Abstract
"Hydrophobicity" plays crucially important roles in a variety of phenomena in aqueous environments. It is widely believed that the hydrophobicity originates from the inability of nonpolar solutes to participate in hydrogen bonds of water. If this is true, the hydrophobicity should be strengthened when the hydrogen bonding is enhanced, for example, by lowering the temperature. However, there are experimental observations manifesting that the hydrophobicity is weakened at low temperatures. Here we clarify the true physical origin of the hydrophobicity by investigating cold denaturation of a protein as an important example. The major conclusions are as follows^ The hydrophobicity is caused primarily by the entropic excluded-volume effect; and its characteristics are ascribed to the interplay of the exceptionally small molecular size and the strongly attractive interaction of water, and not necessarily to its hydrogen-bonding properties.
