A quantum chemical view of enthalpy–entropy compensation

Enthalpy–entropy compensation phenomena are of high importance for processes with dominating non-covalent interactions, like protein–ligand binding. We show here that non-covalent interactions are compensated by entropic effects not on an equal footing, but dependent on their electronic nature. This insight helps us to understand the observed diversity of enthalpy–entropy compensation phenomena and opens up a new route for the prediction of the entropic effects of non-covalent binding.