Microsolvation and hydrogen-bonding topologies critically influence local molecular geometries and electronic structures, especially in biological peptides, where solvent-peptide interactions can perturb the amide bond and affect conformational dynamics. Although peptide bonds are typically near-planar, how and to what extent local solvent molecules affect this geometry remains unresolved. In this study, we investigate stepwise microsolvation effects on the peptide bond planarity of N-ethylformamide (NEF) using rotational spectroscopy. The structures of NEF microsolvated by two to five water molecules, NEF-(H2O)n (n = 2 - 5), have been determined. Conformational analysis reveals a pronounced nitrogen pyramidalization angle (θN > 20°) in the trans-sc-NEF-(H2O)3 complex, far exceeding the typical ±6° observed in proteins. The experimental nuclear quadrupole coupling constants confirm this distortion, yielding the semiexperimental value of θN = 23.01°. This arises from nonideal hydrogen bonds in its microsolvation topology, inducing out-of-plane displacement of the amide hydrogen and thus driving a twist of its planarity. In contrast, no significant deviation is observed for other microsolvation levels, either more or less. Our results demonstrate that specific hydrogen-bonding patterns can directly perturb peptide bond planarity, highlighting the key role of local solvent effects in modulating peptide bond stability.
Jiang et al. (Fri,) studied this question.