Proton nuclear magnetic resonance (1H NMR) titration experiments have been
used to establish the pair-wise interactions that form between simple amino acid amide derivatives and phenolic compounds. In deuterated chloroform (CDCb) the proline derivative, N-Ac-Pro-OMe, relative to other similarly protected amino acid residues, produces enhanced and specific association to phenolics. Through supplementing the experimental data with density functional theory (DFT) calculations, it is proposed that the association of the prolyl model with phenolic compounds is primarily directed by hydrogen-bonding between the phenolic hydroxyl and the amido-carbonyl of the peptide model, with concomitant polarisation that strengthens the interaction. The association mechanism found in this system indicates the possible source of complexation within larger peptide-tannin systems, and that such complexation does not necessarily require a hydrophobic force. The 1 H NMR titration data showed that no significant association was observed to secondary amide derivatives, including histidine functions. However, further NMR experiments were used to show that one of
the histidine derivatives, N-Ac-Af-Ac-His-OMe, was found to produce a ransacetylation reaction, specifically with phenolic compounds and aniline.
Aromatic amino acid 2,5-diketopiperazines (DKPs) have been used as models to
produce intermolecular aromatic stacking interactions between species. The association to phenolic and non-phenolic species was probed, and a specific association to phenolic compounds is observed in CDCh solution. Using the data obtained from 1 H NMR titration experiments, DFT electrostatic calculations, and nuclear Overhauser enhanced spectroscopy (NOESY) NMR experiments it is proposed that the complexation to phenolic compounds is due to a combination of hydrogen-bonding and aromatic off-set face-to-face stacking interactions. The results show that the electrostatic nature of aromatic species drives complexation, rather than the hydrophobic environment that they provide.