Preparation of Novel Chiral Stationary Phases Based on the Chiral Porous Organic Cage by Thiol-ene Click Chemistry for Enantioseparation in HPLC.

Porous organic cages (POCs) are an emerging class of porous materials that have aroused considerable research interest because of their unique characteristics, including good solubility and a well-defined intrinsic cavity. However, there have so far been no reports of chiral POCs as chiral stationary phases (CSPs) for enantioseparation by high-performance liquid chromatography (HPLC). Herein, we report the first immobilization of a chiral POC, NC1-R, on thiol-functionalized silica using a mild thiol-ene click reaction to prepare novel CSPs for HPLC. Two CSPs (CSP-1 and CSP-2) with different spacers have been prepared. CSP-1, with a cationic imidazolium spacer, exhibited excellent enantioselectivity for the resolution of various racemates. Twenty-three and 12 racemic compounds or chiral drugs were well enantioseparated on the CSP-1-packed column under normal-phase and reversed-phase conditions, respectively, including alcohols, diols, esters, ethers, ketones, epoxides, organic acids, and amines. In contrast, chiral resolution using CSP-2 (without a cationic imidazolium spacer)-packed column B was inferior to that of column A, demonstrating the important role of the cationic imidazolium spacer for chiral separation. The chiral separation capability of column A was also compared with that of two most popular commercial chiral columns, Chiralpak AD-H and Chiralcel OD-H, which exhibits good chiral recognition complementarity with the two commercial chiral columns. In addition, five positional isomers dinitrobenzene, nitroaniline, chloroaniline, bromoaniline, and iodoaniline were also well separated on column A. The effects of temperature, mobile phase composition, and injected analyte mass for separation on column A were investigated. Column A also showed good stability and reproducibility after repeated injections. This work demonstrates that chiral POCs are promising chiral materials for HPLC enantioseparation.

Superficial chiral etching on an achiral metal-organic framework for high-performance liquid chromatography enantioseparations.

Chiral metal-organic frameworks have shown great potential in enantioselective separation and asymmetric catalysis due to their diverse and adjustable structures with abundant chiral recognition sites. Herein, a new chiral post-synthetic modification was used for preparing an achiral@chiral metal-organic frameworks core-shell composite [Cu3 (Btc)2 ]@[Cu2 ((+)-Cam)2 Dabco] by a superficial chiral etching method. The [Cu3 (Btc)2 ]@[Cu2 ((+)-Cam)2 Dabco] composite was utilized as a novel chiral stationary phase for HPLC enantioseparation. Various racemates were separated on the [Cu3 (Btc)2 ]@[Cu2 ((+)-Cam)2 Dabco]-packed column (column A). It exhibited good chiral resolving ability toward many different kinds of racemates, especially chiral drugs. Among them, the highest resolution value for 1,2-diphenyl-1,2-ethanediol reaches 2.70. The relative standard deviations of retention time and peak area for repeated separation of 1,2-diphenyl-1,2-ethanol were 0.45% and 0.81%, respectively. Compared with the resolution ability of [Cu2 ((+)-Cam)2 Dabco]-packed column (column B), column A shows higher column efficiency and better separation performance than those of column B. The results indicated that the [Cu3 (Btc)2 ]@[Cu2 ((+)-Cam)2 Dabco] as a stationary phase can greatly improve the column efficiency and chiral resolution ability of chiral metal-organic frameworks, which demonstrated that the superficial chiral etching as an economic and efficient strategy opens up a new way for the application of metal-organic frameworks.

A chiral porous organic polymer COP-1 used as stationary phase for HPLC enantioseparation under normal-phase and reversed-phase conditions.

