Combining microsolvation and polarizable continuum studies: New insights in the rotation mechanism of amides in water

We present a quantum mechanical investigation of the rotation mechanisms of N,N-dimethylformamide (DMF) and NN-dimethylacetamide (DMA) in water. This rotation can happen through two distinct transition states known as TS1 and TS2, where the nitrogen lone pair is on the opposite side of the oxygen atom or on the same side, respectively. The analysis is focused on complementary descriptions of the solvent, either represented by a limited number of explicit solvent molecules (microsolvation), by an implicit (or continuum) solvation, or by combinations of these two approaches. The combined approach (microsolvation + continuum) can provide quantitative agreement with the experimental results for the gas to solution shift of the rotational barrier. For both amides, continuum effects alone are sufficient to select the correct channels. However, hydrogen-bond effects (via the explicit solvent molecules) are necessary to obtain quantitative agreement with experiment, provided this is combined with a continuum description. In the rotation in DMF, it seems that a single water molecule is directly involved, while the other solvent molecules act as a mean field (the bulk), which is well reproduced by a polarizable continuum medium. The mechanism in DMA is less clear. In gas phase the steric repulsive interactions between methyl groups make TS1 clearly favored with respect to TS2. In water, the larger dipole moment of TS2 produces an opposite effect with respect to the repulsion interactions, making the corresponding channel less disfavored than in gas phase. The results are compared with previous Monte Carlo simulations, and this comparison is used to draw a more general picture about how different descriptions of the solvent can take into account long-range and mediated effects on one side and shorter-range and dynamic effects on the other side.