The hydrophobic effect is the property that non-polar molecules tend to form aggregates of
like molecules in water and analogous intramolecular interactions. The name arises from the
combination of water in 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 is 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.
The effect does not involve forces of repulsion between the components; hydration of
hydrophobic substances is enthalpically favorable
Hydrophobic bonds are formed between non-polar hydrocarbon groups on the drug and those
in the receptor site.
These bonds are not very specific but the interactions do occur to exclude water molecules.