Abstract:
The two enantiomeric forms, or mirror-image versions, of a molecule interact differently
when placed in a chiral environment. This difference in behavior arises because each
enantiomer has a unique three-dimensional arrangement of its atoms and functional groups.
In a chiral medium, which itself has a specific spatial orientation, these variations in
structure influence how each enantiomer interacts, leading to distinct chemical or
biological responses. In this study, we employed the chiral P5A macrocycle to recognize
enantiomers of amino acids that contain sulfur, specifically cysteine (CY), methionine
(MT), and homocysteine (HCY), by employing density functional theory (DFT)
calculations. The most notable chiral distinction is observed between the L- and D-cysteine
isomers, showing an energy difference of 7.450 kcal/mol. The interactive conformations
indicate that the amino acids are physically adsorbed within the macrocycle’s central
cavity. The results indicate that the L-CY@P5A shows higher stability compared to its D-
CY counterpart. In contrast, D-HCY and D-MT show higher stability than their L-isomer
counterparts, probably due to the flexibility of these isomers. Analysis of non-covalent
interaction index (NCI) and electron decomposition analysis (EDA) indicates that
complexes involving homocysteine exhibit the strongest attractive components such as
electrostatic, induction, and dispersion with minimal contributions of repulsive exchange.
This trend is followed by cysteine and methionine complexes. All of the results show that
the P5A macrocycle is highly effective in differentiating between L- and D-amino acids,
particularly for amino acids with more rigid and smaller structures.
