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

J Org Chem. 2013 Mar 1;78(5):2099-103. doi: 10.1021/jo302265k. Epub 2012 Dec 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amides / chemistry*
  • Crystallography, X-Ray
  • Halogens / chemistry*
  • Hydrocarbons, Halogenated / chemistry*
  • Models, Molecular
  • Protein Carbonylation
  • Proteins / chemistry*
  • Thermodynamics


  • Amides
  • Halogens
  • Hydrocarbons, Halogenated
  • Proteins