Solvent efficiency and role of dispersion and electrostatic forces for chiral discrimination of sulfur-containing amino acids by tetra-protonated CBPQT macrocycle.

[Display omitted] • The chiral recognition ability of CBPQT4+ is systematically studied using DFT simulations. • Chirodiastalic energy (E chir) indicates the L -enantiomer complexes are more stable than D -complexes. • The quantitative analyses of noncovalent interaction indicate the structures are stabilized by the dispersion forces. • The electronic properties analyses illustrate the high chiral response of CBPQT4+ towards small molecular amino acids. • Overall findings reveal that the CBPQT4+ macrocycle has an excellent ability to differentiate between L - and D -enantiomers. Two enantiomeric forms of amino acids in a chiral medium behave quite differently because of the different orientation of their functional groups in space. Thus, the phenomenon of chiral recognition is crucial with the focus on applications in molecular sensing and enantioselective separations. The present research work is focused on the illustration of the potential chiral recognition of a porous CBPQT4+ macrocycle for sulfur-containing amino acids, which is elucidated by the conformational energies landscape with quantitative non-covalent analysis and their electronic behaviour. Herein, we report the chiral recognition of sulfur-containing amino acids e.g., cysteine (CY), homocysteine (HCY), and methionine (MT), by tetra-protonated (4+) CBPQT macrocycle via density functional theory (DFT) calculations. Geometry optimization, thermodynamic stability, noncovalent interaction analysis, symmetry-adapted perturbation (SAPT), and electronic properties analyses are employed to characterize the chiral response of the complexes formed by CBPQT4+ with D - and L -isomers of selected amino acids. The interactive conformations of complexes indicate physisorption of amino acids through the central cavity of the macrocycle. The maximum chiral discrimination is observed in the case of D - and L -cysteine isomers, which is 3.56 kcal/mol. It is revealed that the complex; D -CY@CBPQT4+ is energetically more stable than the L -CY analogue, whereas, L -HCY and L -MT show higher stability as compared to D -type counterparts, probably due to the interaction of the thiol groups with π-electrons of macrocycle in respective stable complexes. Non-covalent interaction (NCI) analyses including, reduced density gradient-based NCI index and SAPT reveal that the methionine-based complexes show the highest attractive components e.g., electrostatic, dispersion, and induction with the lowest repulsive exchange contribution, which is followed by homocysteine and cysteine. Overall, results show that the CBPQT4+ macrocycle has an excellent ability to differentiate between L - and D -amino acids, the difference is more pronounced when the structure of amino acid is small and rigid. [ABSTRACT FROM AUTHOR]