Designing Powerful Biindole-Based Inherently Chiral Selectors: Enhancing Enantiodiscrimination by Core
Sara Grecchi1, Giorgia Bonetti2, Elisa Emanuele1,3
1Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133, Milan, Italy.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|March 22, 2024
Summary
Researchers developed novel biindole-based chiral selectors with enhanced enantiodiscrimination. The hydroxyethyl-substituted selector showed superior performance, even in a real drug sample, highlighting its potential for chiral analysis.
Area of Science:
- Chiral Chemistry
- Electrochemistry
- Materials Science
Background:
- Inherently chiral selectors, particularly biindole derivatives, offer excellent enantiodiscrimination.
- Biindole selectors allow for easy functionalization at nitrogen atoms to tune properties.
- Exploring substituent effects on nitrogen atoms can enhance chiral recognition capabilities.
Purpose of the Study:
- To synthesize and evaluate novel biindole-based chiral selectors with varying nitrogen substituents.
- To investigate the impact of ethyl, methoxyethyl, and hydroxyethyl groups on enantiodiscrimination.
- To demonstrate the utility of these selectors in chiral voltammetry and chemical resolution.
Main Methods:
- Design and synthesis of three new 2,2'-biindole atropisomeric monomers with bithiophene wings.
- Functionalization of nitrogen atoms with ethyl, methoxyethyl, and hydroxyethyl groups.
- Chiral voltammetry experiments using ferrocenyl probes and chiral non-steroidal anti-inflammatory drugs (NSAIDs) like naproxen and ketoprofen.
- Chemical resolution of biindole selectors via nitrogen alkylation.
Main Results:
- Successful synthesis and characterization of the novel biindole monomers.
- Demonstrated increasing enantiodiscrimination ability in the order: ethyl < methoxyethyl < hydroxyethyl.
- The hydroxyethyl selector exhibited significant enantiomer potential differences, indicating enhanced chiral recognition.
- Achieved chemical resolution of biindole selectors without chiral HPLC.
- Applied the hydroxyethyl selector to analyze ketoprofen in a commercial drug matrix.
Conclusions:
- Nitrogen atom functionalization significantly enhances the enantiodiscrimination ability of biindole selectors.
- The presence of an additional coordination element (hydroxyethyl group) is beneficial for chiral recognition.
- These novel biindole selectors, especially the hydroxyethyl derivative, are promising tools for chiral analysis and resolution.
Related Concept Videos
02:05Prochirality
3.8K
The concept of prochirality leads to the nomenclature of the individual faces of a molecule and plays a crucial role in the enantioselective reaction. It is a concept where two or more achiral molecules react to produce chiral products. A typical process is the reaction of an achiral ketone to generate a chiral alcohol. Here, the achiral reactant reacts with an achiral reducing agent, sodium borohydride, to generate an equimolar mixture of the chiral enantiomers of the product. For example, an...
3.8K
02:30Chirality at Nitrogen, Phosphorus, and Sulfur
5.7K
Chirality is most prevalent in carbon-based tetrahedral compounds, but this important facet of molecular symmetry extends to sp3-hybridized nitrogen, phosphorus and sulfur centers, including trivalent molecules with lone pairs. Here, the lone pair behaves as a functional group in addition to the other three substituents to form an analogous tetrahedral center that can be chiral.
A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all...
A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all...
5.7K
02:25Molecules with Multiple Chiral Centers
11.7K
Molecules that possess multiple chiral centers can afford a large number of stereoisomers. For instance, while some molecules like 2-butanol have one chiral center, defined as a tetrahedral carbon atom with four different substituents attached, several molecules like butane-2,3-diol have multiple chiral centers. A simple formula to predict the number of stereoisomers possible for a molecule with n chiral centers is 2n. However, there can be a lower number where some of the stereoisomers are...
11.7K
02:21Naming Enantiomers
20.3K
The naming of enantiomers employs the Cahn–Ingold–Prelog rules that involve assigning priorities to different substituent groups at a chiral center. Each enantiomer, being a distinct molecule, is assigned a unique name by the Cahn–Ingold–Prelog (CIP) rules, also called the R–S system. The prefix R- or S- attached to the chiral centers in an enantiomer is dependent on the spatial arrangement of the four substituents on the chiral center. The R–S system...
20.3K
02:36Regioselectivity and Stereochemistry of Hydroboration
8.1K
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn...
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn...
8.1K
02:52Stereoisomerism
11.9K
Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula.
Transition metal complexes often exist as geometric isomers, in which the same atoms are connected through the same types of bonds but with differences in their orientation in space. Coordination complexes with two different ligands in the cis and trans positions from a ligand of interest form isomers. For example, the octahedral [Co(NH3)4Cl2]+ ion has two isomers (Figure 1) In the cis...
Isomers are different chemical species that have the same chemical formula.
Transition metal complexes often exist as geometric isomers, in which the same atoms are connected through the same types of bonds but with differences in their orientation in space. Coordination complexes with two different ligands in the cis and trans positions from a ligand of interest form isomers. For example, the octahedral [Co(NH3)4Cl2]+ ion has two isomers (Figure 1) In the cis...
11.9K