Regioselective Synthesis of α-Quaternary Amino Acid Derivatives Enabled by Photoinduced Energy Transfer.

α-Quaternary amino acids have found application in many biologically relevant compounds and pharmaceuticals. Although there are many methods for the synthesis of α-quaternary amino acids, most of them are mainly realized with the aid of transition metals and complex ligands. We present herein a 2,7-Br-4CzIPN catalyzed regioselective alkylation of azlactones with redox-active esters via radical-radical couplings. Strikingly, this approach is devoid of any metal or additive and shows broad scope and superior sensitive functional group compatibility.

Rhodium(III)-catalyzed regioselective C(sp2)-H activation of indoles at the C4-position with iodonium ylides.

Herein, we report a Rh(III)-catalyzed C4-selective activation of indoles by using iodonium ylides as carbene precursors. This protocol proceeded under redox neutral reaction conditions and provided important coupling products with good tolerance of functional groups and high yields. In addition, one-pot synthesis and scale-up and mechanistic studies were also conducted.

Mild Synthesis of 3,4-Dihydroisoquinolin-1(2H)-ones via Rh(III)-Catalyzed Tandem C-H-Allylation/N-Alkylation Annulation with 2-Methylidenetrimethylene Carbonate.

A tandem rhodium(III)-catalyzed system was established to access 3,4-dihydroisoquinolin-1(2H)-one by coupling of N-methoxy-3-methylbenzamide with 2-methylidenetrimethylene carbonate. This one-pot synthesis protocol processed smoothly under mild reaction conditions. Moreover, a total of 28 examples, broad substrate scope, and high functional-group compatibility were observed. Preliminary mechanism studies were also conducted and demonstrated that the rhodium(III) catalyst played a vital role in the C-H-allylation and N-alkylation cyclization process.

Van Der Waals heterogeneous layer-layer carbon nanostructures involving π···H-C-C-H···π···H-C-C-H stacking based on graphene and graphane sheets.

Noncovalent interactions involving aromatic rings, such as π···π stacking, CH···π are very essential for supramolecular carbon nanostructures. Graphite is a typical homogenous carbon matter based on π···π stacking of graphene sheets. Even in systems not involving aromatic groups, the stability of diamondoid dimer and layer-layer graphane dimer originates from C - H···H - C noncovalent interaction. In this article, the structures and properties of novel heterogeneous layer-layer carbon-nanostructures involving π···H-C-C-H···π···H-C-C-H stacking based on [n]-graphane and [n]-graphene and their derivatives are theoretically investigated for n = 16-54 using dispersion corrected density functional theory B3LYP-D3 method. Energy decomposition analysis shows that dispersion interaction is the most important for the stabilization of both double- and multi-layer-layer [n]-graphane@graphene. Binding energy between graphane and graphene sheets shows that there is a distinct additive nature of CH···π interaction. For comparison and simplicity, the concept of H-H bond energy equivalent number of carbon atoms (noted as NHEQ), is used to describe the strength of these noncovalent interactions. The NHEQ of the graphene dimers, graphane dimers, and double-layered graphane@graphene are 103, 143, and 110, indicating that the strength of C-H···π interaction is close to that of π···π and much stronger than that of C-H···H-C in large size systems. Additionally, frontier molecular orbital, electron density difference and visualized noncovalent interaction regions are discussed for deeply understanding the nature of the C-H···π stacking interaction in construction of heterogeneous layer-layer graphane@graphene structures. We hope that the present study would be helpful for creations of new functional supramolecular materials based on graphane and graphene carbon nano-structures. © 2017 Wiley Periodicals, Inc.

Anion Recognition Based on a Combination of Double-Dentate Hydrogen Bond and Double-Side Anion-π Noncovalent Interactions.

