Liquid-crystalline polymers containing macrocyclic polyethers, 2. Side-chain liquid-crystalline copolysiloxanes containing mesogenic units based on 1,3-dioxane-2,5-diyl and benzo[15]-crown-5

Synthesis and characterization of a series of copolysiloxanes containing crown ether and trans-1,3-dioxane based mesogens are presented. The phase behaviour of the copolymers was studied using differential scanning calorimetry and optical polarizing microscopy and compared with the phase behaviour of the corresponding copolysiloxane-containing crown ether and biphenyl-based mesogens. Two copolysiloxanes containing trans-2-(benzo-[15]crown-5)-5-(ω-alkan-1-yloxy)-1,3-dioxane side groups present no liquid-crystalline behaviour. The other four copolysiloxanes exhibit a nematic mesophase and undergo side-chain crystallization at low temperature. Two of the four copolysiloxanes which contain a trans-1,3-dioxane-2,5-diyl group in the mesogenic unit present lower isotropization temperatures and narrower mesophase ranges than the other two. This result reveals that replacing a phenyl ring in the mesogenic unit of a liquid-crystalline polymer by a trans-1,3-dioxane ring will decrease the thermal stability of the mesophase exhibited by this polymer.     

Thermally stimulated current and DSC studies of the dual glass transitions in side-chain liquid crystalline copolysiloxanes containing 4-[(S)-2-methylbutoxy]phenyl 3-chloro-4-alkenyloxybenzoate side groups

The synthesis of side-chain liquid crystalline copolysiloxanes containing ω-[4-[4-[(S)-2-methylbutoxy]phenoxycarbonyl]-2-chlorophenoxy]alkyl side groups is presented. Differential scanning calorimetry, optical polarizing microscopy and X-ray diffractometry reveal smectic mesomorphism for most of the obtained polymers. The copolysiloxane with three methylene units in the spacer is the only one showing no mesomorphic property. The other four copolysiloxanes, containing four, five, six or eleven methylene units in the spacer, display a smectic A phase. All of the obtained polymers present dual glass transition behavior by both DSC and thermally stimulated current (TSC) techniques. The first glass transition (T_g1) at lower temperature is due to the segmental motions of the polysiloxane backbone, while the second glass transition (T_g2) is due to the cooperative relaxation motions of spacers and mesogenic units.     

Cholesteric Liquid‐Crystalline Side‐on Polysiloxanes: Effects of Biaxiality on the Cholesteric Structure

Summary: Biaxial side‐on cholesteric copolysiloxanes with laterally attached mesogenic groups were investigated in mixtures with a low molar mass liquid crystal. While mixtures with a low concentration of the polymer exhibit the conventional fingerprint texture, for concentrations above about 60 mol‐% characteristic irregularities appear in the cholesteric structure that are obviously due to phase biaxiality. Besides the absence of pseudo‐isotropic lines, irregular patterns perpendicular to the helix axis emerge and the periodic distance of regions with similar optical properties along the helix axis is strongly disturbed. This suggests that the photonic band gap width of a uniaxial cholesteric phase becomes strongly affected when a phase transformation into a biaxial cholesteric phase occurs.

Cholesteric fingerprint texture of a mixture of uniaxial nematic monomer and biaxial cholesteric polymer.     

Synthesis and phase behavior of side-chain liquid crystalline polymers with pendant quinoline rings bearing either a polar or a non-polar end group

Four methacrylate monomers, 2a–2d , containing a quinoline ring with a NO₂ or a OCH₃ group at the end of the mesogen were synthesized and polymerized. The copolymers with six methylene units as spacer, 3b–3d , showed a smectic phase induced by electron donor-acceptor interactions of the side groups. The homopolymer with eleven methylene units as spacer and methoxy end group, 3f , showed a smectic phase induced by the large length of the spacer. The copolymers with eleven methylene units, 3g–3i , showed a smectic phase induced by both the electron donor-acceptor interactions of the side groups and the large length of the spacer.     

