Elucidation of molecular recognition of catecholamine enantiomer by cyclodextrin combined ion mobility spectrometry and theoretical calculation

Abstract

Catecholamines, as important neurotransmitter and clinical drugs, have a wide range of regulatory roles in physiological activities. The recognition of catecholamine enantiomer (CE) and the elucidation of recognition mechanism are of great significance for the in-depth understanding of biomolecular interactions. This work reveals the molecular recognition mechanism of cyclodextrin (CD) towards CEs through experimental measurements of ion mobility spectrometry (IMS) and theoretical studies including molecular dynamics (MD) simulation and quantum chemical (QC) calculation. The CEs can be discriminated by constructing multi-nary non-covalent complex with CDs by IMS. MD simulation confirm the binding behavior and conformation preference of binary complexes with CEs and α-CD, and further QC calculation optimize the gas-phase ion structure, demonstrate the differences in geometry and energy. Visualization of non-covalent interactions (NCI) resolve the regions and features of intermolecular interactions and illustrate that recognition originates from different contribution of hydrogen bonds between the chiral center of CE and the larger rim of α-CD. Further topological analysis indicates that the difference in the sum of effective hydrogen bond energies has a positive correlation with the recognition efficiency. This work provides new approach for structure elucidation of supramolecular complexes and mechanism elucidation of molecular recognition under the guidance of IMS.