A Small Change in Structure, a Big Change in Flexibility.

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Spectroscopy

Background:

• Amide bond rotational barriers are crucial for understanding peptide bonds and designing molecular machines.
• Previous studies utilized quantum computing and NMR to model peptide bond properties.
• Fluxionality of amide and enamine bonds is key to molecular conformational dynamics.

Purpose of the Study:

• To investigate the rotational barrier energies of amide and enamine bonds in a specific urea derivative.
• To elucidate the electronic origins of observed differences in rotational barriers using theoretical calculations.
• To compare these findings with a structurally similar acrylamide compound.

Main Methods:

• Advanced dynamic nuclear magnetic resonance (NMR) experiments were employed to study bond fluxionality.
• Density functional theory (DFT) calculations were performed for theoretical evaluation of energy barriers.
• Comparison of experimental and computational data for two related compounds.

Main Results:

• The study identified restricted rotation around the amide group (16.4 kcal/mol) and a higher barrier around the enamine group (18.6 kcal/mol) in the primary compound.
• A structurally similar compound showed lower barriers for both amide (12.4 kcal/mol) and enamine (11.7 kcal/mol) groups.
• DFT calculations indicated that enhanced delocalization of nitrogen lone pair electrons into antibonding orbitals stabilizes the enamine ground state, increasing its rotational barrier.

Conclusions:

• The enamine bond exhibits a significantly higher rotational barrier compared to the amide bond in the investigated urea derivative.
• Electronic delocalization is the primary factor responsible for the elevated enamine barrier.
• These findings contribute to a fundamental understanding of amide and enamine bond dynamics and have implications for molecular design.