A simple approach to C3-ethoxycarbonylmethylation of thiophenes/furans with diethyl bromomalonate.

A mild and efficient visible-light-induced radical method was developed to produce C3-malonated five-membered heterocycles using 2-substituted thiophenes/furans and diethyl bromomalonate as the starting materials. Various 2-substituted (benzo)thiophenes/furans were suitable for the C3-ethoxycarbonylmethylation. The free radical mechanism was proposed based on the results of control experiments, cyclic voltammetry experiments and luminescence quenching experiments. We suggested that the heteroleptic halogen-bridged iridium(III) dimers might play an important role in this system.

"One-Pot" Synthesis of γ-Pyrones from Aromatic Ketones/Heteroarenes and Carboxylic Acids.

Despite the various attractive properties of γ-pyrones, there are still some deficiencies in their synthetic approaches such as lower atom economy, multistep processes, and prefunctionalization of the reagents. In this work, an efficient and simple (CF3CO)2O/CF3SO3H-mediated "one-pot" approach was realized to produce γ-pyrones by applying aromatic ketones/heteroarenes and carboxylic acids as the starting materials. The target products were isolated in moderate to excellent yields. The reaction mechanism was studied by density functional theory calculational methods. The results of experimental and theoretical investigations not only helped us explain the reason of high selectivity formation of ß-diketones but also proved that 1,3,5-ketones might be important intermediates for the cyclization to afford γ-pyrones.

A visible-light-induced "on-off" one-pot synthesis of 3-arylacetylene coumarins with AIE properties.

A mild and simple one-pot stepwise method to synthesize 3-arylacetylene coumarins from alkynoates was demonstrated. This catalytic system involves photosensitizer-free photocatalysis and thermocatalysis processes. A series of alkynoates and phenylacetylenes were well tolerated in the optimized multi-catalytic system. The corresponding 3-arylacetylene coumarins were obtained in moderate to excellent yields. The results of the studies of their optical properties showed that the aromatic ring at the C4-position of coumarins is unfavorable for improving the molecular fluorescence quantum yield in solution. Based on the spectral studies and X-ray single crystal diffraction analysis, it was found that AIE activities may exist in some of the 3-arylvinyl-4-aryl-coumarins in their solid state. We expect that these molecules may have potential optical applications.

Pyrazoles: 'one-pot' synthesis from arenes and carboxylic acids.

A rapid and efficient method for 'one-pot' synthesis of pyrazoles from (hetero)arenes and carboxylic acids via successive formation of ketones and ß-diketones followed by heterocyclization with hydrazine has been developed. The utility of the RCOOH/TfOH/TFAA acylation system for intermediate production of ketones and 1,3-diketones is a key feature of this approach. The preliminary evaluation of the anticancer activity of the synthesized pyrazoles is performed.

An efficient light on-off one-pot method for the synthesis of 3-styryl coumarins from aryl alkynoates.

An efficient one-pot stepwise method to synthesize 3-styryl-4-arylcoumarins from simple alkynoates is demonstrated. On the basis of the control experiments, a possible mechanism involving light-driven radical cyclization and Pd-catalysed cross-coupling processes for this synthesis method is proposed. The results of X-ray analysis and spectroscopy experiments prove that the substituent effect has a significant influence on the absorption and emission properties of the synthesized 3-styryl coumarins.

Regioselective phosphinylation of coumarins under green LED irradiation and its mechanism.

The regioselective synthesis of 3-phosphinylated coumarins in moderate to excellent yields was developed via an EY/BPO-mediated cross-dehydrogenative coupling (CDC) reaction under green LED irradiation. The results of control experiments showed that the active intermediate, a P-centered radical, might be obtained through energy transfer and electron transfer processes.

G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia.

Aberrant activations of Fms-like tyrosine receptor kinase (FLT) 3 are implicated in the pathogenesis of 20% to 30% of patients with acute myeloid leukemia (AML). G-749 is a novel FLT3 inhibitor that showed potent and sustained inhibition of the FLT3 wild type and mutants including FLT3-ITD, FLT3-D835Y, FLT3-ITD/N676D, and FLT3-ITD/F691L in cellular assays. G-749 retained its inhibitory potency in various drug-resistance milieus such as patient plasma, FLT3 ligand surge, and stromal protection. Furthermore, it displayed potent antileukemic activity in bone marrow blasts from AML patients regardless of FLT3 mutation status, including those with little or only minor responses to AC220 or PKC412. Oral administration of G-749 yielded complete tumor regression and increased life span in animal models. Thus, G-749 appears to be a promising next-generation drug candidate for the treatment of relapsed and refractory AML patients with various FLT3-ITD/FLT3-TKD mutants and further shows the ability to overcome drug resistance.

