Chiral Molecules: Properties, Synthesis and Analysis

A special issue of Symmetry (ISSN 2073-8994). This special issue belongs to the section "Chemistry: Symmetry/Asymmetry".

Deadline for manuscript submissions: closed (14 January 2022) | Viewed by 15179

Special Issue Editor


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Guest Editor
Institute of Biomolecular Chemistry – CNR, 95126 Catania, Italy
Interests: chemistry; pharmacology, toxicology and pharmaceutics; materials science

Special Issue Information

Dear Colleagues,

Chirality is a fundamental dimension in molecular structure and plays a central role in living processes, in the transfer of biological intra- and inter-species information as well as in the activity and properties of exogenous compounds as drugs, agrochemicals, flavours, and food additives.

Historically isolated from natural sources, chiral compounds require targeted strategies for their synthesis and separation in optically active forms that can be obtained through stereoselective interactions with other chiral components, as reagents/catalysts or chromatographic supports. 

Although the nature continues to be the origin of an astonishing chiral diversity and complexity, the developments in asymmetric synthesis have led to a wide portfolio of chiral molecules nowadays accessible, thanks to the huge variety of catalysts and stereoselective reactions available.

Techniques for the separation of stereoisomers and the assignment of their absolute configuration have grown in parallel. The relationships’ biological activity and the “right” molecular stereochemistry have been highlighted for many drugs, which are often marketed as single stereoisomers for a better safety and effectiveness.

This Special Issue of Symmetry features articles about all aspects of chirality, covering a broad range of topics including: isolation and structural characterization of novel chiral compounds from natural sources, asymmetric synthesis and development of effective catalysts, stereoselective biotransformations, chiroptical and spectroscopic methods for the assignment of absolute configuration, methods for chiral separations, and chirality-related biological activity.

Submit your paper and select the Journal “Symmetry” and the Special Issue “Chiral Molecules: Properties, Synthesis and Analysis” via: MDPI submission system. Our papers will be published on a rolling basis and we will be pleased to receive your submission once you have finished it.

Dr. Angela Patti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Symmetry is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Chiral natural compounds
  • Asymmetric synthesis
  • Chiral catalysts
  • Stereoselective biocatalytic reactions
  • Stereoisomers
  • Supramolecular chiral assemblies
  • Chiral separations
  • Assignment of stereochemistry
  • Chiroptical properties
  • Chirality and biological activity

Published Papers (6 papers)

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Editorial

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2 pages, 160 KiB  
Editorial
Chiral Molecules: Properties, Synthesis and Analysis
by Angela Patti
Symmetry 2022, 14(3), 579; https://doi.org/10.3390/sym14030579 - 15 Mar 2022
Viewed by 1572
Abstract
Chirality is a fundamental dimension of molecular structures and plays a central role in living processes, in the transfer of biological intra- and inter-species information, and in the activity and properties of exogenous compounds as drugs, agrochemicals, flavors and food additives [...] Full article
(This article belongs to the Special Issue Chiral Molecules: Properties, Synthesis and Analysis)

