Research

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15 pages, 4887 KiB

Open AccessArticle

Daptomycin: A Novel Macrocyclic Antibiotic as a Chiral Selector in an Organic Polymer Monolithic Capillary for the Enantioselective Analysis of a Set of Pharmaceuticals

by Ali Fouad, Adel A. Marzouk, Montaser Sh. A. Shaykoon, Samy M. Ibrahim, Sobhy M. El-Adl and Ashraf Ghanem

Molecules 2021, 26(12), 3527; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26123527 - 09 Jun 2021

Cited by 9 | Viewed by 2666

Abstract

Daptomycin, a macrocyclic antibiotic, is here used as a new chiral selector in preparation of chiral stationary phase (CSP) in a recently prepared polymer monolithic capillary. The latter is prepared using the copolymerization of the monomers glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate [...] Read more.

Daptomycin, a macrocyclic antibiotic, is here used as a new chiral selector in preparation of chiral stationary phase (CSP) in a recently prepared polymer monolithic capillary. The latter is prepared using the copolymerization of the monomers glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EGDMA) in the presence of daptomycin in water. Under reversed phase conditions (RP), the prepared capillaries were tested for the enantioselective nanoliquid chromatographic separation of fifty of the racemic drugs of different pharmacological groups, such as adrenergic blockers, H1-blockers, NSAIDs, antifungal drugs, and others. Baseline separation was attained for many drugs under RP-HPLC. Daptomycin expands the horizon of chiral selectors in HPLC. Full article

(This article belongs to the Special Issue Chiral Stationary Phases for Enantioseparations: Fundamentals, Preparation, Methods, Applications and Chiral Recognition Mechanisms)

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12 pages, 2347 KiB

Open AccessArticle

Polydopamine-Assisted Rapid One-Step Immobilization of L-Arginine in Capillary as Immobilized Chiral Ligands for Enantioseparation of Dansyl Amino Acids by Chiral Ligand Exchange Capillary Electrochromatography

by Yuanqi Gui, Baian Ji, Gaoyi Yi, Xiuju Li, Kailian Zhang and Qifeng Fu

Molecules 2021, 26(6), 1800; https://doi.org/10.3390/molecules26061800 - 23 Mar 2021

Cited by 6 | Viewed by 2872

Abstract

Herein, a novel L-arginine (L-Arg)-modified polydopamine (PDA)-coated capillary (PDA/L-Arg@capillary) was firstly fabricated via the basic amino-acid-induced PDA co-deposition strategy and employed to constitute a new chiral ligand exchange capillary electrochromatography (CLE-CEC) method for the high-performance enantioseparation of D,L-amino acids (D,L-AAs) with L-Arg as [...] Read more.

Herein, a novel L-arginine (L-Arg)-modified polydopamine (PDA)-coated capillary (PDA/L-Arg@capillary) was firstly fabricated via the basic amino-acid-induced PDA co-deposition strategy and employed to constitute a new chiral ligand exchange capillary electrochromatography (CLE-CEC) method for the high-performance enantioseparation of D,L-amino acids (D,L-AAs) with L-Arg as the immobilized chiral ligand coordinating with the central metal ion Zn(II) as running buffer. Assisted by hydrothermal treatment, the robust immobilization of L-Arg on the capillary inner wall could be facilely achieved within 1 h, prominently improving the synthesis efficiency and simplifying the preparation procedure. The successful preparation of PDA/L-Arg coatings in the capillary was systematically characterized and confirmed using several methods. In comparison with bare and PDA-functionalized capillaries, the enantioseparation capability of the presented CLE-CEC system was significantly enhanced. Eight D,L-AAs were completely separated and three pairs were partially separated under the optimal conditions. The prepared PDA/L-Arg@capillary showed good repeatability and stability. The potential mechanism of the greatly enhanced enantioseparation performance obtained by PDA/L-Arg@capillary was also explored. Moreover, the proposed method was further utilized for studying the enzyme kinetics of L-glutamic dehydrogenase, exhibiting its promising prospects in enzyme assays and other related applications. Full article

(This article belongs to the Special Issue Chiral Stationary Phases for Enantioseparations: Fundamentals, Preparation, Methods, Applications and Chiral Recognition Mechanisms)