Thermal reactions of amphotropic copolymers studied by thermogravimetry and temperature-resolved pyrolysis-field ionization mass spectrometry

The thermal degradation mechanisms of amphiphilic acrylic copolymers containing mesogenic pyrimidine side chains and hydrophilic 2-hydroxyethyl acrylate (HEA) main-chain spacer units were investigated by thermogravimetry (TG) and pyrolysis-field ionization mass spectrometry (Py-FIMS). The degradation behaviour of these polymers depends on the amount of HEA incorporated. Thermogravimetry revealed that the main decomposition occurs in a single step for the pyrimidine homopolymer, whereas with increasing HEA content a two-step process evolves. The major products identified by Py-FIMS are two alcohols and one olefin split from the aromatic side chains. Depolymerization is only a minor degradation pathway. The rather complex thermal behaviour can be explained by three different reaction mechanisms: (a) alcohol formation via reaction of the HEA hydroxyl groups with ester groups in the side chains, (b) intramolecular cis-elimination forming a volatile olefin and carboxylic acid groups remaining at the polymer backbone, and (c) the reaction of these acid groups with ester bonds forming the alcohols. Steps (b) and (c) are dominant for the pyrimidine homopolymer. With increasing HEA content in the copolymers step (a) becomes more important and, in addition, chemical crosslinking occurs. The mesogenic monomer, which was also examined, polymerized under the experimental conditions and showed essentially the thermal features of the pyrimidine homopolymer.     

Synthesis and phase behaviour of new carbazole containing liquid crystal side chain polysiloxanes

A series of chiral mesogenic side chain polymers containing a carbazole unit have been synthesized and investigated with regard to their liquid crystal (1c) phase behaviour. The carbazole units are linked either via the 2-position with a 1-oxycarbonyl-4-alkoxylphenyl moiety (end-on) or via the 9-position with an alkyl chain (side-on) to polymethylsiloxane. Only end-on polymers with long spacers or a ratio bigger one of spacer length and the free lateral alkyl chain length exhibit stable or metastable smectic phases. The side-on polymers are only isotropic or crystalline.     

Synthesis of New Side‐Chain Liquid‐Crystalline Polyoxetanes with Two Mesogenic Groups Connected by a Flexible Spacer in the Side Chain

The synthesis of a different geometry of side‐chain liquid‐crystalline polymers is reported where two mesogenic units connected by a flexible spacer are attached as pendent groups of a polymeric chain. The resulting structure is the following, where R₁, R₂ and R₃ are methylenic or oxymethylenic segments: The monomers were obtained by linking the dimer structure to an oxetane ring. These substituted oxetanes were polymerised by a boron trifluoride‐initiated cationic ring‐opening reaction to obtain the corresponding polymers. The polymerisation proceeds with high yields, in spite of the steric hindrance derived from the bulkiness of the side chain, and the presence of some functional groups in the molecule that compete against the cyclic ether for the nucleophilic attack at the propagating centre. A fraction of cyclic oligomer is obtained together with high molecular‐weight polyoxetane, as a result of back‐biting reactions during the polymerisation. Several systems with spacers of different length and parity were synthesised in order to analyse the influence of the nature of the spacer on the phase behaviour. The formation of mesophases was proved by means of differential scanning calorimetry, X‐ray diffraction and microscopic analysis. Most of the monomers form smectic structures at subambient temperatures. The polymers display a similar phase behaviour, although shifted to higher temperatures.     

Liquid-crystal behaviour of some laterally substituted stiffchain polyesters containing 2-phenylbenzoxazole units

The synthesis and the phase behaviour of three laterally substituted stiff-chain polymers containing 2-phenylbenzoxazole units is reported. Polymers were obtained by reaction of 2-(4-acetoxyphenyl)-6-acetoxybenzoxazole with 2-phenoxyterephthalic acid (polymer 2a ), 2-phenylthioterephthalic acid (polymer 2b ) and 2-hexadecylthioterephthalic acid (polymer 2c ). Polymers 2a and 2b are virtually non-crystalline. 2a is nematogenic, while for 2b a smectic-like liquidcrystal phase is observed, whose structural periodicity is probably connected with the intercalated stacking of the lateral phenyl groups along the direction of the chain axes. The solid phase of 2c is of the sanidic type. On melting, a liquid-crystal phase with equatorial periodicity is observed. This periodicity is probably related to the segregation of the stiff chains between the paraffinic layers.     

Extracellular phospholipase A2 secretion is a common effector pathway of interleukin-1 and tumour necrosis factor action

