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Autophagy of granulosa cells (GCs) is involved in follicular atresia, which occurs repeatedly during the ovarian development cycle. Several circadian clock genes are rhythmically expressed in both rodent ovarian tissues and GCs. Nuclear receptor subfamily 1 group D member 1 (NR1D1), an important component of the circadian clock system, is involved in the autophagy process through the regulation of autophagy-related genes. However, there are no reports illustrating the role of the circadian clock system in mouse GC autophagy. In the present study, we found that core circadian clock genes ( Bmal1, Per2, Nr1d1, and Dbp) and an autophagy-related gene ( Atg5) exhibited rhythmic expression patterns across 24 h in mouse ovaries and primary GCs. Treatment with SR9009, an agonist of NR1D1, significantly reduced the expression of Bmal1, Per2, and Dbp in mouse GCs. ATG5 expression was significantly attenuated by SR9009 treatment in mouse GCs. Conversely, Nr1d1 knockdown increased ATG5 expression in mouse GCs. Decreased NR1D1 expression at both the mRNA and protein levels was detected in the ovaries of Bmal1−/− mice, along with elevated expression of ATG5. Dual-luciferase reporter assay and electrophoretic mobility shift assay showed that NR1D1 inhibited Atg5 transcription by binding to two putative retinoic acid-related orphan receptor response elements within the promoter. In addition, rapamycin-induced autophagy and ATG5 expression were partially reversed by SR9009 treatment in mouse GCs. Taken together, our current data demonstrated that the circadian clock regulates GC autophagy through NR1D1-mediated inhibition of ATG5 expression, and thus, plays a role in maintaining autophagy homeostasis in GCs.

The circadian clock system plays an important role in regulating testosterone synthesis in mammals. Male Bmal1-/- mice are infertile with low serum testosterone levels and decreased expression of testicular steroidogenic genes, suggesting that circadian clock genes regulate testosterone biosynthesis by activating steroidogenic gene transcription. However, whether the circadian clock regulates testosterone production via other genes remains unknown. Using Bmal1-/- mice and their wild-type (WT) siblings, we aimed to identify additional genes by which the circadian clock regulates testosterone synthesis. WT and Bmal1-/- mouse testes sections had similar normal morphologies, although there was a decrease in testicular spermatozoa in the Bmal1-/- mice. Low serum testosterone levels were detected in the Bmal1-/- mice. RNA sequencing identified 37 and 48 genes that were differentially expressed between WT and Bmal1-/- mouse testes at circadian time (CT2 and CT14), respectively. The cholesterol metabolism pathway was significantly enriched in the KEGG pathway analysis, and there was lower expression of three apolipoprotein genes (Apoa1, Apoa2, and Apoc3) at CT2 in the testes of Bmal1-/- mice than in those of WT mice. These decreases in Apoa1, Apoa2, and Apoc3 expression were verified by quantitative polymerase chain reaction analysis, which also revealed downregulation of the expression of the circadian clock (Per2, Dbp, and Nr1d1) and steroidogenic (StAR, Cyp11a1, and Hsd17b3) genes. The expression of circadian clock genes was relatively stable in WT mice over a 20-h period, whereas there was clear circadian rhythmic expression of Apoa1, Apoa2, Apoc3, StAR, Cyp11a1, Hsd3b2, and Hsd17b3. Bmal1-/- mice showed severely reduced expression of testicular circadian clock genes at three time points (CT4, CT12, and CT20), and a reduction in mRNA expression levels of Apo (Apoa1, Apoa2, and Apoc3) and steroidogenic (StAR, Cyp11a1, Hsd3b2, and Hsd17b3) genes. Oil Red O staining showed decreased lipid aggregation in the Leydig cells of Bmal1-/- mouse testes. Considering the vital role of Apo genes in high-density lipoprotein formation and cholesterol transport, the present data suggest that the circadian clock system regulates testosterone production by orchestrating the rhythmic expression of Apo genes. These data extend our understanding of the role of the circadian clock in regulating testosterone production in mammals.

An efficient silver-promoted decarboxylative gem-difluoromethylenation of aryl- or alkyl-substituted α,β-unsaturated carboxylic acids with readily available benzo-1,3-diazolic difluoromethyl bromides has been developed. This convenient transformation demonstrated good functional-group tolerability and broad substrate scope, and afforded the allylic difluorides in good to excellent yields with exclusive E-stereoselectivity under mild reaction conditions.

