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Activation Step (activation + step)
Selected AbstractsMetal-Free, Selective Alkane FunctionalizationsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 9-10 2003Andrey Abstract The present overview of alkane functionalization reactions presents comparisons between radical and metal-initiated (sometimes metal-catalyzed) methodologies. While metal-catalyzed processes are excellent approaches to this problem, metal-free alternatives are equally if not, at least from an environmental and cost perspective, more useful. This conclusion is supported by the fact that many so-called metal-catalyzed reactions also work without the metal present, and the large variety of metals showing the same product distributions emphasizes that the metal often just aids in the generation of the active species, i.e., the metal itself is not participating in the crucial CH activation step. Highly selective alkane functionalization reactions such as those derived from nitroxyl and related radicals as well as through radical reactions conducted in phase-transfer catalyzed systems are available but generally underutilized. These systems, in contrast to typical metal-catalyzed approaches, are also applicable to highly strained alkanes and offer the highest 3°/2° CH selectivities reported to date in a radical reaction. The article closes with representative experimental protocols for the PTC bromination of cubane as an example of the applicability of this method to strained hydrocarbons and the direct iodination of cyclohexane as well as adamantane as typical alkanes bearing secondary and tertiary CH bonds. [source] ,O -Acyl isopeptide method' for peptide synthesis: Solvent effects in the synthesis of A,1,42 isopeptide using ,O -acyl isodipeptide unit'JOURNAL OF PEPTIDE SCIENCE, Issue 12 2007Atsuhiko Taniguchi Abstract ,O -Acyl isopeptide method' is an efficient synthetic method for peptides. We designed ,O -acyl isodipeptide units', Boc-Ser/Thr(Fmoc-Xaa)-OH, as important building blocks to enable routine use of the O -acyl isopeptide method. In the synthesis of an A,1,42 isopeptide using O -acyl isodipeptide unit Boc,Ser(Fmoc,Gly),OH, a side reaction, resulting in the deletion of Ser26 in the O -acyl isopeptide structure, was noticed during coupling of the unit. We observed that the side reaction occurred during the activation step and was solvent-dependent. In DMF or NMP, an intramolecular side reaction, originating from the activated species of the unit, occurred during the activation step. In non-polar solvents such as CHCl3 or CH2Cl2, the side reaction was less likely to occur. Using CH2Cl2 as solvent in coupling the unit, the target A,1,42 isopeptide was synthesized with almost no major side reaction. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] Reactivity of organosilicon precursors in remote hydrogen microwave plasma chemical vapor deposition of silicon carbide and silicon carbonitride thin-film coatingsAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 3 2010A. M. Wrobel Abstract A number of organosilicon precursors for silicon carbide and silicon carbonitride thin-film coatings, such as silanes, carbosilanes, aminosilanes, and disilazane, respectively, were characterized in terms of their reactivity in a remote microwave plasma chemical vapor deposition process, which was induced using hydrogen as plasma generating gas. The process displayed high selectivity with respect to the activating species and the chemical bonds in the molecular structure of the precursors. In view of very short life times of excited hydrogen plasma species the activation step takes place with an exclusive contribution of ground-state hydrogen atoms. The CH, CC, SiC, SiN, CN and NH bonds present in the molecules of the precursors are non-reactive and only the SiH or SiSi bonds play a key role in the activation step. The reactivity of the precursors was characterized in a quantitative way by the yield of the film growth parameter. The yield parameter expressing the mass of film per unit mass of the precursor fed to the reactor was calculated from the slopes of linear plots of time dependencies of film mass and precursor mass, which were determined for each investigated precursor. The reactivity of the precursors was found to be strongly dependent on the number of the SiH units present in their molecules and those containing two SiH units appeared to be most reactive. Copyright © 2009 John Wiley & Sons, Ltd. [source] H/D exchange reactions;CHEMPHYSCHEM, Issue 6 2003sigma-bond metathesis; The mechanism of the H/D exchange reaction in alkane/hydrogen mixtures on silica-supported zirconium hydride was investigated by a modelling study using density functional theory (DFT) calculations. The electronic activation enthalpy (,H) for the CH bond activation step (TS3) was calculated to be around 92 kJ,mol,1, whereas it would be 258 kJ,mol,1for a direct exchange process (TS1, also called the kite TS). These data clearly speak in favour of the former as a mechanism for CH bond scrambling. Moreover, the calculated enthalpy of activation (,H) for H/D exchange in H2/D2mixtures (TS2) is 33.5 kJ,mol,1, which shows that this reaction is much faster than the H/D scrambling in alkane/H2mixtures, as shown experimentally. Additionally, the calculated activation entropies (For TS1,4,,S ranges between ,129 and ,174 J,mol,1,K,1) are very negative. Although the calculated activation entropies are also in full agreement with experimental data (,S=,113 J,mol,1,K,1), overall, the calculated activation enthalpies are much higher than the experimental ones. This suggests that the actual catalyst is probably more electrophilic than the model chosen for the calculations. [source] Coupling of Protonation Switches During Rhodopsin Activation,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2007Reiner Vogel Recent studies of the activation mechanism of rhodopsin involving Fourier-transform infrared spectroscopy and a combination of chromophore modifications and site-directed mutagenesis reveal an allosteric coupling between two protonation switches. In particular, the ring and the 9-methyl group of the all- trans retinal chromophore serve to couple two proton-dependent activation steps: proton uptake by a cytoplasmic network between transmembrane (TM) helices 3 and 6 around the conserved ERY (Glu-Arg-Tyr) motif and disruption of a salt bridge between the retinal protonated Schiff base (PSB) and a protein counterion in the TM core of the