Zinc(II) Triflate‐Catalyzed Divergent Synthesis of Polyfunctionalized Pyrroles

The zinc(II) triflate‐catalyzed synthesis of highly functionalized pyrroles is described. The sequence involves the preliminary preparation of α‐aminohydrazones by Michael addition of primary amines to 1,2‐diaza‐1,3‐dienes. The treatment of these intermediates with dialkyl acetylenedicarboxylates produces α‐(N‐enamino)‐hydrazones that are converted into the corresponding pyrroles. The substituents on the carbon in position four of 1,2‐diaza‐1,3‐dienes drive the regioselectivity of the ring closure process. Starting from 4‐aminocarbonyl‐1,2‐diaza‐1,3‐dienes only dialkyl 1‐substituted 5‐aminocarbonyl‐1H‐pyrrole‐2,3‐dicarboxylates are achieved by Lewis acid‐catalyzed ring closure. A screening of several Lewis/Brønsted acid catalysts is performed. Zinc(II) triflate is the most efficient catalyst. Under similar reaction conditions, employing 4‐alkoxycarbonyl‐1,2‐diaza‐1,3‐dienes, only 4‐hydroxy‐1H‐pyrrole‐2,3‐dicarboxylates are synthesized. These latter reactions can be accomplished regioselectively also in one pot. Using 4‐aminocarbonyl‐1,2‐diaza‐1,3‐dienes, diamines and dialkyl acetylenedicarboxylates the sequence provides the corresponding α,ω‐di(N‐pyrrolyl)alkanes.     

Nonisothermal crystallization behavior of a biodegradable segmented copolymer constituted by glycolide and trimethylene carbonate units

Nonisothermal crystallization of a segmented copolymer constituted by glycolide and trimethylene carbonate units was studied from both the melt and the glass state by optical microscopy, differential scanning calorimetry and time‐resolved X‐ray diffraction techniques. Positive spherulites with a fibrilar appearance were always obtained and corresponded to the crystallization of the polyglycolide hard segments. A single crystallization regime and the kinetic parameters were inferred from optical microscopy data on crystallizations performed at different cooling/heating rates. The parameters were in good agreement with values previously deduced from isothermal experiments. Isoconversional data of melt and glass nonisothermal crystallizations were combined to obtain the Lauritzen and Hoffman parameters from calorimetric data. Results revealed again the existence of a single crystallization regime with a secondary nucleation constant close to that deduced from isothermal DSC experiments. Morphological changes occurring during the hot and cold crystallization were evaluated by time‐resolved SAXS/WAXD experiments employing synchrotron radiation. Measurements showed that significant differences on the lamellar thicknesses exist depending on the crystallization process. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Phosphorus‐containing poly(ester‐imide)–polydimethylsiloxane copolymers

New phosphorus‐containing poly(ester‐imide)‐polydimethylsiloxane copolymers were prepared by solution polycondensation of 1,4‐[2‐(6‐oxido‐6H‐dibenz < c,e > < 1, 2 > oxaphosphorin‐6‐yl)]naphthalene‐bis(trimellitate) dianhydride with a mixture of an aromatic diamine (1,3‐bis(4‐aminophenoxy)benzene) and α,ω‐bis(3‐aminopropyl)oligodimethylsiloxane of controlled molecular weight, in various ratios. Poly(amic acid) intermediates were converted quantitatively to the corresponding polyimide structures using a solution imidization procedure. The polymers are easily soluble in polar organic solvents, such as N‐methyl‐2‐pyrrolidone and N,N‐dimethylformamide, as well as in less polar solvents such as tetrahydrofuran. They show good thermal stability, the decomposition temperature being above 370 °C. The glass transition temperatures are in the range 165–216 °C. Solutions of the polymers in N‐methyl‐2‐pyrrolidone exhibit photoluminescence in the blue region. Copyright © 2010 Society of Chemical Industry     

Cooling rate effects on the structure and transformation behavior of Cu-Zn-Al shape memory alloys

