The non-planar amide group

Abstract

Crystal structures of medium-ring lactams and their crystalline hydrochlorides furnish detailed information on the nature of the out-of-plane distortions of the amide group. Caprylolactam has a non-planar transoid amide group in the crystal but exists in solution as an equilibrium mixture of at least two conformations, one with a nearly planar cis-amide group, one with a non-planar transoid-amide group. The corresponding hydrochloride salt is protonated on oxygen and contains a nearly planar cis-amide group. For non-planar amide groups it is found that out-of-plane bending at nitrogen is about as important as pure twisting, the contribution from out-of-plane bending at the carbonyl carbon being smaller. These results, together with rough data on the energy differences between the lactam conformations, can be used to test various potential functions that have been proposed. It is concluded that although the equilibrium conformation of the amide group may be planar or close to it, out-of-plane deformation can be made at a very modest energy cost. In the construction of models of polypeptide chains or in fitting such models to electron-density maps of protein crystals, the strictly planar peptide unit thus incorporates restrictions that may be rather easily relaxed in the actual molecule.