From molecular to macroscopic: predicting liquid–liquid phase equilibria and small-angle scattering of mixtures of organic liquids from atomistic simulation using Kirkwood–Buff theory

Kirkwood-Buff theory. This allows us to accurately estimate the free energy of mixing as a function of temperature, and thus obtain liquid-liquid phase equilibria, including liquid-liquid critical points, associated binodal and spinodal lines, and composition fluctuations across a region of temperature and composition. Results for binary malonamide-alkane systems are validated by comparison to a direct experimental probe of the fluctuations: the small angle X-ray scattering intensity near zero wavenumber. The MDKB → Phase method demonstrated here provides a significant improvement in predicting liquid-liquid equilibria and free energy as a function of temperature for our systems of interest compared to conventional thermodynamic models. The accurate performance of this purely predictive approach lies in its preservation of atomistic details when determining thermodynamic properties. Furthermore, its inherent extensibility to multi-component systems will likely make the MDKB → Phase approach a valuable general tool for connecting molecular interactions to macroscopic phase equilibria and for the computational screening of materials for targeted thermodynamic behavior.