N-methylacetamide is a solvent better than water for amino acid side chains: A rationalization grounded in the solvent-excluded volume effect

Experimental measurements indicate that the Gibbs energy change is negative for the transfer from water to liquid N-methylacetamide of all the amino acid side chains [J.Biol.Chem. 261 (1986) 7220]. The rationalization of these data is still lacking. Classic scaled particle theory calculations, assigning reliable diameters to the molecules of the two liquids, indicate that the reversible work to create molecular-sized cavities is larger in water than in N-methylacetamide. This result provides a physically reliable rationalization since the reversible work of cavity creation opposes solubility, and its magnitude is independent of solute chemical properties.

Automated summary

Experimental measurements show that the Gibbs energy change is negative when amino acid side chains are transferred from water to liquid N-methylacetamide. However, the rationalization of these data is currently lacking. Classic scaled particle theory calculations suggest that the reversible work to create molecular-sized cavities is greater in water than in N-methylacetamide, offering a physically reliable rationale for this phenomenon.