Dynamic Covalent Optical Chirality Sensing with a Sterically Encumbered Aminoborane.

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.

Optical Detection of Stereoselective Interactions with DNA-Wrapped Single-Wall Carbon Nanotubes.

DNA-wrapped carbon nanotubes have been explored increasingly as sensitive near-infrared fluorescence probes for biomolecules. However, notably missing in previous studies is an inquiry on stereoselective interactions between DNA-wrapped carbon nanotubes and biomolecules. Here, enantiopure (+) and (-)(6,5), and (-)(8,3) as well as achiral (11,0) carbon nanotubes wrapped with specific resolving DNA sequences are used to demonstrate their stereoselective detection of amino acid enantiomers. Furthermore, stereoselective sensing abilities are found to be retained by dispersions containing a multitude of chiral nanotube structures. The fluorescence response profiles of six different DNA-wrapped carbon nanotube dispersions to nine standard amino acids, and their enantiomers, demonstrate that DNA-wrapped carbon nanotubes are exquisitely sensitive to the stereoconfiguration and side-chain functionality of amino acids in a manner that is dependent on both DNA sequence and nanotube chirality. Implications of our findings are discussed in the context of developing a machine learning-aided multiplexed biosensing scheme called a molecular perceptron.

Chiroptical sensing of amino acids, amines, amino alcohols, alcohols and terpenes with π-extended acyclic cucurbiturils.

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.

Optical Terpene and Terpenoid Sensing: Chiral Recognition, Determination of Enantiomeric Composition and Total Concentration Analysis with Late Transition Metal Complexes.

Quantitative chirality sensing of terpenes and terpenoids exhibiting a single double bond as the only functional group, such as α-pinene, ß-pinene and camphene, or two alkene moieties like limonene, valencene, and ß-caryophyllene is among the most difficult molecular recognition tasks. In this work, a fast chiroptical sensing method that accomplishes determination of the enantiomeric excess and overall amount of a large variety of terpenes and terpenoids using readily available phosphine derived late transition metal complexes is presented. The terpene coordination is complete within 10 min and coincides with spontaneous induction of strong CD signals at long wavelengths and distinct UV changes which together allow accurate ee and concentration quantification.

Tandem Use of Optical Sensing and Machine Learning for the Determination of Absolute Configuration, Enantiomeric and Diastereomeric Ratios, and Concentration of Chiral Samples.

We have developed an optical method for accurate concentration, er, and dr analysis of amino alcohols based on a simple mix-and-measure workflow that is fully adaptable to multiwell plate technology and microscale analysis. The conversion of the four aminoindanol stereoisomers with salicylaldehyde to the corresponding Schiff base allows analysis of the dr based on a change in the UV maximum at 420 nm that is very different for the homo- and heterochiral diastereomers and of the concentration of the sample using a hypsochromic shift of another absorption band around 340 nm that is independent of the analyte stereochemistry. Subsequent in situ formation of CuII assemblies in the absence and presence of base enables quantification of the er values for each diastereomeric pair by CD analysis. Applying a linear programming method and a parameter sweep algorithm, we determined the concentration and relative amounts of each of the four stereoisomers in 20 samples of vastly different stereoisomeric compositions with an averaged absolute percent error of 1.7 %.

Optical Chirality Sensing with a Stereodynamic Aluminum Biphenolate Probe.

The determination of the enantiopurity and the concentration of chiral compounds by chiroptical sensing with molecular probes is increasingly attractive for high-throughput screening applications including streamlined asymmetric reaction development. In this study, we use stereodynamic aluminum biphenolate complexes for quantitative ee and concentration analysis of amino alcohols and α-hydroxy acids. An important feature of the tropos biphenolate ligand used is the presence of a phenylacetylene antenna for optimal chirality recognition and CD/UV responses at high wavelengths. The complexation-driven chirality amplification yields strong CD signals, which allows quantitative chiroptical sensing with good accuracy. We show that aluminate biphenolate sensors can exhibit linear and nonlinear correlations between the induced CD signals and the enantiomeric composition or concentration of the chiral substrate.

Optical Chirality Sensing with an Auxiliary-Free Earth-Abundant Cobalt Probe.

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.

Chirality sensing with stereodynamic copper(I) complexes.

