Conformational investigation of alpha,beta-dehydropeptides. IX. N-Acetyl-(E)-alpha,beta-methylamide: stereoelectronic properties from infrared and theoretical studies.

The Fourier transform infrared spectra of Ac-(E)-deltaAbu-NHMe were analyzed to determine the predominant solution conformation(s) of this (E)-alpha,beta-dehydropeptide-related compound and the electron density perturbation in its amide groups. The measurements were performed in dichloromethane and acetonitrile in the region of mode vs (N-H), amide I, amide II and vs (C(alpha)=Cbeta). The equilibrium geometrical parameters, calculated by a method based on the density functional theory with the B3LYP functional and the 6-31G* basis set, were used to support spectroscopic interpretation and gain some deeper insight into the molecule. The experimental and theoretical data were compared with those of three previously described molecules: isomeric Ac-(Z)-deltaAbu-NHMe, Ac-deltaAla-NHMe, which is deprived of any beta-substituent, and saturated species Ac-Abu-NHMe. The titled compound assumes two conformational states in equilibrium in the DCM solution. One conformer is extended almost fully and like Ac-deltaAla-NHMe is C5 hydrogen-bonded. The other adopts a warped C5 structure similar to that of Ac-(Z)-deltaAbu-NHMe. The C5 hydrogen bond, unlike the H-bond in Ac-deltaAla-NHMe, is disrupted by acetonitrile. The resonance within the N-terminal amide groups in either of the (E)-deltaAbu conformers is not as well developed as the resonance in Ac-Abu-NHMe. However, these N-terminal groups, compared with the other unsaturated compounds, constitute better resonance systems in each conformationally related couple: the C5 hydrogen-bonded Ac-(E)-deltaAbu-NHMe/Ac-deltaAla-NHMe and the warped C5 Ac-(E)-deltaAbu-NHMe/Ac-(Z)-deltaAbu-NHMe. The resonance within the C-terminal groups of the latter couple apparently is similar, but less developed than the resonance in Ac-Abu-NHMe. The electron distribution within the C-terminal group of the hydrogen-bonded C5 (E)-deltaAbu conformer apparently is determined mainly by the electron influx from the C(alpha)=Cbeta double bond.