Chirality sensing with molecular click chemistry probes

Patent metadata

Field	Value
Publication number	US-12486293-B2
Application number	US-201917265147-A
Country	US
Kind code	B2
Filing date	Jul 30, 2019
Priority date	Jul 30, 2018
Publication date	Dec 2, 2025
Grant date	Dec 2, 2025

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.

First claim

What is claimed is:

1 . An analytical method comprising:
providing a sample containing a chiral analyte that can exist in stereoisomeric forms; providing an achiral 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; contacting the sample with the probe under conditions to permit covalent binding of the probe to the analyte; and 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.

2 . The analytical method of claim 1 , wherein the probe is a coumarin-derived Michael acceptor of Formula I:

wherein:
Y is hydrogen or an electron withdrawing group selected from the group consisting of —CF 3 , —C(O)R a , —SO 2 R a , —CN, and —NO 2 ; wherein each R a is independently selected from the group consisting of —H, -alkyl, —O-alkyl, —N-alkyl, -alkenyl, -alkynyl, -aryl, —O-aryl, —N-aryl, -heteroaryl, —O-heteroaryl, —N-heteroaryl, -cycloalkyl, —O-cycloalkyl, —N-cycloalkyl, -heterocycloalkyl, —O-heterocycloalkyl, and —N-heterocycloalkyl; and
X is a leaving group selected from a halogen, —OR b , —OC(O)R b , —OS(O) 2 R b , —S(O) 2 —O—R b , —N 2 + , —N + (R b ) 3 , —S + (R b ) 2 , and —P + (R b ) 3 ; wherein each R b is independently selected from the group consisting of -alkyl, —O-alkyl, —N-alkyl, -alkenyl, -alkynyl, perfluoroalkyl, -perfluoroalkenyl, -perfluoroalkynyl, -aryl, perfluoroaryl, —O-aryl, —N-aryl, —O-perfluoroaryl, —N-perfluoroaryl, -heteroaryl, —O-heteroaryl, —N-heteroaryl, -cycloalkyl, —O-cycloalkyl, —N-cycloalkyl, -heterocycloalkyl, —O-heterocycloalkyl, and —N-heterocycloalkyl.

3 . The analytical method of claim 2 , wherein the probe is a coumarin-derived Michael acceptor selected from the group consisting of:

4 . The analytical method of claim 2 , wherein the probe is a coumarin-derived Michael acceptor and the analyte is an amino acid or an amino alcohol, or comprises one or more functional groups selected from the group consisting of amines, carboxylic acids, hydroxy acids, and thiols.

5 . The analytical method of claim 1 , wherein the probe is a dinitrofluoroarene or analog thereof of Formula II:

wherein:
each Y is independently selected from the group consisting of —NO 2 , —CN, —C(O)R a , and —SO 2 R a , wherein each R a is independently selected from the group consisting of —H, -alkyl, —O-alkyl, —N-alkyl, -alkenyl, -alkynyl, -perfluoroalkyl, -aryl, -perfluoroaryl, —O-aryl, —N-aryl, -heteroaryl, —O-heteroaryl, —N-heteroaryl, -cycloalkyl, —O-cycloalkyl, —N-cycloalkyl, -heterocycloalkyl, —O-heterocycloalkyl, and —N-heterocycloalkyl;
X is a leaving group selected from halogen, —OR b , —OC(O)R b , —OS(O) 2 R b , —S(O) 2 —O—R b , —N 2 + , —N + (R b ) 3 , —S + (R b ) 2 , and —P + (R b ) 3 ; wherein each R b is independently selected from the group consisting of -alkyl, —O-alkyl, —N-alkyl, -alkenyl, -alkynyl, -perfluoroalkyl, -perfluoroalkenyl, -perfluoroalkynyl, -aryl, -perfluoroaryl, —O-aryl, —N-aryl, -heteroaryl, —O-heteroaryl, —N-heteroaryl, -cycloalkyl, —O-cycloalkyl, —N-cycloalkyl, -heterocycloalkyl, —O-heterocycloalkyl, and —N-heterocycloalkyl; and
R 1 is selected from the group consisting of —NH 2 , —NHC(O)CH 2 Ar, —NHC(O)Ar, -hydrogen, -alkyl, —O-alkyl, —N-alkyl, -alkenyl, -alkynyl, -aryl, —O-aryl, —N-aryl, -heteroaryl, —O-heteroaryl, —N-heteroaryl, -cycloalkyl, —O-cycloalkyl, —N-cycloalkyl, -heterocycloalkyl, —O-heterocycloalkyl, —N-heterocycloalkyl, —CN, —C(O)R c , —CO 2 R c , —SO 2 R c , —C(O)NHR c , —S-alkyl, —S-aryl, and —S-heteroaryl;
wherein:
each R c is independently -Ar, -alkyl, or —CH 2 Ar; and
each Ar is independently an aryl, heteroaryl, cycloalkyl, heterocycloalkyl, perfluoroalkyl, or perfluoroaryl.