A spherical chiral porous organic polymer (POPs) COP-1 is synthesized by the Friedel-Crafts alkylation reaction of Boc-3-(4-biphenyl)-L-alanine (BBLA) and 4,4'-bis(chloromethyl)-1,1'-biphenyl (BCMBP), which was used as a novel chiral stationary phase (CSPs) for mixed-mode high-performance liquid chromatography (HPLC) enantioseparation. The racemic compounds were resolved in normal-phase liquid chromatography (NPLC) using n-hexane/isopropanol as mobile phase and reversed-phase liquid chromatography (RPLC) using methanol/water as mobile phase. The COP-1-packed column exhibited excellent separation performance toward various racemic compounds including alcohols, amines, ketones, esters, epoxy compounds, organic acids, and amino acids in NPLC and RPLC modes. The effects of analyte mass and column temperature on the separation efficiency of racemic compounds were investigated. In addition, the chiral resolution ability of the COP-1-packed column not only can be complementary in RPLC/NPLC modes but also exhibit a good chiral recognition complementarity with Chiralpak AD-H column and chiral porous organic cage (POC) NC1-R column. The relative standard deviations (RSD) (n = 5) of the retention time, resolution value, and peak area by repeated separation of 1-(4-chiorophenyl)ethanol are all below 3.0%. The COP-1 column shows high column efficiency (e.g., 17,320 plates m-1 for 1-(4-chlorophenyl)ethanol on COP-1 column in NPLC), high enantioselectivity, and good reproducibility toward various racemates. This work demonstrates that chiral POPs microspheres are promising chiral materials for HPLC enantioseparation.

A chiral metal-organic framework core-shell microspheres composite for high-performance liquid chromatography enantioseparation.

The unique features of uniform and adjustable cavities, abundant chiral active sites, and high enantioselectivity make chiral metal-organic frameworks popular as an emerging candidate for enantioselective separation. However, the wide particle size distribution and irregular shape of as-synthesized metal-organic frameworks result in low column efficiency, undesired chromatographic peak shape, and high column backpressure of such metal-organic frameworks packed columns. Herein, we report the fabrication of chiral core-shell microspheres [Cu2 (d-Cam)2 (4,4'-bpy)]n @SiO2 composite for high-performance liquid chromatography enantioseparation to overcome the above-mentioned problems. The [Cu2 (d-Cam)2 (4,4'-bpy)]n @SiO2 packed column gave high-resolution separation of racemates under low column backpressure (10-22 bar), indicating its synergistic effect of the good column packing property of the SiO2 microspheres and the chiral recognition ability of [Cu2 (d-Cam)2 (4,4'-bpy)]n crystals. Thirteen kinds of chiral compounds including alcohols, amines, ketones, epoxides, and organic bases were well separated with good peak shapes and high column efficiency (18200 plates/m for 1-(9-anthryl)-2,2,2-trifluoroethanol) on the [Cu2 (d-Cam)2 (4,4'-bpy)]n @SiO2 packed column. Among them, seven pairs of enantiomers achieved baseline separation and the resolution value for 1-(9-anthryl)-2,2,2-trifluoroethanol reached 11.22. Some effects such as column temperature, and analytes mass on the enantioseparations have been investigated. In addition, the [Cu2 (d-Cam)2 (4,4'-bpy)]n @SiO2 packed column exhibited good stability and repeatability for the separation of chiral compounds. The relative standard deviations for five replicate separations of 1-phenylethanol were less than 1.0, 1.5, 3.0, and 2.0% for the retention time, peak area, number of theoretical plates, and resolution, respectively. The research results demonstrated the development of chiral metal-organic frameworks core-shell microspheres composite provide a promising platform for their practical application in chiral separation fields.

Glutamine induces remodeling of tight junctions in Caco-2 colorectal cancer cell.

Malignant cells often exhibit significant metabolic alterations, including the utilization of different nutrients to meet energetic and biosynthetic demands. Recent studies have shown that glutamine can support primary colorectal tumor growth and also serve as an alternate energy source during distant metastasis under glucose-limited conditions. However, the overall effects of glutamine on cancer cell physiology are not completely understood. In this study, we investigated how glutamine impacts epithelial integrity in colorectal cancer cells under glucose deprivation. Human colorectal cancer (Caco-2) cells were grown to confluency in transwells and cultured in glucose/pyruvate-free DMEM with various glutamine concentrations (0-50 mM). Cell viability was assessed, and monolayer integrity was examined in terms of transepithelial resistance (TER) and paracellular permeability. Tight junction (TJ) component proteins were examined by immunofluorescence staining and Western blotting. A dose-dependent decrease in TER was observed in Caco-2 cells, but paracellular permeability was not affected after 24 h incubation with glutamine. At the same time, the TJ proteins, zonula occludens (ZO)-1 and Claudin-1, showed lateral undulations and punctate staining patterns accompanied by enlargement of cellular and nuclear sizes. Furthermore, decreased protein levels of ZO-1, but not claudin-1, were found in detergent-insoluble cellular fractions. Notably, the decreased TER and alterations in TJ structure were not associated with cell viability changes. Moreover, the addition of glutamate, which is produced by the first step of glutamine catabolism, had no impact on TER. Our results suggested that the enteral glutamine may play an important role in the regulation of TJ dynamics in colorectal cancer cells.

