Internal rotation about the C-N bond of amides

The internal rotation about the C-N bond of formamide (FA), acetamide (AA), N-methylformamide (NMF), N-methylacetamide (NMA), N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) in the gas phase, chloroform and water has been investigated at the HF level of theory with 6-31G(d), 6-31G(d,p) and 6-31 + G(d) basis sets in order to figure out the appropriate level of theory in describing the cis-trans isomerization of the X-non-Pro and X-Pro peptide bonds. The conductor-like polarizable continuum model (CPCM) was used to calculate solvation free energies. The conformational electronic energies calculated at three levels predicted satisfactorily the experimental rotational barriers DeltaG(double dagger) of FA, DMF and DMA, and the observed relative enthalpy changes DeltaH(cis/trans) of cis conformers for NMF and NMA to trans ones in the gas phase. The CPCM method at the HF/6-31 + G(d) level predicted well experimental solvation free energies of acetamide derivatives. The DeltaG(double dagger) for FA, NMF, DMF, NMA and DMA, and DeltaH(cis/trans) for NMF and NMA in chloroform and water were satisfactorily described by the CPCM method at HF/6-31G(d) and HF/6-31 + G(d) levels. These results may indicate that the HF/6-31 + G(d) level with the CPCM method appears to be the appropriate method in describing the cis-trans isomerization of the X-non-Pro and X-Pro peptide bonds in solutions. (C) 2004 Elsevier B.V. All rights reserved.