Chirality Sensing with Molecular Click Chemistry Probes

OVERVIEW

The invention relates to an analytical method for the determination of the absolute configuration of an analyte in a sample, and/or the concentration of an analyte in a sample, and/or the enantiomeric composition of an analyte in a sample based on chiroptical testing.The method includes providing a sample potentially containing a chiral analyte that can exist in stereoisomeric forms, contacting the sample with a specific 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 sensor's click chemistry offers advantages over existing chiral optical methods, overcoming limitations related to substrate range, chiral recognition processes, and sensitivity to moisture and chemical interference.

BACKGROUND

Chirality is critical in chemical and pharmaceutical sciences, and stereoselective methods are required for synthesizing and analyzing chiral compounds. High-throughput experiments are common, but traditional chromatographic methods for determining absolute configuration and enantiomeric excess are slow. Optical methods employing dynamic covalent chemistry and metal complex coordination enable high-throughput analysis of chiral samples. However, comprehensive chiral sensing via irreversible covalent product immobilization has been neglected. This chemical sensing strategy can potentially change how asymmetric reactions are developed.

Benefit

●Suitable chromophoric probes that can quickly and quantitatively capture a variety of chiral target compounds through irreversible covalent bond formation at room temperature.

●Avoids complications arising from the formation of diastereomeric mixtures which simplifies the chirality sensing protocol.

●Sensing with the coumarin minimizes time and chemical waste compared to traditional methods.

●Wide solvent compatibility, making it practical for various asymmetric reaction conditions.

●Fast substrate fixation without by-product formation or complicate equilibria often encountered in reversible substrate binding.

Market Application

●The method accelerates chiral recognition processes that can be used in high throughput analysis.

●The method can be used for asymmetric reaction screening in the pharmaceutical industry.

Publications

●Thanzeel FY, Balaraman K, Wolf C. Click chemistry enables quantitative chiroptical sensing of chiral compounds in protic media and complex mixtures. Nat Commun. 2018 Dec 14;9(1):5323. doi: 10.1038/s41467-018-07695-9. PMID: 30552322; PMCID: PMC6294054.

●Pub. No.: US 2022/0380395 A1