Hydrogen bond-aromaticity cooperativity in self-assembling 4-pyridone chains
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Updated: Apr 8, 2026

Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides
Published on: November 21, 2013
Megha Anand1, Israel Fernández2, Henry F Schaefer1
1Center for Computational Quantum Chemistry, University of Georgia, Athens, Georgia, 30602.
Abstract:
Self-assembling building blocks like the 4-pyridone can exhibit extraordinary H-bond-aromaticity coupling effects. Computed dissected nucleus independent chemical shifts (NICS(1)zz), natural bond orbital (NBO) charges, and energy decomposition analyses (EDA) for a series of hydrogen (H-) bonded 4-pyridone chains (4-py)n (n = 2 to 8) reveal that H-bonding interactions can polarize the 4-pyridone exocyclic C=O bonds and increase 4n+2 π-electron delocalization in the six-membered ring. The resulting H-bonded 4-pyridone units display enhanced π-aromatic character (both magnetically and energetically) and their corresponding N-H···O=C interactions are strengthened. These π-electron polarization effects do not depend on the relative orientations (co-planar or perpendicular) of the neighboring 4-pyridone units, but increase with the number of H-bonded units.
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