Surface-up click access to allylimidazolium bridged cyclodextrin dimer phase for efficient enantioseparation.

In this work, a novel allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase was fabricated via a surface-up thiol-ene click chemistry reaction between 7-SH-ß-cyclodextrin and 1-allylimidazole-ß-cyclodextrin bonded on a silica surface. The structure of the allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase was characterized by Fourier transform infrared spectra, 13 C nuclear magnetic resonance, thermogravimetric analysis, and elemental analysis. Its chiral chromatographic performances were systematically evaluated by separating 35 racemic analytes including isoxazolines, dansyl-amino acids, and flavanones under reversed-phase high-performance liquid chromatography. Compared with the corresponding bottom and top layer of the ß-cyclodextrin stationary phase, the allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase afforded significantly accentuated chiral recognition ability due to its abundant hydrogen bond sites, electrostatic interactions, and synergistic inclusion. Furthermore, the allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase showed better enantioseparation ability compared to other reported bridged cyclodextrin stationary phases. In particular, Ar-Phs and dansyl-amino acid could be completely separated by allylimidazolium-bridged bis(ß-mono-6A -deoxy-6-allylimidazolium-ß-cyclodextrin chiral stationary phase) chiral stationary phase with high resolutions of 1.14-7.20 and 3.16-5.82, respectively. Molecular docking reveals that good enantioseparation ability arises from the different interaction modes and the synergistic effect of allylimidazolium-bridged bis(ß-cyclodextrin) chiral stationary phase.

Switchable Separation Strategy via Host-Guest Locks.

Universal separation strategies are the ultimate goal in separation science. However, there is always a tradeoff between universality and selectivity due to the negative influence among different recognition domains. With the goal of universal separation in mind, an unprecedented, switchable, and versatile separation strategy using reversible supramolecular host-guest interactions has been developed. These adjustable separation mediums were prepared using surface-grafted cationic cyclodextrin to firmly bind negatively charged adamantane derivatives. By changing guest structures, the surface functionality of the separation medium can be precisely regulated to be selective for a variety of substrates including chiral or achiral molecules, thus producing satisfactory single-column universality. This method offers a new approach to move beyond conventional separation methodologies and should stimulate the design of switchable functional materials.

[Recent advances in the research of chromatographic separation materials based on click chemistry].

Since Nobel Laureate K. B. Sharpless first introduced the concept of click chemistry in 2001, such reactions have become a powerful modular synthesis tool. Click chemistry reactions have rapidly expanded into many scientific fields, such as materials and life science, owing to their distinct advantages, which include mild conditions, fast reaction rates, high yields, low by-product generation, and simple separation and purification procedures. Nowadays, click chemistry reactions have become an essential means of designing and preparing separation materials; thus, interest in this synthetic technique has quickly grown. Here, the development of click chemistry and its unique advantages are briefly described firstly. The reports on click chemistry-based chromatographic separation materials published in the past five years are then systematically reviewed, focusing on two major separation fields: column chromatography and membrane chromatography. Meanwhile, recent advances in the separation materials obtained from three common types of click reactions, namely, azido-alkyne, thiol-alkene, and thiol-alkyne, are summarized. Finally, an outlook on the future of click chemistry is provided in developing efficient chromatographic separation materials.

Surface-up construction of quinine bridged functional cyclodextrin for single-column versatile enantioseparation.

Seeking for single-column versatile chiral separation methodology is the ultimate goal for analysts engrossed in enantioseparation. However, the versatility and selectivity are always contradictory due to negative influence among the recognition domains and the relatively low surface concentrations in a limited support surface area. Herein, we reported a novel series of quinine (QN) bridged cyclodextrin (CD) chiral stationary phases (CSPs) with satisfied surface concentration of both selectors, prepared via a facile surface-up 'thiol-ene click' approach, where QN and CD can not only nicely exhibit their individual resolution capability but also afford possible synergism in resolving difficult-to-separate analytes. QN bridged phenylcarbamoylated CD CSP exhibits powerful resolution ability by positive combining the resolving ability of QN and functional CD and achieves the resolution of almost a double number of racemates over QN or CD CSPs. Meanwhile, it exhibits comparable and even better chiral selectivity over the widely used chemical-bonded chiral column (CHIRALPAK® IA, CHIRALPAK® IB and CHIRALPAK® IC of Daicel) for the studied analytes. This work thus advances the duplex QN-CD structure as a relatively versatile platform for chiral resolution and commendably promotes the design of functional CSPs with chiral molecular bridge.

Click preparation of multiple-thioether bridged cyclodextrin chiral materials for efficient enantioseparation in high-performance liquid chromatography.

A highly efficient covalent immobilization procedure is considered as an essential tool for obtaining stable and reliable cyclodextrin (CD) chiral stationary phases (CSPs). This work reports the "thiolene" click immobilization of heptakis(6-mercapto-6-deoxy)-ß-CD-CSP onto alkene functional silica to afford novel multiple-thioether bridged CD CSPs by controlling the surface CD concentration. Solid-state NMR, FTIR, TGA and X-ray photoelectron diffraction spectroscopy (XPS) results proved the successful preparation of the desired CSPs with different surface CD loadings. The surface CD concentrations were calculated to be 0.49 and 0.68 µmol m-2 according to the elemental analysis results. More than 60 chiral enantiomers including isoxazolines, chiral lactides, chiral ketones, dansyl amino acids, small molecule acids and alkalis as well as some flavonoids were resolved or partially separated in the reversed-phase HPLC mode. Compared with the previously prepared single thiolene bridged CD-CSP, the current multiple-thioether CD-CSP afforded much better enantioseparation ability due to the existence of the thiol moiety and a confined structure.

Evaluation of the accumulation of disulfiram and its copper complex in A549 cells using mass spectrometry.

The famous alcohol-aversion drug disulfiram (DSF) is a promising candidate for repurposing in cancer therapy, as indicated by many ongoing and completed clinical trials. Existing researches focus on demonstrating that the anti-cancer activity of DSF is enhanced by copper ions, or solving the problem that DSF is easily decomposed in the body to lose its activity. However, the metabolic kinetics of its ultimate anti-cancer metabolite DDC-Cu (bis-diethyldithiocarbamate-copper) in cells and how it exerts anti-cancer mechanisms remain unclear. In this work, mass spectrometric evaluation of the intracellular and extracellular accumulation of DSF and its copper complex DDC-Cu was performed. Combined with cytotoxicity assay, staining analysis and flow cytometry, we found that DDC-Cu could easily pass through the cell membrane of A549 cells, and accumulate intracellularly for a long time. This process can lead to cellular morphological changes, an increase in ROS content, cell cycle arrest in the G0/G1 phase and apoptosis. Besides, molecular cancer-relevant targets of DDC-Cu in cancer cells were further discussed. This work investigated the cytotoxic mechanism of DDC-Cu, which has important clinical significance for its application in cancer therapy.

A Case Study on Preoperative Acupuncture in Reducing the Risk of Operation.

The present study investigated the role of acupuncture as a pretreatment prior to surgery. The 72-y-old female was diagnosed with bilateral breast cancer and suffered from severe anxiety before the operation. The blood pressure of the patient was elevated due to anxiety. With concern regarding the potential risk of planned surgery, the operation was cancelled. Alternatively, acupuncture was used to reduce her blood pressure and relieve the anxiety. Later on, the patient was examined by an anesthetist, who confirmed that the operation could be carried out as planned. Thus, acupuncture is a promising add-on treatment that may stabilize the condition of patients during surgery.