Integrated Anionic Zirconium-Organic Cage and Cationic Boron-Imidazolate Cage for Synergetic Optical Limiting.

Making oppositely charged metal-organic cages (MOCs) into a tightly ordered structure may bring interesting functions. Herein, we report a novel structure composed of anionic (Zr4 L6 )8- (L=embonate) tetrahedral cages and in situ-formed cationic [Zn4 (Bim)4 ]4+ (Bim=[BH(im)3 ]- ; im=imidazole) cubic cages. Chiral transfer is observed from enantiopure (Zr4 L6 )8- cage to enantiopure [Zn4 (Bim)4 ]4+ cage. A pair of enantiomers (PTC-373(Δ) and PTC-373(Λ)) are formed. PTC-373 exhibits high chemical and thermal stabilities, affording an interesting single-crystal-to-single-crystal transformation. More importantly, the combination of ionic pair cages significantly enhances its third-order nonlinear optical property, and its thin-film exhibits an excellent optical limiting effect.

Synthesis and anti-HIV activity of non-nucleoside reverse-transcriptase inhibitor DB02 phosphate derivatives based on water-soluble optimization.

To improve the water solubility of anti-human immunodeficiency virus (HIV) agent DB02, an excellent non-nucleoside reverse-transcriptase inhibitor (NNRTI) obtained in our previous efforts, we designed and synthesized four phosphate derivatives of DB02 based on the molecular model of DB02 with RT. Here, the antiviral activity of these four derivatives was detected, leading to the discovery of compound P-2, which possessed a superior potency to the lead compound DB02 against wild-type HIV-1 and a variety of HIV-resistant mutant viruses significantly. Furthermore, the water solubility of P-2 was nearly 17 times higher than that of DB02, and the pharmacokinetic test in rats showed that P-2 demonstrate significantly improved oral bioavailablity of 14.6%. Our study showed that the introduction of a phosphate ester group at the end of the C-2 side chain of DB02 was beneficial to the improvement of its antiviral activity and pharmacokinetic properties, which provided a promising lead for the further development of S-DACOs type of NNRTIs.

Enhancing Third-Order Nonlinear Optical Property by Regulating Interaction between Zr4(embonate)6 Cage and N, N-Chelated Transition-Metal Cation.

Herein, the combination of anionic Zr4L6 (L = embonate) cages and N, N-chelated transition-metal cations leads to a series of new cage-based architectures, including ion pair structures (PTC-355 and PTC-356), dimer (PTC-357), and 3D frameworks (PTC-358 and PTC-359). Structural analyses show that PTC-358 exhibits a 2-fold interpenetrating framework with a 3,4-connected topology, and PTC-359 shows a 2-fold interpenetrating framework with a 4-connected dia network. Both PTC-358 and PTC-359 can be stable in air and other common solvents at room temperature. The investigations of third-order nonlinear optical (NLO) properties indicate that these materials show different degrees of optical limiting effects. It is surprising that increasing coordination interactions between anion and cation moieties can effectively enhance their third-order NLO properties, which can be attributed to the formation of coordination bonds that facilitate charge transfer. In addition, the phase purity, UV-vis spectra, and photocurrent properties of these materials were also studied. This work provides new ideas for the construction of third-order NLO materials.

Post-Assembly Modification of Homochiral Titanium-Organic Cages for Recognition and Separation of Molecular Isomers.

A chiral metal-organic cage (MOC) was extended and fixed into a porous framework using a post-assembly modification strategy, which made it easier to study the host-guest chemistry of the solid-state MOC using a single-crystal diffraction technique. Anionic Ti4 L6 (L=embonate) cage can be used as a 4-connecting crystal engineering tecton, and its optical resolution was achieved, thus homochiral ΔΔΔΔ- and ΛΛΛΛ-[Ti4 L6 ] cages were obtained. Accordingly, a pair of homochiral cage-based microporous frameworks (PTC-236(Δ) and PTC-236(Λ)) were easily prepared by a post-assembly reaction. PTC-236 has rich recognition sites provided by the Ti4 L6 moieties, chiral channels and high framework stability, affording a single-crystal-to-single-crystal transformation for guest structure analyses. Thus it was successfully utilized for the recognition and separation of isomeric molecules. This study provides a new approach for the orderly combination of well-defined MOCs into functional porous frameworks.

C6-structural optimizations of 2-aryl-1H-pyrazole-S-DABOs: From anti-HIV to anti-DENV activity.

