Nuclear Magnetic Resonance Studies in Amide Chemistry

Nuclear magnetic resonance (NMR) spectroscopy has long been indispensable for probing the structural and dynamic properties of amide bonds, which underpin peptide function, solvent behaviour and synthetic amide reactivity. High-resolution one-dimensional and multidimensional NMR experiments yield detailed information on chemical shifts, coupling patterns and relaxation times, providing insight into local electronic environments and hydrogen-bonding interactions. Variable-temperature NMR and dynamic NMR techniques enable direct measurement of rotational barriers around the carbon–nitrogen amide bond, revealing the energy landscapes that govern cis/trans isomerisation and conformational equilibria. These studies are complemented by quantum chemical calculations, most commonly density functional theory, which rationalise observed barriers in terms of electronic delocalisation and steric effects. Together, experimental NMR and theoretical approaches have elucidated the fundamental origin of restricted amide rotation, informed the design of molecular machines and advanced our understanding of amide activation in both biological and material contexts.

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Nuclear Magnetic Resonance Studies in Amide Chemistry publication trend

The graph below shows the total number of articles in nuclear magnetic resonance studies in amide chemistry across all publications each year (not limited to Nature Index journals).

Technical terms

Nuclear Magnetic Resonance (NMR): A spectroscopic technique that exploits the magnetic properties of atomic nuclei to reveal molecular structure and dynamics.

Dynamic NMR: Variable-temperature NMR methods used to observe and quantify rapid chemical exchange or conformational processes by line-shape analysis.

Rotational barrier: The free-energy hurdle that must be overcome for rotation about the amide C–N bond, often expressed in kcal mol⁻¹.

Cis/trans isomerisation: The interconversion between two geometric forms of an amide bond, where substituents lie on the same (cis) or opposite (trans) side.

Density Functional Theory (DFT): A quantum mechanical modelling approach that calculates electronic structure to support interpretation of spectroscopic data.

References

1. A Small Change in Structure, a Big Change in Flexibility †. Molecules (2023).
2. Bispidine Platform as a Tool for Studying Amide Configuration Stability. Molecules (2022).
3. Density Functional Studies on Secondary Amides: Role of Steric Factors in Cis/Trans Isomerization. Molecules (2018).
4. Weak Interactions in Dimethyl Sulfoxide (DMSO)–Tertiary Amide Solutions: The Versatility of DMSO as a Solvent. The Journal of Physical Chemistry B (2023).