Self-selection in olefin cross-metathesis: the effect of remote functionality

Olefin cross-metathesis (CM) is potentially an attractive method for generating dynamic combinatorial libraries (DCLs). In order for the CM reaction to be useful for DCL production, the course of the reaction and product distribution must be relatively insensitive to functionality remote from the reacting centers. We report on the CM of a series of allyl- and homoallylamides that are strongly dependent on remote functionality. This includes an unusual example of a cis-selective CM. [Reaction: see text]     

A chemical inhibitor reveals the role of Raf kinase inhibitor protein in cell migration

Raf kinase inhibitor protein (RKIP) is a modulator of cell signaling that functions as an endogenous inhibitor of multiple kinases. We demonstrate here a positive role for RKIP in the regulation of cell locomotion. We discovered that RKIP is the relevant cellular target of locostatin, a cell migration inhibitor. Locostatin abrogates RKIP's ability to bind and inhibit Raf-1 kinase, and it acts by disrupting a protein-protein interaction, an uncommon mode of action for a small molecule. Small interfering RNA-mediated silencing of RKIP expression also reduces cell migration rate. Overexpression of RKIP converts epithelial cells to a highly migratory fibroblast-like phenotype, with dramatic reduction in the sensitivity of cells to locostatin. RKIP is therefore the compound's valid target and a key regulator of cell motility.     

Toluene dioxygenase-mediated oxidation of dibromobenzenes. Absolute stereochemistry of new metabolites and synthesis of (−)-conduritol E

Dibromobenzenes (o-, m-, and p-isomers) were converted to the corresponding cis-cyclohexadiene diols by whole-cell fermentation with Escherichia coli JM 109 (pDTG601A), an organism over-expressing the enzyme toluene dioxygenase (TDO). Absolute stereochemistry of new metabolites was determined, and (−)-conduritol was synthesized.     

The synthesis and spectroscopic properties of some but-2-yne tungsten complexes of the type [WIX(CO){Ph2P(CH2)PPh2}(η-MeC2Me)] (X = Cl, Br, I, NO2, NO3, NCS or OH)

Reaction of the cationic complex [WI(CO)(NCMe){Ph₂P(CH₂)PPh₂}(η²-MeC₂ME)][BF₄] with an equimolar amount of MX (MX = NaCl, NaBr, NaI, KNO₂, KNO₃, NaNCS or KOH) in acetone at room temperature gave the neutral complex [WIX(CO){Ph₂P(CH₂)PPh₂}(η²-MeC₂Me)] (1–7) in good yield. Complexes 1–7 have been characterized by elemental analysis (C, H and N), IR and ¹H NMR spectroscopy.     

Lewis-Base Adducts of Group 11 Metal(I) Compounds. LXXVI Structural Studies in the Copper(I) Halide : Norbornadiene System

The structural characterizations of some copper(I) halide (CuX) adducts with norbornadiene (nbd) are recorded. CuCl : nbd (1:1)₄ (a redetermination), (2:1)_2(|), are systems both based around Cu₄Cl₄ cubane-type cluster arrays. CuBr : nbd (7:3)_(|)( 0.5 MeOH), a complex polymer with 3-symmetry, is believed to be the complex previously described as an adduct of 2:1 stoichiometry. Attempts to obtain an iodide counterpart have resulted in the definition of an ephemeral adduct CuI : MeCN (3:2)_(|). 0.5 C₇H₈ in which, remarkably, the nbd is uncoordinated; the complex is a polymer, related to the [AgX(quinoline)]_(|) (X = Cl, Br) saddle polymer.     

EVALUATION OF NEW BENZOPORPHYRIN DERIVATIVES WITH ENHANCED PDT EFFICACY*

Abstract— A first report on the biological evaluation of a series of isomerically pure benzoporphyrin derivatives ( cis- and frarcs-isomers) as methyl esters is described. In preliminary in vivo studies, the n- bexyl ether analogues of both cis- and trans -isomers of benzoporphyrin derivatives were found to be more active than the industrially prepared benzoporphyrin derivative, a mixture of monocarboxylic acids (BPDMA, Quadralogic Technologies, Vancouver). Further studies with 4-de-vinyl-4-(I-hexyloxyethyl) benzoporphyrin derivative showed that, like BPDMA, it had reduced residual skin phototoxicity compared in mice with Photofrin®. The uptake and clearance characteristics of BPDMA were also compared with the 4-(1-hexyloxyethyl)-derivative by in vivo reflection spectroscopy.     

