Comparative conformational study of N-acetyl- N′-methylprolineamide with different basis sets

Abstract

We report here the results on conformational free energies of N-acetyl- N′-methylprolineamide (Ac-Pro-NHMe) calculated using the ab initio and density functional methods with the reaction field theory at HF and B3LYP levels of theory with 6-31G(d,p) and 6-31+G(d) basis sets to investigate the effects of two different basis sets on the structure, cis– trans equilibrium, and rotational barrier of the proline dipeptide. There are no significant differences in the optimized structures for backbone and proline ring of Ac-Pro-NHMe at the HF level with 6-31G(d,p) and 6-31+G(d) basis sets. The relative electronic energies, enthalpies, and free energies with the 6-31+G(d) basis set are lower by 0.2–0.8 and 0.1–1.2 kcal/mol at HF and B3LYP levels than those with the 6-31G(d,p) basis set, respectively, which may be ascribed to the differences in the distribution of atomic charges. The HF/6-31+G(d) level has brought the unfavorable solvation by 0.1–1.5 kcal/mol in chloroform and water than the HF/6-31G(d,p) level, but there are small differences in dipole moments. The calculated cis populations and rotational barriers may indicate that the B3LYP/6-31+G(d)//HF/6-31+G(d) level combined by the frequency and solvation calculations at the HF/6-31+G(d) level appears to be the appropriate method in describing the cis– trans isomerization of the X-Pro peptide bond in solution.