•Two native β-CD CSPs with similar surface concentration were prepared at CD's C2 and C6 positions via click chemistry.•The surface CD orientation plays an essential role in CSP's enantio-differentiation ability.•Elution order of specific racemates can be reversed by tuning the surface CD orientation.•MD simulation provides a robust tool for investigation of the CD's discrimination mechanism under “real” mobile phase.A novel native cyclodextrin (CD) chiral stationary phase (CSP) with single triazole-bridge at CD C2 position (CSP1) was prepared by anchoring mono(2A-azido-2A-deoxy)-β-CD onto alkynyl silica via click chemistry. The effect of CD orientation on single layer CD-CSP's enantioseparation was comprehensively investigated using CSP1 (reversed orientation) and our previously reported CSP2 (C6 single triazole-bridge, normal orientation) as well as a commercial CD-CSP (Cyclobond I 2000, hybrid orientation) by separating several groups of analytes in chiral high performance liquid chromatography. It is found that the CD orientation on silica surface plays an important role in separating different racemates. CSP2 with normal CD orientation affords best separation for isoxazolines while CSP1 with reversed CD orientation better separates naringenin, hesperetin and Tröger's base. CSP2 and Cyclobond I 2000 show comparable separation ability for dansyl amino acids while poor separation was found on CSP1. Besides, molecular dynamics simulation was performed under “real” separation conditions using flavanone as model analyte to reveal the essential factors for CD's chiral discrimination behaviors.Download high-res image (275KB)Download full-size image

The preparation of two novel multifunctional cyclodextrin (CD) separation materials and their ultimate enantioseparation performances in high performance liquid chromatography are reported. A mild thiol–ene click reaction was used to anchor 1-allylimidazolium-per(p-methyl)phenylcarbamoylated-β-CD and 1-allylimidazolium-per(p-chloride)phenylcarbamoylated-β-CD onto thiol-modified porous silica giving structurally well-defined stable cationic multifunctional CD chiral stationary phases (CSP1 and CSP2 respectively). These covalently bonded CD phases have typical interaction modes such as H-bonding, π–π effect, electrostatic and dipole–dipole interactions as well as steric effects which result in superior chiral resolution for a variety of chiral compounds in different separation modes. In a reverse-phase mode, both CSPs exhibited excellent separation abilities for isoxazolines, flavonoids, β-blockers, and some other neutral and basic racemates. In a polar-organic mode, isoxazolines and flavonoids were well resolved. CSP1 with an electron-rich phenyl substitution on the CD rims gave a better resolution for isoxazolines whereas CSP2 with an electron-deficient phenyl substitution on the CD rims gave better resolution for flavonoids. Among isoxazolines, 4ClPh-OPr gained a high selectivity and resolution up to 18.6 and 38.7, respectively, which is an amazing result for CD enantioseparation materials.

•Four single thioether bridged cationic CD-CSPs are fabricated by mild thiol-ene click chemistry.•p-Methylphenylcarbamoylated CD-CSP can be readily prepared by a post-synthetic carbamoylation approach with a high surface loading.•The complementarity between native and phenylcarbamoyl CD significantly broadens the separation profile of CD-CSPs.•CD-CSPs with well-defined structures afford better enantioseparation ability.The preparation and evaluation of four single thioether bridged cationic cyclodextrin (CD) chiral stationary phases (CSPs) with different spacer length, selector concentration and rim functionalities are reported. Mono-6-(1-vinyl/allyl/butenylimidazolium)-β-CDs chloride were synthesized and clicked onto thiol silica to form three novel cationic native-CD-CSPs (CSP1, CSP2 and CSP3) and a post-synthetic phenylcarbamoylation of CSP2 was performed affording CSP4. The enantioseparation ability of the as-prepared CSPs were evaluated in high performance liquid chromatography (HPLC) by separating over forty enantiomers including isoxazolines, dansyl amino acids, flavonoids, tröger’s base, 4-chromanol, bendroflumethiazide and styrene oxide. Most of the enantiomers were well resolved with the resolution (Rs) of 4NPh-OPr reaching 12.68. The effects of spacer length, selector concentration and rim functionalities on the enantioseparation were investigated. A comparison of the current CSP with a commercial column (Cyclobond I 2000) was also conducted to reveal the superiors enantioselectivity of the as-prepared CSPs.