“Click handle”-modified 2′-deoxy-2′-fluoroarabino nucleic acid as a synthetic genetic polymer capable of post-polymerization functionalization

The functions of natural nucleic acids such as DNA and RNA have transcended genetic information carriers and now encompass affinity reagents, molecular catalysts, nanostructures, data storage, and many others. However, the vulnerability of natural nucleic acids to nuclease degradation and the lack of chemical functionality have imposed a significant constraint on their ever-expanding applications. Herein, we report the synthesis and polymerase recognition of a 5-(octa-1,7-diynyl)uracil 2′-deoxy-2′-fluoroarabinonucleic acid (FANA) triphosphate. The DNA-templated, polymerase-mediated primer extension using this “click handle”-modified FANA (cmFANA) triphosphate and other FANA nucleotide triphosphates consisting of canonical nucleobases efficiently generated full-length products. The resulting cmFANA polymers exhibited excellent nuclease resistance and the ability to undergo efficient click conjugation with azide-functionalized molecules, thereby becoming a promising platform for serving as a programmable and evolvable synthetic genetic polymer capable of post-polymerization functionalization.

Polymerase-mediated incorporation of a “click handle”-modified fluoroarabinonucleic acid (cmFANA) triphosphate produces a new class of nuclease-resistant, evolvable genetic polymers that can be functionalized with azide-containing molecules.     

Precise Quantification of Molybdate In Vitro by the FRET-Based Nanosensor ‘MolyProbe’

Molybdenum (Mo) is an essential trace element in all kingdoms of life. Mo is bioavailable as the oxyanion molybdate and gains biological activity in eukaryotes when bound to molybdopterin, forming the molybdenum cofactor. The imbalance of molybdate homeostasis results in growth deficiencies or toxic symptoms within plants, fungi and animals. Recently, fluorescence resonance energy transfer (FRET) methods have emerged, monitoring cellular and subcellular molybdate distribution dynamics using a genetically encoded molybdate-specific FRET nanosensor, named MolyProbe. Here, we show that the MolyProbe system is a fast and reliable in vitro assay for quantitative molybdate determination. We added a Strep-TagII affinity tag to the MolyProbe protein for quick and easy purification. This MolyProbe is highly stable, resistant to freezing and can be stored for several weeks at 4 °C. Furthermore, the molybdate sensitivity of the assay peaked at low nM levels. Additionally, The MolyProbe was applied in vitro for quantitative molybdate determination in cell extracts of the plant Arabidopsis thaliana, the fungus Neurospora crassa and the yeast Saccharomyces cerevisiae. Our results show the functionality of the Arabidopsis thaliana molybdate transporter MOT1.1 and indicate that FRET-based molybdate detection is an excellent tool for measuring bioavailable Mo.     

Bioactive Components and Anticancer Activities of Spray-Dried New Zealand Tamarillo Powder

Tamarillo fruit contains many phytochemicals that have beneficial therapeutic and nutritional properties. Spray-drying is widely used to preserve fruit puree in powder form. However, to obtain high-quality fruit powder, the optimisation of spray-drying conditions is necessary, as a high drying temperature can damage sensitive bioactive compounds. This study investigated the effects of spray-drying on the microstructure, polyphenolics, total flavonoids, total carotenoids, antioxidant activity, and anticancer capacity of tamarillo powder. Response surface methodology (RSM) was used to optimise the spray-drying process to produce tamarillo powder. The independent variables were inlet drying temperature (120–160 °C), flow rate (1–5 g/mL), and maltodextrin concentration (0–10%). These variables influenced the microstructural attributes, bioactive components, and cytotoxicity of the spray-dried tamarillo powder. The increase in polyphenols and antioxidant activities were favoured under high-temperature spray drying conditions and a low carrier concentration. The optimised spray-drying conditions for producing tamarillo powder with high antioxidant and anticancer activities, high yield, and stable bioactive compounds were found to be at 146.8 °C inlet temperature, and a flow rate of 1.76 g/mL.