No abstract

1 We have examined the generation of intracellular reactive oxygen species (ROS) and release of histamine by rat peritoneal mast cells (RPMC) in response to stimulation with antigen (ovalbumin), compound 48/80, nerve growth factor (NGF) and substance P (SP). 2 We have also examined the eects of the non-speci®c nitric oxide synthase inhibitor, L-NAME (100 mM) upon the release of histamine and generation of intracellular ROS in response to the named secretagogues. 3 Ovalbumin (100 ± 1000 mg ml 71 ), compound 48/80 (0.1 ± 100 mg ml 71 ), NGF (0.1 ± 100 mg ml 71 ), and SP (5 ± 50 mM), caused a concentration-dependent release of histamine from RPMC. 4 Ovalbumin (1 ng ml 71 ± 0.1 mg ml 71), compound 48/80 (1 ± 100 mg ml 71 ), NGF (1 pg ml 71 ± 1 mg ml 71 ), and SP (0.005 ± 50 mM) caused a concentration-dependent generation of intracellular ROS by RPMC. 5 Pre-incubation of RPMC with L-NAME (100 mM) caused a signi®cant enhancement of both histamine release and intracellular ROS from RPMC in response to ovalbumin, compound 48/80, NGF and SP. 6 Our data demonstrate that NGF, SP and ovalbumin are capable of causing intracellular ROS generation by RPMC at lower concentrations than those causing signi®cant histamine release and we speculate that this may contribute to the activation of cytokine production. 7 The data also show that NO modulates histamine release, and ROS generation in response to the secretagogues used. This may have signi®cance in pathologies where NO synthesis is decreased, leading to an increased activation of mast cells.

The single crystal X-ray structure of the all-axial conformer of the (R,R,R,R) enantiomer of the chiral donor tetramethyl-BEDT-TTF (TM-BEDT-TTF) was described and compared to the all-equatorial conformer. (S,S,S,S)-Tetramethyl-BEDT-TTF formed crystalline 1 : 1 complexes with TCNQ and TCNQ-F 4 , as well as a THF solvate of the TCNQ complex. Donors bis((2S,4S)-pentane-2,4-dithio)tetrathiafulvalene and (ethylenedithio)((2S,4S)-pentane-2,4-dithio)tetrathiafulvalene, which contain seven-membered rings bearing chirally oriented methyl groups, only formed complexes with TCNQ-F 4. The TCNQ-F 4 complexes contain planar organosulfur systems, in contrast to the TCNQ complexes in which there is minimal charge transfer. A variety of crystal packing modes were observed. Electrocrystallization experiments with both enantiomers and the racemic form of tetramethyl-BEDT-TTF afforded mixed valence radical cation salts with the AsF 6 and SbF 6 anions formulated as (TM-BEDT-TTF) 2 XF 6 (X = As, Sb). Electrical conductivity was only found in one charge transfer complex, while the radical cation salts are all semiconducting.

In vivo, LPS stimulates TxA2 production and p38 MAPK phosphorylation in equine platelets and leukocytes at a concentration within a similar range to those reported in clinical endotoxaemia. These data suggest that LPS-induced eicosanoid production in the early phase of clinical endotoxaemia may involve direct effects of LPS upon platelets, mediated via activation of p38 MAPK.

Abstract.The syntheses of a range of enantiopure organosulfur donors with hydrogen bonding groups are described including TTF related materials with two, four, six and eight hydroxyl groups and multiple stereogenic centres and a pair of chiral N-substituted BEDT-TTF acetamides. Three charge transfer salts of enantiopure poly-hydroxysubstituted donors are reported, including a 4:1 salt with the meso stereoisomer of the dinuclear [Fe2(oxalate)5 ] 4-anion in which both cation and anion have chiral components linked together by hydrogen bonding, and a semiconducting salt with triiodide.

