Horst M. Sulzbach

NMR CHEMICAL SHIELDING SURFACE OF N-ACETYL-N'-METHYLALANINAMIDE : A DENSITY FUNCTIONAL STUDY

The five energetically lowest minima on the potential energy surface of N‐acetyl‐N′‐methylalaninamide were optimized at the Becke3LYP/DZd level of theory to compare these density functional theory results with the literature findings at restricted Hartree‐Fock/3‐21G. While the relative energies are very similar, the amide moiety is predicted to be much more flexible at Becke3LYP/DZd. As a consequence, the three minima that favor a nonplanar amide group differ by up to 14° in their ϕ and ψ values between the two levels. To compare the change in the density functional NMR chemical shifts with respect to ϕ and ψ with experimental results, Becke3LYP/DZd was employed to optimize a structure for N‐acetyl‐N′‐methylalaninamide at each 30° interval on the (ϕ, ψ) surface in the regions that correspond to the α helix and the β‐pleated sheet and at each 60° interval elsewhere. The corresponding NMR chemical shielding surface was computed with the density functional program deMon. The resultant NMR chemical shielding surfaces for N and Cβ are in good agreement with the experiment, while the change in the NMR chemical shielding of C′ and Cα cannot be described only in terms of ϕ and ψ. The chemical shifts for those atoms also depend on the nonplanarity of the amide moiety. We evaluated this dependence for N‐methylacetamide as a model system. Estimates of the parameters derived from N‐methyl‐acetamide allowed the NMR‐shielding surfaces of C′ and Cα to be corrected for the nonplanar nitrogen influence. Although the effect is less pronounced with lower level theoretical geometries, due to the smaller degree of pyramidalization of the amide nitrogen, the (ϕ, ψ) NMR chemical shielding surfaces will need to be corrected. The agreement with the experiment was much better for the corrected surface of C′ when the nitrogen in the α helix had a nonplanar environment.