Research

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8 pages, 1907 KiB  
Article
Homochiral or Heterochiral: A Systematic Study of Threonine Clusters Using a FT ICR Mass Spectrometer
by Luyang Jiao, Mengying Du, Yameng Hou, Yuan Ma and Xianglei Kong
Symmetry 2022, 14(1), 86; https://doi.org/10.3390/sym14010086 - 06 Jan 2022
Cited by 2 | Viewed by 1594
Abstract
The strong chiral preferences of some magic clusters of amino acids have attracted continually increasing interests due to their unique structures, properties and possible roles in homochirogenesis. However, how chirality can influence the generation and stability of cluster ions in a wild range [...] Read more.
The strong chiral preferences of some magic clusters of amino acids have attracted continually increasing interests due to their unique structures, properties and possible roles in homochirogenesis. However, how chirality can influence the generation and stability of cluster ions in a wild range of cluster sizes is still unknown for most amino acids. In this study, the preference for threonine clusters to form homochiral and heterochiral complex ions has been investigated by electrospray ionization (ESI) mass spectrometry. Abundant cluster [Thrn+mH]m+ ions (7 ≤ n ≤ 78, 1 ≤ m ≤ 5) have been observed for both samples of enantiopure (100% L) and racemic (50:50 L:D) threonine solutions. Further analyses of the spectra show that the [Thr14+2H]2+ ion is characterized by its most outstanding homochiral preference, and [Thr7+H]+ and [Thr8+H]+ ions also clearly exhibit their homochiral preferences. Although most of the triply charged clusters (20 ≤ n ≤ 36) are characterized by heterochiral preferences, the quadruply charged [Thrn+4H]4+ ions (40 ≤ n ≤ 59) have no obvious chiral preference in general. On the other hand, a weak homochiral preference exists for most of the quintuply charged ions observed in the experiment. Full article
(This article belongs to the Special Issue Chiral Molecules: Properties, Synthesis and Analysis)
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9 pages, 1880 KiB  
Article
Low Temperature Dynamic Chromatography for the Separation of the Interconverting Conformational Enantiomers of the Benzodiazepines Clonazolam, Flubromazolam, Diclazepam and Flurazepam
by Roberta Franzini, Alessia Rosetti and Claudio Villani
Symmetry 2021, 13(6), 1012; https://doi.org/10.3390/sym13061012 - 04 Jun 2021
Cited by 3 | Viewed by 1957
Abstract
Benzodiazepines (BZDs) are an important class of psychoactive drugs with hypnotic-sedative, myorelaxant, anxiolytic and anticonvulsant properties due to interaction with the GABAa receptor in the central nervous system of mammals. BZDs are interesting both in clinical and forensic toxicology for their pharmacological characteristics [...] Read more.
Benzodiazepines (BZDs) are an important class of psychoactive drugs with hypnotic-sedative, myorelaxant, anxiolytic and anticonvulsant properties due to interaction with the GABAa receptor in the central nervous system of mammals. BZDs are interesting both in clinical and forensic toxicology for their pharmacological characteristics and potential of abuse. The presence of a non-planar diazepine ring generates chiral conformational stereoisomers, even in the absence of stereogenic centers. A conformational enrichment of BZD at the binding sites has been reported in the literature, thus making interesting a stereodynamic screening of a wide range of BZDs. Herein, we report the investigation of three stereolabile 1,4-benzodiazepine included in the class of “designer benzodiazepines” (e.g., diclazepam, a chloro-derivative of diazepam, and two triazolo-benzodiazepines, flubromazolam and clonazolam) and a commercially available BZD known as flurazepam, in order to study the kinetic of the “ring-flip” process that allows two conformational enantiomers to interconvert at high rate at room temperature. A combination of low temperature enantioselective dynamic chromatography on chiral stationary phase and computer simulations of the experimental chromatograms allowed us to measure activation energies of enantiomerization (ΔG) lower than 18.5 kcal/mol. The differences between compounds have been correlated to the pattern of substitutions on the 1,4-benzodiazepinic core. Full article
(This article belongs to the Special Issue Chiral Molecules: Properties, Synthesis and Analysis)
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19 pages, 6465 KiB  
Article
Chirality, Gelation Ability and Crystal Structure: Together or Apart? Alkyl Phenyl Ethers of Glycerol as Simple LMWGs
by Alexander A. Bredikhin, Aidar T. Gubaidullin, Zemfira A. Bredikhina, Robert R. Fayzullin and Olga A. Lodochnikova
Symmetry 2021, 13(4), 732; https://doi.org/10.3390/sym13040732 - 20 Apr 2021
Cited by 4 | Viewed by 1979
Abstract
Chiral recognition plays an important role in the self-assembly of soft materials, in particular supramolecular organogels formed by low molecular weight gelators (LMWGs). Out of 14 pairs of the studied racemic and enantiopure samples of alkyl-substituted phenyl ethers of glycerol, only eight enantiopure [...] Read more.
Chiral recognition plays an important role in the self-assembly of soft materials, in particular supramolecular organogels formed by low molecular weight gelators (LMWGs). Out of 14 pairs of the studied racemic and enantiopure samples of alkyl-substituted phenyl ethers of glycerol, only eight enantiopure diols form the stable gels in nonane. The formation of gels from solutions was studied by polarimetry, and their degradation with the formation of xerogels was studied by the PXRD method. The revealed crystalline characteristics of all studied xerogels corresponded to those for crystalline samples of the parent gelators. In addition to those previously investigated, crystalline samples of enantiopure para-n-alkylphenyl glycerol ethers [alkyl = pentyl (5), hexyl (6), heptyl (7), octyl (8), nonyl (9)] and racemic 3-(3,5-dimethylphenoxy)propane-1,2-diol (rac-14) have been examined by single crystal X-ray diffraction analysis. Among 22 samples of compounds 114 studied by SC-XRD, seven different types of supramolecular motifs are identified, of which only two are realized in crystals of supramolecular gelators. An attempt was made to relate the ability to gel formation with the characteristics of the supramolecular motif of a potential gelling agent, and the frequency of formation of the motif, required for gelation, with the chiral characteristics of the sample. Full article
(This article belongs to the Special Issue Chiral Molecules: Properties, Synthesis and Analysis)
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13 pages, 2741 KiB  
Article
Vibrational Circular Dichroism Detects Symmetry Breaking due to Conformational Mobility in C2-Symmetry Chiral Molecules and Provides Further Insight into Inter-Chromophoric Interactions
by Giuseppe Mazzeo, Sergio Abbate, Stefan E. Boiadjiev, David A. Lightner and Giovanna Longhi
Symmetry 2020, 12(11), 1752; https://doi.org/10.3390/sym12111752 - 22 Oct 2020
Cited by 3 | Viewed by 1935
Abstract
Bicyclo[3.3.1]nonane-2,6-dione (1) and bicyclo[3.3.1]nona-3,7-diene-2,6-dione (2) have been examined by vibrational circular dichroism (VCD), which, as for most C2-symmetric systems, exhibits strong VCD signals. In the [...] Read more.
Bicyclo[3.3.1]nonane-2,6-dione (1) and bicyclo[3.3.1]nona-3,7-diene-2,6-dione (2) have been examined by vibrational circular dichroism (VCD), which, as for most C2-symmetric systems, exhibits strong VCD signals. In the case of 2, VCD signals are stronger and sharper with several bisignate doublets; for 1, signals are less intense and broader. The VCD and IR spectra are excellently predicted by DFT calculations: only one conformer is present for 2, while for 1, three main conformers, related through concerted skeleton torsional motions are present (two of them being interchanged by C2-rotation). The VCD spectrum shows specific features for the different conformers, such that correct population factors are crucial for reproducing experimental data. Also, the TD-DFT prediction of ECD (electronic circular dichroism) spectra is good. By comparing the spectroscopic signature of the two molecules (both VCD and ECD) and by careful analysis of the theoretical results, the role of the C=C double bond in compound (2) is evidenced. The double bond contributes toward enhancing the CD response both electronically and vibrationally. Full article
(This article belongs to the Special Issue Chiral Molecules: Properties, Synthesis and Analysis)
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Review

