/N–H stretching vibrations in the vibrational density of states spectra. These results elucidate the molecular mechanisms underlying the initial stage of impregnation, linking the thermodynamic propensity of MFA conformers in scCO2 to their specific interactions with the cellulose surface.

Keywords: классическая молекулярная динамика, supercritical carbon dioxide, сверхкритический диоксид углерода, Целлюлоза, Mefenamic acid, Ab initio molecular dynamics (AIMD), classical molecular dynamics, квантовая молекулярная динамика, Cellobiose, мефенамовая кислота