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 calculations 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.