Spin Crossover in [Fe(qsal-5-Brq)2]+ Complexes with a Quinoline-Substituted Qsal Ligand.

Using a quinoline substituted Qsal ligand, Hqsal-5-Brq (Hqsal-5-Brq = N-(5-bromo-8-quinolyl)salicylaldimine), four FeIII complexes, [Fe(qsal-5-Brq)2]A·CH3OH (Y = NO3- (1NO3), BF4- (2BF4), PF6- (3PF6), OTf- (4OTf), were prepared and characterized. Structure analysis revealed that complex 2BF4 contained two species (2BF4(P1̅) and 2BF4(C2/c)). In these compounds except 3PF6, the [Fe(qsal-5-Brq)2]+ cations form 1D chains through π-π interactions and other weak interactions. Adjacent chains are connected to form the 2D "Chain Layer" structures and 3D structures through various supramolecular interactions. For 3PF6, a "Dimer Chain" structure is formed from the loosely connected dimers. Magnetic studies revealed that compounds 1NO3 and 2BF4(P1̅) displayed abrupt hysteretic SCO with the transition temperature T1/2↓ = 235 K, T1/2↑ = 240 K for 1NO3 and T1/2↓ = 230 K, T1/2↑ = 235 K for 2BF4(P1̅), while compounds 3PF6 and 4OTf are in the HS state. Desolvation of the complexes significantly modifies their SCO properties: the desolvated 1NO3 and 2BF4 show a gradual SCO, desolvated 3PF6 undergoes a two-step SCO, and desolvated 4OTf exhibits a hysteretic transition. Overall, this work reported the FeIII-SCO complexes of the quinoline-substituted Hqsal ligand and highlighted the potential of these ligands for the development of interesting FeIII-SCO materials.

Hysteretic Spin Crossover with High Transition Temperatures in Two Cobalt(II) Complexes.

Cooperative spin crossover transitions with thermal hysteresis loops are rarely observed in cobalt(II) complexes. Herein, two new mononuclear cobalt(II) complexes with hysteretic spin crossover at relatively high temperatures (from 320 to 400 K), namely, [Co(terpy-CH2OH)2]·X2 (terpy-CH2OH = 4'-(hydroxymethyl)-2,2';6',2″-terpyridine, X = SCN-(1) and SeCN- (2)), have been synthesized and characterized structurally and magnetically. Both compounds are mononuclear CoII complexes with two chelating terpy-CH2OH ligands. Magnetic measurements revealed the existence of the hysteretic SCO transitions for both complexes. For compound 1, a one-step transition with T1/2↑= 334.5 K was observed upon heating, while a two-step transition is observed upon cooling with T1/2↓(1) = 329.3 K and T1/2↓(2) = 324.1 K (at a temperature sweep rate of 5 K/min). As for compound 2, a hysteresis loop with a width of 5 K (T1/2↓ = 391.6 K and T1/2↑ = 396.6 K, at a sweep rate of 5 K/min) can be observed. Thanks to the absence of the crystallized lattice solvents, their single crystals are stable enough at high temperatures for the structure determination at both spin states, which reveals that the hysteretic SCO transitions in both complexes originate from the crystallographic phase transitions involving a thermally induced order-disorder transition of the dangling -CH2OH groups in the ligand. This work shows that the modification of the terpy ligand has an important effect on the magnetic properties of the resulting cobalt(II) complexes.

A modified strategy to improve the dissolution of flavonoids from Artemisiae Argyi Folium using ultrasonic-assisted enzyme-deep eutectic solvent system.