Hierarchical helical assembly of conjugated poly(3-hexylthiophene)-block-poly(3-triethylene glycol thiophene) diblock copolymers.

We report on the solution-state assembly of all-conjugated polythiophene diblock copolymers containing nonpolar (hexyl) and polar (triethylene glycol) side chains. The polar substituents provide a large contrast in solubility, enabling formation of stably suspended crystalline fibrils even under very poor solvent conditions for the poly(3-hexylthiophene) block. For appropriate block ratios, complexation of the triethylene glycol side chains with added potassium ions drives the formation of helical nanowires that further bundle into superhelical structures.

A visible-light-induced photocatalyst-free approach for C-3 dicarbonyl coumarin production.

A mild and efficient visible-light-induced synthesis of C-3 dicarbonyl coumarins from 3-arylacetylene coumarins without a photocatalyst was reported. This iodide-mediated method exhibited broad substrate scope and good functional group tolerance, and a series of C-3 dicarbonyl coumarins were obtained in moderate to excellent yields. Based on the control experimental results, it was found that the visible-light-induced oxidation might be via both radical and ionic processes. Moreover, some synthesized compounds displayed high sensitivity to hydrogen peroxide (H2O2) with a low detection limit (DL, down to 0.149 µM).

Mesoscale surface patterning of a laterally-grafted rod amphiphile: rings and fibers.

An aromatic amphiphilic molecule based on branched oligo(ethylene oxide) was synthesized. Evaporation-driven ring formation and Langmuir-Blodgett films are investigated by utilizing this rigid-flexible block molecule. The size of the rings is strongly dependent on the solvent evaporation rate and the concentration of the molecule. In case of fast evaporation, volcano-like rings are formed by evaporating solution of high concentration. Perfectly symmetrical rings with diameters in the range of 2-6 microm are obtained by evaporating solution of low concentration. The formation mechanism of the ring is briefly discussed. The molecule at the air-water interface exhibits excellent amphiphilic properties. Upon transferring the monolayer onto solid substrates, AFM revealed the formation of fine and long, straight fibers. By combining the data obtained from the isotherms, AFM, water contact angle measurements, and UV/Vis and fluorescence spectra, the fibers are suggested to be formed by pi-pi stacking interaction of the aromatic rod segments as the oligo(ethylene oxide) branches are submerged in the water subphase upon compression. The fiber formation is associated with the transformation of the aromatic rod segments from the face-on conformation to the edge-on conformation.

Interconversion of planar networks and vesicles triggered by temperature.

Dumbbell-shaped amphiphiles based on an elongated rod segment can self-assemble into planar networks with in-plane hexagonally ordered pores in aqueous solution. On increasing temperature, the 2D networks change into hollow capsules passing through the closed sheets as an intermediate structure due to a LCST behavior of the oligoether dendritic exterior. The primary driving force for this interesting feature seems to originate from a consequence of the energy balance between hydrophobic interactions of anisotropic rod segments and alkyl chains, and repulsive interactions between dissimilar blocks. This dynamic structural variation triggered by external stimuli in a self-assembling system can provide a useful strategy to create smart supramolecular materials and biomimetic systems.

Synthesis of Aromatic Macrocyclic Amphiphiles and their Self-Assembling Behavior in Aqueous Solution.

A triblock amphiphilic macrocycle consisting of a macrocyclic aromatic segment, a hydrophilic oligo(ethylene oxide) branch, and a hydrophobic alkyl dendron is successfully synthesized and characterized. The resulting cyclic amphiphile is observed to self-assemble into hollow double-layered capsules in aqueous solution, as confirmed by dynamic light scattering and cryogenic transmission electron microscopy investigations. The capsules are able to encapsulate hydrophobic guest molecules through aromatic interactions with high stability.

Tubular stacking of water-soluble toroids triggered by guest encapsulation.

Coassembly of laterally grafted rod amphiphiles gives rise to the formation of water-soluble toroids with a hydrophobic interior. The toroids stack on top of each other to form a tubular container upon triggering by fullerene encapsulation.

Reversible transformation of helical coils and straight rods in cylindrical assembly of elliptical macrocycles.

We have demonstrated that, as the molecular length of elliptical macrocycle is increased, the self-assembled structure changes from spherical micelles to helical coils and finally to monolayered vesicles, in the order of decreasing interfacial curvature. Notably, the helical coils reversibly transform into straight rods upon heating while maintaining the supramolecular chirality. This structural transition is accompanied by conformational change of the elliptical macrocycles from a boat conformation to a more planar conformation.

Reversible scrolling of two-dimensional sheets from the self-assembly of laterally grafted amphiphilic rods.