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11 pages, 2061 KiB

Open AccessFeature PaperArticle

Comparison of Coated and Immobilized Chiral Stationary Phases Based on Amylose tris-[(S)-α-Methylbenzylcarbamate] for the HPLC Enantiomer Separation of α-Lipoic Acid and Its Reduced Form

by Alessia Rosetti, Claudio Villani, Marco Pierini and Roberto Cirilli

Molecules 2021, 26(6), 1747; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26061747 - 20 Mar 2021

Cited by 10 | Viewed by 2093

Abstract

The couple of chiral sulfur compounds α-lipoic acid (ALA)/α-dihydrolipoic acid (DHALA) has attracted considerable attention in recent years owing to its remarkable anti-inflammatory and antioxidant properties. It is well known that the chirality of the C6 plays a key role in determining the [...] Read more.

The couple of chiral sulfur compounds α-lipoic acid (ALA)/α-dihydrolipoic acid (DHALA) has attracted considerable attention in recent years owing to its remarkable anti-inflammatory and antioxidant properties. It is well known that the chirality of the C6 plays a key role in determining the biological activity of ALA. The natural occurring (R)-ALA enantiomer is an essential cofactor for key oxidative metabolism enzyme complexes and, after oral administration of the racemic mixture, it shows higher plasma concentration than (S)-ALA. Differently, the in vivo enantioselective action difference between the enantiomers of DHALA has not yet been studied. This lacking is perhaps due to the unavailability of analytical methods capable of determining the enantiomeric composition of biological samples during pharmacokinetic and pharmacodynamic events. In the present work, the direct and baseline enantioresolution of both chiral acids by HPLC on two amylose-derived chiral stationary phases is presented. The proposed chiral enantioselective protocol, therefore, does not require pre- or on-column derivatization. The performance of the coated Chiralpak AS-H CSP and the new immobilized Chiralpak IH-3 CSP, which have the same chiral selector amylose tris-[(S)-α-methylbenzylcarbamate], were compared using conventional normal-phase mobile phases containing ethanol or 2-propanol as alcoholic solvents and a fixed percentage of trifluoroacetic acid. Nonconventional eluents containing dichloromethane, ethyl acetate, and 2-methyltetrahydrofuran as organic cosolvents were applied in the separation of the enantiomers of two carboxylic acids on the immobilized Chiralpak IH-3 CSP. The effect of the column temperature was carefully evaluated in order to improve enantioselectivity. Adequate amounts of enantiomers were isolated by an analytical-size Chiralpak IH-3 column and submitted to chiroptical measurements. The absolute configuration assignment of the isolated enantiomers was determined by a multidisciplinary procedure based on the comparison of the experimental and calculated chiroptical properties. Full article

(This article belongs to the Special Issue Chiral Stationary Phases for Enantioseparations: Fundamentals, Preparation, Methods, Applications and Chiral Recognition Mechanisms)

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17 pages, 3692 KiB

Open AccessArticle

Enantioseparation of 5,5′-Dibromo-2,2′-dichloro-3-selanyl-4,4′-bipyridines on Polysaccharide-Based Chiral Stationary Phases: Exploring Chalcogen Bonds in Liquid-Phase Chromatography

by Paola Peluso, Alessandro Dessì, Roberto Dallocchio, Barbara Sechi, Carlo Gatti, Bezhan Chankvetadze, Victor Mamane, Robin Weiss, Patrick Pale, Emmanuel Aubert and Sergio Cossu

Molecules 2021, 26(1), 221; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26010221 - 04 Jan 2021

Cited by 16 | Viewed by 2603

Abstract

The chalcogen bond (ChB) is a noncovalent interaction based on electrophilic features of regions of electron charge density depletion (σ-holes) located on bound atoms of group VI. The σ-holes of sulfur and heavy chalcogen atoms (Se, Te) (donors) can interact through their positive [...] Read more.

