Intimate interactions with carbonyl groups: dipole-dipole or n→π*?

Amide carbonyl groups in proteins can engage in C═O···C═O and C-X···C═O interactions, where X is a halogen. The putative involvement of four poles suggests that these interactions are primarily dipolar. Our survey of crystal structures with a C-X···C═O contact that is short (i.e., within the sum of the X and C van der Waals radii) revealed no preferred C-X···C═O dihedral angle. Moreover, we found that structures with a short X(-)···C═O contact display the signatures of an n→π* interaction. We conclude that intimate interactions with carbonyl groups do not require a dipole.