A comparative theoretical study of the chiral discrimination of phenylalanine enantiomers by the cyclic peptides with different sizes as discriminating agents: A DFT study

Abstract

• DFT calculation were used to study of interaction of phenyl alanine with cyclic peptides. • Cyclic peptides as a chiral host, showed different interaction with phenyl alanine enantiomers. • Chiral discrimination related to the macrocycles size, solvent effect, and geometry of the gust. • NBO calculations are also performed to determine the presence of hydrogen bonds between the enantiomers and cyclic peptides. • The 8-membered cyclic peptide has the highest ability to discriminate the d and l enantiomers. In the present study, the ability of cyclic peptide composed of 4, 5, 6, 7, 8, and 9 alanine building blocks, as the chiral discriminating agents, for the separation of phenylalanine (Phe) enantiomers (D and L) is, theoretically, investigated in the gas phase and water, separately. The calculations are performed using the density functional theory (DFT) employing the CAM-B3LYP functional and 6–31+ G (d) basis set. The adsorption energy ( E ad ) of each cyclic peptide with the enantiomers of the Phe are calculated in the gas phase and water, separately. It is found that the 8-membered cyclic peptide (8mcyc) has the highest ability to discriminate the D and L enantiomers of the Phe from each other in the gas phase based on the difference between its E ad with them (∆ E=- 2.66 kcal/mol). In water, the 9mcyc shows the highest ability for the chiral discrimination of the D and L enantiomers of the Phe with Δ E = -3.75 kcal/mol. The natural bonding orbital (NBO) calculations are also performed to determine the presence of hydrogen bonds between the enantiomers and cyclic peptides and their strength. The results obtained in this work can be used as a guide to support the experimental works in the field of chiral discrimination of amino acids by cyclic peptides and provide a consistent framework for more complex systems.