skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Predictive chirality sensing via Schiff base formation
Among the large number of chiroptical sensors that have been developed to date, few allow rational determination of the absolute configuration of chiral substrates together with quantitative ee analysis. We have prepared and tested stereodynamic N -aryl aminobenzaldehyde sensors that bind chiral amines via Schiff base formation. The covalent binding of the amine substrate generates a conformational bias in the chromophoric sensor moiety which results in characteristic CD signals. Computational analysis revealed that CD prediction of the sign of the Cotton effect and thus determination of the absolute configuration of the substrate becomes practical with a sterically crowded sensor design because the number of conformations to be considered is largely reduced and the chiroptical sensor response is less sensitive to conformational equilibria. The amplitude of the measured CD signal can be used for quantitative ee analysis of nonracemic amine samples with the help of a calibration curve.  more » « less
Award ID(s):
1764135
PAR ID:
10148165
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Organic & Biomolecular Chemistry
Volume:
17
Issue:
27
ISSN:
1477-0520
Page Range / eLocation ID:
6699 to 6705
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; (, 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. 
    more » « less
  2. ; ; (, Chemical Science)
    The widespread occurrence and significance of chiral compounds does not only require new methods for their enantioselective synthesis but also efficient tools that allow rapid determination of the absolute configuration, enantiomeric composition and overall concentration of nonracemic mixtures. Although chiral analysis is a frequently encountered challenge in the chemical, environmental, materials and health sciences it is typically addressed with slow and laborious chromatographic or NMR spectroscopic techniques. We now show with almost 40 analytes representing 5 different compound classes, including mono-alcohols which are particularly challenging sensing targets, that this task can be solved very quickly by chiroptical sensing with a single, readily available arylisocyanate probe. The probe reacts smoothly and irreversibly with amino and alcohol groups when an organocatalyst is used at room temperature toward urea or carbamate products exhibiting characteristic UV and CD signals above 300 nm. The UV signal induction is not enantioselective and correlated to the total concentration of both enantiomers, the concomitant generation of a CD band allows determination of the enantiomeric composition from the same sample, and the sense of the induced Cotton effect reveals the absolute configuration by comparison with a reference. This approach eliminates complications that can arise when enantiomerically impure NMR derivatizing agents are used and it outperforms time-consuming HPLC protocols. The generation of distinct UV and CD signals at high wavelengths overcomes issues with insufficient resolution of overlapping signals often encountered with chiral NMR solvating agents that rely on weak binding forces. The broad solvent compatibility is another noteworthy and important characteristic of this assay. It addresses frequently encountered problems with insufficient solubility of polar analytes, for example pharmaceuticals, in standard mobile phase mixtures required for chiral HPLC analysis. We anticipate that the broad application spectrum, ruggedness and practicality of organocatalytic chiroptical sensing with aryliso(thio)cyanate probes together with the availability of automated CD multi-well plate readers carry exceptional promise to accelerate chiral compound development projects at reduced cost and with less waste production. 
    more » « less
  3. ; ; ; (, 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. 
    more » « less
  4. ; ; ; (, Angewandte Chemie International Edition)
    The analysis of the absolute configuration, enantiomeric composition, and concentration of chiral compounds are frequently encountered tasks across the chemical and health sciences. Chiroptical sensing methods can streamline this work and allow high-throughput screening with remarkable reduction of operational time and cost. During the last few years, significant methodological advances with innovative chirality sensing systems, the use of computer-generated calibration curves, machine learning assistance, and chemometric data processing, to name a few, have emerged and are now matched with commercially available multi-well plate CD readers. These developments have reframed the chirality sensing space and provide new opportunities that are of interest to a large group of chemists. This review will discuss chirality sensing strategies and applications with representative small-molecule CD sensors. Emphasis will be given to important milestones and recent advances that accelerate chiral compound analysis by outperforming traditional methods, conquer new directions, and pioneering efforts that lie at the forefront of chiroptical high-throughput screening developments. The goal is to provide the reader with a thorough understanding of the current state and a perspective of future directions of this rapidly emerging field. 
    more » « less
  5. ; ; (, Organic & Biomolecular Chemistry)
    null (Ed.)
    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. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email