Intrinsic conformational characteristics of alpha,alpha-diphenylglycine

J Org Chem. 2007 Mar 16;72(6):2174-81. doi: 10.1021/jo0624905. Epub 2007 Feb 10.

Abstract

Quantum mechanical calculations at the B3LYP/6-31+G(d,p) level have been used to investigate the intrinsic conformational preferences of alpha,alpha-diphenylglycine, a simple alpha,alpha-dialkylated amino acid bearing two phenyl substituents on the alpha-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...pi and C-H...pi) or repulsive (C=O...pi). On the other hand, comparison with the minimum energy conformations calculated for alpha-aminoisobutyric acid, in which the two phenyl substituents are replaced by methyl groups, revealed that the bulky aromatic rings of alpha,alpha-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Gases
  • Glycine / analogs & derivatives*
  • Glycine / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Motion
  • Quantum Theory
  • Solutions

Substances

  • Gases
  • Solutions
  • diphenyl glycine
  • Glycine