In this study, enzyme-deep eutectic solvent-assisted ultrasonic extraction technique (EnDUE) was developed for the efficient dissolution of flavonoids from Artemisiae Argyi Folium. The extraction results of Artemisiae Argyi Folium flavonoids (quercetin, luteolin, and isorhamnetin) were used as indicators to investigate the influencing factors through single factor experiment, Placket-burman design, and Box-behnken design, so as to obtain satisfactory yields. After systematic optimization, the optimal conditions for extraction of the target flavonoids were: Choline chloride/1,4-butanediol with a water content of 25%, cellulase+pectinase with a concentration of 1.6%, solid-liquid ratio of 1/32 g/mL, pH of 4.2, ultrasonic frequency of 80 kHz, ultrasonic power of 160 W, ultrasonic temperature of 40 °C, and ultrasonic time of 25 min, respectively, which derived a total yield of 8.06 ± 0.29 mg/g. Compared with the reference techniques, the proposed EnDUE technique showed significant advantages in the yield and extraction efficiency of flavonoids. In addition, after preliminary purification, the Artemisiae Argyi Folium flavonoids showed good antioxidant activity. Deep eutectic solvent (DES) can degrade the cell wall components and increase the action site of enzyme, and enzyme can promote the penetration of DES into the cell wall matrix, which is mutually beneficial to the dissolution of intracellular components. Therefore, the extraction technique proposed in this work (EnDUE) greatly promotes the dissolution of flavonoids from Artemisiae Argyi Folium, and provides theoretical support for the further application of plant flavonoids.

Two new alkaloids from the endophytic fungus Schizophyllum sp. HM230 isolated from Vincetoxicum mongolicum Maxim.

Endophytic fungi is an important source for the discovery of bioactive natural compounds. A chemical investigation of the ethyl acetate extract of the endophytic fungus Schizophyllum sp. HM230 derived from stems of the herb Vincetoxicum mongolicum Maxim led to isolation of five alkaloids, including two new compounds, schizophyllins M (1) and N (2), along with three known ones (3-5). The planar structures of two new compounds were elucidated by extensive spectroscopic methods including MS, 1D and 2D NMR. Their absolute configurations were determined by Mosher's method and comparison of the ECD data. All the isolates were evaluated for their cytotoxicity and antioxidant activities. Compounds 1-4 showed middle cytotoxicity against MCF-7 cells with IC50 values range of 68.1 ∼ 87.32 µM. Compounds 1-5 displayed obvious antioxidant activity with the IC50 values range of 0.86 ∼ 5.78 mg/mL.

Modulating the Structures and Magnetic Properties of Dy(III) Single-Molecule Magnets through Acid-Base Regulation.

Chemical modulation on the structures and physical properties of the coordination complexes is of great interest for the preparation of new functional materials. By changing the acidity or basicity of the reaction medium, the deprotonation degree of a multidentate ligand with multiple active protons, H4daps (H4daps = N',N'″-((1E,1'E)-pyridine-2,6-diylbis(ethan-1-yl-1-ylidene))bis(2-hydroxybenzohydrazide)), can be regulated on purpose. With this ligand of different deprotonation and charges, three new DyIII complexes ([Dy(H3daps)(CH3COO)2(EtOH)]·CH3COOH (1Dy), [Dy2(H2daps)2(EtOH)2(H2O)2(MeOH)2](CF3SO3)2·(H2O)2 (2Dy), and [Dy3(H1daps)2(H2daps)(µ3-OH)(EtOH)(H2O)] (3Dy)) of different nuclearities (mono-, di-, and trinuclear for 1Dy to 3Dy, respectively) have been synthesized and characterized structurally and magnetically. Analyses on the related bond lengths and resulting hydrogen bond modes in the complexes provide the details of the deprotonation position and the charge of the ligands, which can be in the form of H3daps-, H2daps2-, and H1daps3-. Interestingly, the more deprotonated ligand can act as a bridging ligand between the DyIII centers using the phenol and/or carbonyl oxygen atoms, which leads to the multinuclear structures. Magnetic studies on these complexes revealed that complex 1Dy is a field-induced single-molecule magnet (SMM), while complexes 2Dy and 3Dy show SMM behavior under a zero dc field.

Deep eutectic solvent-homogenate based microwave-assisted hydrodistillation of essential oil from Litsea cubeba (Lour.) Pers. fruits and its chemical composition and biological activity.