Anion recognitions between common anions and a novel pincer-like receptor (N,N'-bis(5-fluorobenzoyloxyethyl)urea, BFUR) were theoretically explored, particularly on geometric features of the BFUR@X (X = F-, Cl-, Br-, I-, CO32-, NO3-, and SO42-) systems at a molecular level in this work. Complex structures show that two N-H groups as a claw and two -C6F5 rings on BFUR as a pair of tweezers simultaneously interact with captured anions through cooperative double-dentate hydrogen bond and double-side anion-π interactions. The binding energies and thermodynamic information indicate that the recognitions of the seven anions by BFUR in vacuum are enthalpy-driven and entropy-opposed, which occur spontaneously. Although the binding energy ΔEcp between F- and BFUR is relatively high (289.30 kJ·mol-1), ΔEcp, ΔG, and ΔH of the recognition for CO32- and SO42- are much larger than the cases of F-, Cl-, Br-, I-, and NO3-, suggesting that BFUR is an ideal selective anion receptor for CO32- and SO42-. Additionally, energy decomposition analysis based on localized molecular orbital energy decomposition analysis (LMO-EDA) was performed; electronic properties and behaviors of the present systems were further discussed according to calculations on frontier molecular orbital, UV-vis spectra, total electrostatic potential, and visualized weak interaction regions. The present theoretical exploration of BFUR@X (X = F-, Cl-, Br-, I-, CO32-, NO3-, and SO42-) systems is fundamentally crucial to establish an anion recognition structure-property relationship upon combination of different noncovalent interactions, that is, double-dentate hydrogen bond and double-side anion-π interactions.

Designation and Exploration of Halide-Anion Recognition Based on Cooperative Noncovalent Interactions Including Hydrogen Bonds and Anion-π.

A novel urea-based anion receptor with an electron-deficient aromatic structural unit, N-p-nitrophenyl-N-(4-vinyl-2-five-fluoro-benzoic acid benzyl ester)-phenyl-urea (FUR), was designed to probe the potential for halide-anion recognition through the cooperation of two distinct noncovalent interactions including hydrogen bonds and anion-π in this work. The nature of the recognition interactions between halide-anion and the designed receptor was theoretically investigated at the molecular level. The geometric features of the hydrogen bond and anion-π of the FUR@X(-) (X = F, Cl, Br, and I) systems were thoroughly investigated. The binding energies and thermodynamic information on the halide-anion recognitions show that the presently designed FUR might selectively recognize anion F(-) based on the cooperation of the N-H···F(-) hydrogen bond and anion-π interactions both in vacuum and in solvents. IR and UV-visible spectra of free FUR and FUR@F(-) have been simulated and discussed qualitatively, which may be helpful for further experimental investigations in the future. Additionally, the electronic properties and behaviors of the FUR@X(-) systems were discussed according to the calculations on the natural bond orbital (NBO) data, molecular electrostatic potential (MEP), and weak interaction regions.

Stable Expression of Basic Fibroblast Growth Factor in Chloroplasts of Tobacco.

Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins.

Cp*Rh(III)-Catalyzed ortho-Alkylation/Alkenylation of Nitroarenes.

Cp*Rh(III)-catalyzed nitro-directed C-H alkylation/alkenylation of nitroarenes has been reported for the first time. This protocol is associated with the features of high efficiency, broad substrate scope, and good functional group compatibility. Additionally, gram-scale experiments and synthetic applications proved the practicability of the method. Moreover, preliminary mechanistic investigations consistently revealed C-H bond cleavage as the rate-limiting step.

Rh(III)-Catalyzed Dienylation and Cyclopropylation of 1,2,3-Benzotriazinones with Alkylidenecyclopropanes.

Rh (III)-catalyzed dienylation and cyclopropylation of 1,2,3-benzotriazinones with alkylidenecyclopropanes (ACPs) has been achieved. Different from the previous reports of 1,2,3-benzotriazinones, the triazinone ring remained intact in this C-H bond functionlization reaction. Also, the denitrogenative cyclopropylation could also be realized by changing the reaction temperature. This protocol is featured with high E selectivity, wide substrate scope, and divergent structures of products.

Access to Branched Allylarenes via Rhodium(III)-Catalyzed C-H Allylation of (Hetero)arenes with 2-Methylidenetrimethylene Carbonate.

A rhodium(III)-catalyzed C-H allylation of (hetero)arenes by using 2-methylidenetrimethylene carbonate as an efficient allylic source has been developed for the first time. Five different directing groups including oxime, N-nitroso, purine, pyridine, and pyrimidine were compatible, delivering various branched allylarenes bearing an allylic hydroxyl group in moderate to excellent yields.