A novel aggregation induced emission (AIE) active cyclodextrin (CD) was synthesized by combining tetraphenylethene (TPE) and CD via click chemistry. The new material, which is the first reported clicked AIE probe for the specific detection of Cd2+, exhibits an excellent selective turn-on fluorescence response to Cd2+ in neutral environments, with a low detection limit of 0.01 µM.

•The first native-phenylcarbamoylated bilayer CD CSP.•The CSP provides interactions like H-bonding, π–π, dipole–dipole, steric and inclusion effects.•Phenylcarbamoylated CD serves as a moiety to enhance the separation ability of native CD.•An encouraging way for construction of functional materials from molecules with bulky moieties.This paper reports an effective approach for the fabrication of a novel hybrid bilayer cyclodextrin (CD) chiral stationary phase (CSP), where native and perphenylcarbamoylated-β-CD were successively immobilized onto silica surface via a two-step click approach to form a bilayer CD structure. By decorating the bulky phenylcarbamoylated CD onto the unmodified CD silica, the CSP can provide multiple interaction sites such as H-bonding (OH, CO, NH), steric effects, π–π, dipole–dipole and inclusion complexation interactions, which help to broaden the CSP's enantioselectivity profile and enhance the enantioselectivity to some specific analytes. A group of enantiomer pairs such as isoxazolines, bendroflumethiazide, indoprofen, diperodon, fenoterol, atropine, styrene oxide and dansyl amino acids can be baseline or partially separated on the current CSP under reversed phase high performance liquid chromatography (RP-HPLC). The selectivity and resolution of 4NPh-OPr reached 5.25 and 13.97, which is an exciting achievement for the enantioseparations by CD CSPs.

The current work demonstrates a “one-pot” click synthetic procedure for the preparation of triazole bridged cyclodextrin (CD) chiral stationary phases (CSPs) and their application for efficient chiral differentiation of clopidogrel enantiomers under reversed-phase high performance liquid chromatography (HPLC). It was found that native-CD-CSPs and methylated-CD-CSPs showed good enantioselectivity towards clopidogrel enantiomers with acetonitrile (ACN)/water and methanol (MeOH)/water as mobile phases, respectively, while the more versatile phenylcarbamoylated-CD-CSP cannot resolve the enantiomers due to the steric hindrance of bulky phenylcarbamate moieties. Solvent selection plays an important role in CSP chiral recognition ability towards clopidogrel enantiomers. 6-Hydroxyl moieties on CD rims were found to participate in the chiral recognition process. The optimal chiral resolution (Rs) was improved to 1.95 by transferring the separation from 5 μm native-CD-CSPs to 3 μm native-CD-CSPs with ACN/buffer as the mobile phase.

•First demonstration of a novel native CD CSP with cationic imidazolium on the linking bridges.•Cationic moiety strongly enhances the retention and resolution towards anti-charged analytes.•Thiolether linkage and cationic moiety exhibit good stability under various conditions.•This CSP affords improved separation compared to the previous triazole-bridged CD-CSP.This work is the first demonstration of a simple thiol–ene click chemistry to anchor vinyl imidazolium β-CD onto thiol silica to form a novel cationic native cyclodextrin (CD) chiral stationary phase (CSP). The CSP afforded high enantioseparation ability towards dansyl (Dns) amino acids, carboxylic aryl compounds and flavonoids in chiral HPLC. The current CSP demonstrates the highest resolving ability (selectivity >1.1, resolution >1.5) towards Dns amino acids in a mobile phase buffered at pH = 6.5, with the resolution of Dns-dl-leucine as high as 6.97. 2,4-dichloride propionic acid (2,4-ClPOPA) was well resolved with the selectivity and resolution of 1.37 and 4.88, respectively. Compared to a previously reported native CD-CSP based on a triazole linkage, the current cationic CD-CSP shows a stronger retention and higher resolution towards acidic chiral compounds, ascribed to the propitious strong electrostatic attraction. Stability evaluation results indicated that thiol–ene reaction can provide a facile and robust approach for the preparation of positively charged CD CSPs.

