Synthetic Tigliane Intermediates Engage Thiols to Induce Potent Cell Line Selective Anti-Cancer Activity

The tigliane ring system, which encompasses iconic members such as phorbol and TPA, is widely renowned due to numerous observations of displaying potent biological activity, and subsequent use as mainstream biochemical tools. Traditionally, naturally occurring phorboids are regarded as tumor promotors through PKC activation, although in recent times more highly oxidized natural derivatives have been identified as anti-tumor agents. In the view that only limited synthetic investigations toward skeletal stereochemical modification have been undertaken, non-natural systems could be useful for a better understanding of the tigliane pharmacophore via interrogation of cellular sensitivity. In this context the concise construction of a number of highly functionalized non-natural D-ring inverted phorbol esters were synthesized, via a rhodium-catalyzed [4+3] cycloaddition, and biologically evaluated using a range of cancer cell lines. The biological results highlight the notion that subtle changes in structure have dramatic effects on potency. Furthermore, although the non-natural derivatives did not outcompete the natural systems in the PKC-activation sensitive MCF7 cancer cell line, they outperformed in other cancer cell lines (MM96L and CAL27). This observation strongly suggested an alternate mode of action not involving activation of PKC, but instead involves thiol addition as indicated by glutathione addition and NF-κB reporter activity.     

Microwave-Assisted Extraction Coupled to HPLC-UV Combined with Chemometrics for the Determination of Bioactive Compounds in Pistachio Nuts and the Guarantee of Quality and Authenticity

Two novel microwave-assisted extraction (MAE) methods were developed for the isolation of phenols and tocopherols from pistachio nuts. The extracts were analyzed by reversed-phase high-pressure liquid chromatography coupled with a UV detector (RP-HPLC-UV). In total, eighteen pistachio samples, originating from Greece and Turkey, were analyzed and thirteen phenolic compounds, as well as α-tocopherol, (β + γ)-tocopherol, and δ-tocopherol, were identified. The analytical methods were validated and presented good linearity (r² > 0.990) and a high recovery rate over the range of 82.4 to 95.3% for phenols, and 93.1 to 96.4% for tocopherols. Repeatablility was calculated over the range 1.8–5.8%RSD for intra-day experiments, and reproducibility over the range 3.2–9.4%RSD for inter-day experiments, respectively. Principal component analysis (PCA) was employed to analyze the differences between the concentrations of the bioactive compounds with respect to geographical origin, while agglomerative hierarchical clustering (AHC) was used to cluster the samples based on their similarity and according to the geographical origin.     

A new layered Ca–succinate coordination polymer

A new layered Ca–succinate coordination polymer, poly[μ₃‐succinato‐calcium(II)], [Ca(C₄H₅O₄)]_n, was synthesized by reaction of CaCl₂·2H₂O and succinic acid in an aqueous medium under hydrothermal microwave conditions. The structure contains infinite layers of edge‐sharing calcium pentagonal–bipyramidal polyhedra forming six‐membered rings connected through succinate ligands. Such an assembly of inorganic building units is unique for calcium metal–organic framework‐type structures. Adjacent layers are packed into a final pseudo‐three‐dimensional structure through weak C—H...O hydrogen bonds.     

Anthocyanins profile,total phenolics and antioxidant activity of two Romanian red grape varieties: Fetească neagră and Băbească neagră (<Emphasis Type="Italic">Vitis vinifera</Emphasis>)

The phenolic composition of Feteasc? neagr?and B?beasc? neagr? grapes from Dealul Bujorului vineyard (south-east Romania) was studied using the spectrophotometric and high-performance liquid chromatographic (HPLC) methods. The results revealed significant differences between these cultivars. Total anthocyanins ranged from 0.22–5.98 mg g^?1 DW berries in B?beasc? neagr? grapes to 0.54–18.54 mg g^?1 DW berries in Feteasc? neagr?. Both cultivars were characterised by an interesting anthocyanin profile for winemaking with a prevalence of malvidin-3-glucoside. The skins and seeds both had small amounts of flavonoids. In contrast with B?beasc? neagr?, Feteasc? neagr? had more flavonoids in the seeds (69 %) than in the skins. Statistically significant correlations were observed between antioxidant activity and total anthocyanin content in both varieties. The antioxidant activity was also found to be highly correlated to the total phenolic compounds content.     

Switching mechanism in polar columnar mesophases made of bent-core molecules.

The behaviour of polar, broken-layer-type columnar phases made of bent molecules (B(1Rev) and B(1RevTilted)) was studied under an applied electric field. There are two competing mechanisms of ferroelectric switching in the polar B(1RevTilted) columnar phase: collective rotation around the long molecular axis and collective rotation around the tilt cone. The proposed model shows that the main factor discriminating the type of switching is the width of the column cross-section.     

