Hydrophobic Effect - The Origin of Hydrophobic Effect

The Origin of Hydrophobic Effect

The hydrophobic interaction is mostly an entropic effect originating from the disruption of highly dynamic hydrogen bonds between molecules of liquid water by the nonpolar solute. A hydrocarbon chain or a similar nonpolar region or a big molecule is incapable of forming hydrogen bonds with water, introduction of such a non-hydrogen bonding surface into water causes disruption of the hydrogen bonding network between water molecules. The hydrogen bonds are reoriented tangential to such a surface to minimize disruption of the hydrogen bonded 3D network of water molecules and thus leads to a structured water "cage" around the nonpolar surface. The water molecules that form the "cage" (or solvation shell) have restricted mobilities. In the solvation shell of small nonpolar particles, the restriction amounts to some 10%, e.g. in the case of dissolved Xe at room temperature, a mobility restriction of 30% has been found. In the case of larger nonpolar molecules the reorientational and translational motion of the water molecules in the solvation shell may be restricted by a factor of two to four. Thus at 25°C the reorientational correlation time of water increases from 2 to 4-8 picoseconds. Generally, this leads to significant losses in translational and rotational entropy of water molecules and makes the process unfavorable in terms of free energy of the system. By aggregating together, nonpolar molecules reduce the surface area exposed to water and minimize their disruptive effect.

The hydrophobic effect can be quantified by measuring the partition coefficients of non-polar molecules between water and non-polar solvents. The partition coefficients can be transformed to free energy of transfer which includes enthalpic and entropic components, ΔG = ΔH - TΔS. These components are experimentally determined by calorimetry. The hydrophobic effect was found to be entropy-driven at room temperature because of the reduced mobility of water molecules in solvation shell of the non-polar solute. However, the enthalpic component of transfer energy was found to be favorable, meaning strengthening of water-water hydrogen bonds in the solvation shell, apparently due to the reduced mobility of water molecules. At the higher temperature, when water molecules became more mobile, this energy gain decreases, but so does the entropic component. As a result of such entropy-enthalpy compensation, the hydrophobic effect (as measured by the free energy of transfer) is only weakly temperature-dependent and became smaller at the lower temperature, which leads to "cold denaturation" of proteins.