Collision‐induced dissociation study of poly(2‐ethyl‐2‐oxazoline) using survival yields and breakdown curves

Poly(2‐ethyl‐2‐oxazoline), a synthetic polymer was analysed by mass spectrometry using different ion sources. Two distributions could be identified in the mass spectra which related to two different polymer series (one with hydrogen and hydroxyl end‐groups and the other with methyl and hydroxyl end‐groups). The fragmentation behaviour of the protonated oligomers was studied in a quadrupole time‐of‐flight mass spectrometer (MS) with electrospray, atmospheric pressure chemical ionization and direct analysis in real time soft ionization techniques. Three product ion series were identified in the MS/MS spectra independently of the ion source used. Based on the results, a mechanism was proposed for the dissociation by means of the accurate mass of the product ions, pseudo MS³ experiments and the energy dependence of the product ion intensity, i.e. breakdown curves. The survival yield method was used to highlight the correlation between the size of the oligomers and the laboratory frame collision energy. Copyright © 2012 John Wiley & Sons, Ltd.     

Solid-state thermal degradation behaviour of 1-D coordination polymers of Ni(II) and Cu(II) bridged by conjugated ligand

Monometallic complexes [Cudadb·yH₂O]_n (2) and [Nidadb·yH₂O]_n (3) and heterobimetallic complex [Cu_0.5Ni_0.5dadb·yH₂O]_n (4) {where dadbH₂ = 2,5-Diamino-3,6-dichloro-1,4-benzoquinone (1); y = 2–4; n = degree of polymerization} were characterized by elemental analysis, atomic absorption spectroscopy, infrared spectroscopy (FTIR) and powder X-ray diffraction. The thermal behaviour of the complexes was studied by thermal analysis (TG/DTA) under air as well as under helium atmospheres. The released gaseous products were investigated by evolved gas analysis performed by an online coupled mass spectrometer (TG/DTA-MS). Thermal degradation of 2 under helium atmosphere is distributed over five steps, whereas 3 and 4 exhibited only four degradation steps due to overlap of second and third degradation steps of into one major step. All the complexes exhibit three steps degradation under air. The complex 2 loses NH group in the second and HCl/Cl₂, CO groups simultaneously in third steps of decomposition under helium, whereas it loses NH and CO groups simultaneously in low temperature region of second step of degradation under air atmosphere as the loss of CO group is facilitated by air. EGA-MS under air and helium atmospheres shows that HCl, CO/CO₂ and (CN)₂ fragments are lost simultaneously at multiple steps, and not successively as predicted earlier. Rate of evolution of most evolved gases exhibits several maxima as a consequence of degradation followed by recombination reactions. Final residues under air and helium atmospheres correspond to the metal oxides and metals along with some carbonaceous matter.     

Calcium signals in the nucleus accumbens: Activation of astrocytes by ATP and succinate

Background

Late cerebral ischemia carries high morbidity and mortality after subarachnoid hemorrhage (SAH) due to reduced cerebral blood flow (CBF) and the subsequent cerebral ischemia which is associated with upregulation of contractile receptors in the vascular smooth muscle cells (SMC) via activation of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide a therapeutic window for treatment of cerebral ischemia after SAH.

Results

Here we demonstrate that SAH increases the phosphorylation level of ERK1/2 in cerebral vessels and reduces the neurology score in rats in additional with the CBF measured by an autoradiographic method. The intracisternal administration of SB-386023-b, a specific inhibitor of raf, given 6 h after SAH, aborts the receptor changes and protects the brain from the development of late cerebral ischemia at 48 h. This is accompanied by reduced phosphorylation of ERK1/2 in cerebrovascular SMC. SAH per se enhances contractile responses to endothelin-1 (ET-1), 5-carboxamidotryptamine (5-CT) and angiotensin II (Ang II), upregulates ET_B, 5-HT_1B and AT₁ receptor mRNA and protein levels. Treatment with SB-386023-b given as late as at 6 h but not at 12 h after the SAH significantly decreased the receptor upregulation, the reduction in CBF and the neurology score.

Conclusion

These results provide evidence for a role of the ERK1/2 pathway in regulation of expression of cerebrovascular SMC receptors. It is suggested that raf inhibition may reduce late cerebral ischemia after SAH and provides a realistic time window for therapy.     

