Predicting excess free energy of mixing for molecular mixtures by inducing phase separation in simulations.

Excess free energy of mixing governs phase behavior of mixtures. We have developed a method that combines molecular dynamic simulations and thermodynamic integration along the path of transformation of molecules to measure the excess free energy of mixing of molecular mixtures. But this method requires the molecules to be structurally related. To overcome this limitation, we have developed a new method to measure the excess mixing free energy, which involves simulations of molecular mixture where we weaken the cross interactions between different species until they phase separate. We measure the thermodynamic work required to modify the interactions and the interfacial energy between the separated phases to compute the excess free energy of mixing. To verify the method, we determine the excess free energy of mixing Lennard Jones (LJ) beads with themselves and the excess free energy of mixing for benzene-pyridine mixture. We find that for LJ beads mixing with themselves, the excess free energy of mixing approaches the expected value of -kT Log(2) per bead. For the benzene-pyridine mixture, simulation results for the excess mixing free energy agree with experiments.