We investigated the physical effects that lead to synergistic effects in DS -adsorption to a C 12 E 6 monolayer at the air-water interface. Within the framework of the cluster expansion of mixing free energies, this synergistic effect is described by the third order mixing free energy between DS -, C 12 E 6 , and water. Free energy calculations of alchemical intermediates of DS --namely the hydrophobic limit, DS 0 , and the hydrophilic limit , SO 4 CH - 2 -allows one to isolate collective effects on the total binding free energy due to specific interactions.