Acetamide: a strange brew of structure, spectroscopy and theory

The importance of acetamide in prebiotic chemistry and structural biology is well established. Possessing a peptide bond with characteristic resonance, it is expected on chemical grounds to adopt a planar framework (aside from the methyl hydrogens). Spectroscopy supports this assignment, yet high-level quantum chemical calculations predict a non-planar minimum. To investigate this discrepancy, we explore the underlying potential energy surface, focusing on the coupling between two large-amplitude motions: CH₃ rotation and NH₂ inversion. The resulting multidimensional landscape contains symmetry-related, non-planar C₁ minima connected through distinct interconversion pathways. Despite the predicted non-planarity, calculated rotational constants and fundamental vibrational frequencies agree closely with experiment, highlighting the distinction between equilibrium and spectroscopically inferred structures. Systematic comparisons with CCSD(T), MP2, and DFT, reveal that the shallow methyl torsional potential is particularly sensitive to the treatment of electron correlation and the choice of basis set. Fourier analysis further highlights the importance of higher-order terms and phase contributions, providing insight into the longstanding uncertainty surrounding the ground-state A/E splitting. More broadly, these findings emphasize the need to understand coupled large-amplitude motions when interpreting the structure and spectroscopy of flexible molecules of chemical, biological, and astrochemical interest.