The nature of the hydrophobic interaction varies as the solute size increases from methane’s to C60’s

The hydrophobic interaction, often combined with the hydrophilic or ionic interactions, makes the behavior of aqueous solutions very rich and plays an important role in biological systems. Theoretical and computer simulation studies have shown that the water-mediated force depends strongly on the size and other chemical properties of the solute, but how it changes with these factors remains unclear. We report here a computer simulation study that illustrates how the hydrophobic pair interaction and the entropic and enthalpic terms change with the solute size when the solute–solvent weak attractive interaction is unchanged with the solute size. The nature of the hydrophobic interaction changes qualitatively as the solute size increases from that of methane to that of fullerene. The potential of mean force between small solutes has several well-defined extrema, including the third minimum, whereas the potential of mean force between large solutes has the deep contact minimum and the large free-energy barrier between the contact and the water-bilayer separated configurations. The difference in the potential of mean force is related to the differences in the water density, energy, and hydrogen bond number distributions in the vicinity of the pairs of hydrophobic solutes.