Computation of drug solvation free energy in supercritical CO2: alternatives to all-atom computer simulations

Fluid Phase Equilibria. 2021. Vol. 544-545. Article 113096.

Kalikin N., Budkov Y., Kolesnikov A. L., Ivlev D. V., Krestyaninov M. A., Kiselev M. G.

Despite the modern level of development of computational chemistry methods and technological progress, fast and accurate determination of solvation free energy remains a huge problem for physical chemists. In this paper, we describe two computational schemes that can potentially solve this problem. We consider systems of poorly soluble drug compounds in supercritical carbon dioxide. Considering that the biggest contribution among all intermolecular interactions is made by van der Waals interactions, we model solute and solvent particles as coarse-grained ones interacting via the effective Lennard-Jones potential. The first proposed approach is based on the classical density functional theory and the second one relies on molecular dynamics simulation of the Lennard-Jones fluid. Sacrificing the precision of the molecular structure description while capturing the phase behavior of the fluid with sufficient accuracy, we propose computationally advantageous paths to obtaining the solvation free energy values with the accuracy satisfactory for engineering applications. The agreement reached between the results of such coarse-graining models and the experimental data indicates that the use of the all-atom molecular dynamic simulations for the studied systems seems to be excessive.

Keywords: Classical density functional theory, сверхкритические флюиды, Supercritical fluids, Теория классического функционала плотности, molecular dynamics, классическая молекулярная динамика, drug compounds, лекарственные соединения