6 . The analytical method of claim 5 , wherein the probe is a dinitroflourarene selected from:

7 . The analytical method of claim 1 , wherein the probe is an arylsulfonyl chloride or analog thereof of Formula III:

wherein:
X is selected from the group consisting of -halogen, —O-aryl, —O-heteroaryl, —O-cycloalkyl, —O-heterocycloalkyl, —O-alkyl, —O-perfluoroalkyl, —O-perfluoroaryl, —N-aryl, —N-heteroaryl, —N-cycloalkyl, —N-heterocycloalkyl, —N-alkyl, —N-perfluoroalkyl, —N-perfluoroaryl, —N(Ar)SO 2 Ar, —NHSO 2 Ar, and —NHAr; and
R 2 is an aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted with one or more groups selected from-alkyl, —O-alkyl, —N-alkyl, -alkenyl, -alkynyl, —O-aryl, —O-heteroaryl, —N-aryl, —N-heteroaryl, -aryl, —C(O)R c , —CO 2 R c , —O—C(O)R c , —NHC(O)R c , —NR c C(O)R c , —NO 2 , —CN, -halogen, and —SO 2 R c , wherein each R c is independently Ar, alkyl, or CH 2 Ar;
wherein each Ar is independently an aryl or heteroaryl.

8 . The analytical method of claim 7 , wherein the probe is the arylsulfonyl chloride:

9 . The analytical method of claim 1 , wherein the probe is an arylchlorophosphine or analog thereof of Formula IV:

wherein:
X is selected from the group consisting of -halogen, —O-aryl, —O-heteroaryl, —O-cycloalkyl, —O-heterocycloalkyl, —O-alkyl, —O-perfluoroalkyl, and —O-perfluoroaryl; and
each R 2 is independently an aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted with one or more groups selected from-alkyl, —O-alkyl, —N-alkyl, -alkenyl, -alkynyl, —O-aryl, —O-heteroaryl, —N-aryl, —N-heteroaryl, -aryl, —C(O)R c , —CO 2 R c , —O—C(O)R c , —NHC(O)R c , —NR c C(O)R c , —NO 2 , —CN, -halogen, and —SO 2 R c , wherein each R c is independently Ar, alkyl, or CH 2 Ar and Ar is an aryl or heteroaryl.

10 . The analytical method of claim 9 , wherein the probe is the arylchlorophosphine:

11 . The analytical method of claim 1 , wherein the probe is an aryl halophosphite of Formula V:

wherein:
X is a halogen; and
(i) R 3 and R 4 are each independently an aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted with one or more groups selected from-alkyl, —O-alkyl, —N-alkyl, -alkenyl, -alkynyl, —O-aryl, —O-perfluoroaryl, —O-heteroaryl, —N-aryl, —N-heteroaryl, -aryl, —C(O)R c , —CO 2 R c , —O—C(O)R c , —NHC(O)R c , —NR c C(O)R c , —NO 2 , —CN, -halogen, and —SO 2 R c , wherein each R

Assignees

• Univ Georgetown

Inventors

• Wolf Christian
• Thanzeel Fathima Yushra
• Balaraman Kaluvu

Classifications

• G01N21/33

  using ultraviolet light (G01N21/39 takes precedence) · CPC title

• C07F9/65744

  condensed with carbocyclic or heterocyclic rings or ring systems · CPC title

• C07F9/52

  Halophosphines · CPC title

• C07D311/18

  substituted otherwise than in position 3 or 7 · CPC title

• C07F9/65848 Primary

  Cyclic amide derivatives of acids of phosphorus, in which two nitrogen atoms belong to the ring · CPC title