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Intra‐ versus Intermolecular Hydrogen Bonding: Solvent‐Dependent Conformational Preferences of a Common Supramolecular Binding Motif from 1 H NMR and Vibrational Circular Dichroism Spectra
Author(s) -
Demarque Daniel P.,
Merten Christian
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201703643
Subject(s) - hydrogen bond , intramolecular force , chemistry , intermolecular force , solvation , steric effects , supramolecular chemistry , circular dichroism , crystallography , molecule , nuclear magnetic resonance spectroscopy , spectroscopy , chemical shift , computational chemistry , stereochemistry , crystal structure , organic chemistry , physics , quantum mechanics
When predicting binding properties of small molecules or larger supramolecular aggregates, intra‐ and intermolecular hydrogen bonds are often considered the most important factor. Spectroscopic techniques such as 1 H NMR spectroscopy are typically utilized to characterize such binding events, but interpretation is often qualitative and follows chemical intuition. In this study, we compare the effects of intramolecular hydrogen bonding and solvation on two chiral 2,6‐pyridinediyl‐dialkylamides. In comparison with 1 H NMR spectroscopy, vibrational circular dichroism (VCD) spectroscopy proved to be more sensitive to conformational changes. In fact, the change of the solvent from CDCl 3 to [D 6 ]DMSO generates mirror‐image VCD spectra for the same enantiomer. Here, the common sense that the sterically less hindered group is more prone to solvation proved to be wrong according predicted VCD spectra, which clearly show that both asymmetric amide hydrogens are equally likely to be solvated, but never simultaneously. The competition between intra‐ and intermolecular hydrogen bonding and their importance for a correct prediction of spectral properties are discussed.