Both HIV and DENV are serious threats to human life, health and social economy today. So far, no vaccine for either HIV or DENV has been developed successfully. The research on anti-HIV or DENV drugs is still of great significance. In this study we developed a series of novel 2-Aryl-1H-pyrazole-S-DABOs with C6-strucutral optimizations as potent NNRTIs, among which, 8 compounds had low cytotoxicity and EC50 values in the range of 0.0508 âˆ¼ 0.0966 µM, and their selectivity index was SI > 1415 âˆ¼ 3940. In particular, two compounds 4a and 4b were identified to have good inhibitory effects on DENV of four serotypes. The EC50 of compound 4a and 4b against DENV-II (13.2 µM and 9.23 µM, respectively) were better than that of the positive control ribavirin (EC50 = 40.78 µM). In addition, the effect of C-6 substituents on the anti-HIV or anti-DENV activity of these compounds was also discussed.

Coordination Assembly of Tetrahedral Zr4(embonate)6 Cages with Eu3+ Ions.

Herein we systematically investigated the coordination assembly behavior of Zr4L6 cages with Eu3+ ions at room temperature. Through adjustment of the concentration of Eu salt and changes of the type and molar ratio of the solvent, a series of Zr4L6-Eu structures with different structure dimensionalities have been synthesized and structurally characterized. In addition, we also studied the optical properties of these materials in detail, including the fluorescent and third-order nonlinear-optical properties. Most notably, a 2D layer structure with a strong aromatic π···π-stacking force exhibits a good optical-limiting effect.

Combining a Titanium-Organic Cage and a Hydrogen-Bonded Organic Cage for Highly Effective Third-Order Nonlinear Optics.

Many metal-organic cages (MOCs) and a few hydrogen-bonded organic cages (HOCs) have been investigated, but little is reported about cooperative self-assembly of MOCs and HOCs. Herein, we describe an unprecedented MOC&HOC co-crystal composed of tetrahedral Ti4 L6 (L=embonate) cages and in-situ-generated [(NH3 )4 (TIPA)4 ] (TIPA=tris(4-(1H-1,2,4-triazol-1-yl)phenyl)amine) cages. Chiral transfer is observed from the enantiopure Ti4 L6 cage to enantiopure [(NH3 )4 (TIPA)4 ] cage. Two homochiral supramolecular frameworks with opposite handedness (PTC-235(Δ) and PTC-235(Λ)) are formed. Such MOC&HOC co-crystal features high stability in water and other solvents, affording single-crystal-to-single-crystal transformation to trap CH3 CN molecules and identify disordered NH4 + cations. A tablet pressing method is developed to test the third-order nonlinear optical property of KBr-based PTC-235 thin film. Such a thin film exhibits an excellent optical limiting effect.

Ti4(embonate)6 Cage-Ligand Strategy on the Construction of Metal-Organic Frameworks with High Stability and Gas Sorption Properties.

Herein we report an efficient strategy to construct cage-based metal-organic frameworks (MOFs) via the assembly of Ti4L6 (L = embonate) cages and N-contained ligands with Mn2+ and Zn2+ ions, respectively, and two Ti4L6-cage-based MOFs (PTC-219 and PTC-220) with high stability and gas sorption properties have been generated through two-step reactions, respectively.

Self-Assembly of a Ti4(embonate)6 Cage toward Silver.

Herein we report a variety of supramolecular architectures that are self-assembled by the highly charged anionic Ti4L6 (L = embonate) cages and noble-metal Ag+ ions in the presence of the different ligands, including six Ti4L6-Ag(PPh3) cages in whose structures the Ti4L6 cage catches various in situ formed [Ag(PPh3)]+ moieties by a coordination bond and one cocrystal superstructure of a Ti4L6 cage with an in situ generated [Ag2(Ph2P(CH2)5PPh2)3]2+ cage via supramolecular interactions. In addition, the third-order nonlinear-optical properties of these compounds are investigated in detail.

Design, synthesis and anti-HIV evaluation of 5-alkyl- 6-(benzo[d][1,3]dioxol-5-alkyl)-2-mercaptopyrimidin-4(3H)-ones as potent HIV-1 NNRTIs.

