NMR spectroscopic detection of chirality and enantiopurity in referenced systems without formation of diastereomers

Jan Labuta; Shinsuke Ishihara; Tomáš Šikorský; Zdeněk Futera; Atsuomi Shundo; Lenka Hanyková; Jaroslav V. Burda; Katsuhiko Ariga; Jonathan P. Hill

doi:10.1038/ncomms3188

NMR spectroscopic detection of chirality and enantiopurity in referenced systems without formation of diastereomers

Jan Labuta, Shinsuke Ishihara, Tomáš Šikorský, Zdeněk Futera, Atsuomi Shundo, Lenka Hanyková, Jaroslav V. Burda, Katsuhiko Ariga, Jonathan P. Hill

Research output: Contribution to journal › Article › peer-review

95 Citations (Scopus)

Abstract

Enantiomeric excess of chiral compounds is a key parameter that determines their activity or therapeutic action. The current paradigm for rapid measurement of enantiomeric excess using NMR is based on the formation of diastereomeric complexes between the chiral analyte and a chiral resolving agent, leading to (at least) two species with no symmetry relationship. Here we report an effective method of enantiomeric excess determination using a symmetrical achiral molecule as the resolving agent, which is based on the complexation with analyte (in the fast exchange regime) without the formation of diastereomers. The use of N,N′-disubstituted oxoporphyrinogen as the resolving agent makes this novel method extremely versatile, and appropriate for various chiral analytes including carboxylic acids, esters, alcohols and protected amino acids using the same achiral molecule. The model of sensing mechanism exhibits a fundamental linear response between enantiomeric excess and the observed magnitude of induced chemical shift non-equivalence in the ¹H NMR spectra.

Original language	English
Article number	2188
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms3188
Publication status	Published - 2013

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms3188

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@article{2efc7f6eab3c4e2eaf0692e00e787769,

title = "NMR spectroscopic detection of chirality and enantiopurity in referenced systems without formation of diastereomers",

abstract = "Enantiomeric excess of chiral compounds is a key parameter that determines their activity or therapeutic action. The current paradigm for rapid measurement of enantiomeric excess using NMR is based on the formation of diastereomeric complexes between the chiral analyte and a chiral resolving agent, leading to (at least) two species with no symmetry relationship. Here we report an effective method of enantiomeric excess determination using a symmetrical achiral molecule as the resolving agent, which is based on the complexation with analyte (in the fast exchange regime) without the formation of diastereomers. The use of N,N′-disubstituted oxoporphyrinogen as the resolving agent makes this novel method extremely versatile, and appropriate for various chiral analytes including carboxylic acids, esters, alcohols and protected amino acids using the same achiral molecule. The model of sensing mechanism exhibits a fundamental linear response between enantiomeric excess and the observed magnitude of induced chemical shift non-equivalence in the 1H NMR spectra.",

author = "Jan Labuta and Shinsuke Ishihara and Tom{\'a}{\v s} {\v S}ikorsk{\'y} and Zden{\v e}k Futera and Atsuomi Shundo and Lenka Hanykov{\'a} and Burda, {Jaroslav V.} and Katsuhiko Ariga and Hill, {Jonathan P.}",

note = "Funding Information: This research was partly supported by the World Premier International Research Centre Initiative on Materials Nanoarchitechtonics from MEXT, Japan, and the Core Research for Evolutional Science and Technology (CREST) programme of JST, Japan. This work was also supported by Grants-in-Aid for Scientific Research from MEXT, Japan (KAKENHI No. 25810055). We are also grateful for support by grants from the Ministry of Education of the Czech Republic: ME10149, and Grant Agency of Czech Republic No. P205/10/0228. Access to computing and storage facilities owned by parties and projects contributing to the National Grid Infrastructure MetaCentrum, provided under the programme {\textquoteleft}{\textquoteleft}Projects of Large Infrastructure for Research, Development, and Innovations{\textquoteright}{\textquoteright} (LM2010005) is highly appreciated.",

year = "2013",

doi = "10.1038/ncomms3188",

language = "English",

volume = "4",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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T1 - NMR spectroscopic detection of chirality and enantiopurity in referenced systems without formation of diastereomers

AU - Labuta, Jan

AU - Ishihara, Shinsuke

AU - Šikorský, Tomáš

AU - Futera, Zdeněk

AU - Shundo, Atsuomi

AU - Hanyková, Lenka

AU - Burda, Jaroslav V.

AU - Ariga, Katsuhiko

AU - Hill, Jonathan P.

N1 - Funding Information: This research was partly supported by the World Premier International Research Centre Initiative on Materials Nanoarchitechtonics from MEXT, Japan, and the Core Research for Evolutional Science and Technology (CREST) programme of JST, Japan. This work was also supported by Grants-in-Aid for Scientific Research from MEXT, Japan (KAKENHI No. 25810055). We are also grateful for support by grants from the Ministry of Education of the Czech Republic: ME10149, and Grant Agency of Czech Republic No. P205/10/0228. Access to computing and storage facilities owned by parties and projects contributing to the National Grid Infrastructure MetaCentrum, provided under the programme ‘‘Projects of Large Infrastructure for Research, Development, and Innovations’’ (LM2010005) is highly appreciated.

PY - 2013

Y1 - 2013

N2 - Enantiomeric excess of chiral compounds is a key parameter that determines their activity or therapeutic action. The current paradigm for rapid measurement of enantiomeric excess using NMR is based on the formation of diastereomeric complexes between the chiral analyte and a chiral resolving agent, leading to (at least) two species with no symmetry relationship. Here we report an effective method of enantiomeric excess determination using a symmetrical achiral molecule as the resolving agent, which is based on the complexation with analyte (in the fast exchange regime) without the formation of diastereomers. The use of N,N′-disubstituted oxoporphyrinogen as the resolving agent makes this novel method extremely versatile, and appropriate for various chiral analytes including carboxylic acids, esters, alcohols and protected amino acids using the same achiral molecule. The model of sensing mechanism exhibits a fundamental linear response between enantiomeric excess and the observed magnitude of induced chemical shift non-equivalence in the 1H NMR spectra.

AB - Enantiomeric excess of chiral compounds is a key parameter that determines their activity or therapeutic action. The current paradigm for rapid measurement of enantiomeric excess using NMR is based on the formation of diastereomeric complexes between the chiral analyte and a chiral resolving agent, leading to (at least) two species with no symmetry relationship. Here we report an effective method of enantiomeric excess determination using a symmetrical achiral molecule as the resolving agent, which is based on the complexation with analyte (in the fast exchange regime) without the formation of diastereomers. The use of N,N′-disubstituted oxoporphyrinogen as the resolving agent makes this novel method extremely versatile, and appropriate for various chiral analytes including carboxylic acids, esters, alcohols and protected amino acids using the same achiral molecule. The model of sensing mechanism exhibits a fundamental linear response between enantiomeric excess and the observed magnitude of induced chemical shift non-equivalence in the 1H NMR spectra.

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JO - Nature communications

JF - Nature communications

M1 - 2188

ER -

NMR spectroscopic detection of chirality and enantiopurity in referenced systems without formation of diastereomers

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