Determination of absolute stereochemistry of flexible molecules using a vibrational circular dichroism spectra alignment algorithm

Böselt, Lennard; Sidler, Dominik; Kittelmann, Tobias; Stohner, Jürgen; Zindel, Daniel; Wagner, Trixie; Riniker, Sereina

doi:10.1021/acs.jcim.8b00789

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
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
DOI:	10.1021/acs.jcim.8b00789
Published in:	Journal of Chemical Information and Modeling
Volume(Issue):	59
Issue:	5
Page(s):	1826
Pages to:	1838
Issue Date:	2019
Publisher / Ed. Institution:	American Chemical Society
ISSN:	1549-9596 1549-960X
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.
URI:	https://digitalcollection.zhaw.ch/handle/11475/17475
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:	Publikationen Life Sciences und Facility Management

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Böselt, L., Sidler, D., Kittelmann, T., Stohner, J., Zindel, D., Wagner, T., & Riniker, S. (2019). Determination of absolute stereochemistry of flexible molecules using a vibrational circular dichroism spectra alignment algorithm. Journal of Chemical Information and Modeling, 59(5), 1826–1838. https://doi.org/10.1021/acs.jcim.8b00789

Böselt, L. et al. (2019) ‘Determination of absolute stereochemistry of flexible molecules using a vibrational circular dichroism spectra alignment algorithm’, Journal of Chemical Information and Modeling, 59(5), pp. 1826–1838. Available at: https://doi.org/10.1021/acs.jcim.8b00789.

L. Böselt et al., “Determination of absolute stereochemistry of flexible molecules using a vibrational circular dichroism spectra alignment algorithm,” Journal of Chemical Information and Modeling, vol. 59, no. 5, pp. 1826–1838, 2019, doi: 10.1021/acs.jcim.8b00789.

BÖSELT, Lennard, Dominik SIDLER, Tobias KITTELMANN, Jürgen STOHNER, Daniel ZINDEL, Trixie WAGNER und Sereina RINIKER, 2019. Determination of absolute stereochemistry of flexible molecules using a vibrational circular dichroism spectra alignment algorithm. Journal of Chemical Information and Modeling. 2019. Bd. 59, Nr. 5, S. 1826–1838. DOI 10.1021/acs.jcim.8b00789

Böselt, Lennard, Dominik Sidler, Tobias Kittelmann, Jürgen Stohner, Daniel Zindel, Trixie Wagner, and Sereina Riniker. 2019. “Determination of Absolute Stereochemistry of Flexible Molecules Using a Vibrational Circular Dichroism Spectra Alignment Algorithm.” Journal of Chemical Information and Modeling 59 (5): 1826–38. https://doi.org/10.1021/acs.jcim.8b00789.

Böselt, Lennard, et al. “Determination of Absolute Stereochemistry of Flexible Molecules Using a Vibrational Circular Dichroism Spectra Alignment Algorithm.” Journal of Chemical Information and Modeling, vol. 59, no. 5, 2019, pp. 1826–38, https://doi.org/10.1021/acs.jcim.8b00789.