Can the roles of polar and non-polar moieties be reversed in non-polar solvents?

TL;DR

This study uses thermodynamics integration to analyze amino acid side chain solvation in solvents of varying polarity, revealing that the roles of polar and non-polar parts cannot generally be reversed in non-polar solvents, highlighting water's unique role.

Contribution

It provides a detailed thermodynamic analysis of amino acid solvation across different solvents, clarifying the limitations of role reversal of polar and non-polar moieties.

Findings

Negative entropy-enthalpy correlation in water and ethanol

Reduced correlation in cyclohexane

Supports water's unique biological solvent role

Abstract

Using thermodynamics integration, we study the solvation free energy of 18 amino acid side chain equivalents in solvents with different polarity, ranging from the most polar water to the most non-polar cyclohexane. The amino acid side chain equivalents are obtained from the 20 natural amino acids by replacing the backbone part with a hydrogen atom, and discarding proline and glycine that have special properties. A detailed analysis of the relative solvation free energies suggests how it is possible to achieve a robust and unambiguous hydrophobic scale for the amino acids. By discriminating the relative contributions of the entropic and enthalpic terms, we find strong negative correlations in water and ethanol, associated with the well-known entropy-enthalpy compensation, and a much reduced correlation in cyclohexane. This shows that in general the role of the polar and non-polar moieties cannot be reversed in a non-polar solvent. Our findings are compared with past experimental as well as numerical results, and may shed additional light on the unique role of water as biological solvent.