Prostaglandin G/H synthase 2 (PTGS2) is a rate-limiting enzyme in prostaglandin synthesis. The present study assessed the role of the uterine circadian clock on Ptgs2 transcription in response to steroid hormones during early pregnancy. We demonstrated that the core clock genes (Bmal1, Per2, Nr1d1, and Dbp), Vegf, and Ptgs2, and their encoded proteins, have rhythmic expression in the mouse uterus from days 3.5 to 4.5 (D3.5-4.5) of pregnancy. Progesterone (P4) treatment of cultured uterus endometrial stromal cells (UESCs) isolated from mPer2Luciferase reporter gene knock-in mice on D4 induced a phase shift in PER2::LUCIFERASE oscillations. This P4-induced phase shift of PER2::LUCIFERASE oscillations was significantly attenuated by the P4 antagonist RU486. Additionally, the amplitude of PER2::LUCIFERASE oscillations was increased by estradiol (E2) treatment in the presence of P4. Consistently, the mRNA levels of clock genes (Bmal1 and Per2), Vegf, and Ptgs2 were markedly increased by E2 treatment of UESCs in the presence of P4. Treatment with E2 also promoted prostaglandin E2 (PGE2) synthesis by UESCs. Depletion of Bmal1 in UESCs by small-interfering RNA (siRNA) decreased the transcript levels of clock genes (Nr1d1 and Dbp), Vegf, and Ptgs2 compared with nonsilencing siRNA treatment. Bmal1 knockdown also inhibited PGE2 synthesis. Moreover, the mRNA expression levels of clock genes (Nr1d1 and Dbp), Vegf, and Ptgs2, and their respective proteins were significantly decreased in the uterus of Bmal1-/- mice. Thus, these data suggest that Bmal1 in mice promotes PGE2 synthesis by upregulating Ptgs2 in response to increases in E2 on D4 of pregnancy.NEW & NOTEWORTHY Rhythmic expression of Bmal1 and Ptgs2 was observed in the uterus isolated from D3.5-4.5 of pregnant mice. E2 increased the expression of Bmal1 and Ptg2 in UESCs isolated from mice on D4. The expression of Ptgs2 was significantly decreased in Bmal1-siRNA treated UESCs. Bmal1 knockdown also inhibited PGE2 synthesis. Thus, these data suggest that Bmal1 in mice promotes PGE2 synthesis by upregulating Ptgs2 in response to increases in E2 on D4 of pregnancy.

An efficient silver-catalyzed method of decarboxylative radical allylation of α,α-difluoroarylacetic acids to build CF2-allyl bonds has been developed. Using allylsulfone as an allyl donor, α,α-difluorine substituted arylacetic acids bearing various functional groups are successfully allylated to access a series of 3-(α,α-difluorobenzyl)-1-propylene compounds in moderate to excellent yields in aqueous CH3CN solution under the mild conditions. Experimental studies disclosed that the α-fluorine substitution of arylacetic acid has a great influence on free radical activity and reactivity.

An efficient method for silver-catalyzed radical cascade arylthiodifluoromethylation/cyclization of isonitriles is disclosed. The transformation comprised addition of an arylthiodifluoromethyl radical generated in situ by the oxidative decarboxylation of arylthiodifluoroacetic salts to the isonitrile functionality to construct an ArSCF

Zearalenone (ZEA), a mycotoxin, is known to impair reproductive capability by disrupting the synthesis and secretion of testosterone by Leydig cells (LCs), although the mechanism is unknown. Robust rhythmicity of circadian clock and steroidogenic genes were identified in LCs. The aim of this study was to examine whether ZEA significantly attenuated the transcription of core clock genes (

A cathepsin B (Cat B)-responsive optical nanoprobe is designed and prepared for report of HL60 differentiation into macrophage. A peptide sequence FRFK is linked to fluorescein (FITC) via the distant amino group of its lysine and N-terminated with acrylic acid (AA) to yield a molecular fluorescent probe AA-FRFK (FITC). The molecular probe is further embedded in poly(lactic-co-glycolic acid) (PLGA) to form a fluorescent nanoprobe AA-FRFK (FITC)@PLGA. The resultant optical nanoprobe is degradable by lysosomal Cat B, which is expressed in macrophages with a level of 5-10 times of that in HL60 cells. As a result, a significant decrease in fluorescence intensity is associated with the differentiation process of HL60 to macrophage and can be used as an indication of the differentiation process. The findings may pave a way toward the development of a universal in vitro labeling strategy of exogenous stem cells for report of in vivo cell differentiation by a dual-mode imaging modality involving optical imaging and magnetic resonance imaging.

