Publication
Title
Absolute configuration assignment of highly fluorinated carboxylic acids via VCD and MRR spectroscopy
Author
Abstract
Chiral analysis has become a crucial step in studying the stereospecific synthesis of Active Pharmaceutical Ingredients (APIs). Both Vibrational Circular Dichroism (VCD) and Molecular Rotational Resonance (MRR) spectroscopy are capable of determining absolute configurations (ACs) via comparison of experimental and calculated data. In this regard, each technique has its own caveats. In VCD analysis, accurate prediction of the normal modes as well as rigorous conformational searches of both the analyte and potential (self-)aggregation products are required to optimally match experimental spectra. In MRR analysis, chiral species are resolved through complexation with a chiral tag to prepare spectrally distinct diastereomeric complexes. Although individual complex isomers can be distinguished, spectral assignments need to be matched to unique isomer geometries for unambiguous AC assignment. In this work, the ACs of two highly fluorinated carboxylic acids were successfully assigned using VCD and MRR spectroscopy. In the VCD analysis, the M06-2X functional was demonstrated to be superior to B3LYP and B3LYP-GD3 in accurately predicting the C-F normal modes and both monomeric and dimeric spectral contributions were observed. In a similar analysis with broadband MRR, most experimentally identified geometries had more than one possible computational match. Nevertheless, consideration of the chiral tag, as well as additional isomer assignments, resulted in successful assignment AC. This comparative study demonstrates the power of contemporary VCD analysis and the unique contributions of MRR to the analytical toolbox.
Language
English
Source (journal)
Spectrochimica acta: part A: molecular and biomolecular spectroscopy. - Oxford
Publication
Oxford : 2024
ISSN
1386-1425
DOI
10.1016/J.SAA.2023.123625
Volume/pages
306 (2024) , p. 1-10
Article Reference
123625
ISI
001111323500001
Pubmed ID
37950934
Full text (Publisher's DOI)
Full text (open access)
The author-created version that incorporates referee comments and is the accepted for publication version Available from 09.05.2024
Full text (publisher's version - intranet only)
UAntwerpen
Research group
Project info
MRR in the Pharma Industry
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 09.01.2024
Last edited 15.01.2024
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