Chiral recognition in self‐complexes of diketopiperazine derivatives

Abstract

The chiral discrimination in the self‐association of 2,5‐diketopiperazines derivatives has been studied using density functional theory (DFT) methods. Hence, clusters from dimers to tetramers have been considered. We have found a variety of linear and cyclic structures depending on the geometry of the monomers. In general, the heterochiral dimers (RR:SS or SS:RR) are more stable than the homochiral ones (RR:RR or SS:SS) with slight energetic differences. Nevertheless, most of the larger clusters (trimers and tetramers) show changes in stability, the homochiral cyclic structures being favored due to the better geometry of the hydrogen bond and/or the higher number of interactions. Some interesting correlations between the hydrogen bond geometrical descriptors and theoretical parameters obtained from the Natural Bond Orbital analysis (NBO), Natural energy decomposition analysis (NEDA), and the Atoms in Molecules theory (AIM) have been found. The chiral discrimination in the recognition process of these self‐complexes has been evaluated. In addition, evidence of cooperative effects has been observed. Copyright © 2010 John Wiley & Sons, Ltd.

Determination of Absolute Configuration and Conformation of a Cyclic Dipeptide by NMR and Chiral Spectroscopic Methods

“…Different enantiomeric forms create different macromolecular self-assemblies, e.g., due to differences in intra-and intermolecular hydrogen bonding. 17 Investigations of the conformational and electronic properties of DKPs are thus valuable also for an understanding of their biological activity.…”

“…The molecular recognition and thermodynamic properties of DKP derivatives are expected to be useful for understanding protein folding. , For example, the absolute configuration (AC) of the compounds determines their supramolecular structure. Different enantiomeric forms create different macromolecular self-assemblies, e.g., due to differences in intra- and intermolecular hydrogen bonding . Investigations of the conformational and electronic properties of DKPs are thus valuable also for an understanding of their biological activity.…”

Absolute Configuration of a Cyclic Dipeptide Reflected in Vibrational Optical Activity: Ab Initio and Experimental Investigation

“…16,17 The chirality of the cyclic dipeptides determines the supramolecular structures of these compounds and their abilities to engage in molecular recognition arising from their self-assembled hydrogen-bonded structures. 18,19 DKPs are the smallest cyclic peptides possible and represent an excellent polypeptide mimic with controlled substituent stereochemistry. Furthermore, the DKP ring contains both hydrogen bonding donor and acceptor moieties and is more conformationally rigid than linear dipeptides.…”

“…In addition, DPK derivatives may have antitumor, antibacterial, , antifungal, and antiviral effects. They have also been used in protein folding studies. , The chirality of the cyclic dipeptides determines the supramolecular structures of these compounds and their abilities to engage in molecular recognition arising from their self-assembled hydrogen-bonded structures. , …”

Cyclic dipeptides: catalyst/promoter-free, rapid and environmentally benign cyclization of free amino acids

“…17 Blanco et al evaluated discrimination in the recognition of selfassembled complexes of DKPs using density functional theory (DFT) calculations. 18 It has been suggested that microbial peptides are derived partly or completely by enzymatic condensation and ring expansion of diketopiperazines. 19 Recent findings using hydrothermal conditions also showed the importance of DKPs towards the origin and evolution of life in primordial earth.…”