PLGA/ß-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis.

OBJECTIVES: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a tetracyclic terpene derived from Cucurbitaceae family plants, facilitates the induction of angiogenesis in vitro. METHODS: We incorporated CuB into a biodegradable poly (lactide-co-glycolide) (PLGA) and ß-tricalcium phosphate (ß-TCP) biomaterial scaffold (PT/CuB) Using 3D low-temperature rapid prototyping (LT-RP) technology. A rat skull defect model was used to verify whether the drug-incorporated scaffold has the effects of angiogenesis and osteogenesis in vivo for the regeneration of bone defect. Cytotoxicity assay was performed to determine the safe dose range of the CuB. Tube formation assay and western blot assay were used to analyze the angiogenesis effect of CuB. RESULTS: PT/CuB scaffold possessed well-designed bio-mimic structure and improved mechanical properties. CuB was linear release from the composite scaffold without affecting pH value. The results demonstrated that the PT/CuB scaffold significantly enhanced neovascularization and bone regeneration in a rat critical size calvarial defect model compared to the scaffold implants without CuB. Furthermore, CuB stimulated angiogenic signaling via up-regulating VEGFR2 and VEGFR-related signaling pathways. CONCLUSION: CuB can serve as promising candidate compound for promoting neovascularization and osteogenesis, especially in tissue engineering for repair of bone defects. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study highlights the potential use of CuB as a therapeutic agent and strongly support its adoption as a component of composite scaffolds for tissue-engineering of bone repair.

Theoretical Prediction on a Novel Reduction-Responsive Nanoring Having a Disulfide Group for Facile Encapsulation and Release of Fullerenes C60 and C70.

In this work, a novel reduction-responsive disulfide bond-containing cycloparaphenylene nanoring molecule (DSCPP) with a pyriform shape has been designed. In addition, the interactions between the designed nanoring (host) and fullerenes C60 and C70 (guests) were investigated theoretically at the M06-2X/6-31G(d,p) and M06-L/MIDI! levels of theory. By analyzing geometric characteristics and host-guest binding energies, it is revealed that the designed DSCPP is an ideal host molecule of guests C60 and C70. DSCPP presents excellent elastic deformation during the encapsulation of C60 and C70. The high binding energies suggest that both DSCPP⊃C60 and DSCPP⊃C70 (∼92 and 118 kJ·mol-1 at the M06-2X/6-31G(d,p) level of theory) are stable host-guest complexes, and the guest C70 is more strongly encapsulated than C60 in the gas phase. The thermodynamic information indicates that the formation of the two host-guest complexes is thermodynamically spontaneous. In addition, the frontier molecular orbital (FMO) features and intermolecular weak interaction region between DSCPP and fullerenes gusts are discussed to further understand the structures and properties of the DSCPP⊃fullerene systems. Finally, the ring-opening mechanism of the DSCPP under reduction conditions is investigated.

Glucocorticoid-induced delayed fracture healing and impaired bone biomechanical properties in mice.

BACKGROUND: The objective of the study was to investigate the effects of glucocorticoid (GC) on the fracture healing process in a closed femur fracture mice model. MATERIALS AND METHODS: Forty 12-week-old female CD-1 mice were randomly allocated into four groups: healthy control and mice with prednisone exposure (oral gavage), 6 mg/kg/day (GC-L), 9 mg/kg/day (GC-M) and 12 mg/kg/day (GC-H). Three weeks after the initiation of prednisone dosing, closed femur fractures were created on prednisone-exposed mice and the healthy control. Prednisone administration was continued for 9 weeks post-fracture, and X-ray imaging was performed weekly to monitor the fracture healing process until the mice were euthanized. Necropsy was performed after 9 weeks and the fractured femurs were isolated and processed at necropsy for micro-CT and biomechanical property analysis. Another 20 mice (control and GC-H, 10 mice/group) were used for histology and micro-CT analysis at early time point (2-week post fracture) with continued prednisone exposure. RESULTS: The results showed that oral administration of prednisone for 3 months in this strain of mice could inhibit endochondral ossification and delay the healing process, especially hard callus formation (woven bone) and bone remodeling during healing. It also could significantly decrease bone biomechanical properties. CONCLUSION: Long-term GC administration leads to significantly delayed fracture healing and impaired bone biomechanical properties. This mouse model may be used to systematically study the cellular and molecular mechanisms underlying fracture healing with GC treatment background and may also be used to study the influence of different therapeutic interventions for bone fracture healing.

