Gas- and liquid-phase NMR studies of conformational exchange in N,N-diisopropylacetamide

The gas-phase free activation energy, ΔG^≠, for internal rotation about the carbon-nitrogen bond in N,N-diisopropylacetamide is 14.3 (0.1) kcal mol^-1. For neat N,N-diisopropylacetamide, and solutions in CCl₄, CDCl₃, dimethylsulphoxide (DMSO) and D₂O, ΔG^≠ values are 16.1 (0.1), 15.6 (0.01), 16.4 (0.1), 16.4 (0.1) and 17.8 (0.1) kcal mol^-1, respectively. Phase effects on the kinetic parameters for this amide are similar to those found for amides studied previously; this is compatible with solvent internal pressure effects and consistent with a process that proceeds via a transition state that has greater steric requirements than the ground-state configurations. We also demonstrate that gas-phase dynamic NMR can provide valuable data for evaluating the accuracy of molecular mechanics and semiempirical molecular orbital calculations, as well as for generating torsional potential parameters useful for their parameterization. These calculations have extreme importance in the future development of the ability to model the structural and dynamic characteristics of proteins and other biologically important molecules.