How strong is the C-alpha-H center dot center dot center dot O=C hydrogen bond?

Although the existence of C-alpha-H...O=C hydrogen bonds in protein structu res recently has been established, little is known about their strength and , therefore, the relative importance of these interactions. We have discove red that similar interactions occur in N,N-dimethylformamide dimers. High l evel nb initio calculations (MP2/aug-cc-pTZV) yield electronic association energies (D-e) and association enthalpies (Delta H-298) for four dimer geom etries. 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 e nergies and gas-phase proton affinities is reported. The gas-phase anion pr oton 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 Del ta 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 inter actions represent a hitherto unrecognized, significant contribution in the determination of protein conformation.