Quantitative Auxiliary-free Chirality Sensing with a Metal Probe

OVERVIEW

Georgetown University researchers have pioneered a groundbreaking quantitative chiral sensing assay for determining the absolute configuration/concentration and/or the enantiomeric composition of the analyte in a sample, leveraging metal salts without additional adjuvants. This innovative optical chirality sensing method utilizes ligand-free, earth-abundant metal salts, eliminating the need for an organic reporter moiety. Introducing these cost-effective and easily accessible metal salts directly into the analysis significantly streamlines assay development. It eliminates the necessity to optimize an organic ligand, resulting in a simplified sensing protocol that reduces operational costs and minimizes waste.

BACKGROUND

The ubiquity, diversity, and general importance of chiral compounds in the chemical and pharmaceutical sciences continue to nurture the search for high-throughput methods that achieve fast quantification of analyte concentration and enantiomeric composition and are compatible with multi-well plate technology and parallel data acquisition.Optical chirality sensing employing metal complexes conventionally relies on the rapid coordination of analytes or the integration of the target compound into a supramolecular assembly. These processes impact the photophysical characteristics of one or more chromophoric reporter units within the sensor scaffold through intramolecular interactions, leading to the formation of distinct spatial arrangements. Consequently, this results in induced or altered circular dichroism, fluorescence, or UV signals, which are then compared to a calibration curve for sample value determination. However, a persistent challenge is that the requisite sensor scaffold can be expensive, sensitive to moisture, or unavailable commercially.

Circular dichroism spectroscopy is a powerful technique widely utilized for unraveling the three-dimensional structure, molecular recognition events, and stereo-dynamic processes of chiral compounds. Recent attention has been directed toward the potential of chiroptical assays involving circular dichroism (CD) and circularly polarized luminescence (CPL). Specially designed probes generate a circular dichroism signal upon recognizing a chiral substrate, holding promise for high-throughput screening. While the CD output of a chemosensor often facilitates the determination of the absolute configuration and enantiomeric composition of the chiral analyte, assessing the concentration and enantiomeric composition of various chiral substrates with a single optical chemosensor poses a challenging task. Consequently, a practical method applicable to numerous chiral compounds, bypassing time-consuming derivatization and purification steps, is highly desirable.

Benefit

●Eliminates derivatization time by avoiding the construction of complex auxiliary ligands and libraries.

●It can be performed in aqueous or alcoholic solvents.

●It only requires a readily available inorganic salt of an earth-abundant metal.

Market Application

●The method can replace previous assays to measure enantiomeric excess without requiring complex derivatization or specialized auxiliary ligands.

●The method uses probes to assess the degree of chiral asymmetry.

Publications

US Patent No. 11,860,084.