Details
Originalsprache | Englisch |
---|---|
Aufsatznummer | e202116794 |
Fachzeitschrift | Angewandte Chemie - International Edition |
Jahrgang | 61 |
Ausgabenummer | 9 |
Frühes Online-Datum | 15 Feb. 2022 |
Publikationsstatus | Elektronisch veröffentlicht (E-Pub) - 15 Feb. 2022 |
Extern publiziert | Ja |
Abstract
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.
ASJC Scopus Sachgebiete
- Chemische Verfahrenstechnik (insg.)
- Katalyse
- Chemie (insg.)
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in: Angewandte Chemie - International Edition, Jahrgang 61, Nr. 9, e202116794, 15.02.2022.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Protonation-Induced Chirality Drives Separation by Differential Ion Mobility Spectrometry
AU - Ieritano, Christian
AU - Yves Le Blanc, J. C.
AU - Schneider, Bradley B.
AU - Bissonnette, Justine R.
AU - Haack, Alexander
AU - Hopkins, W. Scott
N1 - Funding Information: The authors would like to acknowledge the high‐performance computing support from Compute Canada. W.S.H would like to acknowledge the financial support provided by the Natural Sciences and Engineering Research Council (NSERC) of Canada in the form of Discovery, Engage, and Alliance grants, the Ontario Centres of Excellence in the form of a VIP‐II grant, as well as the government of Ontario for an Ontario Early Researcher Award. WSH also acknowledges funding from the InnoHK initiative and the Hong Kong Special Administrative Region Government. C.I. acknowledges financial support from the Government of Canada through the Vanier Canada Graduate Scholarship. A.H. acknowledges his contribution being funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—449651261. J.R.B acknowledges financial support from the NSERC Undergraduate Student Research Award (USRA). Molecular graphics were generated using the UCSF ChimeraX package. ChimeraX is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco supported by National Institutes of Health R01‐GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases. [52]
PY - 2022/2/15
Y1 - 2022/2/15
N2 - 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.
AB - 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.
KW - Chiral Derivatization
KW - Diastereomer
KW - Ion Mobility
KW - Mass Spectrometry
KW - Verapamil
UR - http://www.scopus.com/inward/record.url?scp=85122798801&partnerID=8YFLogxK
U2 - 10.1002/anie.202116794
DO - 10.1002/anie.202116794
M3 - Article
C2 - 34963024
AN - SCOPUS:85122798801
VL - 61
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 1433-7851
IS - 9
M1 - e202116794
ER -