Glyphosate is a broad-spectrum herbicide that impairs testosterone synthesis in mammals. Leydig cells (LCs), the primary producers of testosterone, demonstrate rhythmic expression of circadian clock genes both in vivo and in vitro. The nuclear receptor NR1D1 is an important clock component that constitutes the subsidiary transcriptional/translational loop in the circadian clock system. Nr1d1 deficiency resulted in diminished fertility in both male and female mice. However, whether NR1D1 is involved in the glyphosate-mediated inhibition of testosterone synthesis in LCs remains unclear. Here, the involvement of NR1D1 in glyphosate-mediated inhibition of testosterone synthesis was investigated both in vitro and in vivo. Glyphosate exposure of TM3 cells significantly increased Nr1d1 mRNA levels, but decreased Bmal1, Per2, StAR, Cyp11a1, and Cyp17a1 mRNA levels. Western blotting confirmed elevated NR1D1 and reduced StAR protein levels following glyphosate exposure. Glyphosate exposure also reduced testosterone production in TM3 cells. In primary LCs, glyphosate exposure also upregulated Nr1d1 mRNA levels and downregulated the mRNA levels of other clock genes (Bmal1 and Per2) and steroidogenic genes (StAR, Cyp17a1, Cyp11a1, and Hsd3b2), and inhibited testosterone synthesis. Moreover, glyphosate exposure significantly reduced the amplitude and shortened the period of PER2::LUCIFERASE oscillations in primary LCs isolated from mPer2Luciferase knock-in mice. Four weeks of oral glyphosate upregulated NR1D1 at both the mRNA and protein levels in mouse testes, and this was accompanied by a reduction in StAR expression. Notably, serum testosterone levels were also drastically reduced in mice treated with glyphosate. Moreover, dual-luciferase reporter and EMSA assays revealed that in TM3 cells NR1D1 inhibits the expression of StAR by binding to a canonical RORE element present within its promoter. Together, these data demonstrate that glyphosate perturbs testosterone synthesis via NR1D1 mediated inhibition of StAR expression in mouse LCs. These findings extend our understanding of how glyphosate impairs male fertility.

An efficient silver-catalyzed method of decarboxylative radical allylation of α,α-difluoroarylacetic acids to build CF2-allyl bonds has been developed. Using allylsulfone as an allyl donor, α,α-difluorine substituted arylacetic acids bearing various functional groups are successfully allylated to access a series of 3-(α,α-difluorobenzyl)-1-propylene compounds in moderate to excellent yields in aqueous CH3CN solution under the mild conditions. Experimental studies disclosed that the α-fluorine substitution of arylacetic acid has a great influence on free radical activity and reactivity.

Testosterone is produced by Leydig cells (LCs) and undergoes diurnal changes in serum levels in rats, mice, and humans, but little is known in goats. The present study revealed that goat serum testosterone levels displayed diurnal rhythmic changes (peak time at ZT11.2). Immunohistochemical staining showed that BMAL1, a circadian clock protein, is highly expressed in goat LCs. ELISA revealed that both hCG (0-5 IU/ml) and 22R-OH-cholesterol (0-30 μM) addition stimulated testosterone synthesis in primary goat LCs in a dose-dependent manner. Treating goat LCs with hCG (5 IU/ml) significantly increased intracellular cAMP levels. Additionally, real-time quantitative polymerase chain reaction (PCR) analysis revealed that the circadian clock (BMAL1, PER1, PER2, DBP, and NR1D1) and steroidogenesis-related genes (SF1, NUR77, StAR, HSD3B2, CYP17A1, CYP11A1, and HSD17B3) showed rhythmic expression patterns in goat LCs following dexamethasone synchronization. Several Bmal1-Luc circadian oscillations were clearly observed in dexamethasone-treated goat LCs transfected with the pLV6-Bmal1-Luc plasmid. BMAL1 knockdown significantly downregulated mRNA levels of PER2, NR1D1, DBP, StAR, HSD3B2, SF1, NUR77, and GATA4, and dramatically decreased StAR and HSD3B2 protein levels and testosterone production. In contrast, BMAL1 overexpression significantly increased the mRNA and protein expression levels of StAR and HSD17B3 and enhanced testosterone production. Reporter assays revealed that goat BMAL1, or in combination with mouse CLOCK, activated goat HSD17B3 transcription in vitro. These data indicate that BMAL1 contributes to testosterone production by regulating transcription of steroidogenesis-related genes in goat LCs, providing a basis for further exploring the underlying mechanism by which the circadian clock regulates ruminant reproductive capability.

