Cis-trans isomerism of the peptide bond

The molecular orbital method PCILO is applied to eight. N-monsubstituted amides. Experimentally known geometric properties are reasonably predicted by minimization of total energy with respect to molecular geometry. The same procedure shows that molecular deformations during rotation around the peptide bond significantly lower calculated barriers. Experimental heats of activation and the free-energy changes associated with cis–trans isomerism are in good agreement with those calculated, which include qualitative estimates of configurational entropy contributions to the isomerism energies. Both the calculations and revised infrared data indicate that N-phenylurethane, which has been used as a model for the cis peptide bond, should be predominantly trans. However the variations in rotational barriers and cis–trans isomerism energies among the N-monosubstituted amides provide no reason to suppose that the cis peptide bond should be excluded from stable protein conformations.