Inflammatory processes are characterized by increased levels of extracellular phospholipase A2 (PLA2) and cytokines such as interleukin 1 (IL-1) and tumour necrosis factor (TNF). IL-1, TNF and PLA2 share a number of proinflammatory, arthritogenic effects. The sequential induction, first of the cytokines followed by PLA2, suggests that these cytokines may regulate synthesis and secretion of PLA2. To test this postulate, foetal rat calvarial bone-forming cells (FRCC) were treated with recombinant human IL-1 and TNF and extracellular PLA2 release was quantitated. Both IL-1 and TNF induced the de novo synthesis of PLA2 in a concentration-dependent manner. Continuous exposure of FRCC in primary culture to IL-1 (50 units/ml) over 15 days resulted in as much as 100-fold increase in PLA2 secretion. IL-1 (50 units/ml) added to post-confluent cultures for a 48-h pulse increased PLA2 activity 9.4-fold. The combination of IL-1 (50 units/ml) and TNF (500 units/ml) was synergistic with an observed increase in extracellular PLA2 secretion of 146-fold following a 48-h pulse. Interleukin-6, alone or in combination with IL-1 or TNF, did not further enhance PLA2 synthesis of secretion. Cytokine-induced synthesis of PLA2 was inhibited 80% by 10 microM cycloheximide but not by dexamethasone over the range of 10(-6) to 10(-8) M. FRCC-derived PLA2 was neutral-active with a pH optimum of 6-7.5 and was calcium-dependent with optimal activity in the presence of 2-7 mM calcium. It had absolute 2-acyl specificity using micellar phosphatidylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ferroelectric liquid crystalline polysiloxanes designed for high second-order nonlinear susceptibilities

Ferroelectric liquid crystalline (FLC) copolysiloxanes containing suitable comonomers (“NLO-chromophores”) for second harmonic generation (SHG) have been prepared. Their important feature is a donor-acceptor π-system sited perpendicular to the long axis of the side-group moieties in order to adopt the polar ordering of the ferroelectric LC phase. The influences of the mesogen structure and of the content of NLO-chromophores on the liquid crystalline and ferroelectric properties are studied. The desired chiral smectic C^* phase is retained up to 30 mol-% of chromophore. Also, first measurements of second harmonic generation have been performed.     

TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

Tumour necrosis factor (TNF) is an important pro-inflammatory cytokine produced in sepsis. Studies examining the association of individual TNF single nucleotide polymorphisms with sepsis have produced conflicting results. This study investigated whether common polymorphisms of the TNF locus and the two receptor genes, TNFRSF1A and TNFRSF1B, influence circulating levels of encoded proteins, and whether individual polymorphisms or extended haplotypes of these genes are associated with susceptibility, severity of illness or outcome in adult patients with severe sepsis or septic shock. A total of 213 Caucasian patients were recruited from eight intensive care units (ICU) in the UK and Australia. Plasma levels of TNF (P = 0.02), sTNFRSF1A (P = 0.005) and sTNFRSF1B (P = 0.01) were significantly higher in those who died on ICU compared to those who survived. There was a positive correlation between increasing soluble receptor levels and organ dysfunction (increasing SOFA score) (sTNFRSF1A R = 0.51, P < 0.001; sTNFRSF1B R = 0.53, P < 0.001), and in particular with the degree of renal dysfunction. In this study, there were no significant associations between the selected candidate TNF or TNF receptor polymorphisms, or their haplotypes, and susceptibility to sepsis, illness severity or outcome. The influence of polymorphisms of the TNF locus on susceptibility to, and outcome from sepsis remains uncertain.     

Frustrated Behavior of a Side‐Chain Liquid Crystalline Polyacrylate

Polyacrylate with phenyl benzoate mesogenic side groups was synthesized and fractionated into narrow fractions. Structure and phase behavior of the narrow‐molecular‐weight samples have been studied by X‐ray diffraction. Depending on the degree of polymerization the polymer shows nematic, smectic A_d, re‐entrant nematic and new phase with two‐dimensional (2D) periodicity. Such behaviour is implicit to so‐called frustrated systems. However, the mesogenic side chains are nonpolar and thus the origin of frustration is different from that in conventional polar liquid crystals. We found that this phenomenon is steric (entropic) in nature and depends on the length of the polymer backbone. The phase transformations of mesogen side chain polyacrylates are discussed in terms of coupling between the smectic ordering of the side groups and the polymer backbone conformations.     

Synchrotron X‐Ray Study of Liquid Crystalline Polyoxetanes Containing Two Mesogenic Groups Connected by a Flexible Spacer in the Side Chain

The study of the mesophase behaviour of a family of new side chain liquid crystalline polymers by means of synchrotron X‐ray diffraction is reported. These systems contain two bibenzoate rigid units in the side chain that are interconnected through a flexible spacer. A polymerisable oxetane unit is linked to one end of the dimer structure, and a flexible terminal chain is linked to the other end. All the polymers form phases with variable degree of order (from low ordered smectic to crystalline) depending on the chemical constitution of the different segments. The influence of the length, parity, and lateral substitution of the spacers on the transitional parameters and the symmetry of the mesophases that are formed is analysed. Close similarities were found between the phase behaviour of the monomer precursors and the derived polyoxetanes. The arrangement of the mesogens, the flexible groups and the polymeric backbone in the layered structure is discussed with respect to the L/d ratio. Different values were obtained depending on the parity of the central spacer and on the degree of order of the mesophase. Interpenetrated structures, where the flexible groups of different lengths are mixed, seem to be compatible with low ordered smectic phases, but sterically disfavoured when building up highly ordered mesophases.

