Enhancing Separation Abilities of "Low-Performance" Metal-Organic Framework Stationary Phases through Size Control.

Peak broadening and peak tailing are common but rebarbative phenomena that always occur when using metal-organic frameworks (MOFs) as stationary phases. These phenomena result in diverse "low-performance" MOF stationary phases. Here, by adjusting the particle size of MOF stationary phases from microscale to nanoscale, we successfully enhance the separation abilities of these "low-performance" MOFs. Three zirconium-based MOFs (NU-1000, PCN-608, and PCN-222) with different organic ligands were synthesized with sizes of tens of micrometers and hundreds of nanometers, respectively. All the nanoscale MOFs exhibited exceedingly higher separation abilities than the respective microscale MOFs. The mechanism investigation proved that reducing the particle size can reduce the mass transfer resistance, thus enhancing the column efficiency by controlling the separation kinetics. Modulating the particle size of MOFs is an efficient way to enhance the separation capability of "low-performance" MOFs and to design high-performance MOF stationary phases.

Anisotropic flexibility and rigidification in a TPE-based Zr-MOFs with scu topology.

Tetraphenylethylene (TPE)-based ligands are appealing for constructing metal-organic frameworks (MOFs) with new functions and responsiveness. Here, we report a non-interpenetrated TPE-based scu Zr-MOF with anisotropic flexibility, that is, Zr-TCPE (H4TCPE = 1,1,2,2-tetra(4-carboxylphenyl)ethylene), remaining two anisotropic pockets. The framework flexibility is further anisotropically rigidified by installing linkers individually at specific pockets. By individually installing dicarboxylic acid L1 or L2 at pocket A or B, the framework flexibility along the b-axis or c-axis is rigidified, and the intermolecular or intramolecular motions of organic ligands are restricted, respectively. Synergistically, with dual linker installation, the flexibility is completely rigidified with the restriction of ligand motion, resulting in MOFs with enhanced stability and improved separation ability. Furthermore, in situ observation of the flipping of the phenyl ring and its rigidification process is made by 2H solid-state NMR. The anisotropic rigidification of flexibility in scu Zr-MOFs guides the directional control of ligand motion for designing stimuli-responsive emitting or efficient separation materials.

Anti-tumor effects of novel alkannin derivatives with potent selectivity on comprehensive analysis.

BACKGROUND: Therapeutic approaches based on glycolysis and energy metabolism of tumor cells are new promising strategies for the treatment of cancer. Currently, researches on the inhibition of pyruvate kinase M2, a key rate limiting enzyme in glycolysis, have been corroborated as an effective cancer therapy. Alkannin is a potent pyruvate kinase M2 inhibitor. However, its non-selective cytotoxicity has affected its subsequent clinical application. Thus, it needs to be structurally modified to develop novel derivatives with high selectivity. PURPOSE: Our study aimed to ameliorate the toxicity of alkannin through structural modification and elucidate the mechanism of the superior derivative 23 in lung cancer therapy. METHODS: On the basis of the principle of collocation, different amino acids and oxygen-containing heterocycles were introduced into the hydroxyl group of the alkannin side chain. We examined the cell viability of all derivatives on three tumor cells (HepG2, A549 and HCT116) and two normal cells (L02 and MDCK) by MTT assay. Besides, the effect of derivative 23 on the morphology of A549 cells as observed by Giemsa and DAPI staining, respectively. Flow cytometry was performed to assess the effects of derivative 23 on apoptosis and cell cycle arrest. To further assess the effect of derivative 23 on the Pyruvate kinase M2 in glycolysis, an enzyme activity assay and western blot assay were performed. Finally, in vivo the antitumor activity and safety of the derivative 23 were evaluated by using Lewis mouse lung cancer xenograft model. RESULTS: Twenty-three novel alkannin derivatives were designed and synthesized to improve the cytotoxicity selectivity. Among these derivatives, derivative 23 showed the highest cytotoxicity selectivity between cancer and normal cells. The anti-proliferative activity of derivative 23 on A549 cells (IC50 = 1.67 ± 0.34 µM) was 10-fold higher than L02 cells (IC50 = 16.77 ± 1.44 µM) and 5-fold higher than MDCK cells (IC50 = 9.23 ± 0.29 µM) respectively. Subsequently, fluorescent staining and flow cytometric analysis showed that derivative 23 was able to induce apoptosis of A549 cells and arrest the cell cycle in the G0/G1 phase. In addition, the mechanistic studies suggested derivative 23 was an inhibitor of pyruvate kinase; it could regulate glycolysis by inhibiting the activation of the phosphorylation of PKM2/STAT3 signaling pathway. Furthermore, studies in vivo demonstrated derivative 23 significantly inhibited the growth of xenograft tumor. CONCLUSION: In this study, alkannin selectivity is reported to be significantly improved following structural modification, and derivative 23 is first shown to be able to inhibit lung cancer growth via the PKM2/STAT3 phosphorylation signaling pathway in vitro, indicating the potential value of derivative 23 in treating lung cancer.

A miniatured helical antenna based on the sinusoidal folding structure with exponential spacing.

