Conformational investigation of α,β-dehydropeptides. IX. N-Acetyl-(E)-α,β-dehydrobutyrine N′-methylamide: stereoelectronic properties from infrared and theoretical studies*

Abstract: : The Fourier transform infrared spectra of Ac-(E)-ΔAbu-NHMe were analyzed to determine the predominant solution conformation (s) of this (E)-α,β-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 v_s (N–H), amide I, amide II and v_s (C^α= C^β). 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)-ΔAbu-NHMe, Ac-ΔAla-NHMe, which is deprived of any β-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-ΔAla-NHMe is C₅ hydrogen-bonded. The other adopts a warped C₅ structure similar to that of Ac-(Z)-ΔAbu-NHMe. The C₅ hydrogen bond, unlike the H-bond in Ac-ΔAla-NHMe, is disrupted by acetonitrile. The resonance within the N-terminal amide groups in either of the (E)-ΔAbu 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)-ΔAbu-NHMe/Ac-ΔAla-NHMe and the warped C₅ Ac-(E)-ΔAbu-NHMe/Ac-(Z)-ΔAbu-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)-ΔAbu conformer apparently is determined mainly by the electron influx from the C^α= C^β double bond.