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Piano stool complexes have been studied over many years and found widespread applications in organic synthesis, catalysis, materials and drug development. We now report the first examples of quantitative chiroptical molecular recognition of chiral compounds through click‐like η6-arene coordination with readily available half sandwich complexes. This conceptually new approach to chirality sensing is based on irreversible acetonitrile displacement of [Cp*Ru(CH3CN)3]PF6 by an aromatic target molecule, a process that is fast and complete within a few minutes at room temperature. The metal coordination coincides with characteristic circular dichroism inductions that can be easily correlated to the absolute configuration and enantiomeric ratio of the bound molecule. A relay assay that decouples the determination of the enantiomeric composition and of the total sample amount by a practical CD/UV measurement protocol was developed and successfully tested. The introduction of piano stool complexes to the chiroptical sensing realm is mechanistically unique and extends the scope of currently known methods with small‐molecule probes that require the presence of amino, alcohol, carboxylate or other privileged functional groups for binding of the target compound. A broad application range including pharmaceutically relevant multifunctional molecules and the use in chromatography‐free asymmetric reaction analysis are also demonstrated. 

A chromophoric bifunctional probe design that allows selective chiroptical sensing of cysteine in aqueous solution is introduced. The common need for chiral HPLC separation is eliminated which expedites and simplifies the sample analysis while reducing solvent waste. Screening of the reaction between six phenacyl bromides and the enantiomers of cysteine showed that cyclization to an unsaturated thiomorpholine scaffold coincides with characteristic UV and CD effects, in particular when the reagent carries a proximate auxochromic nitro group. The UV changes and CD inductions were successfully used for determination of the absolute configuration, enantiomeric composition and total concentration of 18 test samples. This assay is highly selective for free cysteine while other amino acids, cysteine derived small peptides and biothiols do not interfere with the chiroptical signal generation. 

We report chemoselective and modular peptide bioconjugation using stoichiometric amounts of 4-halocoumarin and arylsulfonate agents that undergo metal-free C(sp 2 )-heteroatom bond formation at micromolar concentrations. The underlying ipso -substitution click chemistry is irreversible and generates stable and inherently fluorescent bioconjugates, and the broad selection of coumarin tags offers high labeling flexibility and versatility. Different coumarins and arylsulfonates can be selectively attached to amino and thiol groups in the small peptides glutathione and ornipressin, and both free as well as latent thiols captured in disulfide bridges can be targeted if desired. The broad utility, ease of use, storage, and preparation of 4-halocoumarins and arylsulfonates are very attractive features that extend currently available dual bioconjugation capabilities. 

The cyclization reaction between ortho -phthalaldehyde and l -homocysteine coincides with the generation of a pronounced positive CD signal at approximately 335 nm. Under identical conditions, other amino acids including cysteine produce very weak CD responses. This unusual substrate specificity allows accurate chiroptical analysis of the enantiomeric composition of homocysteine samples in the presence of cysteine without the need for time-consuming chromatographic separation. This significantly simplifies and speeds up ee determination at reduced solvent waste production.