As an important natural product, the sufficient separation of plant essential oil (EO) is helpful to improve its utilization value. In this work, deep eutectic solvent-homogenate based microwave-assisted hydrodistillation (DES-HMAHD) was developed and applied to isolate EO from the fruits of Litsea cubeba (Lour.) Pers. Different types of DES were investigated in terms of the EO kinetics and composition, among which oxalic acid/choline chloride (OA/ChCl) had obvious advantages. Following, molar ratio of OA and ChCl (1:1), water content (50%), liquid-solid ratio (12.5:1 mL/g), homogenate time (2 min), and microwave power (700 W) were found to be the optimum conditions. Gas chromatography-mass spectrometer (GC-MS) analysis showed that the EO isolated from DES-HMAHD contained a large proportion of m-cymene and trans-linalool oxide, which were quite different from the conventionally reported L. cubeba EO. In addition, the proposed DES-HMAHD resulted in higher separation efficiency and economic value, as well as lower environmental impact, as compared with other techniques. Afterwards, the EO isolated by different methods was evaluated from the perspective of biological activity. The EO obtained by DES-HMAHD showed higher antioxidant activity (DPPH and ABTS) but lower antifungal activity, which was related to its chemical composition. In general, DES-HMAHD produced a kind of L. cubeba EO with different components, which provided a scientific foundation for the sufficient isolation of plant EO and its application in the natural products.

Setosphlides A-D, New Isocoumarin Derivatives from the Entomogenous Fungus Setosphaeria rostrate LGWB-10.

Investigation of the entomogenous fungus Setosphaeria rostrate LGWB-10 from Harmonia axyridis led to the isolation of four new isocoumarin derivatives, setosphlides A-D (1-4), and four known analogues (5-8). Their planar structures and the relative configurations were elucidated by comprehensive spectroscopic methods. The absolute configurations of isocoumarin nucleus for 1-4 were elucidated by their ECD spectra. The C-10 relative configurations for the pair of C-10 epimers (1 and 2) were established by comparing the magnitude of the computed 13C NMR chemical shifts (Δδcalcd.) with the experimental 13C NMR values (Δδexp.) for the epimers. All of the isolated compounds (1-8) were evaluated for their cytotoxicities against four human tumor cell lines MCF-7, MGC-803, HeLa, and Huh-7.

Structure determination and cytotoxic evaluation of metabolites from the entomogenous fungus Fusarium equiseti.

Investigation of the entomogenous fungus Fusarium equiseti LGWB-9 from Harmonia axyridis led to the isolation of fusarisetin B (2) and its analog, fusaketide A (1), along with two known compounds (3 and 4). Among them, fusaketide A (1) represent the first example of natural polyketide carbon skeleton with a [6/6/5/5] tetracyclic ring system. The planar structure and relative configuration of 1 was established on the basis of NMR spectroscopic data and 13C NMR chemical shift calculation. The absolute configuration of 1 was assigned by quantum chemical TDDFT calculation of its ECD spectrum and single-crystal X-ray diffraction analysis using Cu Kα radiation. Compounds 1 and 2 showed cytotoxicities against MCF-7, MGC-803, HeLa and Huh-7 cell lines with the IC50 values ranging from 2.4 to 69.7 µg ml-1. Cell invasion, migration, DAPI staining, and flow cytometry experiments were carried out to examine the effect of 2 against MGC-803 cells. Western blot results showed that 2 could induce MGC-803 apoptosis through up-regulation of Bax and down-regulation of Bcl-2.

Synthesis and application of novel silver magnetic amino silicone adhesive particles for preparation of high purity α-linolenic acid from tree peony seed oil under applied magnetic field.

