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If hydrophobic molecules are inserted into an aqueous medium, the water molecules order around the hydrophobic ones to build a quasi crystalline surface. In this way, the hydrogen bonding of the water molecules around a hydrophobic surface is maximized. If two hydrophobic molecules meet they will associate with their hydrophobic surfaces towards each other. The water molecules, previously attached to these surfaces, will be distributed back into the bulk solvent resulting in favourable entropy. The entropic gain is responsible for almost all associations in the medium water and hence extremely important for life (e.g. formation of membranes, micelles, and for protein folding where folding starts often with tryptophan residues forming a hydrophobic core). The hydrophobic effect is shown below (Figure 1).

Water-Soluble Calix[4]arene Derivatives: Binding Stoichiometry and Spectroscopic Evaluation of the Host-Guest Recognition Mechanism