Chiral recognition of amino acids through homochiral metallacycle [ZnCl₂L]₂

Chiral recognition holds tremendous significance in both life science and chemistry. The ability to differentiate between enantiomers is crucial because one enantiomer typically holds greater biological relevance while its counterpart is often not only unnecessary but also potentially harmful. In this regard, homochiral metallacycle [ZnCl₂L]₂ is used in this study to understand and differentiate between the R and S enantiomers of amino acids (alanine, proline, serine, and valine). The electronic, geometric, and thermodynamic stabilities of the amino acid enantiomers inside the metallacycle are determined through various analyses. The greater interaction energy (E_int) is obtained for the ser@metallacycle complexes i.e., -33.03 and -30.75 kcal mol^-1, respectively for the S and R enantiomers. The highest chiral discrimination energy of 3.11 kcal mol^-1 is achieved for ala@metallacycle complexes. Regarding the electronic properties, the frontier molecular orbital (FMO) analysis indicates that the energy gap decreases after complexation, which is confirmed through density of states (DOS) analysis. Moreover, natural bond orbital (NBO) analysis determines the amount and direction of charge transfer i.e., from metallacycle towards amino acids. The maximum NBO charge transfer is observed for S-pro@metallacycle complex i.e., -0.291 |e|. Electron density difference (EDD) analysis further proves the direction of charge transfer. Noncovalent interaction index (NCI) and quantum theory of atoms in molecules (QTAIM) analyses demonstrate that the noncovalent interactions present between the host and guest are the weak van der Waals forces and hydrogen bonding. The results of NCI and QTAIM analyses for all the complexes are in alignment with those of the interaction energy (E_int) and chiral discrimination energy (E_chir) analyses, i.e., significantly greater non-bonding interactions are observed for the complexes with greater E_chir, i.e., for ala@metallacycle. Overall, our analyses demonstrate the excellent chiral discrimination ability of metallacycle towards chiral molecules, i.e., for enantiomers of amino acids through host-guest supramolecular chemistry.