Water Molecule Adsorption on Protonated Dipeptides

Equilibrium constants for the adsorption of the first water molecule on six protonated dipeptides
(Gly−Gly+H+, Gly−Ala+H+, Ala−Gly+H+, Ala−Ala+H+, Pro−Gly+H+, and Gly−Trp+H+) have been
measured as a function of temperature, and ΔH° and ΔS° determined. Density functional theory calculations
were performed for both the unsolvated peptides and the peptide water complexes at the B3LYP/6-311++G** level. MP2/6-311++G** calculations were also carried out for Gly/Ala peptides. The calculations
suggest that adsorption of a water molecule by these simple dipeptides is a complex process, both the
unsolvated peptide and the peptide−water complexes have multiple conformations with similar free energies. Average ΔH° and ΔS° values derived from the calculations are in reasonable agreement with the
experimental results. According to the calculations, the dominant water adsorption process involves a
significant conformational change to accommodate a bridging water molecule. ΔH° is diminished for
Pro−Gly+H+ mainly because the water interacts with a secondary amine, whereas for Gly−Trp+H+, ΔH°
is significantly decreased by the loss of cation-π interactions upon water adsorption. For unsolvated peptides
the proton affinities of the N-terminus and the backbone carbonyl groups are known to be similar. Addition
of a single water molecule causes a significant stabilization of the N-terminus protonation site.