Absolute configuration assignment of highly fluorinated carboxylic acids via VCD and MRR spectroscopy.

Autor: De Waele DJS; Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium., Luyten S; Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium., Sonstrom RE; BrightSpec, Inc., 770 Harris Street Suite 104b, Charlottesville, VA 22903, United States., Bogaerts J; Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium., Neill JL; BrightSpec, Inc., 770 Harris Street Suite 104b, Charlottesville, VA 22903, United States., Viereck P; Chemical Process R&D, Discovery Process Research, Janssen R&D, Turnhoutseweg 30, B-2340 Beerse, Belgium., Goossens K; Chemical Process R&D, Process Analytical Research, Janssen R&D, Turnhoutseweg 30, B-2340 Beerse, Belgium., Baeten M; Chemical Process R&D, Process Analytical Research, Janssen R&D, Turnhoutseweg 30, B-2340 Beerse, Belgium., Vervoort N; Chemical Process R&D, Process Analytical Research, Janssen R&D, Turnhoutseweg 30, B-2340 Beerse, Belgium., Herrebout W; Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. Electronic address: wouter.herrebout@uantwerpen.be.
Jazyk: angličtina
Zdroj: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy [Spectrochim Acta A Mol Biomol Spectrosc] 2024 Feb 05; Vol. 306, pp. 123625. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1016/j.saa.2023.123625
Abstrakt: 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, careful consideration of the chiral tag, as well as additional isomer assignments, resulted in successful assignment of the AC. This comparative study demonstrates the power of contemporary VCD analysis and the unique contributions of MRR to the analytical toolbox.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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