Ab initio MO and density functional studies on trans and cis conformers of N-methylacetamide

The effect of basis sets on the structures and energetics of the rotation for the peptide bond of N-methylacetamide (NMA) has been investigated at high levels of theory. The structures, dipole moments and thermodynamic properties for trans- and cis-NMA have been determined at the BF, MP2 and B3LYP levels with 6-31G(d), 6-31G(d,p), 6-31+G(d), 6-31+G(d,p), 6-31++G(d,p), 6-311+G(d,p) and 6-311++G(d,p) basis sets. By comparing the calculated structure and dipole moment of trans-NMA and the relative enthalpy (DeltaH) of cis-NMA in the gas phase with corresponding experimental data, the B3LYP level with 6-31G(d) or 6-31G(d,p) basis sets appears to be the most appropriate among several levels of theory and basis sets considered here. Trans-NMA is computed to be favored by a total free energy of 2.7 kcal/mol than cis-NMA in water at the B3LYP/6-31G(d,p) level with the SCI-PCM method, which corresponds to 1.1% population of cis-NMA. This is consistent with the results of NMR experiments in aqueous solution that estimate the cis population to be 1.5 +/- 0.1% and the free energy difference of 2.5 +/- 0.3 kcal/mol. In addition, the change in relative solvation. free energies is computed to be -0.1 kcal/mol at the BF and B3LYP levels with the 6-31G(d,p) basis set as transferred from water to chloroform, which corresponds to the increase of the cis population by about 0.3%, consistent with the value from NMR measurements. Therefore, the SCRF method with proper levels of theory and basis sets seems to be reasonable to describe the solvation. of NMA. Our calculated results confirmed that the relative distribution of trans and cis conformers of NMA is insensitive to the solvent polarity. (C) 2001 Elsevier Science B.V. All rights reserved.