The chalcogen bond (ChB) is a noncovalent interaction based on electrophilic features of regions of electron charge density depletion (σ-holes) located on bound atoms of group VI. The σ-holes of sulfur and heavy chalcogen atoms (Se, Te) (donors) can interact through their positive electrostatic potential (V) with nucleophilic partners such as lone pairs, π-clouds, and anions (acceptors). In the last few years, promising applications of ChBs in catalysis, crystal engineering, molecular biology, and supramolecular chemistry have been reported. Recently, we explored the high-performance liquid chromatography (HPLC) enantioseparation of fluorinated 3-arylthio-4,4′-bipyridines containing sulfur atoms as ChB donors. Following this study, herein we describe the comparative enantioseparation of three 5,5′-dibromo-2,2′-dichloro-3-selanyl-4,4′-bipyridines on polysaccharide-based chiral stationary phases (CSPs) aiming to understand function and potentialities of selenium σ-holes in the enantiodiscrimination process. The impact of the chalcogen substituent on enantioseparation was explored by using sulfur and non-chalcogen derivatives as reference substances for comparison. Our investigation also focused on the function of the perfluorinated aromatic ring as a π-hole donor recognition site. Thermodynamic quantities associated with the enantioseparation were derived from van’t Hoff plots and local electron charge density of specific molecular regions of the interacting partners were inspected in terms of calculated V. On this basis, by correlating theoretical data and experimental results, the participation of ChBs and π-hole bonds in the enantiodiscrimination process was reasonably confirmed. Full article

(This article belongs to the Special Issue Chiral Stationary Phases for Enantioseparations: Fundamentals, Preparation, Methods, Applications and Chiral Recognition Mechanisms)

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10 pages, 1333 KiB

Open AccessFeature PaperArticle

Enantiomeric Separation of New Chiral Azole Compounds

by Marziyeh E. Kenari, Joshua I. Putman, Ravi P. Singh, Brandon B. Fulton, Huy Phan, Reem K. Haimour, Key Tse, Alain Berthod, Carl J. Lovely and Daniel W. Armstrong

Molecules 2021, 26(1), 213; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26010213 - 04 Jan 2021

Cited by 6 | Viewed by 3235

Abstract

Twelve new azole compounds were synthesized through an ene reaction involving methylidene heterocycles and phenylmaleimide, producing four oxazoles, five thiazoles, and one pyridine derivative, and ethyl glyoxylate for an oxazole and a thiazole compound. The twelve azoles have a stereogenic center in their [...] Read more.

Twelve new azole compounds were synthesized through an ene reaction involving methylidene heterocycles and phenylmaleimide, producing four oxazoles, five thiazoles, and one pyridine derivative, and ethyl glyoxylate for an oxazole and a thiazole compound. The twelve azoles have a stereogenic center in their structure. Hence, a method to separate the enantiomeric pairs, must be provided if any further study of chemical and pharmacological importance of these compounds is to be accomplished. Six chiral stationary phases were assayed: four were based on macrocyclic glycopeptide selectors and two on linear carbohydrates, i.e., derivatized maltodextrin and amylose. The enantiomers of the entire set of new chiral azole compounds were separated using three different mobile phase elution modes: normal phase, polar organic, and reversed phase. The most effective chiral stationary phase was the MaltoShell column, which was able to separate ten of the twelve compounds in one elution mode or another. Structural similarities in the newly synthesized oxazoles provided some insights into possible chiral recognition mechanisms. Full article

(This article belongs to the Special Issue Chiral Stationary Phases for Enantioseparations: Fundamentals, Preparation, Methods, Applications and Chiral Recognition Mechanisms)

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11 pages, 1016 KiB

Open AccessArticle

Enantioseparation and Determination of Penconazole in Rat Plasma by Chiral LC-MS/MS: Application to a Stereoselective Toxicokinetic Study

by Siman Ma, Jia Lun, Yanru Liu, Zhen Jiang and Xingjie Guo

Molecules 2020, 25(13), 2964; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25132964 - 28 Jun 2020

Cited by 5 | Viewed by 2018

Abstract

In this study, a specific and sensitive method of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the determination of penconazole enantiomers in rat plasma. The enantioseparation was achieved on a Chiralpak IC column by using acetonitrile/water (80:20, v/ [...] Read more.