Two series of fluorine-containing fluorenyl anthracenes linked by a rigid sp3-hybridized carbon atom have been synthesized and characterized. The effect of a fluorine auxochrome at different positions in fluorene moiety on bulk properties, such as photophysical, electrochemical properties and thermal stabilities were investigated. The non-doped organic light-emitting diodes (OLEDs) utilizing C9-methylated fluorinated fluorenyl anthracene 4b as the emitter exhibits deep-blue emissions CIE x, y (0.159, 0.106) with efficiency of 1.31 cd/A and a maximum brightness of 2040 cd/m2 at 14 V. It was found that the introduction of fluorine auxochrome to the C2 position of fluorene could afford the best performances of OLEDs among the fluorinated materials.

Purpose Compared with traditional industrial processing technologies of sulfurized isobutylene, the one-step synthesis method involving high pressure is more environment-friendly and leads to better product performance. However, products from various sources perform differently because of the difference in the contents of their components. Therefore, the purpose of this study was to investigate the relationships between sulfide components of high-pressure sulfurized isobutylene and load carrying capacities. Design/methodology/approach A typical high-pressure sulfurized isobutylene was chosen, and the structure and contents of its sulfide components were characterized using gas chromatography-mass spectrometry and gas chromatography (GC). Extreme-pressure properties of the sample at different concentrations were evaluated using a four-ball tribometer. Findings A multiple regression equation model was established, and tert-butyl trisulfide made the greatest contribution to the extreme-pressure properties according to the equation coefficient, while tert-butyl tetrasulfide had no effect. The results can be attributed to the fact that the structure of a sulfurized additive having an impact is application-specific. Originality/value A precise and fast way to predict weld load values of high-pressure sulfurized isobutylene by using GC and the established equation model were successfully developed. Moreover, the empirical equation shows the relationships between sulfide component concentrations and load carrying capacities.

Purpose The purpose of this paper is to prepare metallocene polyalphaolefin 8 (mPAO8) by the oligomerization of olefin from coal with metallocene catalyst system and compare it with commercially available polyalphaolefin 8 (PAO8) from Chevron. Design/methodology/approach Molecular structures, component and mass were determined by nuclear magnetic resonance spectroscopy, gas chromatography and gel permeation chromatography, respectively. The physico-chemical properties, including Noack volatility, viscosity index and elemental analyses, were studied. The oxidative stability was evaluated by pressurized differential scanning calorimetry, whereas the thermal stability was studied by thermo-gravimetric analysis. Findings The produced mPAO8 consisted of a large part of tetramer, pentamer and a small part of trimer and hexamer. Additive T501 significantly improved the oxidation stability of PAO8 from Chevron and the synthesized mPAO8. Both samples had similar properties, such as oxidative stability, additive response, pour point and Noack volatility loss. But mPAO8 possessed a higher thermal stability, better viscosity index and flash point than PAO8. Therefore, the mPAO8 prepared by the oligomerization of olefin from coal could be used as base oil for lubricant development. Originality/value The mPAO8 base oil was successfully prepared by successive carbon numbers and shows similar properties with commercially available PAO8 products from Chevron. The findings can cover the shortage of the synthesis lubricants market in China.

A small molecule tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd‑DOTA)4‑TPP agent is used to label human mesenchymal stem cells (hMSCs) via electroporation (EP). The present study assessed the cytotoxicity of cell labeling, in addition to its effect on cell differentiation potential. There were no significant adverse effects on cell viability or differentiation induced by either EP or cellular uptake of (Gd‑DOTA)4‑TPP. Labeled live and dead hMSCs were transplanted into mouse forelimb muscles. T2‑weighted magnetic resonance imaging (MRI) was used to track the in vivo fate of the cell transplants. The labeling and imaging strategy allowed long term tracking of the cell transplants and unambiguous distinguishing of the cell transplants from their surrounding tissues. Cell migration was observed for live hMSCs injected into subcutaneous tissues, however not for either live or dead hMSCS injected into limb muscles. A slow clearance process occurred of the dead cell transplants in the limb muscular tissue. The MRI results therefore reveal that the fate and physiological activities of cell transplants depend on the nature of their host tissue.

