ON THE RELATIVE STRENGTHS OF AMIDE ... AMIDE AND AMIDE ... WATER HYDROGEN-BONDS

We have performed Hayes-Stone intermolecular perturbation theory (IMPT) calculations on amide...water and amide...amide complexes in order to estimate the change DELTA-W in intermolecular interaction energy associated with the hydrogen bond exchange process amide(NH)...water + water...(OC)amide equivalent to amide (NH)...(OC)amide + water...water. DELTA-W is found to be small and varies by almost 5 kJ/mol and in sign for the amides formamide, acetamide, N-methyl formamide and N-methyl acetamide. The main variations in the amide hydrogen bond energies occur in the electrostatic and exchange-repulsion contributions. This reflects the variation in the charge distributions of the hydrogen bonding groups between the different amides. Thus, we cannot quantify an isolated hydrogen bond strength with any great accuracy, and care must be used in extrapolating model potentials based on small model systems to peptides and proteins.