In this study, a specific and sensitive method of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the determination of penconazole enantiomers in rat plasma. The enantioseparation was achieved on a Chiralpak IC column by using acetonitrile/water (80:20, v/v) as the mobile phase. Penconazole enantiomers and internal standard l-lansoprazole (IS) were detected in multiple reaction monitoring (MRM) mode with positive electrospray ionization source. The method was validated over the concentration range of 2.5–250.0 ng mL⁻¹ for penconazole enantiomers. Good linearity was obtained for both enantiomers with correlation coefficients (R) greater than 0.995. The relative error was well within the admissible range of −1.1–3.2%, and relative standard deviation was less than 6.0%. After validation, the established method was successfully applied to a stereoselective toxicokinetic study in female and male rats after oral administration of 50 mg kg⁻¹ racemic penconazole. This is the first experiment regarding the stereospecific toxicokinetic study of penconazole and the bioanalytical approach for its quantitation in vivo. Full article

(This article belongs to the Special Issue Chiral Stationary Phases for Enantioseparations: Fundamentals, Preparation, Methods, Applications and Chiral Recognition Mechanisms)

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Review

Jump to: Research

18 pages, 2201 KiB

Open AccessReview

Chiral Monolithic Silica-Based HPLC Columns for Enantiomeric Separation and Determination: Functionalization of Chiral Selector and Recognition of Selector-Selectand Interaction

by Mufarreh Asmari, Xiaoyu Wang, Natalia Casado, Marjan Piponski, Sergiy Kovalenko, Liliya Logoyda, Rasha Sayed Hanafi and Sami El Deeb

Molecules 2021, 26(17), 5241; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26175241 - 29 Aug 2021

Cited by 13 | Viewed by 3919

Abstract

This review draws attention to the use of chiral monolithic silica HPLC columns for the enantiomeric separation and determination of chiral compounds. Properties and advantages of monolithic silica HPLC columns are also highlighted in comparison to conventional particle-packed, fused-core, and sub-2-µm HPLC columns. [...] Read more.

This review draws attention to the use of chiral monolithic silica HPLC columns for the enantiomeric separation and determination of chiral compounds. Properties and advantages of monolithic silica HPLC columns are also highlighted in comparison to conventional particle-packed, fused-core, and sub-2-µm HPLC columns. Nano-LC capillary monolithic silica columns as well as polymeric-based and hybrid-based monolithic columns are also demonstrated to show good enantioresolution abilities. Methods for introducing the chiral selector into the monolithic silica column in the form of mobile phase additive, by encapsulation and surface coating, or by covalent functionalization are described. The application of molecular modeling methods to elucidate the selector–selectand interaction is discussed. An application for enantiomeric impurity determination is also considered. Full article

(This article belongs to the Special Issue Chiral Stationary Phases for Enantioseparations: Fundamentals, Preparation, Methods, Applications and Chiral Recognition Mechanisms)

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20 pages, 1199 KiB

Open AccessReview

Enantioselective Liquid Chromatographic Separations Using Macrocyclic Glycopeptide-Based Chiral Selectors

by Róbert Berkecz, Dániel Tanács, Antal Péter and István Ilisz

Molecules 2021, 26(11), 3380; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26113380 - 03 Jun 2021

Cited by 22 | Viewed by 3294

Abstract

Numerous chemical compounds of high practical importance, such as drugs, fertilizers, and food additives are being commercialized as racemic mixtures, although in most cases only one of the isomers possesses the desirable properties. As our understanding of the biological actions of chiral compounds [...] Read more.

Numerous chemical compounds of high practical importance, such as drugs, fertilizers, and food additives are being commercialized as racemic mixtures, although in most cases only one of the isomers possesses the desirable properties. As our understanding of the biological actions of chiral compounds has improved, the investigation of the pharmacological and toxicological properties has become more and more important. Chirality has become a major issue in the pharmaceutical industry; therefore, there is a continuous demand to extend the available analytical methods for enantiomeric separations and enhance their efficiency. Direct liquid chromatography methods based on the application of chiral stationary phases have become a very sophisticated field of enantiomeric separations by now. Hundreds of chiral stationary phases have been commercialized so far. Among these, macrocyclic glycopeptide-based chiral selectors have proved to be an exceptionally useful class of chiral selectors for the separation of enantiomers of biological and pharmacological importance. This review focuses on direct liquid chromatography-based enantiomer separations, applying macrocyclic glycopeptide-based chiral selectors. Special attention is paid to the characterization of the physico-chemical properties of these macrocyclic glycopeptide antibiotics providing detailed information on their applications published recently. Full article

(This article belongs to the Special Issue Chiral Stationary Phases for Enantioseparations: Fundamentals, Preparation, Methods, Applications and Chiral Recognition Mechanisms)

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