Deep-water scrolls: It is demonstrated that amphiphilic rods containing lateral flexible chains self-assemble into two-dimensional sheets in aqueous solution (see picture). Remarkably, the sheets roll up reversibly into tubular scrolls upon heating, as confirmed by cryo-transmission electron microscopy and fluorescence microscopy.

Interfacial organization of Y-shaped rod-coil molecules packed into cylindrical nanoarchitectures.

The behavior at the air/water interface and the structures of Langmuir-Blodgett monolayers at different surface pressures of rod-coil molecules, which consist of a Y-shaped rigid aromatic segment containing peripheral tetradecyloxy groups and a flexible poly(ethylene oxide) (PEO) chain with 17, 21, 34, or 45 repeating ethylene oxide units (Y17, Y21, Y34, and Y45), were investigated. For the Y21 and Y34 molecules, AFM images revealed two kinds of cylindrical nanoarchitectures formed upon compression. The nanostructured films were further investigated by UV/Vis and FTIR spectroscopy. The formation of the cylindrical nanoarchitectures was due to different tilting angles offered by the mismatch of the cross-sectional areas of the PEO chain and the benzene ring with attached alkyl chains, and the different PEO contents of the molecules. The multiple pi-pi stacking and hydrophobic interactions provide exceptional stability of the nanostructures and allow them to be preserved in the course of flipping. For the shortest PEO chain of the Y17 molecule, spontaneous aggregation occurred. The Y45 molecule revealed the formation of 2D circular domains caused by entanglement of the longest PEO chains and coiling at the air/water interface. In addition, an interesting vortical morphology was obtained for the Y21 molecule upon deposition of the film onto a mica substrate, which indicates that the substrate chemistry also has an effect on the morphologies during the film-transfer process.

Modulatory Functionalization of Gold Nanorods Using Supramolecular Assemblies.

Supramolecular-assembly-mediated functionalization of gold nanorods (GNRs) has been developed by reversible phase transfer between water and oils, which offers a facile method for fabricating robust GNRs with surface-charge tunability. In this regard, trimethylammonium (TMA) GNRs were initially prepared from conventional cetyltrimethylammonium bromide (CTAB) GNRs by means of a ligand-exchange reaction in the presence of an excess amount of TMA ligands. To further expand their functionality and potential applications, electrostatic assemblies of positively charged TMA-GNRs with negatively charged oleate ions were prepared. These assemblies (OA-GNRs) can undergo facile phase transfer from water to hexane. Interestingly, the reversible electrostatic assembly between the TMA and OA ions fabricated onto GNRs can be easily disrupted by treatment with HCl, which removes the OA ions from the GNRs to re-form the TMA-GNRs, which can be made soluble in aqueous media again. In addition, OA-GNRs can be further used for the synthesis of negatively charged GNRs such as 11-mercaptoundecanoic acid (MUA) GNRs, which are hard to prepare directly from CTAB-GNRs. This versatile method for phase transfer and functionalization on GNRs is expected to broaden the scope of their applications in sensing, biomedical imaging, photothermal therapies, and drug delivery systems.

Method for Direct Synthesis of α-Cyanomethyl-ß-dicarbonyl Compounds with Acetonitrile and 1,3-Dicarbonyls.

A novel and efficient method for the synthesis of α-cyanomethyl-ß-dicarbonyls in moderate to excellent yields is developed by using inactive CH3CN and simple 1,3-dicarbonyls. A radical mechanism is proposed under the ESI-MS (electrospray ionization mass spectrometry) analysis results of control experiments.

Suppressive effect of AIF, a water extract from three herbs, on collagen-induced arthritis in mice.

AIF has been formulated using three herbs known to have anti-inflammatory and anti-osteolytic effects. In this study, the potential therapeutic effects of AIF for rheumatoid arthritis were assessed in vitro and in vivo. The effects of AIF on the inflammation (TNF-alpha, IL-1, iNO), cartilage protection (MMP-13), and selective killing of activated T cells were examined, in vitro. In addition, the therapeutic effect of AIF was evaluated using a collagen-induced arthritis (CIA) mouse model. DBA/1 mice were immunized with type II collagen. Following booster immunization, mice were treated with the oral administration of 276 mg/kg/d AIF once a day for 18 days, then, the severity of CIA was evaluated by macroscopic scoring and histopathological assessment. AIF significantly inhibited the production of TNF-alpha, IL-1, iNO, and MMP-13 in a dose dependent manner in vitro. Also, AIF killed activated T cells selectively, conserving naïve T cells. The oral administration of AIF in CIA mice suppressed the progression of CIA significantly and decreased synovial hyperplasia, cartilage destruction, and bone erosion. AIF showed potent anti-inflammatory effects in vitro and substantial protective effect for the progression of CIA in vivo. These results suggest that AIF contains effective compound(s) which may modify the progression of rheumatoid arthritis.