An exponential spacing and sinusoidal folded helical (ESSFH) antenna backed with a cavity is developed in this paper. Compared with the conventional helical (CH) antenna, the proposed antenna not only has smaller dimension but also exhibits a wider working bandwidth, a higher gain, and a better circular polarization (CP) characteristic. To reduce the dimension of the helical antenna, a sinusoidal structure is adopted along the circumference of the helix. However, it deteriorates the CP characteristic of the antenna. Therefore, the structure of the exponential helix spacing is introduced into the sinusoidal folded helical (SFH) antenna. Then, to further improve the gain of the ESSFH antenna, its ground plane is replaced by an optimized cavity. Compared with the CH antenna, the helix diameter of the ESSFH antenna Dλ is reduced from 0.32 to 0.23, and its volume is reduced to 53%. The ESSFH antenna backed with a cavity has an impedance bandwidth of 0.43-1.02 GHz, which is much wider than 0.48-0.60 GHz of the CH antenna. Moreover, it has an axial ratio of 1.77, while the axial ratio of the CH antenna is 2.61. In addition, its effective potential gain is 0.56, which is 22% higher than that of the CH antenna.

Homogeneously Mixing Different Metal-Organic Framework Structures in Single Nanocrystals through Forming Solid Solutions.

Pore engineering plays a significant role in the applications of porous materials, especially in the area of separation and catalysis. Here, we demonstrated a metal-organic framework (MOF) solid solution (MOSS) strategy to homogeneously and controllably mix NU-1000 and NU-901 structures inside single MOF nanocrystals. The key for the homogeneous mixing and forming of MOSS was the bidentate modulator, which was designed to have a slightly longer distance between two carboxylate groups than the original tetratopic ligand. All of the MOSS nanocrystals showed a uniform pore size distribution with a well-tuned ratio of mesopores to micropores. Because of the appropriate pore ratio, MOSS nanocrystals can balance the thermodynamic interactions and kinetic diffusion of the substrates, thus showing exceedingly higher separation abilities and a unique elution sequence. Our work proposes a rational strategy to design mixed-porous MOFs with controlled pore ratios and provides a new direction to design homogeneously mixed MOFs with a high separation ability and unique separation selectivity.

Regulating metal-organic frameworks as stationary phases and absorbents for analytical separations.

Metal-organic frameworks (MOFs) are highly ordered framework systems composed of metal centers and organic linkers formed through coordination bonds. The diversity of metal elements and easily modified organic ligands, together with controllable synthetic approaches, gives rise to the designability of various MOF structures and topologies and the capability of MOFs to be functionalized. Their structural diversity provides MOFs with many unique properties, such as permanent porosity, flexible structures, thermostability, and high adsorption capacity, leading to great practicability in technical applications. In this review, we concentrate on the applications of MOFs in the field of gas chromatography, high-performance liquid chromatography, and the enrichment of biomolecules, based on rational arrangements in the structures and functions of MOFs. Moreover, we emphasize the importance of structural and chemical regulations for the improvement of separation efficiency.

Design, synthesis, and biological evaluation of a novel dual peroxisome proliferator-activated receptor alpha/delta agonist for the treatment of diabetic kidney disease through anti-inflammatory mechanisms.

Diabetic kidney disease (DKD) is a major feature of the final stage of nearly all cause types of diabetes mellitus (DM). To date, few safe and effective drugs are available to treat. Peroxisome proliferator-activated receptors (PPARs), comprised of three members: PPAR-α, PPAR-δ and PPAR-γ, play a protective role in the DKD through glycemic control and lipid metabolism, whereas systemic activation of PPAR-γ causes serious side-effects in clinical trials. GFT505 is a dual PPAR-α/δ agonist, and the selectivity against PPAR-γ is still to be improved. Sulfuretin has been shown to suppress the expression of PPAR-γ and improve the pathogenesis of diabetic complications. In this study, by hybridizing the carboxylic acid of GFT505 and the parent nucleus of sulfuretin, we pioneeringly designed and synthetized a series of novel dual PPAR-α/δ agonists, expecting to provide a better benefit/risk ratio for PPARs. Of all the synthesized compounds, compound 12 was identified with highly activity on PPAR-α/δ and higher selectivity against PPAR-γ than that of GFT505 (EC50: hPPAR-α: 0.26 µM vs.0.76 µM; hPPAR-δ: 0.50 µM vs.0.73 µM; hPPAR-γ: 4.22 µM vs.2.79 µM). The molecular docking studies also depicted good binding affinity of compound 12 for PPAR-α and PPAR-δ compared to GFT505. Furthermore, compound 12 exhibited an evidently renoprotective effect on the DKD through inhibiting inflammatory process, which might at least partly via JNK/NF-κB pathways in vivo and in vitro. Overall, compound 12 hold therapeutic promise for DKD.

High power and high pulse repetition frequency transistorized pulser by time base stability improvement and power synthesis technique.

Output power of a transistorized pulser is usually limited by the power capacity of avalanche transistors. To improve the total output power, the power synthesis method is widely used, in which a single pulser with high output power and high time base stability is required. However, the time base stability tends to deteriorate as the output power increases. To improve the output power under the premise of high time base stability, from the perspective of carrier movement, the mechanisms of pulse jitter and pulse drift are investigated. It is found that the pulse jitter is caused by time dispersion of the ionization process in the collector depletion region, while the pulse drift is due to the decrement of the diffusion coefficient Dn and the electron mobility µn, which are both temperature-dependent. Based on the microscopic theoretical study, some macroscopic improvements on the time base stability are made. Some parameters of the trigger pulse and the circuit (e.g., charging capacitance) are optimized experimentally. Consequently, we achieved a pulser with an amplitude of 1.8 kV, pulse jitter of 25 ps, pulse drift of 100 ps/min at a pulse repetition frequency (PRF) of 100 kHz. Additionally, a new parameter k, the product of the highest PRF f and the peak power Ep, is defined to evaluate the output power. With almost the same time base stability, the proposed pulser has a k of 6.48 GHz W, which is improved significantly. Finally, a synthesized pulser with an amplitude of 2.5 kV and highest PRF of 100 kHz is achieved.