Affinity‐Driven Covalent Modulator of the Glyceraldehyde‐3‐Phosphate Dehydrogenase (GAPDH) Cascade

Traditional medicines provide a fertile ground to explore potent lead compounds, yet their transformation into modern drugs is fraught with challenges in deciphering the target that is mechanistically valid for its biological activity. Herein we reveal that (Z)‐(+)‐isochaihulactone ( 1 ) exhibited significant inhibition against multiple‐drug‐resistant (MDR) cancer cell lines and mice xenografts. NMR spectroscopy showed that 1 resisted an off‐target thiolate, thus indicating that 1 was a target covalent inhibitor (TCI). By identifying the pharmacophore of 1 (α,β‐unsaturated moiety), a probe derived from 1 was designed and synthesized for TCI‐oriented activity‐based proteome profiling. By MS/MS and computer‐guided molecular biology approaches, an affinity‐driven Michael addition of the noncatalytic C247 residue of GAPDH was found to control the “ON/OFF” switch of apoptosis through non‐canonically nuclear GAPDH translocation, which bypasses the common apoptosis‐resistant route of MDR cancers.     

Morphological development in water assisted injection molded polyethylene/polyamide‐6 blends

Water assisted injection molding (WAIM) has gradually become one of the most important polymer processing methods for making hollowed parts. This study examined the morphological development in water assisted injection molded high density polyethylene (HDPE)/polyamide‐6 (PA‐6) blends. Samples for microscopic observation were prepared by an 80‐ton injection‐molding machine equipped with a tube cavity and with a water injection unit. A distinct skin layer, core region, and channel layer were observed across the thickness. The shape and size of the dispersed phase depended on the position both across the part thickness and along the flow direction. Small and large particles coexisted in the skin and channel layers, indicating that both coalescence and disintegration of the dispersed phase occurred in these layers. High water pressures were found to mold parts with smaller polyamide particle distributions. Additionally, the morphology of water assisted injection molded parts was compared to that of gas assisted injection molded products. It was found that water molded parts exhibit a smaller polyamide particle distribution than their gas counterparts. Copyright © 2010 John Wiley & Sons, Ltd.     

Solid Polymer Electrolyte Based on Pluronic P123 Triblock Copolymer‐Siloxane Organic‐Inorganic Hybrid

A novel organic‐inorganic hybrid electrolyte based on poly(ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide) triblock copolymer (Pluronic P123) complexed with LiClO₄ via the co‐condensation of an epoxy trialkoxysilane and tetraethylorthosilicate was prepared. Characterization was made by a variety of techniques including powder X‐ray diffraction, AC impedance, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and multinuclear solid state NMR measurements. The hybrid with [O]/[Li] = 16 exhibited a mesophase with a certain degree of ordering, which arose by the self‐assembly of P123 with the silica network. The P123 triblock copolymer acts as a structure‐directing surfactant to organize with silica networks and as a polymer matrix to dissolve alkali lithium salts as well. The DSC results indicated the formation of transient crosslinking between Li⁺ ions and the ether oxygens of the EO and PO segments, resulting in an increase the T_g with increasing salt concentrations. Variable temperature ⁷Li‐{¹H} MAS NMR spectra revealed the presence of two different local environments for lithium cations, probably due to the lithium cations in the polymer‐rich domain and in the silica‐rich domain, respectively. A combination of XRD and conductivity results suggests that the drastically enhanced conductivity for the ordered hybrid electrolyte is closely related to the formation of mesophase, which may provide unique Li⁺ conducting pathways.     

Catalytic asymmetric Staudinger reactions to form beta-lactams: an unanticipated dependence of diastereoselectivity on the choice of the nitrogen substituent

There are relatively few methods for the catalytic asymmetric synthesis of beta-lactams, and those that have been reported are generally cis selective. This communication describes the first catalytic enantioselective Staudinger reactions that preferentially furnish trans beta-lactams (trans = relationship of Ph to R1). The key to this method is the use of an N-triflyl protecting group for the imine. Along with serving as interesting targets in their own right, N-triflyl beta-lactams readily react with nucleophiles to generate useful families of compounds, such as gamma-amino alcohols and beta-amino acids.     

