Quantum-chemical study of N-methylacetamide and N,N-dimethylacetamide as models for peptidic bond in hydrogen-bond interaction with water, methanol and phenol

The PCILO quantum-chemical method with geometry optimization has been used to study rotation barriers of methyl groups in N-methylacetamide and N,N-dimethylacetamide. In all the cases studied, the eclipsed conformation have been found to be the most stable. Cis form of N-methylacetamide is less stable than the corresponding trans form by 2.0 kJ mol-1. Moreover, the PCILO method has been used to study linear n-mers (n = 4) of N-methylacetamide. On going from the dimer to tri- and tetramers, the hydrogen-bond energies have been found non-additive, and positive cooperativity has been observed. Finally, hydrogen-bond complexes have been studied which were formed by C=O groups of N-methylacetamide and N,N-dimethylacetamide with water, methanol or phenol as proton-donors. The said proton-donors have been found to act as breakers of inter-peptide hydrogen bonds N-H...O=C. The hydrogen bonds formed by methanol are somewhat stronger than those formed by water. In accordance with experiment, the strongest hydrogen bonds with the studied proton-acceptors are formed by phenol.