Conformational investigation of alpha,beta-dehydropeptides. VIII. N-acetyl-alpha,beta-dehydroamino acid N'-methylamides: conformation and electron density perturbation from infrared and theoretical studies.

The Fourier transform infrared spectra are analyzed in the regions of Vs(N-H), amide I, amide II and Vs(C alpha = C beta) bands for a series of Ac-delta Xaa-NHMe, where delta Xaa = delta Ala, (Z)-delta Abu, (Z)-delta Leu, (Z)-delta Phe and delta Val, to determine the predominant solution conformation of these alpha,beta-dehydropeptide-related molecules and the electron distribution perturbation in their amide bonds. The measurements were performed in dichloromethane (DCM). To confirm and rationalize the assignments, the spectra of the respective series of saturated Ac-Xaa-NHMe, recorded in DCM, and the spectra of these two series of unsaturated and saturated compounds, recorded in acetonitrile, were examined. To help interpret the spectroscopic results, the equilibrium geometrical parameters for some selected amides were used. These were optimized with ab initio methods in the 6-31G** basis set. Each of the dehydroamides studied adopted a C5 structure, which in Ac-delta Ala-NHMe is fully extended and accompanied by the strong C5 hydrogen bond. Interaction with the C alpha = C beta bond lessened the amidic resonance within each of the flanking amide groups. The N-terminal C = O bond was noticeably shorter, both amide bonds were longer than the corresponding bonds in the saturated entities and the N-terminal amide system was distorted. Ac-delta Ala-NHMe constituted an exception. Its C-terminal amide bond was shorter than the standard one and both amide systems were prototypically planar.