Spectroscopic discrimination of diastereomeric complexes involving an axially chiral receptor

Introduction: Different stability and reactivity of diastereomeric aggregates reflect the number and intensity of the interactions between the chiral species involved. Therefore, investigating diastereomeric aggregates in the gas phase helps to understand the mechanism of chiral recognition through detailed knowledge of the structure of the chiral receptor, as well as of the size- and shape-specific non-covalent interactions in its aggregate with a chiral molecule[1-3]. Methods: An ESI-MS-IRMPD analysis has been employed to assess the structural features of diastereomeric complexes[4] between an axially chiral receptor (M) and two amino acids, phenylalanine (Phe) and dopa (DOPA), differing only for the aromatic substituents. The results have been interpreted through a computational analysis at the B3LYP/6-31G** level, to assess both the coordination site and the preferential conformation adopted by the complexed guest. Results: IRMPD spectra of the [M∙H∙Phe]+ diastereomeric complexes did not exhibit any appreciable difference, in contrast to the significant discrimination exerted by M on the enantiomers of dopa. The comparison between experimental bands and theoretical results indicate that the guest is located out of the cavity, in close proximity of the binaphthyl moiety of M. Furthermore, the computational analysis performed on several rotamers pointed out that the enantiodiscrimination is mostly due to the short range interaction between the hydroxyl groups and the core of the axial chirality. It is worth noting that the structures spectroscopically observed are not the most stable ones. Conclusions The IRMPD of the ESI-formed [M∙H∙DOPA]+ diastereisomers were consistent with an out of cavity structure, not corresponding to the lower energy coordination site. The observed discrimination on the dopa enantiomers is due to the hydroxyl groups, absent in the structure of phenylalanine, that are oriented towards the chiral core of M. Finally, the different spectroscopic signatures indicate the coexistence of several conformers for the diastereomeric aggregates. Novel Aspect: Subtle structural differences between non-covalent diastereomeric complexes have been pointed out through IRMPD technique.