Three Cu(I) complexes derived from stereodynamic diphosphine ligands were synthesized and used for chirality sensing. The coordination of diamines and amino acids to these complexes generates distinct circular dichroism signals. The chiroptical sensor response allows determination of the absolute configuration and the enantiomeric excess of the analyte at low concentrations. This method is operationally simple, fast, and attractive for high-throughput sensing applications.

Chiroptical Asymmetric Reaction Screening via Multicomponent Self-Assembly.

Self-assembly of a stereodynamic phosphine ligand, Pd(II), and a chiral amine, amino alcohol, or amino acid generates characteristic UV and CD signals that can be used for quantitative stereochemical analysis of the bound substrate. A robust mix-and-measure chiroptical sensing protocol has been developed and used to determine the absolute configuration, ee, and yield of an amine produced by Ir-catalyzed asymmetric hydrogenation of an iminium salt. The analysis requires only 1 mg of the crude reaction mixture and minimizes cost, labor, time, and waste.

Quantitative chirality sensing of amines and amino alcohols via Schiff base formation with a stereodynamic UV/CD probe.

A stereodynamic chemosensor that can be used for simultaneous determination of the absolute configuration, enantiomeric composition and total concentration of chiral amines and amino alcohols based on two fast optical measurements was prepared and tested. The free sensor is CD-silent and produces characteristic blue-shifted UV and CD signals upon substrate binding via Schiff base formation. The potential in high-throughput screening applications and for rational sensor developments are discussed.

Chirality sensing with stereodynamic biphenolate zinc complexes.

Two bidentate ligands consisting of a fluxional polyarylacetylene framework with terminal phenol groups were synthesized. Reaction with diethylzinc gives stereodynamic complexes that undergo distinct asymmetric transformation of the first kind upon binding of chiral amines and amino alcohols. The substrate-to-ligand chirality imprinting at the zinc coordination sphere results in characteristic circular dichroism signals that can be used for direct enantiomeric excess (ee) analysis. This chemosensing approach bears potential for high-throughput ee screening with small sample amounts and reduced solvent waste compared to traditional high-performance liquid chromatography methods.

DNA-guided lattice remodeling of carbon nanotubes.

Covalent modification of carbon nanotubes is a promising strategy for engineering their electronic structures. However, keeping modification sites in registration with a nanotube lattice is challenging. We report a solution using DNA-directed, guanine (G)-specific cross-linking chemistry. Through DNA screening we identify a sequence, C3GC7GC3, whose reaction with an (8,3) enantiomer yields minimum disorder-induced Raman mode intensities and photoluminescence Stokes shift, suggesting ordered defect array formation. Single-particle cryo-electron microscopy shows that the C3GC7GC3 functionalized (8,3) has an ordered helical structure with a 6.5 angstroms periodicity. Reaction mechanism analysis suggests that the helical periodicity arises from an array of G-modified carbon-carbon bonds separated by a fixed distance along an armchair helical line. Our findings may be used to remodel nanotube lattices for novel electronic properties.

Catalytic Asymmetric Mannich Reaction of α-Fluoronitriles with Ketimines: Enantioselective and Diastereodivergent Construction of Vicinal Tetrasubstituted Stereocenters.

Diastereodivergent and enantioselective conversion of isatin ketimines to α-fluoro-ß-aminonitriles with vicinal tetrasubstituted stereocenters is achieved by a chiral copper complex/guanidine base catalyzed Mannich reaction with proper choice of the bisphosphine ligand. The reaction is broad in scope, scalable, and provides efficient access to a series of 3-aminoindolinones exhibiting a quaternary carbon-fluorine stereocenter with high yields and stereoselectivities. Selective transformations of the Mannich reaction products into multifunctional 3-aminooxindoles without erosion of enantiomeric and diastereomeric purity highlight the synthetic utility.

Chiroptical sensing of unprotected amino acids, hydroxy acids, amino alcohols, amines and carboxylic acids with metal salts.

Optical chirality sensing of unprotected amino acids, hydroxy acids, amino alcohols, amines and carboxylic acids based on a practical mix-and-measure protocol with readily available copper, iron, palladium, manganese, cerium or rhodium salts is demonstrated. The generation of strong cotton effects allows quantitative ee analysis of small sample amounts with high speed. In contrast to previously reported assays the use of chromophoric reporter ligands and the control of metal coordination kinetics and redox chemistry are not necessary which greatly simplifies the sensing procedure with the benefit of reduced waste production and cost.