Role of fractalkine/CX3CR1 signaling pathway in the recovery of neurological function after early ischemic stroke in a rat model.

This study aims to explore the role of fractalkine/CX3C chemokine receptor 1 (CX3CR1) signaling pathway in the recovery of neurological functioning after an early ischemic stroke in rats. After establishment of permanent middle cerebral artery occlusion (pMCAO) models, 50 rats were divided into blank, sham, model, positive control and CX3CR1 inhibitor groups. Neurological impairment, walking and grip abilities, and cortical and hippocampal infarctions were evaluated by Zea Longa scoring criterion, beam-walking assay and grip strength test, and diffusion-weighted magnetic resonance imaging. qRT-PCR and Western blotting were performed to detect mRNA and protein expressions. ELISA was conducted to measure concentration of sFractalkine (sFkn), interleukin-1ß (IL-1ß) and TNF-α. The recovery rate of neurological functioning impairment and reduced walking and grip abilities was faster in the positive control and CX3CR1 inhibitor groups than the model group. The model, positive control and CX3CR1 inhibitor groups showed increased mRNA and protein expression of chemokine C-X3-C motif ligand 1 (CX3CL1) and CX3CR1, concentration of sFkn, IL-1ß and TNF-α, and size of cortical and cerebral infarctions while decreased expression of NGF and BDNF compared with the blank and sham groups. Compared with the model group, the mRNA and protein expression of CX3CL1 and CX3CR1, concentration of sFkn, IL-1ß and TNF-α, and size of cortical and cerebral infarctions decreased while expression of NGF and BDNF increased in the positive control and CX3CR1 inhibitor groups. Thus, the study suggests that inhibition of fractalkine/CX3CR1 signaling pathway promotes the recovery of neurological functioning after the occurrence of an early ischemic stroke.

[The research of the progesterone and estrogen secretion level and the FSHR, LHR gene quantitative in granular cells cultured in vitro in different time of laying hens].

OBJECTIVE: To research the hormone secretion levels of progesterone and estrogen and the gene expression levels of two go-nadotropin receptors follicle stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) in granular cells of laying hen, and the effect of culture time on the levels of hormone secretion and expression of related receptor gene in granulosa cells was inferred. METHODS: The experiment using the method of cells culture in vitro, the granular cells supernatants of hens were collected at 0 h, 24 h, 48 h, 72 h, 96 h, the progesterone and estrogen concentrations in cell supernatants were determined by ELISA kits, and detected the expression of FSHR and LHR gene in granular cells by real-time fluorescent quantitative PCR. RESULTS: The results showed that the progesterone and estrogen secretion reduced in the early culture of 0 h~48 h(P < 0.05), with the culture time increases to 72 h, the secretion of two hormones began to in-crease, and reaching the level of the initial level of culture. When the cells were cultured to 96 h, the rogesterone and estrogen secretion was reduced again. The lower levels of FSHR and LHR mRNA expression in granular cells appeared with the increase of culture time, compared with the group of cell culture to 0 h, the mRNA expression levels of each groups reduced obviously(P < 0.05). CONCLUSIONS: The amount of progesterone and estrogen in the cultured follicular granulosa cells decreased with the increase of in vitro culture time, and then increased. This might be related to the growth state of cells cultured in vitro. But on the whole, with the extension of the training time, the secretion of proges-terone and estrogen in the cells decreased. This may be related to the decreased expression of the FSHR and LHR genes in the two go-nadotropin receptors.

[Study on the fluorescence of poly (amidoamine) dendrimers decorated with coumarin-3-methyl acyl chloride on the periphery].

