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. 2015 Apr 14;51(29):6395-8.
doi: 10.1039/c5cc01034a.

An efficient computational model to predict protonation at the amide nitrogen and reactivity along the C-N rotational pathway

Roman Szostak  1 , Jeffrey Aubé, Michal Szostak
Affiliations

An efficient computational model to predict protonation at the amide nitrogen and reactivity along the C-N rotational pathway

Roman Szostak et al. Chem Commun (Camb). .

Abstract

N-Protonation of amides is critical in numerous biological processes, including amide bonds proteolysis and protein folding as well as in organic synthesis as a method to activate amide bonds towards unconventional reactivity. A computational model enabling prediction of protonation at the amide bond nitrogen atom along the C-N rotational pathway is reported. Notably, this study provides a blueprint for the rational design and application of amides with a controlled degree of rotation in synthetic chemistry and biology.

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Figures

Fig. 1
Fig. 1
(a) Resonance description of amides. (b) Geometric changes resulting in non-planarity. (c) Conformational restriction of amides.
Fig. 2
Fig. 2
Correlation of N–C(O) bond length [Å] to the sum of twist and pyramidalization at nitrogen angles (Στ+χN).
Fig. 3
Fig. 3
Correlation of ΔPA to the sum of twist and pyramidalization at nitrogen angles (Στ+χN).
Scheme 1
Scheme 1
Structures of model lactams calculated in the current study.
See this image and copyright information in PMC

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