Title: Determination of absolute stereochemistry of flexible molecules using a vibrational circular dichroism spectra alignment algorithm
Authors : Böselt, Lennard
Sidler, Dominik
Kittelmann, Tobias
Stohner, Jürgen
Zindel, Daniel
Wagner, Trixie
Riniker, Sereina
et. al : No
Published in : Journal of Chemical Information and Modeling
Volume(Issue) : 59
Issue : 5
Pages : 1826
Pages to: 1838
Publisher / Ed. Institution : American Chemical Society
Issue Date: 2019
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (publication)
Language : English
Subject (DDC) : 572: Biochemistry
Abstract: Experimental determination of the absolute stereochemistry of chiral molecules has been a fundamental challenge in natural sciences for decades. Vibrational circular dichroism (VCD) spectroscopy represents an attractive alternative to traditional methods like X-ray crystallography due to the use of molecules in solution. The interpretation of measured VCD spectra and thus the assignment of the absolute configuration relies on quantum-mechanical calculations. While such calculations are straightforward for rigid molecules with a single conformation, the need to estimate the correct conformational ensemble and energy landscape to obtain the appropriate theoretical spectra poses significant challenges for flexible molecules. In this work, we present the development of a VCD spectra alignment (VSA) algorithm to compare theoretical and experimental VCD spectra. The algorithm determines which enantiomer is more likely to reproduce the experimental spectrum and thus allows the correct assignment of the absolute stereochemistry. The VSA algorithm is successfully applied to determine the absolute chirality of highly flexible molecules, including commercial drug substances. Furthermore, we show that the computational cost can be reduced by performing the full frequency calculation only for a reduced set of conformers. The presented approach has the potential to allow the determination of the absolute configuration of chiral molecules in a robust and efficient manner.
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Article in scientific journal
DOI : 10.1021/acs.jcim.8b00789
ISSN: 1549-9596
URI: https://digitalcollection.zhaw.ch/handle/11475/17475
Appears in Collections:Publikationen Life Sciences und Facility Management

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