Enthalpy-entropy Compensation - Causes

Causes

Mathematically, this is because of the Gibbs free energy equation (ΔG = ΔH – TΔS), where the change in enthalpy (ΔH) and the change in entropy (ΔS) have opposite signs—ΔG will change very little if both enthalpy and entropy increase. For instance, in a reaction where the chemical bonds become stronger or where chemical bonds are being formed throughout the course of a reaction a negative ΔH value will result. At the same time, this aforementioned act of forming or even strengthening a bond will limit the movement of the molecule (in terms of the molecule’s ability to rotate, vibrate, etc.) and hence decrease the molecule’s entropy. This leads to a fairly small ΔG value. This effect is frequently invoked in the discussion of the thermodynamics of proteins, ligands, and nucleic acids. Enthalpy and entropy are part of the laws of thermodynamics.

There are two variations on the usage of enthalpy-entropy compensation in explaining a reaction: the weak, and the strong form of compensation.

• The weak form of compensation is described when ΔH and ΔS have the same sign as a change occurs in some thermodynamic quantity excluding temperature. The weak form of compensation is a result of the rules of thermodynamics. Statistical mechanics shows qualitatively that as a system populates the lower energy levels, the enthalpy and entropy will both decrease.
• Given a regular change in some experimental variable (such as a series of homologous molecules, or a series of experimental conditions excluding temperature), the strong form of compensation occurs when ΔH and ΔS exhibit a linear correlation. In this case ΔG will be small relative to the range of values expected from the experiment.