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26 pages, 6769 KiB  
Review
Breaking Molecular Symmetry through Biocatalytic Reactions to Gain Access to Valuable Chiral Synthons
by Angela Patti and Claudia Sanfilippo
Symmetry 2020, 12(9), 1454; https://doi.org/10.3390/sym12091454 - 04 Sep 2020
Cited by 16 | Viewed by 3883
Abstract
In this review the recent reports of biocatalytic reactions applied to the desymmetrization of meso-compounds or symmetric prochiral molecules are summarized. The survey of literature from 2015 up to date reveals that lipases are still the most used enzymes for this goal, [...] Read more.
In this review the recent reports of biocatalytic reactions applied to the desymmetrization of meso-compounds or symmetric prochiral molecules are summarized. The survey of literature from 2015 up to date reveals that lipases are still the most used enzymes for this goal, due to their large substrate tolerance, stability in different reaction conditions and commercial availability. However, a growing interest is focused on the use of other purified enzymes or microbial whole cells to expand the portfolio of exploitable reactions and the molecular diversity of substrates to be transformed. Biocatalyzed desymmetrization is nowadays recognized as a reliable and efficient approach for the preparation of pharmaceuticals or natural bioactive compounds and many processes have been scaled up for multigram preparative purposes, also in continuous-flow conditions. Full article
(This article belongs to the Special Issue Chiral Molecules: Properties, Synthesis and Analysis)
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