A chiral metal-organic cage [Fe4L6](ClO4)8 used for capillary gas chromatographic separations.

Metal-organic cages (MOCs), as a promising class of crystalline porous materials with well-defined cavities, have attracted wide attention due to their multifarious potential applications in gas storage, host-guest chemistry, molecular recognition, separation, catalysis, sensing, and drug delivery and so on. Herein, we report that a chiral MOC [Fe4L6](ClO4)8 coated capillary column was fabricated for high-resolution gas chromatographic separation of various analytes, including n-alkanes, n-alcohols, positional isomers, aromatic hydrocarbon mixture, especially for racemic compounds. A series of racemic compounds such as alcohols, epoxides, aldehydes, ketones, ethers, esters, alkenes, sulfoxides and amino acid derivatives could be well separated on the [Fe4L6](ClO4)8 coated capillary column with high enantioselectivity and good reproducibility. Comparing the chiral resolution ability of the MOC [Fe4L6](ClO4)8 coated column with the commercial ß-DEX 120 column and the porous organic cage (POC) CC10 coated column, the chiral MOC column can be complementary to the two different types of columns. The results show that the chiral MOC [Fe4L6](ClO4)8 exhibited excellent separation performance toward a wide range of organic compounds, which will be very attractive as a new chiral separation media and has potential application prospects in separation science.

Chiral core-shell microspheres ß-CD-COF@SiO2 used for HPLC enantioseparation.

Chiral covalent organic frameworks (CCOFs) have potential application in enantioseparation due to their advantages, such as large surface area, abundant chiral recognition sites and good chemical stability in organic solvents. However, the application of CCOFs in high performance liquid chromatography (HPLC) for enantioseparation has been rarely reported because of the shortcomings of CCOFs, such as light weight, irregular shape, and wide particle size distribution. In order to overcome the above shortcomings, a one-pot synthetic method was adopted to prepare a core-shell composite (ß-CD-COF@SiO2) via the growth of chiral ß-CD COF on the surface of amino-functionalized SiO2 microspheres. The as-prepared ß-CD-COF@SiO2 microspheres were used as a stationary phase for HPLC enantioseparation. The resolution ability of the ß-CD-COF@SiO2-packed column toward various chiral compounds was investigated using n-hexane/isopropanol as the mobile phase. The results show that the chiral ß-CD-COF@SiO2-packed column exhibited excellent chiral recognition ability for 24 pairs of chiral compounds with good reproducibility. These successful applications indicate that the preparation of the chiral COFs@SiO2 core-shell microspheres as a novel stationary phase for enantioseparation has good application prospects in HPLC.

Clothing Landmark Detection Using Deep Networks With Prior of Key Point Associations.

This paper considers a problem of landmark point detection in clothes, which is important and valuable for clothing industry. A novel method for landmark localization has been proposed, which is based on a deep end-to-end architecture using prior of key point associations. With the estimated landmark points as input, a deep network has been proposed to predict clothing categories and attributes. A systematic design of the proposed detecting system is implemented by using deep learning techniques and a large-scale clothes dataset containing 145 000 upper-body clothing images with landmark annotations. Experimental results indicate that clothing categories and attributes can be well classified by using the detected landmark points, which are associated with regions of interest in clothes (e.g., the sleeves and the collars) and share robust learning representation property with respect to large variances of human poses, nonfrontal views, or occlusion. A comprehensive performance evaluation over two newly released datasets is carried out in this paper, showing that the proposed system with deep architecture for clothing landmark detection outperforms the state-of-the-art techniques.