     

Transient early expression of TNF-alpha in sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy

The proinflammatory cytokine tumor necrosis factor-alpha (TNF) is an important mediator in neuropathic pain. We investigated the temporal pattern of TNF mRNA expression in the sciatic nerve, in dorsal root ganglia (DRG) and spinal cord in the mouse chronic constriction injury model of neuropathy with quantitative real-time polymerase chain reaction. Neuropathic pain-like behaviour was monitored by evaluating thermal hyperalgesia and mechanical allodynia. Pain-related behaviour and TNF expression were evaluated 6 h, 1, 3, 7 and 14 days after injury. Naive animals and sham-operated mice were used as controls. We found an early upregulation of sciatic nerve TNF mRNA levels in chronic constriction injury (CCI) and sham-operated animals 6 h after surgery: 1 day later TNF overexpression was present in CCI mice only and disappeared 3 days after injury. The mRNA cytokine levels were elevated in DRG 1 and 3 days after surgery in CCI animals only, while the cytokine was not modulated in the spinal cord. A significant hyperalgesia was present in CCI and sham-operated mice at 6 h and 1 day, while at later time point only CCI mice presented lower thresholds. Mechanical allodynia was already present only in CCI animals 6 h from surgery and remained constant up to the 14 th day. The results indicate that a transient early TNF upregulation takes place in peripheral nervous system after CCI that can activate a cascade of proinflammatory/pronociceptive mediators.     

Thermotropic polyesters,copolyesters and model compounds based on terephthalic acid and 4,4′-alkylenediphenols

Main chain thermotropic polyesters 1a and 1b and random copolyesters 1ab , based on terephthalic acid and 4,4′-hexamethylenediphenol ( 5a ) or 4,4′-decamethylenediphenol ( 5b ) were synthesized in good yields by a solution reaction in presence of benzenesulfonyl chloride. A mechanism is discussed. Low molar mass models 4a and 4b and oligomers 2a, 2b, 3a and 3b , with the same mesogenic unit and end groups comparable to the spacers used in polymers 1 , were synthesized and their liquid-crystalline properties compared to those of polymers. Models with at least two mesogenic units and polymers exhibit both smectic and nematic mesophases. Increasing spacer length decreases dramatically the stability of the nematic mesophases, but lowers only slightly the melting points. The phase diagram for random copolyesters 1ab were determined by DSC. Broad endotherms with overlapping multiple peaks were found for most of the copolymers. Monomeric units of 1a and 1b cocrystallize in 1ab , which leads only to slight melting point depression. The variations of nematic-isotropic transition versus composition of copolymers are linear, while the smectic phase stability appreciably decreases.     

Crystal structure of fibers from a novel rigid-rod aromatic polyamide containing a pyrimidine moiety

Fibers of a novel rigid-rod polyamide containing a 1:1 ratio of phenylene:pyrimidine moieties have been produced and evaluated. The lyotropic liquid-crystalline behavior of the polymer and the spinnability of the nematic dope were established. The as-spun fibers exhibit low degrees of orientation and crystallinity. Heat treatment of the dry fibers resulted in crystallinities as high as 45% in coexistence with an amorphous phase component. Evaluation of the crystal structure by wide-angle X-ray diffraction suggests a pseudo-orthorhombic crystal cell with lattice dimensions (a; b; c) of (7,3 Å; 5,1 Å; 12,8 Å) and containing two repeating units per unit cell.     

Kinetics of tumour necrosis factor-alpha,soluble tumour necrosis factor receptors,interleukin 1-beta and its receptor antagonist during serious infections

Tumour necrosis factor-α (TNF) and interleukin-1β (IL-1β) are the central mediators in the genesis of sepsis. The proinflammatory effects of these cytokines are counteracted in vivo by natural inhibitors. Soluble TNF receptors (sTNFR) are shed upon inflammatory stimuli such as IL-1β and TNF itself. Circulating TNF can be complexed by these receptors, thus preventing TNF from binding to effector cells. The binding of IL-1β to its receptor can be blocked by high concentrations of interleukin-1 receptor antagonist (IL-1Ra), which is produced and released upon nearly the same stimuli as IL-1β. This review presents some aspects of the kinetic behaviour of native sTNFR and of the production of native IL-1Ra during severe infections. It appears that in fulminant septicaemia, the plasma concentration of TNF is increased only transiently, during the very early stage of the infection. The concentration of sTNFR, in contrast, remains elevated much longer, probably due to a slower clearance. During the acute stage of severe infectious diseases, peripheral blood cells cannot be stimulated to produce IL-1β. The production of IL-1Ra, in contrast, is not affected. Thus, the kinetic behaviour and regulation of TNF and IL-1β, is different from that of their antiinflammatory counterparts.     

