NMR and Computational Investigations of the Chiral Discrimination Processes Involving a Cyclic Tetraamidic Chiral Selector

The chiral recognition mechanism of a macrocyclic tetraamidic receptor for the enantiomers of N-(3,5-dinitrobenzoyl) valine-N-hexylamide has been investigated in detail through a combination of NMR spectroscopy and molecular modeling studies. Intra- and intermolecular ROE effects provided information on the conformations of the free and complexed partners, and also on their relative arrangement in solution during complexation. Molecular mechanics calcula-tions and molecular docking studies gave results in agreement with the spectroscopic data, correctly reproducing the relative stability of the two diastereoisomeric complexes. A stereochemical model for the complexed species is presented in which hydrogen-bonding interactions between amide fragments drive the association process, and the enantioselectivity is modulated by aromatic–aromatic interactions and steric hindrance.