Chirality sensing with molecular click chemistry probes
Inventors
Wolf, Christian • Thanzeel, Fathima Yushra • BALARAMAN, Kaluvu
Assignees
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Publication Number
US-12486293-B2
Publication Date
2025-12-02
Expiration Date
Abstract
The present invention relates to an analytical method that includes providing a sample potentially containing a chiral analyte that can exist in stereoisomeric forms, and providing a probe selected from the group consisting of coumarin-derived Michael acceptors, dinitrofluoroarenes and analogs thereof, arylsulfonyl chlorides and analogs thereof, arylchlorophosphines and analogs thereof, aryl halophosphites, and halodiazaphosphites. The sample is contacted with the probe under conditions to permit covalent binding of the probe to the analyte, if present in the sample; and, based on any binding that occurs, the absolute configuration of the analyte in the sample, and/or the concentration of the analyte in the sample, and/or the enantiomeric composition of the analyte in the sample is/are determined. The probe may be a coumarin-derived Michael acceptor, a di nitrofluoroarene or analog thereof, an arylsulfonyl chloride or analog thereof, an arylchlorophosphine or analog thereof, an aryl halophosphite, or a halodiazaphosphite.
Core Innovation
The invention provides an analytical method for a sample containing a chiral analyte that can exist in stereoisomeric forms. An achiral probe is selected from coumarin-derived Michael acceptors, dinitrofluoroarenes and analogs thereof, arylsulfonyl chlorides and analogs thereof, arylchlorophosphines and analogs thereof, aryl halophosphites, and halodiazaphosphites. The probe is contacted with the sample under conditions to permit covalent binding of the probe to the analyte.
After contacting, the method performs a first spectroscopic analysis using one of circular dichroism (CD), optical rotatory dispersion, and polarimetry, and/or a second spectroscopic analysis using one of ultraviolet (UV) spectroscopy and fluorescence spectroscopy. The obtained spectroscopic results are used, based on any covalent binding that occurs during the contacting, to determine one or more of an absolute configuration of the analyte in the sample, concentration of the analyte in the sample, and an enantiomeric composition of the analyte in the sample.
The document further describes probe structures expressed in structural formulae and frames the method as sensing of chiral analytes, including nonracemic and crude reaction mixtures. It also notes multi-well plate CD/UV readers, along with solvent compatibility and tolerance to air and water.
Claims Coverage
The document includes one independent claim directed to an analytical method with two core inventive features: covalent binding of a selected achiral probe to a chiral analyte, and spectroscopic analysis to obtain stereochemical and/or quantitative information based on that binding.
Covalent probe binding to a chiral analyte
An analytical method comprising providing a sample containing a chiral analyte that can exist in stereoisomeric forms; providing an achiral probe selected from coumarin-derived Michael acceptors, dinitrofluoroarenes and analogs thereof, arylsulfonyl chlorides and analogs thereof, arylchlorophosphines and analogs thereof, aryl halophosphites, and halodiazaphosphites; and contacting the sample with the probe under conditions to permit covalent binding of the probe to the analyte.
Spectroscopic determination of analyte properties
Performing a first spectroscopic analysis using one of circular dichroism (CD), optical rotatory dispersion and polarimetry, and/or a second spectroscopic analysis using one of ultraviolet (UV) spectroscopy and fluorescence spectroscopy to obtain, based on any covalent binding that occurs during said contacting, one or more of an absolute configuration of the analyte in the sample, concentration of the analyte in the sample, and an enantiomeric composition of the analyte in the sample.
Overall, the claim coverage centers on covalent binding between a selected achiral probe class and a chiral analyte, followed by CD/optical rotatory dispersion/polarimetry and/or UV/fluorescence spectroscopy to obtain absolute configuration, concentration, and/or enantiomeric composition. Dependent refinements further constrain the probe scaffold and analyte scope.
Stated Advantages
Solvent compatibility.
Tolerance to air and water.
Operational simplicity/robustness is emphasized.
High-throughput compatibility is described, including multi-well plate CD/UV readers.
Documented Applications
Sensing of specific nonracemic and crude reaction mixtures using the described probe-analyte covalent binding approach and spectroscopic readouts.
Use with multi-well plate CD/UV readers for sensing.
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