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Abstract A reaction‐based optical relay sensing strategy that enables accurate determination of the concentration and enantiomeric ratio (er) of challenging chiral alcohols exhibiting stereocenters at the α‐, β‐, γ‐ or even δ‐position or hard‐to‐detect cryptochirality arising from H/D substitution is described. This unmatched application scope is achieved with a conceptually new sensing approach by which the alcohol moiety is replaced with an optimized achiral sulfonamide chromophore to minimize the distance between the covalently attached chiroptical reporter unit and the stereogenic center in the substrate. The result is a remarkably strong, red‐shifted CD induction that increases linearly with the sampleer. The CD sensing part of the tandem assay is seamlessly coupled to a redox reaction with a quinone molecule to generate a characteristic UV response that is independent of the enantiopurity of the alcohol and thus allows determination of the total analyte concentration. The robustness and utility of the CD/UV relay are further verified by chromatography‐free asymmetric reaction analysis with small aliquots of crude product mixtures, paving the way toward high‐throughput chiral compound screening workflows which is a highly sought‐after goal in the pharmaceutical industry.
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Chemometric sensing of stereoisomeric compound mixtures with a redox-responsive optical probe
The analysis of mixtures of chiral compounds is a common task in academic and industrial laboratories typically achieved by laborious and time-consuming physical separation of the individual stereoisomers to allow interference-free quantification, for example using chiral chromatography coupled with UV detection. Current practice thus impedes high-throughput and slows down progress in countless chiral compound development projects. Here we describe a chemometric solution to this problem using a redox-responsive naphthoquinone that enables chromatography-free click chemistry sensing of challenging mixtures. The achiral probe covalently binds amino alcohols within a few minutes at room temperature and generates characteristic UVA and CDA spectra that are intentionally altered via sodium borohydride reduction to provide a second, strikingly different chiroptical data set (UVB and CDB). Chemometric partial least squares processing of the chiroptical outputs then enables spectral deconvolution and accurate determination of individual analyte concentrations. The success of this approach is demonstrated with 35 samples covering considerably varied total analyte amounts and stereoisomeric ratios. All chemicals and machine learning algorithms are readily available and can be immediately adapted by any laboratory.
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- Award ID(s):
- 2246747
- PAR ID:
- 10511913
- Publisher / Repository:
- Royal Society of Chemistry
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 15
- Issue:
- 4
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 1498 to 1504
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D3SC05706B