receptor. Retinal analogs lacking the ring or 9-methyl group are only partial agonists,the conformational equilibrium between inactive Meta I and active Meta II photoproduct states is shifted to Meta I. An artificial pigment was engineered, in which the ring of retinal was removed and the PSB salt bridge was weakened by fluorination of C14 of the retinal polyene. These modifications abolished allosteric coupling of the proton switches and resulted in a stabilized Meta I state with a deprotonated Schiff base (Meta ISB). This state had a partial Meta II-like conformation due to disruption of the PSB salt bridge, but still lacked the cytoplasmic proton uptake reaction characteristic of the final transition to Meta II. As activation of native rhodopsin is known to involve deprotonation of the retinal Schiff base prior to formation of Meta II, this Meta ISB state may serve as a model for the structural characterization of a key transient species in the activation pathway of a prototypical G protein-coupled receptor. [source] Anti,cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate complement via both the classical and alternative pathwaysARTHRITIS & RHEUMATISM, Issue 7 2009L. A. Trouw Objective It has been suggested that anti,citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of rheumatoid arthritis (RA). To exert their pathologic effects, ACPAs must recruit immune effector mechanisms such as activation of the complement system. Mouse models of RA have shown that, surprisingly, arthritogenic antibodies activate the alternative pathway of complement rather than the expected classical pathway. This study was undertaken to investigate whether human anti,cyclic citrullinated peptide (anti-CCP) antibodies activate the complement system in vitro and, if so, which pathways of complement activation are used. Methods We set up novel assays to analyze complement activation by anti-CCP antibodies, using cyclic citrullinated peptide,coated plates, specific buffers, and normal and complement-deficient sera as a source of complement. Results Anti-CCP antibodies activated complement in a dose-dependent manner via the classical pathway of complement, and, surprisingly, via the alternative pathway of complement. The lectin pathway was not activated by anti-CCP antibodies. Complement activation proceeded in vitro up to the formation of the membrane attack complex, indicating that all activation steps, including the release of C5a, took place. Conclusion Our findings indicate that anti-CCP antibodies activate the complement system in vitro via the classical and alternative pathways but not via the lectin pathway. These findings are relevant for the design of interventions aimed at inhibition of complement-mediated damage in RA. [source] Effects of anti-CD154 treatment on B cells in murine systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 2 2003Xiaobo Wang Objective To determine the immunologic effects of anti-CD154 (CD40L) therapy in the (NZB × NZW)F1 mouse model of systemic lupus erythematosus. Methods Twenty-week-old and 26-week-old (NZB × NZW)F1 mice were treated with continuous anti-CD154 therapy. Mice were followed up clinically, and their spleens were studied at intervals for B and T cell numbers and subsets and frequency of anti,double-stranded DNA (anti-dsDNA),producing B cells. T cell,dependent immunity was assessed by studying the humoral response to the hapten oxazolone. Results IgG anti-dsDNA antibodies decreased during therapy and disease onset was delayed, but immune tolerance did not occur. During treatment, there was marked depletion of CD19+ cells in the spleen; however, autoreactive IgM-producing B cells could still be detected by enzyme-linked immunospot assay. In contrast, few IgG- and IgG anti-dsDNA,secreting B cells were detected. Eight weeks after treatment cessation, the frequency of B cells producing IgG anti-dsDNA antibodies was still decreased in 50% of the mice, and activation and transition of T cells from the naive to the memory compartment were blocked. Anti-CD154 treatment blocked both class switching and somatic mutation and induced a variable period of relative unresponsiveness of IgG anti-dsDNA,producing B cells, as shown by decreased expression of the CD69 marker and failure to generate spontaneous IgG anti-dsDNA,producing hybridomas. Treated mice mounted an attenuated IgM response to the hapten oxazolone and produced no IgG antioxazolone antibodies. Conclusion Anti-CD154 is a B cell,depleting therapy that affects multiple B cell subsets. Activation of both B and T cells is prevented during therapy. After treatment cessation, autoreactive B cells progress through a series of activation steps before they become fully competent antibody-producing cells. The general immunosuppression induced during treatment will need to be taken into account when using B cell,depleting regimens in humans. [source] Cysteine-reactive covalent capture tags for enrichment of cysteine-containing peptidesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 21 2009Priscille Giron Considering the tremendous complexity and the wide dynamic range of protein samples from biological origin and their proteolytic peptide mixtures, proteomics largely requires simplification strategies. One common approach to reduce sample complexity is to target a particular amino acid in proteins or peptides, such as cysteine (Cys), with chemical tags in order to reduce the analysis to a subset of the whole proteome. The present work describes the synthesis and the use of two new cysteinyl tags, so-called cysteine-reactive covalent capture tags (C3T), for the isolation of Cys-containing peptides. These bifunctional molecules were specifically designed to react with cysteines through iodoacetyl and acryloyl moieties and permit efficient selection of the tagged peptides. To do so, a thioproline was chosen as the isolating group to form, after a deprotection/activation step, a thiazolidine with an aldehyde resin by the covalent capture (CC) method. The applicability of the enrichment strategy was demonstrated on small synthetic peptides as well as on peptides derived from digested proteins. Mass spectrometric (MS) analysis and tandem mass spectrometric (MS/MS) sequencing confirmed the efficient and straightforward selection of the cysteine-containing peptides. The combination of C3T and CC methods provides an effective alternative to reduce sample complexity and access low abundance proteins. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||