Chirality Sensing in Molecular Systems

Chirality sensing in molecular systems encompasses techniques designed to distinguish and quantify enantiomers—mirror-image forms of chiral compounds that often display markedly different biological or pharmacological activities. Accurate determination of enantiomeric composition is crucial in drug development, agrochemical formulations and fundamental studies of biomolecular interactions. Approaches span spectroscopic methods such as circular dichroism and fluorescence detection, nuclear magnetic resonance with chiral auxiliaries and multicomponent assemblies, as well as supramolecular host–guest complexes and dynamic covalent frameworks. Recent advances integrate high-throughput platforms, chemometric algorithms and click-type chemistries to streamline analysis of complex or multi-component mixtures. The field is characterised by continual innovation in sensor design—ranging from aggregation-induced emission rotors to stereodynamic receptors—that enhances sensitivity, selectivity and operational simplicity, thereby accelerating asymmetric reaction screening and ensuring rigorous enantiopurity assessments.

Research from Nature Portfolio

One study introduced a multi-modal sensing protocol combining small-molecule optical probes that bind amines and amino alcohols via dynamic covalent or click reactions with advanced chemometric data-fusion methods. This platform enables rapid deconvolution of overlapping signals, delivering absolute configuration, enantiomeric composition and concentration for quaternary and octonary mixtures without physical separation, and is compatible with multiwell plate screening. Another report employed aggregation-induced emission rotors whose fluorescence wavelength shifts linearly with the enantiomeric excess of various chiral carboxylic acids. This colourimetric change, rather than mere intensity variation, allowed accurate quantification of enantiomeric excess with low error margins. Additionally, a coumarin-based click sensor achieved quantitative chiroptical analysis of amines and alcohols in protic media and crude mixtures, affording rapid fixation of substrate stereochemistry and minimising interference from reversible equilibria.

Research from all publishers

A supramolecular cage constructed from tris(2-pyridylmethyl)amine motifs was shown to amplify the circular dichroism signals of chiral dicarboxylic acids even in complex matrices. This system enabled quantification of tartaric acid in wine samples and discrimination of different sample types via principal component analysis of raw CD data. In a separate advance, fluorescence-detected circular dichroism was demonstrated for the first time in host–guest and host–protein assemblies, achieving high sensitivity at micromolar concentrations and in auto-emissive biofluids, and complementing traditional electronic CD measurements. Furthermore, achiral acyclic cucurbiturils and molecular tweezers were found to induce characteristic CD responses upon binding a diverse set of chiral hydrocarbons, steroids, amino acids and pharmaceuticals in aqueous solution, facilitating rapid analyte identification and reaction monitoring.

Chirality Sensing in Molecular Systems publication trend

The graph below shows the total number of articles in chirality sensing in molecular systems across all publications each year (not limited to Nature Index journals).

Technical terms

Enantiomeric excess (ee): the difference in proportion between two enantiomers in a mixture, expressed as a percentage.

Circular dichroism (CD): the differential absorption of left- and right-circularly polarised light by chiral molecules, yielding characteristic spectra.

Aggregation-induced emission (AIE): a photophysical phenomenon whereby certain fluorophores become emissive upon aggregation.

Dynamic covalent chemistry: reversible bond formation that allows molecular assemblies to adapt and equilibrate in response to analytes.

Chiroptical sensing: the detection of molecular chirality through optical measurements such as CD or fluorescence changes.

Chemometric analysis: the use of statistical and mathematical tools to extract meaningful information from complex chemical data sets.

References

1. Chiral recognition and enantiomer excess determination based on emission wavelength change of AIEgen rotor. Nature Communications (2020).
2. Chirality imprinting and direct asymmetric reaction screening using a stereodynamic Brønsted/Lewis acid receptor. Nature Communications (2016).
3. Click chemistry enables quantitative chiroptical sensing of chiral compounds in protic media and complex mixtures. Nature Communications (2018).
4. Chirality sensing of terpenes, steroids, amino acids, peptides and drugs with acyclic cucurbit[ n ]urils and molecular tweezers. Chemical Communications (2020).
5. Fluorescence detected circular dichroism (FDCD) for supramolecular host–guest complexes. Chemical Science (2021).
6. Chiroptical Enhancement of Chiral Dicarboxylic Acids from Confinement in a Stereodynamic Supramolecular Cage. ACS Sensors (2022).
7. Optical deciphering of multinary chiral compound mixtures through organic reaction based chemometric chirality sensing. Nature Communications (2021).