Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution

• Published in: European biophysics journal Vol. 53; no. 7-8; pp. 373 - 384
• Main Authors: Scott, David J., Winzor, Donald J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-11-2024
• Subjects: Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Cell Biology; Life Sciences; Membrane Biology; Nanotechnology; Neurobiology; Review; Urea; Enthalpy‒entropy compensation; N-methylformamide; Small solute dimerization; Aliphatic carboxylic acids
• ISSN: 0175-7571; 1432-1017; 1432-1017
• DOI: 10.1007/s00249-024-01722-y

This communication summarizes findings from the earliest encounters with extreme enthalpy‒entropy compensation, a phenomenon first detected in the 1950s by a reappraisal of isopiestic and calorimetric measurements on aqueous urea solutions in terms of solute self-association. Because concurrent studies of carboxylic acid association were confined to measurement of the equilibrium constant by conductance, IR spectrophotometry or potentiometric titration measurements, temperature-independence of the dimerization constant was mistakenly taken to signify a value of zero for Δ
H
o
instead of (Δ
H
o
 ‒ TΔ
S
o
). In those studies of small-solute self-association the extreme enthalpy‒entropy compensation was reflecting the action of water as a reactant whose hydroxyl groups were competing for the solute carbonyl involved in self-association. Such action gives rise to a positive temperature dependence of Δ
H
o
that could well be operating in concert with that responsible for the commonly observed negative dependence for protein‒ligand interactions exhibiting extreme enthalpy‒entropy compensation, where the solvent contribution to the energetics reflects changes in the extent of ordered water structure in hydrophobic environments.