The polyamidoamine dendrimers, PAMAM-CMAC, was synthesized by decorating PAMAM dendrimer with coumarin-3-methyl acyl chlorine on the periphery. The structures were characterized by FTIR and H-NMR spectra. The fluorescence analysis indicated the PAMAM-CMAC exhibits strong fluorescence emission. The fluorescence intensity of PAMAM-CMAC is much higher than that of PAMAM dendrimer. The fluorescence intensity of PAMAM-CMAC was affected by pH, concentration and solvent. At a considerably big pH value range, the fluorescence emission of PAMAM-CMAC is comparatively stable. Meanwhile, the fluorescence emission of PAMAM-CMAC shifts to longer wavelength with the increase in solvent polarity.

[Effect of root-zone CO2 enrichment on tomato photosynthetic physiology].

The root system of tomato plant (Lycopersicon esculentum L. cv. Liaoyuanduoli) was treated with CO2 enrichment by aeroponical culture for 60 days. The experiment showed that the chlorophyll content and leaf area of tomato plant were significantly lower under 2500 µL . L-1 or above CO2 condition of root zones than under 370 µL . L-1 CO2 condition. At the same time the Ca2+-ATPase, Mg2+ -ATPase and phosphoenolpyruvate carboxylase (PEPC) of plant leaf were significantly reduced while the PEPC of root increased significantly, which resulted in the significant decreases of net photosynthetic rate, stomatal conductance and intercellular CO2 concentration of plant leaves. The results indicated that under a long-term root-zone CO2 enrichment condition, the decline of photosynthetic physiological parameters of tomato leaf maybe mainly result from the increased PEPC of root, and the decreased CO2 fixation, Mg2+-ATPase and Ca2+-ATPase of leaves.

Effects of insulin resistance on myometrial growth.

To observe the effects of insulin resistance on gonadal steroid hormone stimulation and the myometrial growth of female rats in order to elucidate the relationship between insulin resistance and the development of uterine leiomyomas. We divided 180 nonpregnant female Wistar rats into three groups as follows: group A, as the control group; group B, as the "model by exogenous sex hormone" group; and group C, as the "model by exogenous sex hormone plus insulin-resistance" group. All the animals were raised for 16 weeks. Uterine coefficient and homeostasis model assessment of insulin resistance (HOMA-IR) index were calculated. Myometrial depth and expression levels of the oestrogen receptor (ER), progesterone receptor (PR), and proliferating cell nuclear antigen (PCNA) were measured. HOMA-IR index, serum oestrogen level, uterine coefficient, and myometrial depth were lower in group B than in group C (P < 0.05). The expression levels of ER, PR, and PCNA were higher in group C than in group B (P < 0.05). An auxo-action of insulin resistance in myometrial growth was observed when exogenous oestrogen and progesterone were administered to the female rats in this study. Thus, we suspected that insulin resistance may affect the development of uterine leiomyomas.

[Screening differentially expressed plasma proteins in cold stress rats based on iTRAQ combined with mass spectrometry technology].

OBJECTIVE: Isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry were used to screen differentially expressed plasma proteins in cold stress rats. METHODS: Thirty health SPF Wistar rats were randomly divided into cold stress group A and control group B, then A and B were randomly divided into 3 groups (n = 5): A1, A2, A3 and B1, B2, B3. The temperature of room raising was (24.0 +/- 0.1) degrees C, and the cold stress temperature was (4.0 +/- 0.1) degrees C. The rats were treated with different temperatures until 12 h. The abdominal aortic blood was collected with heparin anticoagulation suction tube. Then, the plasma was separated for protein extraction, quantitative, enzymolysis, iTHAQ labeling, scx fractionation and mass spectrometry analysis. RESULTS: Totally, 1085 proteins were identified in the test, 39 differentially expressed proteins were screened, including 29 up-regulated proteins and 10 down-regulated proteins. Three important differentially expressed proteins related to cold stress were screened by bioinfonnatics analysis (Minor histocompatihility protein HA-1, Has-related protein Rap-1b, Integrin beta-1). CONCLUSION: In the experiment, the differentially expressed plasma proteins were successfully screened in cold stress rats. iTRAQ technology provided a good platform to screen protein diaguostic markers on cold stress rats, and laid a good foundation for further. study on animal cold stress mechanism.