How strong is the Cα-H•••O=C hydrogen bond?

Although the existence of C-alpha-H...O=C hydrogen bonds in protein structures recently has been established, little is known about their strength and, therefore, the relative importance of these interactions. We have discovered that similar interactions occur in N,N-dimethylformamide dimers. High level nb initio calculations (MP2/aug-cc-pTZV) yield electronic association energies (D-e) and association enthalpies (Delta H-298) for four dimer geometries. These data provide a lower limit of D-e = -2.1 kcal mol(-1) for the C-alpha-H...O=C hydrogen bond. A linear correlation between C-H...O bond energies and gas-phase proton affinities is reported. The gas-phase anion proton affinity of a peptide C-alpha-H hydrogen was calculated (355 kcal mol(-1)) and used to estimate values of D-e = -4.0 +/- 0.5 kcal mol(-1) and Delta H-298 = -3.0 +/- 0.5 kcal mol(-1) for the C-alpha-H...O=C hydrogen bond. The magnitude of this interaction, roughly one-half the strength of the N-H...O=C hydrogen bond, suggests that C-alpha-H...O=C hydrogen bonding interactions represent a hitherto unrecognized, significant contribution in the determination of protein conformation.