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Updated: Apr 29, 2026

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
Interplay between molecular conformation and intermolecular interactions in conformational polymorphism: a molecular
Alessandra Mattei1, Tonglei Li
1Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, United States.
Abstract:
Tolfenamic acid exhibits conformational polymorphism. The molecules in its two commonly occurred crystal structures form similar hydrogen-bonded dimers but differ in conformation. The conformational variance was analyzed by electronic calculation methods with the aim to unravel intrinsic connection between the conformational flexibility and intermolecular interactions in the polymorphs. The study was conducted mainly by conceptual density functional theory (DFT) and natural bond orbital (NBO) analysis. It is found that the conformational polymorphism is resulted from the energy competition between intramolecular π-conjugation and intermolecular hydrogen bonding. By adapting conformation that departs from being the most energetically stable, tolfenamic acid molecules can strengthen the intermolecular hydrogen-bonding interactions in the crystals. The study illustrates how the molecule's electronic properties are influenced by conformational variation and, inherently, how the intermolecular interactions become regulated. Moreover, understanding molecular interaction and crystal packing necessitates electronic structure calculation and analysis, which can be further facilitated by utilizing DFT and NBO concepts.
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