An AgI-mediated ethoxycarbonyldifluoromethylation of isocyanides has been developed. This radical cascade reaction involves the addition of difluoromethylene radical to the isocyanide functionality, and subsequent homolytic aromatic substitution to give difluoromethylated phenanthridines with a good functional-group tolerance.

Copper-catalyzed gem-difluoromethylenation of the C(sp2)–H bonds of alkenes has been developed. This protocol is the first to efficiently achieve gem-difluoromethylenation of C(sp2)–H bonds of unactivated aliphatic terminal olefins and is applied in gem-difluoromethylenation/cyclization of alkenes.

A silver-catalyzed oxidative decarboxylative gem-difluoromethylenation of difluoroacetates with activated alkenes under mild reaction conditions has been developed. This radical cascade reaction provides a new method for the construction of a variety of gem-difluoromethylenated oxindoles.

Manganese-mediated/-catalyzed oxidative carboazidation of acrylamides was developed for the synthesis of various azido oxindoles in 32% to 99% yields. tert-Butyl peroxybenzoate (TBPB) was used as an oxidant for the Mn-catalyzed method. And a Mn(II)/Mn(IV)/Mn(III) catalysis cycle via a stepwise or concerted regeneration of high-valent manganese was proposed for this protocol. This reaction system exhibits great functional group tolerance.

The Acinetobacter sp. strain M isolated from a contaminated soil sample in Jiangsu Province of China was found to be able to degrade perfluorooctane sulfonamide (PFOSA) effectively. Fluoride anion (F- ) released from PFOSA degradation was detected by ion chromatography, and showed positive correlation to the growth curve of Acinetobacter sp. strain M. The PFOSA degradation efficiency of strain M was approximately 27 %, as assessed by GC analysis. It was shown that enzymes localized outside of cells of Acinetobacter sp. strain M catalyzed the degradation of PFOSA. This further indicates a possibly new (multi-step/pathway) mechanism for PFOSA degradation. It revealed that the extracellular enzyme of the Acinetobacter strain M preferentially cleaves carbon-carbon and carbon-fluorine bonds instead of destroying the carbon-sulfur bond. The growth condition for Acinetobacter sp. strain M was optimized at 30 °C and pH 7.0 in the presence of 2000 mg L-1 of PFOSA and 0.5 % (v/v) of Tween-20. The optimal PFOSA degradation time was found to be 12 h, with a degradation efficiency of 76 % by extracellular enzymes in strain M as determined by GC analysis. The result may provide potential applications for biodegradition of perfluoro organic compounds, such as derivatives of perfluorooctane (C8).

Mechanical operation could be seriously affected by friction and controlling it by oil lubrication has been considered as an effective way. Good lubricant additives are very necessary to avoid the friction damages, and to find or design new additives is always a challenge. In this study, a systematic investigation of using cholesteryl liquid crystals (LCs) as lubricant additives to obtain exceptional tribological behaviors was performed. In total, four cholesteryl LC compounds were synthesized targetedly and their thermal and mesogenic properties were studied to see the inherent relationship between the mesogenic phases and antifriction and antiwear performance. Through a series of tribological and related tests, including the UMT TriboLab test, three-dimensional optical microscopy, oil film thickness and viscosity tests, etc., the effect of the mesogenic phases and structures of the synthesized cholesteryl LCs on their tribological properties as lubricant additives was investigated and a related mechanism was analyzed. The result showed that within and close to the mesogenic phase temperature ranges, which we called as effective temperature ranges of LC additives ( T

The Ag(I)-catalyzed decarboxylative homocoupling from the difluoroacetate has been developed to the synthesis of symmetric CF2–CF2 containing dimers. This radical dimerization overpasses the prefunctionalization of the substrate and provides a direct and efficient method for construction of tetrafluoroethylene bridge-linked homodimers.

The first AgI-mediated C–H ethoxycarbonyl difluoromethylation with TMSCF2COOEt (TMS = trimethylsilyl) has been developed. The radical difluoromethylation proceeds smoothly to give the difluoromethylated arenes in moderate to high yields with Friedel–Crafts-type regioselectivity. Mechanistic studies indicate that the innate C–H difluoromethylation proceeds through an electrophilic radical-type pathway.

A simple AgI-mediated direct difluoromethylation reaction of activated alkenes by using TMSCF2COOEt (TMS = trimethylsilyl) under mild reaction conditions has been described. This reaction tolerates a variety of functional groups and allows for a highly efficient synthesis of various difluoro-containing oxindoles. Mechanistic investigations indicate that a difluoromethyl radical initiated the cascade sequence by undergoing an addition reaction to the alkene.

