Differing Effects of Nonlinearity around the Proton Acceptor on CH<middle dot><middle dot>O and NH<middle dot><middle dot>O H-Bond Strength within Proteins

The effects of deviations from nonlinearity around the carbonyl proton acceptor of an amide group are assessed by DFT quantum chemical calculations for both CH<middle dot><middle dot>O and NH<middle dot><middle dot>O H-bonds. The proton donors are the imidazole functional group of His and the indole of Trp, which are paired respectively with N-methylacetamide and acetamide. The displacement of either CH or NH group toward the carbonyl O sp(2) lone pairs stabilizes the system and strengthens the H-bond. But the two donor groups differ in their response to a shift out of the amide plane. While the NH<middle dot><middle dot>O H-bond is weakened by this displacement, a substantial strengthening is observed when the CH donor is moved out of this plane, in one direction versus the other. This pattern is explained on the basis of simple Coulombic considerations.