In order to discover and develop the new HIV-1 NNRTIs, a series of 5-alkyl-6-(benzo[d][1,3]dioxol-5-ylalkyl)-2-mercaptopyrimidin-4(3H)-ones was synthesized and screened for their in vitro cytotoxicity against HIV-1. Most of the compounds we synthetized showed high activity against wild-type HIV-1 strain (IIIB) while IC50 values are in the range of 0.06-12.95 µM. Among them, the most active HIV-1 inhibitor was compound 6-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one (5b), which exhibited similar HIV-1 inhibitory potency (IC50 = 0.06 µM, CC50 = 96.23 µM) compared with nevirapine (IC50 = 0.04 µM, CC50 >200 µM) and most of compounds exhibited submicromolar IC50 values indicating they were specific RT inhibitors. The compounds 5b, 6-(benzo[d] [1,3]dioxol-5-yl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one (5c) and 4-(2-((4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-6-oxo-1,6-dihydropyrimidin-2-yl)thio)acetyl)phenylbenzo[d][1,3]dioxole-5-carboxylate (5r) were selected for further study. It was found that all of them had little toxicity to peripheral blood mononuclear cell (PBMC), and had a good inhibitory effect on the replication of HIV-1 protease inhibitor resistant strains, fusion inhibitor resistant strains and nucleosides reverse transcriptase inhibitor resistant strains, as well as on clinical isolates. Besides, compound 5b and 5c showed inhibition of HIV-1 RT RNA-dependent DNA polymerization activity and DNA-dependent DNA polymerization activity, while compound 5r only showed inhibition of HIV DNA-dependent DNA polymerization activity, which was different from classical reverse transcriptase inhibitors. Our study which offered the preliminary structure-activity relationships and modeling studies of these new compounds has provided the valuable avenues for future molecular optimization.

Identifying risk factors for chronic kidney disease stage 3 in adults with acquired solitary kidney from unilateral nephrectomy: a retrospective cohort study.

BACKGROUND: We aimed to examine the risk factors for chronic kidney disease (CKD) stage 3 among adults with ASK from unilateral nephrectomy. METHODS: We retrospectively collected data from adult patients with ASK between January, 2009 and January, 2019, identified from a tertiary hospital in China. The clinical data were compared between patients who developed CKD stage 3 and those who did not develop CKD stage 3 during follow-up. RESULTS: In total, 172 patients with ASK (110 men; median 58.0 years) were enrolled, with a median follow-up duration of 5.0 years. During follow-up, 91 (52.9%) and 24 (14.0%) patients developed CKD stage 3 and end-stage renal disease, respectively. Multiple regression analyses showed that age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.039-1.115, p < 0.001), diabetes (OR 4.401, 95% CI 1.693-11.44, p = 0.002), hyperuricemia (OR 2.733, 95% CI 1.104-6.764, p = 0.03), a history of cardiovascular disease (CVD) (OR 5.583, 95% CI 1.884-18.068, p = 0.002), and ASK due to renal tuberculosis (OR 8.816, 95% CI 2.92-26.62, p < 0.001) were independent risk factors for developing CKD stage 3 among patients with ASK. CONCLUSIONS: Regular follow-up of renal function is needed among adult patients with ASK. Optimal management of diabetes, hyperuricemia, and CVD may reduce their risk of CKD stage 3, especially among those that undergo unilateral nephrectomy for renal tuberculosis.

Synthesis and Photoelectric Properties of Metal-Organic Zeolites Built from TO4 and Organotin.

Herein we report a novel strategy capable of generating a new class of metal-organic zeolite (MOZ) materials. When the MoO4 or WO4 tetrahedra are employed to assemble with triorganotin R3Sn fragments, four 3D networks with the zeolite BCT topology and nonzeotype 4-connected topological net (such as lon and dia) have been generated. The photocurrent study results show that these materials have good photoelectric response and high photophysical stability.

Neuroprotective Effect of Oxysophocarpine by Modulation of MAPK Pathway in Rat Hippocampal Neurons Subject to Oxygen-Glucose Deprivation and Reperfusion.

