Density function studies of peptides Part I. Vibrational frequencies including isotopic effects and NMR chemical shifts of N-methylacetamide, a peptide model, from density function and MP2 calculations

Isotopic effects on vibrational frequencies and chemical shifts of N-methylacetamide (NMA) are of significance to the further development of multi-dimensional NMR and IR studies in protein structural biology. Density functional theory (DFT) has proven to be a powerful method for the calculation of molecular structure, conformation, and torsional barriers for small molecules. In the first part of the paper we demonstrate that DFT reproduces experimentally observed geometries, conformation, and torsional barriers before we proceed to a discussion of chemical shifts in NMA, whose accurate calculation has been made possible by sum-over-states density functional perturbation theory. There is good agreement between the calculated proton and carbon chemical shifts of NMA and the experimentally derived values of the same in DMSO-d6. We have used gradient corrected non-local functional BPW91/6-31 G(d,p) for the calculation of vibrational frequencies of NMA and the effect of 2H, 13C, 15N isotopic effects. The unscaled calculated vibrational frequencies of NMA are in agreement with the gas-phase vibrational frequencies of NMA obtained from electron diffraction of NMA at low temperatures in an inert matrix. The results presented in this paper auger well for the application of DFT to di-, tri, and larger peptides and we have such studies in progress in our laboratories.