Silver magnetic amino silicone adhesive (Fe3O4@SiO2@NH2@Ag) particles were prepared for the purification of α-linolenic acid from tree peony seed oil under applied magnetic field. First, Fe3O4@SiO2@NH2@Ag particles were prepared and physicochemically characterized, including XRD, TG, FTIR, SEM, magnetic hysteresis curves and elemental analysis. The static process for the purification of α-linolenic acid using Fe3O4@SiO2@NH2@Ag particles was investigated, including adsorption curve, desorption curve, elution solvent composition and adsorption isotherm. The result indicated that 0-1-4% acetone-n-hexane elution solvent was selected for the gradient elution process, 2 h and 60 min were the time required to reach adsorption and desorption equilibrium, 20 °C was selected as the adsorption temperature, Langmuir model was suitable to fit and explain the equilibrium data, and the adsorption process was spontaneous and exothermic. Under applied magnetic field, the dynamic process for the purification of α-linolenic acid using Fe3O4@SiO2@NH2@Ag particles was investigated, and the optimum conditions were 20:1 µL/g loading amount, 0.5 mL/min flow rate and 51.73 Oe magnetic field intensity. After purification, the purity and recovery ratio of α-linolenic acid were calculated to be 94% and 74%, respectively. Furthermore, the recycled Fe3O4@SiO2@NH2@Ag particles still achieved better purification result. Therefore, the developed method shows a good application prospect in the field of separation and purification of α-linolenic acid.

Magnetically stabilized bed packed with synthesized magnetic silicone loaded with ionic liquid particles for efficient enrichment of flavonoids from tree peony petals.

In this work, synthesized magnetic silicone loaded with ionic liquid (Fe3O4@SiO2@IL) particles combined with gas-liquid-solid magnetically stabilized bed (GLS-MSB) were applied to enrich flavonoids from tree peony petal extraction solution. The magnetic core (Fe3O4) encased in silica was conducive to its rapid and efficient separation, and the modification of silica with ionic liquids (ILs) could provide the functional groups for selective adsorption of flavonoids. Furthermore, the magnetic materials were evenly dispersed in the GLS-MSB system, realizing the adequate contact and causing the positive influence on the result. After physicochemical characterization, the prepared Fe3O4@SiO2@IL (IL=VBimBr) particles were validated in the enrichment performance of flavonoids, including the type of ionic liquid loaded, desorption solution, adsorption and desorption kinetics. The adsorption kinetics obeyed the pseudo-second-order model, the adsorption isotherms were consistent with the Langmuir equation, and the adsorption process was spontaneous and exothermic. Additionally, the dynamic processes using GLS-MSB packed with Fe3O4@SiO2@IL particles were evaluated systematically, deriving the optimum conditions (5 mL/min liquid flow rate, 130 mL Loading amount and 42.55 Oe magnetic field intensity) and improving the purity of flavonoids. After enrichment, the Fe3O4@SiO2@IL particles were successfully recycled and reused. Overall, the developed method offers a great potential for the enrichment of flavonoids from natural materials.

microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1.

Activation of mTOR complex 1 (mTORC1) could protect human osteoblasts from dexamethasone. Tuberous sclerosis complex 1 (TSC1) is mTORC1 upstream inhibitory protein. We demonstrate here that microRNA-19a ("miR-19a", -3p) targets the 3' untranslated regions of TSC1 mRNA. Expression of miR-19a downregulated TSC1 in OB-6 osteoblastic cells and primary human osteoblasts. miR-19a activated mTORC1 and protected human osteoblasts from dexamethasone. mTORC1 inhibition, by RAD001 or Raptor shRNA, almost completely abolished miR-19a-induced osteoblast cytoprotection against dexamethasone. Knockdown of TSC1 by targeted shRNA similarly induced mTORC1 activation and protected osteoblasts. Moreover, miR-19a activated mTORC1-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited dexamethasone-induced reactive oxygen species production in osteoblasts. Together, miR-19a protects human osteoblasts from dexamethasone possibly via targeting TSC1-mTORC1 signaling.

A pair of polymorphous metal-organic frameworks based on an angular diisophthalate linker: synthesis, characterization and gas adsorption properties.

