6533b855fe1ef96bd12b1315

RESEARCH PRODUCT

Conformational analysis of α,β-dehydropeptide models at the HF and DFT levels

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Abstract The Ramachandran potential energy surfaces of N-acetyl-α,β-dehydroamino acid N′-monomethylamides Ac-ΔXaa-NHMe (ΔXaa=ΔAla, (Z)-ΔPhe; 1, 2) and N-acetyl-α,β-dehydroamino acid N′,N′-dimethylamides Ac-ΔXaa-NMe2 (ΔXaa=ΔAla, (Z)-ΔPhe, (Z)-ΔAbu; 3–5) were calculated at the HF/6-31G*//HF/3-21G level. The conformers localised were fully optimised at the DFT/B3LYP/6-31+G** level and their relative stabilities were analysed in terms of both π-conjugation and internal hydrogen bonding. The Ac-ΔXaa-NMe2 molecules reveal the low-energy conformer H/F, φ=−41±4°, ψ=128±4°, which is not too easily accessible for common amino acid residues. This conformer is stabilised by the bifurcated N2–CH3 O1 interaction, which makes it the second lowest in energy for Ac-ΔAla-NMe2 and Ac-(Z)-ΔAbu-NMe2, and the lowest one for Ac-(Z)-ΔPhe-NMe2. In the latter the additional N–H⋯π interaction also operates. The conformer H/F, with its C2O2 group outside exposed, has great potency in intermolecular interactions and to date is the only molecular structure that has been found in the crystal of Ac-ΔXaa-NMe2 compounds. For Ac-ΔXaa-NHMe, the conformer in question is one of the highest in energy order. The analysed molecules have different conformational profiles and conformational freedom.