Diastereomeric discrimination by achiral substances: the effect of diverse ions in the stability of amphi-ionophore cystine-based cyclopeptide stereoisomers

Cyclic peptides are a large class of natural compounds which attracted a great deal of attention, especially as potential amphi-ionophores. Herein, a theoretical study on the stability of new cystine-based tricyclopeptide (TCP) stereoisomers in achiral media in the presence of Li⁺, Na⁺, K⁺, F⁻, Cl⁻, and Br⁻ ions was performed at the M06-2X/6-311++G(d,p) level of theory in both gas and aqueous phases. The nature of the intermolecular interaction between TCPs and ions were studied by natural bond orbital analysis (NBO) and the quantum theory of atoms in molecules (QTAIM) methods in gas phase. According to the size of the ions and configuration of TCPs, the location of ions (within or above the TCPs) and the types of formed intermolecular interactions are different. The results revealed that the free TCP7 and TCP8 enantiomers in gas phase and also TCP1 and TCP2 enantiomers in aqueous phase are the most stable structures among all TCPs. Moreover, the calculated energies of the optimised complexes containing the same ion show different stability order as compared to the free TCPs.