The combination of an angular diisophthalate ligand, 5,5'-(naphthyl-2,7-yl)diisophthalate (H4L), and copper ions under different solvothermal conditions afforded two polymorphous metal-organic frameworks (ZJNU-77 and ZJNU-78) with the same framework composition of [Cu2(L)(H2O)2], providing a platform to investigate the relationship between MOF polymorphism and gas adsorption properties. As determined by single-crystal X-ray diffraction, ZJNU-77 and ZJNU-78 exhibited three-dimensional networks crystallizing in different space groups. Their structural differences were mainly manifested by the ligand's conformation, the level of framework interpenetration and the network's topology. Interestingly, gas adsorption studies showed that the two compounds after desolvation displayed comparable gas adsorption properties with respect to C2H2, CO2 and CH4, despite their different surface areas and pore volumes. The C2H2, CO2, and CH4 uptake capacities at 298 K and 1 atm are 120.2, 78.1, and 18.4 cm3 (STP) g-1 for ZJNU-77, and 122.0, 82.0, and 18.9 cm3 (STP) g-1 for ZJNU-78, respectively. The IAST adsorption selectivities for the equimolar C2H2/CH4 and CO2/CH4 mixtures are 28.6 and 5.7 for ZJNU-77, and 28.4 and 5.9 for ZJNU-78 at 298 K and 1 atm. These results indicate that besides the surface area, the pore size also plays a crucial role in gas adsorption. This work not only represents an intriguing example of MOF polymorphism achieved by controlling solvothermal conditions, but also provides an insight into the correlation between MOF polymorphism and gas adsorption properties.

Activation of AMP-activated protein kinase by compound 991 protects osteoblasts from dexamethasone.

Dexamethasone (Dex) induces direct cytotoxicity to cultured osteoblasts. The benzimidazole derivative compound 991 ("C991") is a novel and highly-efficient AMP-activated protein kinase (AMPK) activator. Here, in both MC3T3-E1 osteoblastic cells and primary murine osteoblasts, treatment with C991 activated AMPK signaling, and significantly attenuated Dex-induced apoptotic and non-apoptotic cell death. AMPKα1 knockdown (by shRNA), complete knockout (by CRISPR/Cas9 method) or dominant negative mutation (T172A) not only blocked C991-mediated AMPK activation, but also abolished its pro-survival effect against Dex in osteoblasts. Further studies showed that C991 boosted nicotinamide adenine dinucleotide phosphate (NADPH) activity and induced mRNA expression of NF-E2-related factor 2 (Nrf2)-regulated genes (heme oxygenase-1 and NADPH quinone oxidoreductase 1). Additionally, C991 alleviated Dex-induced reactive oxygen species (ROS) production in osteoblasts. Notably, genetic AMPK inhibition reversed the anti-oxidant actions by C991 in Dex-treated osteoblasts. Together, we conclude that C991 activates AMPK signaling to protect osteoblasts from Dex.

MicroRNA-200a activates Nrf2 signaling to protect osteoblasts from dexamethasone.

Treatment with dexamethasone in human osteoblasts leads to oxidative stress and cell injures. NF-E2-related factor 2 (Nrf2) is a key anti-oxidant signaling. We want to induce Nrf2 activation via microRNA-mediated silencing its suppressor Keap1. Our results show that microRNA-200a ("miR-200a") expression depleted Keap1, causing Nrf2 protein stabilization in OB-6 osteoblastic cells. Reversely, the miR-200a anti-sense led to Keap1 upregulation and Nrf2 degradation. miR-200a expression activated Nrf2 signaling, which inhibited dexamethasone-induced reactive oxygen species production and OB-6 cell death/apoptosis. Keap1 shRNA also activated Nrf2 and protected OB-6 cells from dexamethasone. Importantly, miR-200a was in-effective in Keap1-silenced (by shRNA) OB-6 cells. In the primary human osteoblasts, Keap1 silence by targeted-shRNA or miR-200a protected cells from dexamethasone. Significantly, miR-200a level was decreased in necrotic femoral head tissues, which was correlated with Keap1 mRNA upregulation. Together, miR-200a expression activates Nrf2 signaling and protects human osteoblasts from dexamethasone.