•The first demonstration of a surface-up bilayer CD structure on silica surfaces.•Synergistic effect of the duplex CDs affords superior enantioselectivity and adsorption ability.•A practical approach to design novel functional materials with cooperative CD dimers.A new generation of triazole-bridged bilayer cyclodextrins (CDs) chiral stationary phase (CSP) material was constructed via a surface-up ‘click’ approach. The synergistic effect of the tandem-inverted duplex CDs was evidenced by the superior enantioresolution ability toward selected chiral compounds and the enhanced adsorption ability toward hesperetin. The enantioselectivities of dansyl amino acids and aryl carboxylic acids were promoted by 10–20%, while the resolutions of some aryl carboxylic acids were significantly increased from 0 to 3.5 and beyond. Adsorption experiments of hesperetin reveal that the binding ability of the target bilayer CDCSP is nearly 2.8 times than that of the single layer CDCSP. The current work provides a simple and practical approach to design and synthesize novel functional materials with cooperative CD dimers on surfaces.

Isoxazoline derivatives have been disclosed in the art as having acaricidal and insecticidal activity and as potential precursors for the syntheses of natural products. This work first demonstrates the chiral resolution of isoxazoline derivatives that had not been studied before on native cyclodextrin (CD) chiral stationary phases (CSPs). Two structurally well-defined CSPs based on native CD were prepared via different click procedures and applied for the enantioseparation of isoxazolines. Most of the studied isoxazolines were found to be well resolved (Rs > 1.5) under reversed phase mode, especially 4NPh-OPr, which exhibits the best enantioselectivity and resolution (α = 2.22; Rs = 4.16). Optimal resolutions were achieved by evaluating the influences of mobile phase composition, substitution moieties and CSP linkages on the separation. This contribution verifies that excellent enantioseparation of isoxazolines can be accomplished on smartly designed native CD-CSP, which provides a facile and economic way to obtain enantiopure isoxazoline derivatives.

The current article reviews the development and applications of novel cyclodextrin chiral stationary phases (CD-CSPs) in liquid chromatography (LC), capillary electrochromatography (CEC), gas chromatography (GC) and supercritical fluid chromatography (SFC) over the period of January 2007 to March 2012. The synthetic routes of CD-CSPs, as well as the presence of selective functional groups in effecting inclusion complexation and molecular interactions have been found to exert profound influence in the enantioseparation process. In this article, various synthetic and functional groups immobilization strategies of novel CD-CSPs, and their applications in chiral resolution using different chromatography techniques are discussed. After introducing the topic in Section 1, Section 2 describes novel CD-CSPs in LC applications, where the CSPs are classified according to its coating approaches (physical and chemical manners) for ease of readership. Section 3 discusses recent development of CD-CSPs in open tubular CEC (OT-CEC), packed-bed CEC (P-CEC), pseudostationary phase CEC (PSP-CEC) and monolithic CEC. The last part illustrates novel CD-CSPs in gas chromatography (GC) and supercritical fluid chromatography (SFC).Highlights► Review of novel cyclodextrin chiral stationary phases (CD-CSPs) in chromatography. ► Review period from January 2007 to March 2012. ► The synthetic strategy of CD-CSPs was found to affect enantioseparation. ► CD functional groups affect inclusion complexation and molecular interactions.

The current work demonstrates a “one-pot” click synthetic procedure for the preparation of triazole bridged cyclodextrin (CD) chiral stationary phases (CSPs) and their application for efficient chiral differentiation of clopidogrel enantiomers under reversed-phase high performance liquid chromatography (HPLC). It was found that native-CD-CSPs and methylated-CD-CSPs showed good enantioselectivity towards clopidogrel enantiomers with acetonitrile (ACN)/water and methanol (MeOH)/water as mobile phases, respectively, while the more versatile phenylcarbamoylated-CD-CSP cannot resolve the enantiomers due to the steric hindrance of bulky phenylcarbamate moieties. Solvent selection plays an important role in CSP chiral recognition ability towards clopidogrel enantiomers. 6-Hydroxyl moieties on CD rims were found to participate in the chiral recognition process. The optimal chiral resolution (Rs) was improved to 1.95 by transferring the separation from 5 μm native-CD-CSPs to 3 μm native-CD-CSPs with ACN/buffer as the mobile phase.

A novel aggregation induced emission (AIE) active cyclodextrin (CD) was synthesized by combining tetraphenylethene (TPE) and CD via click chemistry. The new material, which is the first reported clicked AIE probe for the specific detection of Cd2+, exhibits an excellent selective turn-on fluorescence response to Cd2+ in neutral environments, with a low detection limit of 0.01 µM.