Oxysophocarpine (OSC), an alkaloid isolated from Sophora flavescens Ait, has been traditionally used as a medicinal agent based on the observed pharmacological effects. In this study, the direct effect of OSC against neuronal injuries induced by oxygen and glucose deprivation (OGD) in neonatal rat primary-cultured hippocampal neurons and its mechanisms were investigated. Cultured hippocampal neurons, which were exposed to OGD for 2 h followed by a 24 h reoxygenation, were used as an in vitro model of ischemia and reperfusion. 2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay were used to confirm neural damage and to further evaluate the protective effects of OSC. The concentration of intracellular-free calcium [Ca2+]i and mitochondrial membrane potential (MMP) were measured to determine the intracellular mechanisms and to further estimate the degree of neuronal damage. Changes in expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, p-ERK1/2, p-JNK1/2, and p-p38 MAPK were also observed in the in vitro model. It was shown that OSC (0.8, 2, or 5 µmol/L) significantly attenuated the increased absorbance of MTT, and the release of LDH manifests the neuronal damage by the OGD/R. Meanwhile, the pretreatment of the neurons during the reoxygenation period with OSC significantly increased MMP; it also inhibited [Ca2+]i the elevation in a dose-dependent manner. Furthermore, the pretreatment with OSC (0.8, 2, or 5 µmol/L) significantly down-regulated expressions of IL-1ß, TNF-α, p-ERK1/2, p-JNK1/2, and p-p38 MAPK in neonatal rat primary-cultured hippocampal neurons induced by OGD/R injury. In conclusion, OSC displays a protective effect on OGD-injured hippocampal neurons by attenuating expression of inflammatory factors via down-regulated the MAPK signaling pathway.

Embonic Acid Functionalized Niobium Complexes with Selective Dye Sorption Properties.

Presented here are binuclear Nb2, tetranuclear Ti2Nb2, and dodecanuclear Nb12 complexes decorated by embonic acid ligands. These structures feature a unique Ti-O-Nb or Nb-O-Nb subunit. Besides, the unprecedented dodecanuclear Nb12 cluster further displays a porous three-dimensional packing framework and stability in water, affording an interesting selective uptake for methylene blue molecules over rhodamine B.

Water-Soluble and Ultrastable Ti4L6 Tetrahedron with Coordination Assembly Function.

We have successfully constructed a tetrahedral Ti4L6 cage with calixarene-like coordination-active vertices. It further features high solubility and stability in H2O and DMF/H2O solution, affording an interesting stepwise assembly function with other metal ions. Through trapping of different amounts of Co or Ln ions, the Ti4L6 tetrahedra can be organized into various dimensional architectures, including a Ti4L6-Co3 cage, a Ti4L6-Ln2 cage, a Ti4L6-Ln2 chain, and a three-dimensional Ti4L6-Ln framework. An unusual mixed-valence phenomenon was observed in the Ti4L6 cage, whose Ti3+/4+ compositions were adequately identified by electron spin resonance and X-ray photoelectron spectroscopy analyses. More remarkably, the calixarene-like oxygen vertices of the Ti4L6 cage can also be used for the recognition of C3-symmetric dye molecules through N-H···O hydrogen bonding. Accordingly, driven by visible light, selective and efficient homogeneous photodecomposition of acid blue 93 and alkali blue 4B were successfully achieved. Therefore, this work not only represents a milestone in constructing symmetric Ti-based cages with interesting coordination assembly function but also provides a new method for preparing technologically important soluble photoactive cages.

Gas Sorption, Second-Order Nonlinear Optics, and Luminescence Properties of a Multifunctional srs-Type Metal-Organic Framework Built by Tris(4-carboxylphenylduryl)amine.

A chiral 8-fold interpenetrating srs-type metal-organic framework FIR-28 (FIR denotes Fujian Institute of Research) exhibits a surface area of 1029 m(2)/g and high C3H8/CH4 separation capacity in excess of 154 and displays strong powder second-harmonic-generation efficiency, with more than half over potassium dihydrogen phosphate powder. Moreover, the luminescence properties of FIR-28 are dependent on the solvent guests.

Nanoporous cobalt(II) MOF exhibiting four magnetic ground states and changes in gas sorption upon post-synthetic modification.

