Intrinsic Conformational Characteristics of α,α-Diphenylglycine

Quantum mechanical calculations at the B3LYP/6-31+G(d,p) level have been used to investigate the intrinsic conformational preferences of α,α-diphenylglycine, a simple α,α-dialkylated amino acid bearing two phenyl substituents on the α-carbon, in both the gas phase and aqueous solution. Nine minimum energy conformations have been characterized for the N-acetyl-N‘-methylamide derivative within a relative energy range of about 9 kcal/mol. The relative stability of these structures is largely influenced by specific backbone···side chain and side chain···side chain interactions that can be attractive (N−H···π and C−H···π) or repulsive (CO···π). On the other hand, comparison with the minimum energy conformations calculated for α-aminoisobutyric acid, in which the two phenyl substituents are replaced by methyl groups, revealed that the bulky aromatic rings of α,α-diphenylglycine induce strain in the internal geometry of the peptide. Finally, a set of force-field parameters for classical Molecular Mechanics calculations was developed for the investigated amino acid. Molecular Dynamics simulations in aqueous solutions have been carried out to validate the parameters obtained.