The Polar Cosolvent Effect on Caffeine Solvation in Supercritical CO2-Ethanol Mixtures: A Molecular Modeling Approach

Abstract

The effect of the addition of a small amount of ethanol cosolvent in supercritical CO2 on the solvation structure and dynamics of caffeine in a mixed supercritical solvent has been investigated using a systematic multiscale molecular modeling approach. An effective interaction potential model has been employed for caffeine, using the intramolecular geometry and charge distribution from quantum chemical calculations performed in the present treatment and adopting well-established Lennard-Jones parameters from the literature. The solvation structure and related dynamics have been further investigated by means of classical molecular dynamics simulations. The results obtained have revealed an enhancement of the local mole fraction of ethanol around caffeine due to the formation of hydrogen bonds between caffeine and its nearest ethanol molecules. This effect becomes less pronounced as the pressure of the system increases due to the denser packing of CO2 molecules in the first solvation shell of caffeine. The reorientational dynamics of caffeine is controlled by the intermittent hydrogen-bond dynamics, and its translational diffusion has been found to be significantly lower in comparison with the values obtained for ethanol and CO2. The pressure effects on the self-diffusion have also been found to be more pronounced in the cases of CO2 and EtOH in comparison with caffeine. The findings of the present study confirm a previous hypothesis in the literature, according to which polar solutes approach the polar domains formed by the alcohol aggregates and become more easily dissolved in the mixed CO2-ethanol solvent than in pure supercritical CO2. © 2021 American Chemical Society