The hydrophobic effect is the property that non-polar molecules tend to form intermolecular aggregates in an aqueous medium and analogous intramolecular interactions. The name arises from the combination of water in Attic Greek hydro- and for fear phobos, which describes the apparent repulsion between water and hydrocarbons. At the macroscopic level, the hydrophobic effect is apparent when oil and water are mixed together and form separate layers or the beading of water on hydrophobic surfaces such as waxy leafs. At the molecular level, the hydrophobic effect is an important driving force for biological structures and responsible for protein folding, protein-protein interactions, formation of lipid bilayer membranes, nucleic acid structures, and protein-small molecule interactions.
According to the solvophobic theory of Reversed Phase Chromatography (RPC), the hydrophobic effect is driven by the loss of hydrogen bonding and the higher entropic cost of forming a cavity around nonpolar molecules. These losses can be minimized by forcing nonpolar molecules together (see Thermodynamics).
The energetics of DNA tertiary structure assembly were determined to be primarily driven by the hydrophobic effect, as opposed to Watson-Crick base pairing (which is responsible for sequence selectivity), although there is also a significant contribution from stacking interactions between the aromatic bases.
Another way of understanding the hydrophobic effect is the example of a hydrophobic substance in water. Pure water molecules adopt a structure which maximizes entropy (S). A hydrophobic molecule will disrupt this structure and decrease entropy, and creates a 'cavity' as it is unable to interact electrostatically with the water molecules. When more than one 'cavity' is present, the surface area of disruptions is high, meaning that there are fewer free water molecules. To counter this, the water molecules push the hydrophobic molecules together and form a 'cage' structure around them which will have a smaller surface area than the total surface area of the cavities. This maximizes the amount of free water and thus the entropy. Therefore the hydrophobic effect might also be understood as the "the lipophobicity of water".