Synthesis and characterization of liquid crystalline polysiloxanes with “two-chain” diol units in the side chain

The synthesis and the thermal behaviour of different polysiloxanes containing cis,cis-(3,5-dihydroxycyclohexyl) 3,4-bis(alkoxy)benzoate mesogens (“two-chain” diol unit) in the side chain are described. Aggregation via intermolecular hydrogen bonding between different “two-chain” diol units leads to the formation of mesomorphic supramolecular structures. The phase behaviour changes drastically by variation of the dimethylsiloxane content of the backbone. Thus, the homopolysiloxane is the first example of a polymer with a thermotropic cubic mesophase, being observed below a hexagonal columnar one. However, the copolymers exclusively form the hexagonal columnar mesophase. The thermal transitions of all polymers, investigated by means of differential scanning calorimetry (DSC) as well as by polarizing microscopy, are discussed. The mesophase structures have been determined by X-ray measurements in combination with miscibility studies.     

Susceptibility to multiple sclerosis mediated by HLA-DRB1 is influenced by a second gene telomeric of the TNF cluster

Susceptibility to multiple sclerosis (MS) is clearly associated with human leukocyte antigen (HLA)-DRB1*1501, but some studies show associations with HLA-B7 and -B18. These are often co-expressed with DRB1*1501 in the ancestral haplotypes (AH) denoted 7.1 (HLA-A3, B7, tumor necrosis factor [TNF]a11b4, DRB1*1501) and 18.1 (HLA-A25, B18, TNFa10b4, DRB1*1501). Here we present a systematic study of 218 patients and 274 controls typed at all standard class II and TNF microsatellite loci, and a novel non-synonymous polymorphism in the central major histocompatibility complex gene, inhibitor of κ B-like protein (IKBL). The C allele at IKBL+738 is only found on the 7.1 haplotype. HLA-DRB1*1501 was associated with disease, as expected. When subjects expressing DRB1*1501 were analyzed separately, TNFa11b4 and IKBL+738C were less common in the patients and, hence, mark an allele that mediates resistance which lies telomeric of IKBL.

TNFa10b4 and TNFa1b5 were more common in DRB1*1501 patients than in controls. These alleles have been associated with the 18.1 and 18.2 AH, respectively. Since no component of these haplotypes was an independent risk factor in this study, it appears likely that a gene linked to TNFa10b4 and TNFa1b5 modifies the effect of the susceptibility locus marked by HLA-DRB1*1501. Potential candidate genes telomeric of the TNF cluster are discussed.     

Interleukin 2 Induces Tumor Necrosis Factor Gene Expression In Vivo

Interleukin 2 (IL-2) treatment of malignancies is often associated with severs toxicity, and the alterations observed after high dose administration of IL-2 are similar to those induced by recombinant tumor necrosis factor (TNF). We therefore examined the hypothesis that IL-2 induces TNF gene expression in vivo. Purified, recombinant human IL-2 was injected intraperitonealy into mice which had been previously primed with complete Freund's adjuvant (CFA). Biologically-active TNF was detected in the ascites fluid of CD-1 mice; it was detectable 30 minutes after IL-2 and peaked at 1 hour (500 ± 158 units/ml). Plasma levels of TNF also peaked at 1 hour at 32 ± 4 units/ml. Similar kinetics were observed in CBA/J mice. TNF specific mRNA was also present in the ascites cells, and peaked 30 minutes after IL-2 injection into CBA/J mice. Injection of vehicle containing 10 times the maximum contaminating dose of endotoxin did not induce TNF above background levels. As a further control for potential endotoxin contamination, IL-2 was injected into endotoxin hyporesponsive C3H/HeJ mice. These mice also demonstrated the rapid upregulation of biologically-active TNF in the ascites, with peak production occuring at 1 hour (125 ± 47 units/ml). The induction of biologically-active TNF in the C3H/HeJ mice was associated with a peripheral blood neutrophilia and lymphopenia, pathophysiologic alterations that have been attributed to TNF. These data show that a single injection of purified, recombinant IL-2 induces TNF gene expression in vivo.