Unveiling the Influence of Hydrogen-Bonding Dynamics on Water-Affected Methyl Internal Rotation by Microwave Spectroscopy

What intrinsic mechanism governs the water-mediated modulation of methyl rotation? Here we unveil that the distinct dynamic variations in hydrogen bonds between methyl and water, dictated by H-bonding architecture, serve as an intrinsic mechanism. In <i>N</i>,<i>N</i>-dimethylformamide (DMF)-water, an anomalous acceleration of the DMF methyl rotation was observed, which contrasts entirely with the changes seen in <i>N</i>-methylformamide (NMF). Slight structural differences in the monohydrated forms lead to opposite effects on methyl rotation in DMF and NMF, which can be attributed to the flexible variations in hydrogen bonding. The structures of DMF-(H₂O)_0-2 were clearly identified from microwave spectra, where the splitting of rotational transition lines indicated varying methyl rotation barriers. Transition state analysis unveiled that enhanced hydrogen bonding in DMF-H₂O promotes methyl rotation, while weakened hydrogen bonding in NMF-H₂O hinders methyl rotation. The findings in this work could give clues to further understand the dynamic variations in hydrogen bonds and the dynamics of proteins in aqueous solution.