The synthetic hydrogel owns huge potential and broad prospects in cartilage tissue engineering due to a series of unique properties, such as bioactivity, the nutrition ions release ability, high mechanical properties and chondrogenesis capacity. Bioactive glass (BG) and PVA have been widely investigated and reported with safety and excellent biocompatibility as tissue engineering materials. In this study, we have synthesized a novel composite hydrogel formed by crosslinking between bioactive glass and PVA for cartilage repair, furthermore, we have explored the reaction mechanism of this hydrogel. It was found that hydrogen bonding was formed by the hydroxyl groups in PVA combining with the oxygen atoms from the non-bridge Si-O bond in bioactive glass, which can explain better mechanical properties for PM group than that of PVA. The tensile and compressive stress of PM5 hydrogel group has reached 4.8 MPa and 1.8 MPa equaling mechanical properties of natural articular cartilage. Moreover, the hydrogel can significantly support the proliferation of mice chondrocytes in vitro. Meanwhile, it can also effectively upregulate the expression of chondrogenesis related genes (AGGRECAN, SOX9, COL2). Therefore, the novel hydrogel possesses excellent properties in cartilage repair, and exhibits potential medical applications in the future.

An efficient method of copper-catalyzed aryldifluoromethylenation of N-arylacrylamides is described to step-economic synthesis of the various biologically important biheterocyclic compounds linked by gem-difluoromethylene moiety through addition of benzo-1,3-azolic (oxa- or thia-)difluoromethyl radicals generated in situ to terminal of C–C double bond of N-arylacrylamides then cyclization cascade. This protocol has demonstrated to have broad substrate scope and excellent functional-group tolerance under mild reaction conditions.

Organic dyes containing trifluoromethylated-pyrazolo[3, 4-b]quinoline were synthesized by using condensation reaction between substituted pyrazolo-4-formaldehyde and aryl amines in moderate yields. Quantum calculation, electrochemical, photophysical, and electroluminescent properties were discussed in detail. Electron-withdrawing groups at 6-position of dyes stabilized the LUMO energy levels significantly resulting in red-shifted absorption/emission spectra. Addition of electron-donating group destabilized the HOMO strongly and the LUMO energy levels slightly resulting in red-shifted absorption maxima, but in blue-shifted emission maxima. Experimental and quantum calculation results are presented here to explain this unusual phenomenon. A linear relationship of dipole moments versus Stokes shifts is obtained for these fluorophores, where the increase of dipole moment is accompanied by a decrease in Stokes shift. Organic light-emitting diodes based on selected dyes showed emission at 456 nm, maximum external quantum efficiency at 1.43%, and current efficiency at 1.95 cd/A.

Efficient direct gem-difluoromethylenation of an sp(3)-hybridized carbon center in benzyl bromides using benzo-1,3-azolic (oxa-, thia- or aza-) difluoromethyl bromides for construction of a CH2-CF2 linkage has been developed through radical/radical C-C cross-coupling via two separate single electron transfer processes (SET) under the promotion of different copper sources.

An efficient method for the synthesis of the thermally stable and pharmaceutically important gem-difluoromethylene azo compounds is developed. This protocol achieved gem-difluoromethylenation of the nitrogen center of arenediazonium salts through in situ generated benzo-1,3-diazolic difluoromethylene radical addition to arenediazonium salts under mild Ag-initiated conditions.

A copper(0)-promoted direct reductive gem-difluoromethylenation of unactivated aryl or alkenyl halides with benzo-1,3-azolic (oxa-, thia- or aza-) difluoromethyl bromides or 2-bromodifluoromethyl-1,3-oxazoline has been developed for the construction of pharmaceutically important gem-difluoromethylene-linked twin molecules. The unique π-conjugated aryl-fused 1,3-azolic moiety in difluoromethyl bromide substrates could stabilise the reaction intermediates, which promotes the reactivities, providing facile access to the cross-coupling products in good to excellent yields, and allowing significant functional group tolerance. The reaction exhibits an enhanced neighbouring-group-participation effect. This method could provide a new strategy for the construction of gem-difluoromethylene-linked identical or nonidentical twin drugs through further functionalisation of 1,3-azolic skeletons.

A copper-mediated gem-difluoromethylenation of aryl, heteroaryl and vinyl boronic acids with bromodifluoromethylated oxazole or thiazole derivatives has been developed. This novel reaction showed an excellent functional group tolerance and wide substrate scope, providing facile access to practical application in drug discovery and development.

