Taking the less-traditional approach of considering FEDs within the framework of a cluster expansion highlights the role of collective effects between multiple species. As an added benefit, the cluster expansion circumvents any issues of path dependence of the decomposition along alchemical transformations due to the fact that each term within the cluster expansion is a thermodynamic state function. Within this perspective, the synergistic effect is simply the third-order collective mixing free energy between DS -, C 12 E 6 , and the interfacial water. Furthermore, the synergistic effect of either alchemical intermediate state can be used to quantify the electrostatic and tail components of the synergy through higher-order collective effects. In particular, the electrostatic component of the synergistic effect mostly reflects the change in the water-solvation around the DS -head group as a result of the re-structuring of the interfacial water due to the presence of the C 12 E 6 monolayer, while the tail effect quantifies the component of the DS -binding free energy due to van der Waals stabilization of the DS -tail group within the tail region of the C 12 E 6 monolayer.