We present the syntheses, structural characterization, gas sorption, I2 uptake, and magnetic properties of a double-walled porous metal-organic framework, [Co(II)3(lac)2(pybz)2]·3DMF (1·3DMF, purple, where pybz = 4-pyridyl benzoate, lac = d- and l-lactate) and of its post-synthetic modified (PSM) congeners, [Co(II)3(lac)2(pybz)2]·xGuest (xGuest = 6MeOH, purple; 4.5EtOH, purple; 3PrOH, purple; 2C6H6, purple; 2.7I2, black), [Co(II)3(lac)2(pybz)2] (1, purple), [Co(II)3(pybz)2(lac)2(H2O)2]·7H2O (1a·7H2O, green), and [Co(III)Co(II)2(pybz)2(lac)2(H2O)2]I·2H2O·1.5DMSO (1b·I(-)·2H2O·1.5DMSO, yellow, DMSO = dimethyl sulfoxide). Crystallography shows that the framework is not altered by the replacement of DMF by different solvents or by the removal of the solvent molecules during the single-crystal to single-crystal (SC-SC) transformations, while upon exchange with H2O or partial oxidation by molecular iodine, the crystallinity is affected. 1 absorbs N2, H2, CH4, CH3OH, C2H5OH, PrOH, C6H6, and I2, but once it is in contact with H2O the absorption efficiency is drastically reduced. Upon PSM, the magnetism is transformed from a canted antiferromagnet (1·3DMF and 1·xGuest) to single-chain magnet (1), to a ferrimagnet (1a·7H2O), and to a ferromagnet (1b·I(-)·2H2O·1.5DMSO). Raman spectroscopy suggests the color change (purple to green 1a·7H2O or yellow 1b·I(-)·2H2O·1.5DMSO) is associated with a change of geometry from a strained octahedron due to the very acute chelating angle (∼60°) of the lactate of a cobalt center to a regular octahedron with a monodentate carboxylate and one H2O. The magnetic transformation is explained by the different interchain exchanges (J'), antiferromagnetic for 1·3DMF and 1·xSolvent (J' < 0), SCM for 1 (J' verge to 0), and ferromagnetic for 1a·7H2O (J' > 0), between homometal topological ferrimagnetic chains (two octahedral and one tetrahedral Co(II) ions) connected by the double walls of pybz at 13.3 Å (shortest Co···Co). For 1b·I(-)·2H2O·1.5DMSO the moment of the tetrahedral site is turned off, thus stabilizing a ferromagnetic state (J' > 0). The present stabilization of four magnetic ground states is unique in the field of metal-organic frameworks as well as the electrical conductivity of 1·2.7I2.

Multifunctional anionic MOF material for dye enrichment and selective sorption of C2 hydrocarbons over methane via Ag(+)-exchange.

The anionic Zn-2,5-thiophenedicarboxylate framework material (1) built from the connection of Johnson cages can perform Ag(+)-exchange to upgrade the uptakes of C2 hydrocarbons (C2s) and separation properties of C2s over methane (C1). Moreover, its activated phase (1a) can enrich organic dyes from ethanol and make a significant red-shift in photoluminescent spectra of Rhodamine B (Rh B) via varying the aggregation states of dye molecules.

[Problems in quality standard research of new traditional Chinese medicine compound].

The new traditional Chinese medicine compound is the main part of the research of new drug of traditional Chinese medicine (TCM), and the new Chinese herbal compound reflects the characteristics of TCM theory. The new traditional Chinese medicine compound quality standard research is one of the main content of pharmaceutical research, and is also the focus of the new medicine pharmaceutical evaluation content. Although in recent years the research level of new traditional Chinese medicine compound has been greatly improved, but the author during the review found still some common problems existing in new traditional Chinese medicine compound quality standard research data, this paper analyzed the current quality standards for new traditional Chinese medicine compound and the problems existing in the research data, respectively from measurement of the content of index selection, determine the scope of the content, and the quality standard design concept, the paper expounds developers need to concern. The quality of new traditional Chinese medicine compound quality standard is not only itself can be solved, but quality standards is to ensure the key and important content of product quality, improving the quality of products cannot do without quality standards. With the development of science and technology, on the basis of quality by design under the guidance of the concept, new traditional Chinese medicine compound quality standard system will be more scientific, systematic and perfect.

[Problems in medicinal materials research of new traditional Chinese medicine].

Medicinal materials research and development of new drug of traditional Chinese medicine (TCM) research is the premise and foundation of new drug research and development, it throughout the whole process of new drug research. Medicinal materials research is one of the main content of the pharmaceutical research of new drug of TCM, and it is also the focus of the new medicine pharmaceutical evaluation content. This article through the analysis of the present problems existing in the development of TCM research of new drug of TCM, from medicine research concept, quality stability, quality standard, etc are expounded, including medicine research idea value medicine study should focus on the important role and from the purpose for the top-level design of new drug research problem. Medicinal materials quality stability should pay attention to the original, medicinal part, origin, processing, storage, planting (breeding), and other aspects. Aspect of quality standard of medicinal materials should pay attention to establish the quality standards of conform to the characteristics of new drug of TCM. As the instruction of TCM new drug research and development and the scientific nature of the review, and provide the basis for medicinal material standards.