A mild, versatile and efficient method for the regioselective hydrodifluoromethylation of unactivated alkenes has been developed. This Ag-mediated Csp3–CF2 bond forming reaction provides easy access to a variety of vicinal α-difluoroacetate-containing alkanes.

A class of chiral bifunctional N-prolyl sulfinamide and its TFA salts were prepared and proven to be effective for catalyzing the aldol reaction under solvent-free conditions. In general, the corresponding aldol adducts were obtained with high to excellent yields, and satisfactory diastereo-selectivities and enantioselectivities. A matching effect between chiral proline and sulfinamide moieties was observed in the catalysts. The enantioswitching of both enantiomers in the asymmetric aldol synthesis is found to be dominated by the prolyl moiety.

In this new Ag(I)-promoted reaction between N-arylacrylamides and ethyl trimethylsilyldifluoroacetate, the corresponding 3-(2-ethoxycarbonyl-2,2-difluoroethyl)-2-oxo-2,3-dihydro-1H-indoles have been prepared in good yields.

The aim of this work is to investigate the tribological behavior of a series of newly synthesized cholesterol liquid crystals used as oil-based lubricant additives and the relationship with their chemical structures and mesogenic phases. Totally five cholesterol ester type liquid crystals with flexible chain lengths of different carbon numbers were synthesized and all of them exhibited relatively wide chiral mesogenic phase temperature ranges. The chemical structures and purities of the liquid crystals were confirmed by different analytical methods; the mesophase behaviors were also characterized. UMT-tribolab and four ball tester were applied to test the anti-friction abilities of the liquid crystal additives in 150N and PAO 4 base oils, respectively; 3D optical profiler and atomic force microscope (AFM) were used to observe the generated wear scars and molecular layout of the synthesized additives; reflection-absorption fourier transform infrared spectrometry (RA-FT-IR) was employed to explain the possible changes in molecular orientation of liquid crystal additives and produced tribological effect. The results showed the tribological properties of the liquid crystal additives were closely related to their chemical structures and mesogenic behaviors. The liquid crystals with wider mesophase temperature ranges presented better tribological behaviors, and the ester groups with long alky tail lengths in their structures also played a crucial role. Among the five liquid crystal additives, LC-8 showed the widest mesogenic phase temperature range and the best tribological performance. Most of the series of cholesterol liquid crystals possessed the potential to be used as friction modifiers in some temperature sensitive applications.

A series of twisted fluorenyl anthracenes linked by a rigid sp3-hybridized carbon atom, containing an end-capping aryl substituent at either the C2-position of fluorene or at the C10-position of anthracene, have been synthesized and characterized. These materials exhibited good thermal stabilities and amorphous properties. Theoretical calculations and X-ray diffraction studies revealed that the six blue emitters possess non-coplanar structures to suppress intermolecular interactions. The relationship between the chemical structures with different end-capping groups and the electroluminescent properties has been investigated. Organic light-emitting diodes utilizing 9-(2-phenyl-9H-fluoren-9-yl) anthracene as the emitter exhibited deep-blue emissions CIE x, y (0.166, 0.153) with a current efficiency of 1.47 cd/A, external quantum efficiency of 1.84% at 20 mA/cm2 and a maximum brightness of 3013 cd/m2 at 11 V. It was found that the introduction of the aryl substituents to the C2 position of fluorene could improve the performance of OLEDs based on C9-fluorenyl anthracenes.

Optically active (S)-2-aryl-4 (or 5)-phenyl-1,3-oxazolines and (S)-2-fluoroalkyl-4-phenyl-1,3-oxazolines were synthesized from a tandem one-pot reaction of (S)-2-amino-2-phenylethanol with a corresponding carboxylic acid in toluene at 90 °C in the presence of PPh3/CBr4 and excess Et3N. The use of aromatic carboxylic acids were determined to proceed through N-(2-bromo-1-phenyl-ethyl)-arylamides 5 and N-aroyl aziridine intermediates 6, which resulted in the formation of (S)-2-aryl-4-phenyl-1,3-oxazolines and (S)-2-aryl-5-phenyl-1,3-oxazolines, respectively. Concurrently, the reaction with fluorinated aliphatic carboxylic acid substrates proceeded via N-(2-hydroxy-1-phenyl-ethyl)-fluoroalkyl amide intermediates 8, which were converted into N-(2-bromo-1-phenyl-ethyl)-fluoroalkyl amide intermediates 9, and then into (S)-2-fluoroalkyl-4-phenyl-1,3-oxazolines as final products. Reaction mechanisms that mainly passed through the formation of aziridine intermediates 6 in the reaction with aromatic carboxylic acids and the formation of fluoroalkyl amide intermediates 8 and 9 in the reaction with fluorinated aliphatic carboxylic acid were proposed. The acidities of the carboxylic acids that were employed were found to play a key role in the selective formation of various intermediates during this reaction.

