The Role of the Concentration Scale in the Definition of Transfer Free Energies

TL;DR

This paper clarifies that the dependence of transfer free energies on concentration scale arises from volume-entropy effects, impacting interpretations of solute-solvent interactions and protein stability studies.

Contribution

It provides a clear explanation of how concentration-scale choice influences transfer free energies through volume-entropy effects, resolving a longstanding ambiguity.

Findings

Concentration-scale dependence is due to volume-entropy effects.

Transfer free energies are affected by the choice of concentration measurement.

Implications for protein stability and cosolvent effects are significant.

Abstract

The Gibbs free energy of transferring a solute at infinite dilution between two solvents quantifies differences in solute-solvent interactions $-$ if the transfer takes place at constant molarity of the solute. Yet, many calculation formulae and measuring instructions that are commonly used to quantify solute-solvent interactions correspond to transfer processes in which not the molarity of the solute but its concentration measured in another concentration scale is constant. Here, we demonstrate that in this case, not only the change in solute-solvent interactions is quantified but also the entropic effect of a volume change during the transfer. Consequently, the "phenomenon" which is known as "concentration-scale dependence" of transfer free energies is simply explained by a volume-entropy effect. Our explanations are of high importance for the study of cosolvent effects on protein stability.