Capillary electrochromatography, which combined the high selectivity of high‐performance liquid chromatography and the high separation efficiency of capillary electrophoresis, is an attractive ...separation tool. In this review, the developments on monolithic and open tubular capillary electrochromatography during 2017 to August 2019 are summarized. Considering the development of novel stationary phases is the most active research field in capillary electrochromatography, monolithic capillary electrochromatography is classified according to the polymer‐based and hybrid monolithic columns, while open‐tubular capillary electrochromatography is categorized by cyclodextrin, silica, polymer, nanomaterials, microporous materials, and biomaterials‐based open tubular columns.
The difluoromethyl group (CF2H) is of great interest in the area of medicinal chemistry. However, the investigation of molecular scaffolds containing this group has been hampered by the limitation of ...synthetic methods for the introduction of CF2H into heteroarenes. Herein we disclose a new strategy for the direct introduction of a difluoromethyl group into heteroarenes via the copper-mediated C–H oxidative difluoromethylation of heteroarenes with TMSCF2H. This mild and regioselective method enables the convenient synthesis of a range of difluoromethylated heteroarenes in high yields. The usage of 9,10-phenanthrenequinone (PQ) as an oxidant is critical to the success of this new difluoromethylation reaction.
Aromaticity lost: In the presence of {Ir(cod)Cl}2 and a binol‐derived phosphoramidite ligand, spirocyclohexadienone derivatives were obtained with up to 97 % ee through iridium‐catalyzed ...intramolecular asymmetric allylic dearomatization of phenols (see scheme; cod=cycloocta‐1,5‐diene).
•Summarize the applications of magnetic solid-phase extraction in phytochemical analysis.•Introduce different preparation methods for the functionalized magnetic nanoparticles.•Discuss the adsorption ...mechanism and performance of the material in the extraction
Sample preparation such as isolation and pre-concentration is a crucial step for the phytochemical analysis. Magnetic solid-phase extraction (MSPE) has received considerable attention, mainly due to its phase separation more conveniently by facile magnetic decantation as compared to traditional SPE. This review focused on the recent applications of MSPE in sample preparation for the analysis of phytochemical compounds in plants, biological samples and Chinese herbal preparations. In addition, the enzymes immobilized on the magnetic materials and used for the biospecific extraction of enzyme inhibitors were also discussed. The information summarized in this article may provide a reference to the further applications of MSPE in phytochemical analysis.
Profiling of lipid–water partition coefficients (KL/W) of drugs is an essential issue during the early stage of drug development. In this study, two liposomes, including ...1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC) + cholesterol (Chol) (DSPC/Chol liposomes) and soybean lecithin (SPC) + Chol (SPC/Chol liposomes), were prepared for the liposome electrokinetic chromatography (LEKC) analysis, and the logarithm of lipid–water partition coefficients (log KL/W) of neutral and ionic drugs were determined based on an iterative method. The log KL/W values determined by the SPC/Chol or DSPC/Chol liposomes LEKC were linearly fitted, which showed a good fitting coefficient (R2 = 0.89). Furthermore, the linear relationship between the data obtained from LEKC system and octanol–water system, immobilized artificial membrane, Caco‐2 cell model, and software prediction was analyzed, respectively. Results illustrated that DSPC/Chol liposomes or SPC/Chol liposomes had a good linear relationship with Caco‐2 cell model, and R2 was 0.81 and 0.72, respectively. Moreover, the linear free energy relationship analysis suggested that the solute volume, hydrogen bond basicity, and J– were the main descriptors that drove the partition process of solutes in the SPC/Chol or DSPC/Chol LEKC system. In addition, the normalized properties of the SPC/Chol and DSPC/Chol LEKC systems through linear free energy relationship analysis were very close. In short, DSPC/Chol liposomes are more suitable for simulating cell membranes than SPC/Chol liposomes, and the developed LEKC is an effective partitioning model for measuring the log KL/W of drugs.
Reactive oxygen species (ROS) burst from mitochondrial complex I is considered the critical cause of ischemia/reperfusion (I/R) injury. Ginsenoside Rb1 has been reported to protect the heart against ...I/R injury; however, the underlying mechanism remains unclear. This work aimed to investigate if ginsenoside Rb1 attenuates cardiac I/R injury by inhibiting ROS production from mitochondrial complex I.
In
experiments, mice were given ginsenoside Rb1 and then subjected to I/R injury. Mitochondrial ROS levels in the heart were determined using the mitochondrial-targeted probe MitoB. Mitochondrial proteins were used for TMT-based quantitative proteomic analysis. In
experiments, adult mouse cardiomyocytes were pretreated with ginsenoside Rb1 and then subjected to hypoxia and reoxygenation insult. Mitochondrial ROS, NADH dehydrogenase activity, and conformational changes of mitochondrial complex I were analyzed.