Two-Dimensional Anisotropic Random Walks: Fixed Versus Random Column Configurations for Transport Phenomena

We consider random walks on the square lattice of the plane along the lines of Heyde (J Stat Phys 27:721–730, 1982, Stochastic processes, Springer, New York, 1993) and den Hollander (J Stat Phys 75:891–918, 1994), whose studies have in part been inspired by the so-called transport phenomena of statistical physics. Two-dimensional anisotropic random walks with anisotropic density conditions á  la Heyde (J Stat Phys 27:721–730, 1982, Stochastic processes, Springer, New York, 1993) yield fixed column configurations and nearest-neighbour random walks in a random environment on the square lattice of the plane as in den Hollander (J Stat Phys 75:891–918, 1994) result in random column configurations. In both cases we conclude simultaneous weak Donsker and strong Strassen type invariance principles in terms of appropriately constructed anisotropic Brownian motions on the plane, with self-contained proofs in both cases. The style of presentation throughout will be that of a semi-expository survey of related results in a historical context.     

Interaction of non-ionic hydrogels with weak aromatic acids

Measurements are reported of the swelling behaviour at 20°C of poly (N isopropylacrylamide) (PNIPA) gels in aqueous solutions of two weak aromatic acids, phenol and resorcinol. For solute concentrations below 45 mmol/l the uptake of these solutions is similar. Due to selective solvation phenol exhibits an excess equilibrium concentration inside the gel of 5% over that in the surrounding bath, while for resorcinol, the excess is found to be 12%. At 50 mmol/l solute concentration, both systems display a volume transition accompanied by expulsion of the solvent. The solubility limits in water of these aromatic compounds, which are significantly different from each other (870 mmol/l and 9080 mmol/l respectively), are far above this critical concentration. In the collapsed condition the expelled liquid spreads on the surface of the phenol treated gel, while an ordered arrangement of separate droplets is generated in the case of resorcinol. In the latter case an acute contact angle was observed. It is also shown by acid-base titration that the PNIPA/water system may exhibit a slight ion exchanging character.     

Characterization of Electrospun Polysuccinimide-Dopamine Conjugates and Effect on Cell Viability and Uptake

Biocompatible nanofibrous systems made by electrospinning have been studied widely for pharmaceutical applications since they have a high specific surface and the capability to make the entrapped drug molecule amorphous, which increases bioavailability. By covalently conjugating drugs onto polymers, the degradation of the drug as well as the fast clearance from the circulation can be avoided. Although covalent polymer–drug conjugates have a lot of advantages, there is a lack of research focusing on their nano-formulation by electrospinning. In this study, polysuccinimide (PSI) based electrospun fibrous meshes conjugated with dopamine (DA) are prepared. Fiber diameter, mechanical properties, dissolution kinetics and membrane permeability are thoroughly investigated, as these are crucial for drug delivery and implantation. Dopamine release kinetics prove the prolonged release that influenced the viability and morphology of periodontal ligament stem cells (PDLSCs) and SH-SY5Y cells. The presence of dopamine receptors on both cell types is also demonstrated and the uptake of the conjugates is measured. According to flow cytometry analysis, the conjugates are internalized by both cell types, which is influenced by the chemical structure and physical properties. In conclusion, electrospinning of PSI-DA conjugates alters release kinetics, meanwhile, conjugated dopamine can play a key role in cellular uptake.     

Novel 2-phosphabicyclo[2.2.2]oct-5-ene derivatives and their use in phosphinylations

The [4 + 2] cycloaddition of the double-bond isomers ( A and B ) of dihydrophosphinine oxide 1 afforded novel phosphabicyclo[2.2.2]oct-5-ene derivates ( 2–4 ), formation of which was justified by PM3 semiempirical calculations. The compounds of dimer type ( 2–4 ) were utilized in the UV light-mediated fragmentation-related phosphinylation of nucleophiles, especially in that of alcohols. To explore the role of structural modifications on the fragmentation ability, disulfide 5 , phosphabicyclooctane 7 obtained by the hydrogenation of 2 , and the adduct of dihydrophosphinine oxide 1 with benzoquinone ( 7 ) were also synthesized and tested in fragmentation. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:97–106, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10221