Enantioseparation of fluorinated 3-arylthio-4,4’-bipyridines: Insights into chalcogen and π-hole bonds in high-performance liquid chromatography

Peluso, Paola; Gatti, Carlo; Dessì, Alessandro; Dallocchio, Roberto; Weiss, Robin; Aubert, Emmanuel; Pale, Patrick; Cossu, Sergio; Mamane, Victor

doi:10.1016/j.chroma.2018.06.060

Cited by 23 publications

(49 citation statements)

References 38 publications

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“…Beer's group described a chiral selenium-containing receptor for enantiomeric discrimination of dicarboxylates [24]. Following previous studies on XB-based high performance liquid chromatography (HPLC) enantioseparations [31][32][33][34][35][36], our groups demonstrated that ChB can participate in the recognition process underlying the enantioseparation of sulfur-containing atropisomeric 4,4 -bipyridine 1 on a cellulose-based chiral stationary phase [37].…”

Section: Introductionmentioning

confidence: 87%

“…The thio-substituted 4,4 -bipyridine 1 was prepared in 21% yield from the readily available pentahalogeno-4,4 -bipyridine 3 [38] by selective iodine/lithium exchange and trapping with bis(pentafluorophenyl)disulfide 4, according to our own method [37]. The same conditions were used to prepare the selenium derivatives 2, 6, and 7 starting from 3 and the corresponding diselenides 5a-c (Scheme 1).…”

Section: Synthesismentioning

confidence: 99%

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Chiral Chalcogen Bond Donors Based on the 4,4′-Bipyridine Scaffold

et al. 2019

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Organocatalysis through chalcogen bonding (ChB) is in its infancy, as its proof-of-principle was only reported in 2016. Herein, we report the design and synthesis of new chiral ChB donors, as well as the catalytic activity evaluation of the 5,5′-dibromo-2,2′-dichloro-3-((perfluorophenyl)selanyl)-4,4′-bipyridine as organocatalyst. The latter is based on the use of two electron-withdrawing groups, a pentafluorophenyl ring and a tetrahalo-4,4′-bipyridine skeleton, as substituents at the selenium center. Atropisomery of the tetrahalo-4,4′-bipyridine motif provides a chiral environment to these new ChB donors. Their synthesis was achieved through either selective lithium exchange and trapping or a site-selective copper-mediated reaction. Pure enantiomers of the 3-selanyl-4,4′-bipyridine were obtained by high performance liquid chromatography enantioseparation on specific chiral stationary phase, and their absolute configuration was assigned by comparison of the measured and calculated electronic circular dichroism spectra. The capability of the selenium compound to participate in σ-hole-based interactions in solution was studied by 19F NMR. Even if no asymmetric induction has been observed so far, the new selenium motif proved to be catalytically active in the reduction of 2-phenylquinoline by Hantzsch ester.

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Section: Introductionmentioning

confidence: 87%

Section: Synthesismentioning

confidence: 99%

Chiral Chalcogen Bond Donors Based on the 4,4′-Bipyridine Scaffold

et al. 2019

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“…In the last years, our groups investigated the factors governing HPLC enantioseparation of atropisomeric halogenated 4,4’‐bipyridines on polysaccharide‐based CSPs . Following these studies, we have demonstrated the contribution of XB and chalcogen bonds (ChBs) for the enantiorecognition of analytes on CDMPC under NP elution conditions.…”

Section: Molecular Dynamics Simulations Of σ‐Hole‐driven Enantioseparmentioning

confidence: 99%

“…a) with the CDMPC, hypothesizing the occurrence of a chalcogen bond between the electrophilic sulfur on 29 and the CSP carbonyls as acceptors (Fig. ) .…”

Section: Molecular Dynamics Simulations Of σ‐Hole‐driven Enantioseparmentioning

confidence: 99%

Recent studies of docking and molecular dynamics simulation for liquid‐phase enantioseparations

et al. 2019

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Liquid‐phase enantioseparations have been fruitfully applied in several fields of science. Various applications along with technical and theoretical advancements contributed to increase significantly the knowledge in this area. Nowadays, chromatographic techniques, in particular HPLC on chiral stationary phase, are considered as mature technologies. In the last thirty years, CE has been also recognized as one of the most versatile technique for analytical scale separation of enantiomers. Despite the huge number of papers published in these fields, understanding mechanistic details of the stereoselective interaction between selector and selectand is still an open issue, in particular for high‐molecular weight chiral selectors like polysaccharide derivatives. With the ever growing improvement of computer facilities, hardware and software, computational techniques have become a basic tool in enantioseparation science. In this field, molecular docking and dynamics simulations proved to be extremely adaptable to model and visualize at molecular level the spatial proximity of interacting molecules in order to predict retention, selectivity, enantiomer elution order, and profile noncovalent interaction patterns underlying the recognition process. On this basis, topics and trends in using docking and molecular dynamics as theoretical complement of experimental LC and CE chiral separations are described herein. The basic concepts of these computational strategies and seminal studies performed over time are presented, with a specific focus on literature published between 2015 and November 2018. A systematic compilation of all published literature has not been attempted.

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“…In recent years, the computational approach applied in the study of DCs has been reported in the literature as a complementary tool to HPLC analyses. [10][11][12][13][14][15][16][17][18][19][20][21][22][23] The main goal of these theoretical works is to aid in the elucidation mechanism of chiral discrimination, as well as in the EEO, by obtaining structural and energetic parameters at the molecular level involved in the complexation process.…”

Section: Introductionmentioning

confidence: 99%

Elucidation of the chromatographic enantiomer elution order for praziquantel: An experimental and theoretical assessment

et al. 2020

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In this work, we have studied both experimentally and theoretically the praziquantel (PZQ) chiral discrimination. According to the main results, the enantioseparation of PZQ was efficiently optimized by HPLC on the reverse phase from the Chiralpak IB column, which has cellulose tris (3,5‐dimethylphenylcarbamate) (CDMPC) as a chiral selector. The thermodynamic and structural parameters obtained via density functional theory (DFT) calculations pointed out the chiral discrimination as well as the enantiomeric elution order of PZQ, thus elucidating the experimental data and validating our proposed method. Finally, the hydrogen bonds and π‐π stacking interactions played a key role in the discrimination between the PZQ diastereomeric complexes formed.

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Enantioseparation of fluorinated 3-arylthio-4,4’-bipyridines: Insights into chalcogen and π-hole bonds in high-performance liquid chromatography

Cited by 23 publications

References 38 publications

Chiral Chalcogen Bond Donors Based on the 4,4′-Bipyridine Scaffold

Chiral Chalcogen Bond Donors Based on the 4,4′-Bipyridine Scaffold

Recent studies of docking and molecular dynamics simulation for liquid‐phase enantioseparations

Elucidation of the chromatographic enantiomer elution order for praziquantel: An experimental and theoretical assessment

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