Flotation activity is related to the Excess Gibbs Free Energies (G(ex)) of the binary system, [adsorbed collector-water]. In this investigation, the studied variables are; activity coefficients, surface coverage by collector molecules (mole fraction) and absolute temperature. The Unifac method and principles based on liquid-liquid equilibria were used to calculate G(ex) values for twenty four different molecules. G(ex) values correlated well with flotation activity. Water interactions with N, S, O and organic functional groups of collector molecules were quantified With isomorphous substitution, the effectiveness of substituents followed the order S>O>N and is interpreted in terms of partial and total miscibility in the liquid-liquid bi-phasic system.