Ginsenoside Rb1 decreased mitochondrial ROS production, reduced myocardial infarct size, preserved cardiac function, and limited cardiac fibrosis. Proteomic analysis showed that subunits of NADH dehydrogenase in mitochondrial complex I might be the effector proteins regulated by ginsenoside Rb1. Ginsenoside Rb1 inhibited complex I- but not complex II- or IV-dependent O
consumption and enzyme activity. The inhibitory effects of ginsenoside Rb1 on mitochondrial I-dependent respiration and reperfusion-induced ROS production were rescued by bypassing complex I using yeast NADH dehydrogenase. Molecular docking and surface plasmon resonance experiments indicated that ginsenoside Rb1 reduced NADH dehydrogenase activity, probably via binding to the ND3 subunit to trap mitochondrial complex I in a deactive form upon reperfusion.
Inhibition of mitochondrial complex I-mediated ROS burst elucidated the probable underlying mechanism of ginsenoside Rb1 in alleviating cardiac I/R injury.
A core-shell-derived structural magnetic zeolite imidazolate framework-67 (Fe
O
-COOH@ZIF-67) nanocomposite was fabricated through a single-step coating of zeolite imidazolate framework-67 on ...glutaric anhydride-functionalized Fe
O
nanosphere for the magnetic solid-phase extraction (MSPE) of theophylline (TP). The Fe
O
-COOH@ZIF-67 nanocomposite was characterized through scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectrometry, Fourier transform infrared spectroscopy, Zeta potential analysis, X-ray diffraction, Brunauer-Emmett-Teller, and vibrating sample magnetometer. The material has a high specific surface area and good magnetism, which maintains the regular dodecahedron structure of ZIF-67 without being destroyed by the addition of Fe
O
-COOH nanospheres. The Fe
O
-COOH@ZIF-67 can rapidly adsorb TP mainly through the strong coordination interaction between undercoordinated Co
on ZIF-67 and -NH from imidazole of TP. The adsorption and desorption conditions, such as the amount of adsorbent, adsorption time, pH value, and elution solvent, were optimized. The kinetics of TP adsorption on Fe
O
-COOH@ZIF-67 was found to follow pseudo-second-order kinetics. The Langmuir model fits the adsorption data well and the maximum adsorption capacity is 1764 mg/g. Finally, the developed MSPE-HPLC method was applied in the enrichment and analysis of TP in four tea samples and rabbit plasma. TP was not detected in oolong tea and rabbit plasma, and its contents in jasmine tea, black tea, and green tea are 5.80, 4.31, and 1.53 μg/g, respectively. The recoveries of spiked samples are between 74.41% and 86.07% with RSD in the range of 0.81-3.83%. The adsorption performance of Fe
O
-COOH@ZIF-67 nanocomposite was nearly unchanged after being stored at room temperature for at least 80 days and two consecutive adsorption-desorption cycles. The results demonstrate that Fe
O
-COOH@ZIF-67 nanocomposite is a promising magnetic adsorbent for the preconcentration of TP in complex samples.
Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene that results in the production of neurotoxic mutant HTT (mHTT) protein. Suppressing HTT ...production with antisense oligonucleotides (ASOs) is a promising treatment strategy for HD; however, the difficulty of delivering ASOs to deep brain structures is a major barrier for its clinical application. The glymphatic system of astrocytes involving aquaporin 4 (AQP‐4) controls the entry of macromolecules from the cerebrospinal fluid into the brain. Mesenchymal stem cells (MSCs) target astrocytes to inhibit neuroinflammation. Here we examined the glymphatic distribution of ASO in the brain and the therapeutic potential of combining intravenously injection of mesenchymal stem cells (IV‐MSC) and ASOs for the treatment of HD. Our results show that Cy3‐labeled ASOs entered the brain parenchyma via the perivascular space following cisternal injection, but the brain distribution was significantly lower in AQP‐4−/− as compared with wild‐type mice. Downregulation of the AQP‐4 M23 isoform was accompanied by decreased brain levels of ASOs in BACHD mice as well as an increase in astrogliosis and phosphorylation of nuclear factor κB (NF‐κB) p65. IV‐MSC treatment restored AQP‐4 M23 expression, attenuated astrogliosis, and decreased NF‐κB p65 phosphorylation; it also increased the brain distribution of ASOs and enhanced the suppression of mHTT in BACHD mice. These results suggest that modulating glymphatic activity using IV‐MSC is a novel strategy for improving the potency of ASO in the treatment of HD.
Summary of mechanism by which MSCs improve brain distribution of ASOs in HD. ASO, antisense oligonucleotide; AQP4, aquaporin 4; PBS, phosphate‐buffered saline; MSCs, mesenchymal stem cells; PVS, perivascular space.
PDF
