Protonation‐Induced Chirality Drives Separation by Differential Ion Mobility Spectrometry

Upon development of a workflow to analyze (±)‐Verapamil and its metabolites using differential mobility spectrometry (DMS), we noticed that the ionogram of protonated Verapamil consisted of two peaks. This was inconsistent with its metabolites, as each exhibited only a single peak in the respective...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-02, Vol.61 (9), p.e202116794-n/a
Main Authors: Ieritano, Christian, Yves Le Blanc, J. C., Schneider, Bradley B., Bissonnette, Justine R., Haack, Alexander, Hopkins, W. Scott
Format: Article
Language:English
Subjects:
Amines
Chiral Derivatization
Chirality
Diastereoisomers
Diastereomer
Ion Mobility
Ionic mobility
Ionograms
Ions
Mass Spectrometry
Metabolites
Mobility
Protonation
Quaternary ammonium salts
Scientific imaging
Spectrometry
Spectroscopy
Verapamil
Workflow
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Upon development of a workflow to analyze (±)‐Verapamil and its metabolites using differential mobility spectrometry (DMS), we noticed that the ionogram of protonated Verapamil consisted of two peaks. This was inconsistent with its metabolites, as each exhibited only a single peak in the respective ionograms. The unique behaviour of Verapamil was attributed to protonation at its tertiary amino moiety, which generated a stereogenic quaternary amine. The introduction of additional chirality upon N‐protonation of Verapamil renders four possible stereochemical configurations for the protonated ion: (R,R), (S,S), (R,S), or (S,R). The (R,R)/(S,S) and (R,S)/(S,R) enantiomeric pairs are diastereomeric and thus exhibit unique conformations that are resolvable by linear and differential ion mobility techniques. Protonation‐induced chirality appears to be a general phenomenon, as N‐protonation of 12 additional chiral amines generated diastereomers that were readily resolved by DMS. Ionization of N‐protonated Verapamil by electrospray ionization (ESI) yields two peaks when measured by differential mobility spectrometry (DMS). This strange behaviour is caused by protonation‐induced chirality, whereby protonation of Verapamil's tertiary amino moiety during ESI generates diastereomers that can be resolved in the gas phase.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202116794