Synthesis and redox behavior of biferrocenyl-functionalized ruthenium(II) terpyridine gold clusters

Spectroscopic and electrochemical characterizations of ferrocene- and biferrocene-functionalized terpyridine octanethiolate monolayer-protected clusters were investigated and reported. The electrochemical measurements of Ru2+ coordinated with 4'-ferrocenyl-2,2':6',2' '-terpyridine and 4'-biferrocenyl-2,2':6',2' '-terpyridine complexes were dominated by the Ru2+/Ru3+ redox couple (E(1/2) at approximately 1.3 V), Fe(2+)/Fe(3+) redox couples (E(1/2) from approximately 0.6 to approximately 0.9 V), and terpy/terpy-/terpy2- redox couples (E(1/)(2) at ca. -1.2 and ca. -1.4 V). The substantial appreciable variations detected in the Ru2+/Ru3+ and Fe2+/Fe3+ oxidation potentials indicate that there is an interaction between the Ru2+ and Fe2+ metal centers. The coordination of the Ru2+ metal center with 4'-ferrocenyl-2,2':6',2' '-terpyridine and 4'-biferrocenyl-2,2':6',2' '-terpyridine leads to an intense 1[(d(pi)Fe)6] --> 1[d(pi)Fe)5(pi*terpyRu)1] transition in the visible region. The 1[(d(pi)Fe)6] -->1[d(pi)Fe)5(pi*terpyRu)1] transition observed at approximately 510 nm revealed that there was a qualitative electronic coupling between metal centers. The coordination of the Ru2+ transition metal center lowers the energy of the pi*terpy orbitals, causing this transition.     

Synthesis of aryl- and heteroaryl[a]pyrrolo[3,4-c]carbazoles

Synthesis of aryl- and hetero[a]pyrrolo[3,4-c]carbazoles by photochemical oxidation and Heck cyclization are described. Photochemical oxidation of 2-naphthyl indolyl maleimide affords two different carbazole regioisomers, depending on the reaction conditions. The regiochemistry of the cyclization can be controlled using the Heck reaction.     

Facile synthesis of 9-substituted 9-deazapurines as potential purine nucleoside phosphorylase inhibitors

A facile synthesis of 9-substituted 9-deazapurines as potential inhibitors of purine nucleoside phosphorylase has been achieved by the direct Friedel-Crafts aroylation or arylmethylation of 9-deazapurines using trifluoromethanesulfonic acid as catalyst. The aroylated 9-deazapurines could be transformed into the corresponding 9-aryimethyl derivatives by the Wolff-Kishner reaction. A novel synthesis of 9-deazahypoxanthine was also developed by treatment of 4-hydroxy-5-phenylazo-6-methylpyrimidin-2-thione with triethyl orthoformate in trifluoroacetic acid (TFA) to yield 8-oxo-7H-2-phenylpyrimido[5,4-c]pyridazin-6-thione followed by Raney nickel reduction.     

Determining eight colorants in milk beverages by capillary electrophoresis

Milk beverages are popular because of their high nutritional value, and milk products that are enhanced with various fruit flavors are especially in high demand in Asia. Colorants are usually added to fruit flavored milk in order to increase its attraction and appearance, therefore, the detection and measurement of colorants in this type of beverage are relatively important for health issue reasons. Carminic acid, a natural colorant, along with tartrazine, Fast green FCF, Brilliant blue FCF, Allura Red AC, Indigo carmine, Sunset yellow FCF, and New coccine, which are seven different synthetic food colorants, are commonly used as food additives, therefore, this study would focus on the development of an analytical method for the detection of these common colorants in milk beverages. A high efficiency capillary electrophoresis separation method was finished by a pH 10.0 running buffer containing 7.0 mM beta-cyclodextrin, and the eight colorants were separated with baseline resolution within 9 min. In order to reduce the matrix interference resulting from the constituents of milk, a suitable polyamide column solid-phase extraction (SPE) was also investigated for milk sample pretreatment. The combination of the simple SPE pretreatment and the fast separation method of capillary electrophoresis, was able to determine successfully without matrix interference the content of these colorant additives in commercial milk beverages. The recoveries of the eight food colorants in milk beverages were better than 85% and the detection limits were also lower than 0.5 microg/ml by the developed method.