An Efficient Iterative Procedure for Solution of Plasma Loaded Helical Waveguide Problems

The behaviour of axially-symmetric waves travelling on plasma filled screened helical coil is comprehensively studied by Anicin [J. Phys. D： Appl. Phys. 33 （2000） 1276], where all analytical expressions are derived in the full-wave theory, but the diagrams are computed in the quasistatic approximation. We use an iterative procedure to overcome this limitation. The iterative procedure is rapid and we have proven that often the first-order approximant is sufficient to improve defects which are known as immanent to the quasistatic approximation. The fixed point method appears as the natural choice for numerical treatment of formulae which could arise in a broad class of physical problems usually recognized as guided surface plasma waves.     

Substrate-promoted formation of a catalytically competent binuclear center and regulation of reactivity in a glycerophosphodiesterase from Enterobacter aerogenes

The glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes is a promiscuous binuclear metallohydrolase that catalyzes the hydrolysis of mono-, di-, and triester substrates, including some organophosphate pesticides and products of the degradation of nerve agents. GpdQ has attracted recent attention as a promising enzymatic bioremediator. Here, we have investigated the catalytic mechanism of this versatile enzyme using a range of techniques. An improved crystal structure (1.9 A resolution) illustrates the presence of (i) an extended hydrogen bond network in the active site, and (ii) two possible nucleophiles, i.e., water/hydroxide ligands, coordinated to one or both metal ions. While it is at present not possible to unambiguously distinguish between these two possibilities, a reaction mechanism is proposed whereby the terminally bound H2O/OH(-) acts as the nucleophile, activated via hydrogen bonding by the bridging water molecule. Furthermore, the presence of substrate promotes the formation of a catalytically competent binuclear center by significantly enhancing the binding affinity of one of the metal ions in the active site. Asn80 appears to display coordination flexibility that may modulate enzyme activity. Kinetic data suggest that the rate-limiting step occurs after hydrolysis, i.e., the release of the phosphate moiety and the concomitant dissociation of one of the metal ions and/or associated conformational changes. Thus, it is proposed that GpdQ employs an intricate regulatory mechanism for catalysis, where coordination flexibility in one of the two metal binding sites is essential for optimal activity.     

Modulated structures in bent-core liquid crystals: two faces of one phase

The Landau-de Gennes type continuous model is used to describe the 2D modulated structures made of bent-core liquid crystals. It is shown that modulation is a direct consequence of the chiral symmetry breaking. Structures with synclinic and anticlinic layer tilt are found to coexist in the polarization modulated and layer undulated (PM-LU) liquid crystal phase. The synclinic PM-LU structure corresponds to the columnar B(1RevTilted) phase. Experimentally obtained electron density maps are included, which support theoretical findings.     

On the thermal degradation of 3-methylaminopropylamine captured inside the aluminum phosphate analog of ULM-3

An open-framework aluminophosphate analog of the fluorogallophosphate structure-type ULM-3 was obtained by hydrothermal crystallization of an aqueous aluminum phosphate suspension in the presence of 3-methylpropylamine (MAPA) and hydrofluoric acid. The open-framework fluorinated aluminophosphate structure was confirmed by Rietveld analysis and the ²⁷Al, ³¹P, and ¹⁹F MAS NMR spectroscopy. The MAPA, located in the ten-membered ring channels, is doubly protonated to balance the negative charge of the Al₃P₃O₁₂F₂ ^2– framework. Thermogravimetric analysis data have been used to study kinetics of the thermal decomposition of MAPA. The decomposition was found to be a complex process, its activation energy varied from 177 to 259 kJ mol⁻¹. The relatively high E values are explained by the fact that the MAPA cations are bound to the anionic framework both by electrostatic forces as well as strong N-H…O hydrogen bonds. The strength of the interactions is indirectly confirmed by the in situ high temperature X-ray diffraction analysis which shows that the MAPA decomposition leads to a phase transformation of the open-framework structure to the dense trydimite phase.     

Structure investigation of fluorinated aluminophosphate ULM-3 Al templated by 3-methylaminopropylamine

A single-crystal X-ray diffraction analysis of an open-framework aluminophosphate ULM-3 Al prepared by 3-methylaminopropylamine (MAPA) as structure-directing agent revealed an orthorhombic Pcab symmetry (a=9.9949(4) Å, b=15.8229(7) Å, c=18.1963(5) Å, R=0.0648, Z=8, unit cell formula [Al₂₄P₂₄O₉₆F₁₆·C₃₂H₁₁₂N₁₆]), which differs from the Pbc2₁ symmetry of the structural analogue prepared in the presence of 1,4-diaminobutane. The ²⁷Al, ³¹P, ¹⁹F, ¹³C and ¹H NMR investigations, which were performed to study in detail MAPA arrangement inside the framework as well as the interactions of MAPA with the aluminophosphate host, confirmed the crystal symmetry and the proposed hydrogen bonding scheme between the template and the framework.