The Role of Water in the Deformation of the Amide Bond: Ab Initio Quantum Mechanics Studies

Abstract

The role of water in the deformation of an amide unit (N-methylacetamide, NMA) and the formation of a chiral center at the amide nitrogen was investigated, for the first time, by the use of ab initio molecular orbital calculations techniques (HONDO 7) [1] with full gradient optimization. Calculations were performed at the Hartree-Fock (HF) level with 4–31G* basis set and at the second order Möller-Plesset perturbation (MP2) level on three NMA-water clusters: trans-NMA with one molecule of water at the CO group and one at the NH group (complex (A)) [2]; trans-NMA with two molecules of water forming a ring cluster at the amide oxygen (complex (B)); trans-NMA with two molecules of water at the amide oxygen forming hydrogen bonds along the direction of the lone-pair electrons (complex (C)) [3]. Following Winkler and Dunitz [4] we may denote the non-planarity of the three bonds at the C’ and N atoms by the descriptive notations, ${\theta_{C'}}$ and ${\theta_N}$ where ${\theta_{C'}} = \theta \left( {C_i^\alpha, \,O;\,C'\,N} \right)$, and ${\theta_N} = \theta \left( {C_2^\alpha, \,H;\,N\,C'} \right)$ dihedral angles. The optimized intermolecular geometries of (A), (B) and (C) complexes are presented in Table 1 and the energy optimized structures are illustrated in Figure 1. For complex (B), calculations at the HF level demonstrate the importance of cooperative hydrogen bond interactions of the bound molecules of water which result in the formation of a nonplanar amide bond and the generation of a chiral center at the amide nitrogen (Figure 2). The stability of complexes (B) and (C) is reversed with MP2 calculations.