Background: A functional vascular network is essential for the survival, growth and spread of solid tumours, making blood vessels a key target for therapeutic strategies. Combretastatin A-4 phosphate (CA-4-P) is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent. Not much is known of the molecular effect of CA-4-P under tumour conditions. The tumour microenvironment differs markedly from that in normal tissue, specifically with respect to oxygenation (hypoxia). Gene regulation under tumour conditions is governed by hypoxia inducible factor 1 (HIF-1), controlling angiogenic and metastatic pathways.

Abstract. Six new enantiopure chiral organosulfur donors, with structures related to BEDT-TTF, have been synthesised for use in the preparation of organic metals, starting either by double nucleophilic substitutions on the bis-mesylate of 2R,4R-pentane-2,4-diol or by a cycloaddition with subsequent elimination of acetic acid on the enol acetate of (+)-nopinone. Crystal structures of some of their radical cation triiodides salts and TCNQ complexes are reported. 2 IntroductionThe radical cation salts and charge transfer molecular complexes of TTF 1 and BEDT-TTF 2 show a wide range of electrical behaviour, and have found use in a range of systems including metallic systems, semiconductors and low-temperature superconductors. Here we report the synthesis of a group of novel chiral organosulfur donors, 11-16, in which chirality is provided by one or more hydrocarbon groupings. The structures of products from initial experiments to form charge transfer complexes are also described. 4 Discussion Synthesis of 11 and 12Electrocrystallisation of the enantiopure donor (S,S,S,S)-tetramethylBEDT-TTF 5 has given a series of radical cation salts, but their crystal structures were pseudocentrosymmetric, with the methyl groups adopting equatorial orientations. 6 However, we reasoned that insertion of a methylene group between each pair of stereogenic centres to give 11 would provide a more promising system. The outer seven-membered rings of donor 11 would be expected to adopt chair conformations and give two possible molecular conformations, A and B (Fig. 1), in analogy with the structures of 17-19. 17 The trans orientation of the methyl groups on the propylene bridge would force one into an axial position and the other into an equatorial position.Molecules in conformation B could be envisaged to stack in a helix. The synthesis of donor 11 started with the cyclisation of the dithiolate 20, prepared in three steps from carbon disulfide, 18 with the bis-mesylate of R,R-pentane-5 2,4-diol (Scheme 1). The first mesylate group is substituted by reaction in methanol at room temperature, but it was necessary to replace the methanol with THF and heat to reflux to complete the cyclisation to give the thione 21 in 45% yield. The thione was converted to oxo compound 22 using mercuric acetate in quantitative yield, and this was then homocoupled in refluxing trimethyl phosphite over 24 hours to give 11 in 75% yield. Cross-coupling, under similar conditions, of oxo compound 22 with a three-fold excess of the unsubstituted thione 23 yielded the cross-coupled donor 12 in 22% yield after chromatography. The low yield of 12 is a consequence of the faster homocoupling of thione 23 to give BEDT-TTF. Scheme 1The molecular structures of donors 11 and 12 were determined by X-ray crystallography. For both donors the seven-membered rings adopt chair conformations with one methyl group in an axial position and one in an equatorial position. For the homocoupled donor 11 (Fig. 2) the structure of the organosulfur system deviates very strongly from plana...

Two novel enantiopure bis(pyrrolo|3,4-d|)tetrathiafulvalene i « derivatives, substrates for preparing chirol conducting materials, show chiral crystal packing arrangements in which successive layers are rotated in accordance with an exact or approximate 4 S axis. The corresponding donors containing fused di hydro pyrrole groups, and thus four more hydrogen i5 atoms, form stacks along a crystal axis.bisfpyrrolo [3,4-d]tetrathiafulvalene system and the helical-type 45 chiral packing arrangements of donors 8 and 10, an important stepping stone to the production of electroactive materials with chiral packing arrangements. The preparative route (Scheme) builds on Becher's approach to bisjpyrroloJTTF.