The Fundamental Origin of the Polar Contribution to Heat Capacity Changes in Hydration in an Aqueous Solution

ABSTRACT The current understanding of the nature of the physical factors making up the experimentally measured heat capacity change () for hydration/solvation occurring with net‐neutral solutes at equilibrium in an aqueous solution is based on a large body of experimental work done from 1970 to 2000 which postulates the leading role of the hydrophobic effect (HE) in . Other contributions have also been identified, but their relative role and nature are not well understood. In the present work, we provide a new insight into the nature of the fundamental terms contributing to for a wide variety of molecular processes in an aqueous solution. The crux of our findings is the identification of two leading physical factors, viz., the long known HE and the newly found non‐specific solute‐solvent van der Waals orientational interactions (Keesom force), making up the magnitude of experimental in a general case under the standard conditions of an aqueous solution, “classical” manifestation of HE and employing the model of a rigid net‐neutral solute. As a consequence, one can now characterize the thermodynamic nature of various molecular interactions in a solution based on the level of from a single viewpoint, including the identification of the leading factor, understanding the interrelation of different factors, the interpretation of the sign of , and providing a molecular view on the origin of its temperature dependence.