How Strong Is the C^α−H···OC Hydrogen Bond?

Abstract

Although the existence of Cα−H···OC 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 ab initio calculations (MP2/aug-cc-pTZV) yield electronic association energies (De) and association enthalpies (ΔH298) for four dimer geometries. These data provide a lower limit of De = −2.1 kcal mol-1 for the Cα−H···OC 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 Cα−H hydrogen was calculated (355 kcal mol-1) and used to estimate values of De = −4.0 ± 0.5 kcal mol-1 and ΔH298 = −3.0 ± 0.5 kcal mol-1 for the Cα−H···OC hydrogen bond. The magnitude of this interaction, roughly one-half the strength of the N−H···OC hydrogen bond, suggests that Cα−H···OC hydrogen bonding interactions represent a hitherto unrecognized, significant contribution in the determination of protein conformation.