The hydrophobic interaction is long range, decaying exponentially with distance

Abstract

The attractive interaction between organic nonpolar molecules, such as hydrocarbons, in water is unusually strong. This ‘hydrophobic interaction’¹ is responsible for the very low solubility of hydrophobic molecules in water, and has a central role in micelle formation, biological membrane structure, and in determining the conformations of proteins^2,3. It was once believed that because the interaction is so strong there is a ‘hydrophobic bond’ associated with it^2,4; but it is now recognized that the interaction involves the configurational rearrangement of water molecules as two hydrophobic species come together^5–9 and is therefore of longer range than a typical covalent bond. However, there has been no experimental information available concerning the distance dependence and effective range of this interaction. From measurements of the total force as a function of distance between two hydrophobic surfaces immersed in aqueous electrolyte solutions we have determined accurately the attractive component due to the hydrophobic interaction and found that the hydrophobic interaction has the same range as, but is about an order of magnitude stronger than, the van der Waals-dispersion force; and that in the range 0–10 nm it decays exponentially with distance with a decay length of ∼1 nm. The results can be roughly extrapolated to molecular interactions and show that the interaction free energy of two hydrophobic solute molecules of radius R (nm) in water at 21 °C is approximately given by ΔG_H = −40R kJ mol⁻¹, which is in agreement with previous estimates. However, the hydrophobic interaction is not due to a ‘hydrophobic bond’, and its long-range nature has obvious implications for the mechanism and rates of folding as well as the equilibrium conformations of proteins and other macromolecules.