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.

尽管计算化学方法和技术进步的现代水平，溶剂化自由能的快速和准确测定仍然是物理化学家的一个巨大问题。在本文中，我们描述了两种可能解决这个问题的计算方案。我们考虑在超临界二氧化碳中溶解性差的药物化合物系统。考虑到所有分子间相互作用中最大的贡献是范德瓦尔斯相互作用，我们将溶质和溶剂粒子建模为通过有效 Lennard-Jones 势相互作用的粗粒粒子。第一个提议的方法基于经典密度泛函理论，第二个方法依赖于 Lennard-Jones 流体的分子动力学模拟。牺牲分子结构描述的精度，同时以足够的精度捕获流体的相行为，我们提出了计算上有利的路径来获得具有工程应用满意精度的溶剂化自由能值。这种粗粒度模型的结果与实验数据之间达成的一致表明，对研究系统使用全原子分子动力学模拟似乎是过度的。