Activation of Nrf2 by MIND4-17 protects osteoblasts from hydrogen peroxide-induced oxidative stress.

MIND4-17 is a recently developed NF-E2-related factor 2 (Nrf2) activator, which uniquely causes Nrf2 disassociation from Keap1. Here, we showed that pretreatment with MIND4-17 significantly inhibited hydrogen peroxide (H2O2)-induced viability reduction of primary osteoblasts and OB-6 osteoblastic cells. Meanwhile, MIND4-17 inhibited both apoptotic and non-apoptotic osteoblast cell death by H2O2. MIND4-17 treatment induced Keap1-Nrf2 disassociation, causing Nrf2 stabilization, accumulation and nuclear translocation in osteoblasts, leading to transcription of several Nrf2-dependent genes, including heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase modifier subunit (GCLM) and catalytic subunit (GCLC). Additionally, MIND4-17 largely attenuated H2O2-reactive oxygen species (ROS) production, lipid peroxidation and DNA damages. Nrf2 knockdown by targeted short hairpin RNA (shRNA) exacerbated H2O2-induced cytotoxicity in OB-6 osteoblastic cells, and nullified MIND4-17-mediated cytoprotection against H2O2. Meanwhile, Keap1 shRNA took over MIND4-17's actions and protected OB-6 cells from H2O2. Together, MIND4-17 activates Nrf2 signaling and protects osteoblasts from H2O2.

Vitamin D deficiency causes insulin resistance by provoking oxidative stress in hepatocytes.

Vitamin D deficiency could cause insulin resistance. However, the underlying mechanisms are unclear. The 1α-Hydroxylase ["1α(OH)ase"] is a key enzyme for activate vitamin D3 synthesis. Here, we show that 1α(OH)ase stable knockdown by targeted shRNA led to vitamin D3 depletion in L02 hepatocytes. 1α(OH)ase silence also inhibited insulin-induced downstream signaling (IRS-1, ERK and AKT) transduction and glucose transporter 4 expression. Further, 1α(OH)ase shRNA in L02 hepatocytes led to significant reactive oxygen species production, p53-p21 activation and DNA damages. Such effects were almost completely reversed with co-treatment of n-acetylcysteine, which is an established anti-oxidant. Remarkably, insulin-induced downstream signaling transduction and glucose transporter 4 expression were recovered with n-acetylcysteine co-treatment in 1α(OH)ase-silenced L02 hepatocytes. Together, our results suggest that vitamin D deficiency-induced insulin resistance is possibly caused by oxidative stress in hepatocytes.

A modified approach for isolation of essential oil from fruit of Amorpha fruticosa Linn using microwave-assisted hydrodistillation concatenated liquid-liquid extraction.

In this work, a modified technique was developed to separate essential oil from the fruit of Amorpha fruticosa using microwave-assisted hydrodistillation concatenated liquid-liquid extraction (MHD-LLE). The new apparatus consists of two series-wound separation columns for separating essential oil, one is the conventional oil-water separation column, and the other is the extraction column of components from hydrosol using an organic solvent. Therefore, the apparatus can simultaneously collect the essential oil separated on the top of hydrosol and the components extracted from hydrosol using an organic solvent. Based on the yield of essential oil in the first and second separation columns, the effects of parameters were investigated by single factor experiments and Box-Behnken design. Under the optimum conditions (2mL ethyl ether as the extraction solvent in the second separation column, 12mL/g liquid-solid ratio, 4.0min homogenate time, 35min microwave irradiation time and 540W microwave irradiation power), satisfactory yields for the essential oil in the first separation column (10.31±0.33g/kg) and second separation column (0.82±0.03g/kg) were obtained. Compared with traditional methods, the developed method gave a higher yield of essential oil in a shorter time. In addition, GC-MS analysis of the essential oil indicated significant differences of the relative contents of individual volatile components in the essential oils obtained in the two separation columns. Therefore, the MHD-LLE technique developed here is a good alternative for the isolation of essential oil from A. fruticosa fruit as well as other herbs.

Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine.

Vitamin D deficiency will lead to insulin resistance. In the current study, vitamin D3 1α-Hydroxylase ["1α(OH)ase"] knockout mice were generated to mimic vitamin D deficiency in vivo. As compared to the wild-type mice, the liver tissues of the knockout mice showed impaired insulin signaling, decreased glucose transporter 4 expression and increased reactive oxygen species production. Meanwhile, p53-p21 activation, apoptosis intensity and pro-inflammatory cytokines (IL-6, IL-1 and MIP-1α) level were significantly increased in the knockout mice livers. Significantly, such effects in the knockout mice were largely attenuated by supplement with anti-oxidant n-acetylcysteine (NAC). Remarkably, insulin resistance and metabolic abnormalities in the knockout mice were largely alleviated after treatment of NAC. Therefore, inhibition of oxidative stress by NAC alleviated insulin resistance in vitamin D-deficient mice. Oxidative stress could be the primary cause of insulin resistance by vitamin D deficiency.

A comparative study of C2H2 adsorption properties in five isomeric copper-based MOFs based on naphthalene-derived diisophthalates.

In this work, five positional isomeric ligands consisting of two peripheral isophthalate moieties attached to the central naphthyl core in different ways, namely, 5,5'-(naphthyl-1,3-diyl) diisophthalate (H4L1), 5,5'-(naphthyl-1,4-diyl) diisophthalate (H4L2), 5,5'-(naphthyl-1,5-diyl) diisophthalate (H4L3), 5,5'-(naphthyl-1,6-diyl) diisophthalate (H4L4) and 5,5'-(naphthyl-2,6-diyl) diisophthalate (H4L5), have been used to generate five copper-based MOF isomers. As revealed by single-crystal X-ray diffraction studies, they adopted two different types of topologies depending on the organic ligands: ssa topology for the MOFs ZJNU-71 and ZJNU-74 based on the ligands H4L1 and H4L4, respectively, and nbo topology for the MOFs ZJNU-72, ZJNU-73 and NOTT-103 derived from the ligands H4L2, H4L3 and H4L5, respectively. Furthermore, their C2H2 adsorption properties were systematically investigated, revealing that their different C2H2 uptake capacities can be mainly related to their different pore sizes since they possess the same chemical compositions and gravimetric densities of open metal sites. In particular, among these five MOF compounds investigated, ZJNU-71 exhibits the highest gravimetric C2H2 uptake of 208.1 cm3 (STP) g-1 at 295 K and 1 atm. The value is also among the highest reported for MOF compounds under the same conditions. This work provides a fundamental understanding of the impact of the positional isomerism of the organic ligands on the structures as well as gas adsorption properties of the resulting MOFs.

Assessment of GSK1904529A as a promising anti-osteosarcoma agent.

The insulin growth factor-I receptor (IGF1R) signaling is a key mechanism for osteosarcoma (OS) cell proliferation. GSK1904529A is a novel small molecule IGF1R kinase inhibitor. Its activity against OS cells was tested. In both established OS cell lines (Saos-2 and MG-63) and primary human OS cells, treatment with GSK1904529A (at nM concentrations) significantly inhibited cell proliferation. At the molecular level, GSK1904529A almost completely blocked IGF1R activation in OS cells, and inhibited downstream AKT-ERK activation. IGF1R silence by targeted shRNA also inhibited AKT-ERK activation and Saos-2 cell proliferation. Significantly, GSK1904529A was unable to further inhibit proliferation of IGF1R-silenced Saos-2 cells. In vivo, GSK1904529A administration orally inhibited Saos-2 tumor growth in nude mice. Together, these results suggest that targeting IGF1R by GSK1904529A inhibits OS cell growth in vitro and in vivo.