Title: Optical Chirality Sensing with an Auxiliary‐Free Earth‐Abundant Cobalt Probe
Abstract Broadly useful chiroptical enantiomeric excess (ee) sensing remains challenging and typically involves carefully designed molecular receptors or supramolecular assemblies. Herein, we report on the enantioselective sensing of 35 amino acids, amino phosphonic acids, hydroxy acids, amino alcohols, and diamines with an auxiliary‐free cobalt probe. Chiroptical analysis of the enantiomeric composition and concentration of minute sample amounts was achieved with high accuracy by using earth‐abundant cobalt salts and hydrogen peroxide as the oxidant. Despite the absence of an auxiliary ligand, the cobalt assay is applicable to aromatic and aliphatic compounds and yields strong CD signals at high wavelengths. This method obviates the general prerequisite for chromophoric metal ligands to generate chiroptical signals through ECCD (exciton‐coupled circular dichroism) effects or through analyte‐to‐ligand chirality induction, and it offers operational simplicity, cost efficiency, waste reduction, and speed. more »« less
Hassan, Diandra S.; De los Santos, Zeus A.; Brady, Kimberly G.; Murkli, Steven; Isaacs, Lyle; Wolf, Christian
(, Organic & Biomolecular Chemistry)
null
(Ed.)
The efficiency and scope of two acyclic π-wall extended cucurbiturils, M2 and M3 , exhibiting rapidly interconverting helical conformers for chiroptical sensing of amines, amino acids, alcohols, and terpenes at micromolar concentrations in water is evaluated. The formation of 1 : 1 host–guest complexes results in spontaneous induction of circular dichroism signals that can be used for accurate determination of the absolute configuration and enantiomeric composition of the analyte based on a simple mix-and-measure protocol.
Hassan, Diandra S.; De los Santos, Zeus A.; Brady, Kimberly G.; Murkli, Steven; Isaacs, Lyle; Wolf, Christian
(, Organic & Biomolecular Chemistry)
null
(Ed.)
The efficiency and scope of two acyclic π-wall extended cucurbiturils, M2 and M3 , exhibiting rapidly interconverting helical conformers for chiroptical sensing of amines, amino acids, alcohols, and terpenes at micromolar concentrations in water is evaluated. The formation of 1 : 1 host–guest complexes results in spontaneous induction of circular dichroism signals that can be used for accurate determination of the absolute configuration and enantiomeric composition of the analyte based on a simple mix-and-measure protocol.
Kariapper, F. Safia; Thanzeel, F. Yushra; Zandi, Lily S.; Wolf, Christian
(, Organic & Biomolecular Chemistry)
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.
Nelson, Eryn; Bertke, Jeffery_A; Thanzeel, F_Yushra; Wolf, Christian
(, Angewandte Chemie International Edition)
Abstract 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]PF6by 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.
De_los_Santos, Zeus_A; Lynch, Ciarán_C; Wolf, Christian
(, Chemistry – A European Journal)
Abstract A sterically encumbered aminoborane sensor is introduced and used for quantitative stereochemical analysis of monoalcohols, diols and amino alcohols. The small‐molecule probe exhibits a rigid ortho‐substituted arene scaffold with a proximate boron binding site and a triarylamine circular dichroism (CD) reporter unit which proved to be crucial for the observed chiroptical signal induction. Coordination of the chiral target molecule produces strong Cotton effects and UV changes that are readily correlated to its absolute configuration, enantiomeric composition and concentration to achieve comprehensive stereochemical analysis within a 5 % absolute error margin. The sensing method was successfully applied in the chromatography‐free analysis of less than one milligram of a crude asymmetric reaction mixture and the advantages of this chiroptical sensing approach, which is amenable to high‐throughput experimentation equipment and automation, over traditional methods is discussed.
De los Santos, Zeus A., Lynch, Ciarán C., and Wolf, Christian. Optical Chirality Sensing with an Auxiliary‐Free Earth‐Abundant Cobalt Probe. Angewandte Chemie International Edition 58.4 Web. doi:10.1002/anie.201811761.
De los Santos, Zeus A., Lynch, Ciarán C., & Wolf, Christian. Optical Chirality Sensing with an Auxiliary‐Free Earth‐Abundant Cobalt Probe. Angewandte Chemie International Edition, 58 (4). https://doi.org/10.1002/anie.201811761
De los Santos, Zeus A., Lynch, Ciarán C., and Wolf, Christian.
"Optical Chirality Sensing with an Auxiliary‐Free Earth‐Abundant Cobalt Probe". Angewandte Chemie International Edition 58 (4). Country unknown/Code not available: Wiley Blackwell (John Wiley & Sons). https://doi.org/10.1002/anie.201811761.https://par.nsf.gov/biblio/10083378.
@article{osti_10083378,
place = {Country unknown/Code not available},
title = {Optical Chirality Sensing with an Auxiliary‐Free Earth‐Abundant Cobalt Probe},
url = {https://par.nsf.gov/biblio/10083378},
DOI = {10.1002/anie.201811761},
abstractNote = {Abstract Broadly useful chiroptical enantiomeric excess (ee) sensing remains challenging and typically involves carefully designed molecular receptors or supramolecular assemblies. Herein, we report on the enantioselective sensing of 35 amino acids, amino phosphonic acids, hydroxy acids, amino alcohols, and diamines with an auxiliary‐free cobalt probe. Chiroptical analysis of the enantiomeric composition and concentration of minute sample amounts was achieved with high accuracy by using earth‐abundant cobalt salts and hydrogen peroxide as the oxidant. Despite the absence of an auxiliary ligand, the cobalt assay is applicable to aromatic and aliphatic compounds and yields strong CD signals at high wavelengths. This method obviates the general prerequisite for chromophoric metal ligands to generate chiroptical signals through ECCD (exciton‐coupled circular dichroism) effects or through analyte‐to‐ligand chirality induction, and it offers operational simplicity, cost efficiency, waste reduction, and speed.},
journal = {Angewandte Chemie International Edition},
volume = {58},
number = {4},
publisher = {Wiley Blackwell (John Wiley & Sons)},
author = {De los Santos, Zeus A. and Lynch, Ciarán C. and Wolf, Christian},
}
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