Intrinsic conformational preferences of C-alpha,C-alpha-dibenzylglycine

[GRAPHICS] The intrinsic conformational preferences of C-alpha,C-alpha-dibenzylglycine, a symmetric alpha,alpha-dialkyiated amino acid bearing two benzyl substituents on the alpha-carbon atom, have been determined using quantum chemical calculations at the B3LYP/6-31 +G(d,p) level. A total of 46 minimum energy conformations were found for the N-acetyl-M-niethylamide derivative, even though only nine of them showed a relative energy lower than 5.0 kcal/mol. The latter involves C-7, C-5, and alpha' backbone conformations stabilized by intramolecular hydrogen bonds and/or N-H center dot center dot center dot pi interactions. Calculation of the conformational free energies in different environments (gas-phase, carbon tetrachloride, chloroform, methanol, and water solutions) indicates that four different minima (two C-5 and two C-7) are energetically accessible at room temperature in the gas phase, while in methanol and aqueous solutions one such minimum (C-5) becomes the only significant conformation. Comparison with results recently reported for C-alpha,C-alpha-diphenylglycine indicates that substitution of phenyl side groups by benzyl enhances the conformational flexibility leading to (i) a reduction of the strain of the peptide backbone and (ii) alleviating the repulsive interactions between the T electron density of the phenyl groups and the lone pairs of the carbonyl oxygen atoms.

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