A mild, versatile and efficient method for the silver(I)-catalyzed oxidative decarboxylative gem-difluoromethylenation has been developed. The radical cascade reaction comprises the addition of an oxidatively generated difluoromethylene radical to the isonitrile functionality and subsequent homolytic aromatic substitution. It provides a novel and efficient access to the C-CF2 bond formation.

Efficient direct gem-difluoromethylenation of an sp3-hybridized carbon center in benzyl bromides using benzo-1,3-azolic (oxa-, thia- or aza-) difluoromethyl bromides for construction of a CH2–CF2 linkage has been developed through radical/radical C–C cross-coupling via two separate single electron transfer processes (SET) under the promotion of different copper sources.

A facile one-pot procedure has been developed for the synthesis of 1,3-imidazolines and 1,3-oxazolines bearing fluorinated alkyl groups at the 2-position. The reaction involves the condensation of N-monosubstituted ethane-1,2-diamines or 2-aminoethanols with a fluorinated carboxylic acid in the presence of PPh3/CX4. The proposed mechanism is that the amide intermediates were initially formed, and then converted to the imidoyl halide intermediates in the presence of PPh3/CX4, followed by rapid intramolecular cyclization to 1,3-diazoline products. This protocol allows for the synthesis of 2-bromodifluoromethyl-1,3-imidazoline, a useful CF2Br-heterocyclic building block, which can be used for the synthesis of gem-difluoromethylene linked compounds.

A facile preparation of 2-bromodifluoromethyl benzo-1,3-diazoles as novel CF2Br-containing heterocyclic building blocks has been developed through a one-pot process of reaction of 2-OH, 2-SH, or 2-NH2 substituted aniline with bromodifluoroacetic acid in the presence of 3 molar equivalents of CBR4 and Ph3P in refluxing toluene. 2-Bromodifluoromethyl benzo-1,3-thiazole (2b) was successfully utilized in the preparation of gem-difluoromethylene linked aryl ether compounds through the reaction with phenolates or thiophenolate in DMF in good yields. (C) 2011 Elsevier B.V. All rights reserved.

A mild, versatile and efficient method for the silver(I)-catalyzed oxidative decarboxylative gem-difluoromethylenation has been developed. The radical cascade reaction comprises the addition of an oxidatively generated difluoromethylene radical to the isonitrile functionality and subsequent homolytic aromatic substitution. It provides a novel and efficient access to the C-CF2 bond formation.

Syntheses, optical, and electrochemical properties of novel C-9 fluorenyl substituted anthracenes linked by a tetrahedral sp(3)-hybridized carbon atom are reported for blue light emitting materials. Remarkably, an unoptimized organic light-emitting diode based on 1-fold fluorene-functionalized anthracene 3 exhibits a radiance of 4100 cd/m(2) at 12 V and a maximum EL efficiency of 1.36 cd/A with color purity CIE x, y (0.157, 0.082), which is very close to the National Television System Committee standard blue.

Optically active 2-aryl-1,3-oxazolines, such as aromatic carbocycles, heterocycle-binding 4-benzyl (or phenyl)-1,3-oxazolines and their 5-benzyl (or phenyl)-1,3-oxazoline isomers were successfully prepared through a bromotriphenylphosphonium salt promoted aziridine ring formation and ring opening sequential process involving tandem one-pot cyclization of chiral 2-amino-3-phenylpropanol or 2-amino-2-phenylethanol with various aromatic acids in toluene at 90 °C in moderate to excellent yields. The mechanism of this tandem process was also substantiated experimentally.

A reductive amination/cyclization approach towards biologically interesting trifluoromethylated four- to seven-membered ring lactams from simply prepared ω-trifluoromethyl keto esters in good to excellent yields has been developed. In addition, trifluoromethylated δ-amino alcohols were also obtained directly from an unexpected reduction of the corresponding y-imino esters in the presence of an excess amount of NaBH 4 .