Different fragments of a hot-rolled and homogenized Cu–Zn–Al shape memory alloy（SMA） were subjected to thermal cycling by means of a differential scanning calorimetric（DSC） device. During thermal cycling, heating was performed at the same constant rate of increasing temperature while cooling was carried out at different rates of decreasing temperature. For each cooling rate, the temperature decreased in the same thermal interval. During each cooling stage, an exothermic peak（maximum） was observed on the DSC thermogram. This peak was associated with forward martensitic transformation. The DSC thermograms were analyzed with PROTEUS software： the critical martensitic transformation start（Ms） and finish（Mf） temperatures were determined by means of integral and tangent methods, and the dissipated heat was evaluated by the area between the corresponding maximum plot and a sigmoid baseline. The effects of the increase in cooling rate, assessed from a calorimetric viewpoint, consisted in the augmentation of the exothermic peak and the delay of direct martensitic transformation. The latter had the tendency to move to lower critical transformation temperatures. The martensite plates changed in morphology by becoming more oriented and by an augmenting in surface relief, which corresponded with the increase in cooling rate as observed by scanning electron microscopy（SEM） and atomic force microscopy（AFM）.     

Flow Instabilities in Linear and Branched Syndiotactic Poly(propylene)s

Extrusion flow experiments of linear and branched syndiotactic poly(propylene)s were carried out. The work was focused on flow instabilities. Ionized radiation was employed to induce long chain branching in linear samples. Sharkskin and melt fracture were postponed in the case of slightly long branched samples, which possess an enhanced melt elasticity compared to linear samples. For the most elastic samples the nature of the flow instability changed: sharkskin disappeared and melt fracture was observed instead. The correlation between sharkskin and melt strength results is discussed.

     

Continuous production of single-walled carbon nanotubes using a supported floating catalyst

Using catalytic decomposition, a technique for the production of singe-walled carbon nanotubes (SWCNTs) is reported with a production rate up to 6 g h⁻¹ after purification, and scaling capability up to 220 g h⁻¹. This is achieved by injection of pre-prepared alumina supported catalyst powder into a modified vertical floating reactor. The product is collected in several cyclones connected in series. Wide range Raman studies (laser excitations from λ = 1064 to 488 nm) and temperature programmed oxidation measurements of the samples collected from the different cyclones show that SWCNTs were separated in situ by tube diameter. This is attributed to the different residual times of the catalyst in the reaction zone depending on particle diameter. A series of computational fluid dynamics calculations of the flow and heat transfer in the reactor, as well as modeling of catalyst particle transport reveals the parametrical dependence of the process.     

Synthesis of 4,4-diphenyl-3,4-dihydro-2H-1,4-thiasiline

4,4-Diphenyl-3,4-dihydro-2H-1,4-thiasiline (3) was synthesized starting from diphenyl(divinyl)silane by a sequence of reactions including free-radical thiylation with thioacetic acid, reduction of thioacetate to thiol, heterocyclization of the latter, oxidation and the Pummerer rearrangement of the cyclic sulfoxide to the unsaturated cyclic organosilicon sulfide. Although compound 3 is hydrolytically more stable than its Si-dimethylated analogue, both compounds are hydrolyzed to the corresponding siloxanes with the cleavage of the Si? C_sp2 rather than the Si? C_sp3 bond. A theoretical rationalization for this is given.     

Protective Effect of Memantine on Bergmann Glia and Purkinje Cells Morphology in Optogenetic Model of Neurodegeneration in Mice

Spinocerebellar ataxias are a family of fatal inherited diseases affecting the brain. Although specific mutated proteins are different, they may have a common pathogenetic mechanism, such as insufficient glutamate clearance. This function fails in reactive glia, leading to excitotoxicity and overactivation of NMDA receptors. Therefore, NMDA receptor blockers could be considered for the management of excitotoxicity. One such drug, memantine, currently used for the treatment of Alzheimer’s disease, could potentially be used for the treatment of other forms of neurodegeneration, for example, spinocerebellar ataxias (SCA). We previously demonstrated close parallels between optogenetically induced cerebellar degeneration and SCA1. Here we induced reactive transformation of cerebellar Bergmann glia (BG) using this novel optogenetic approach and tested whether memantine could counteract changes in BG and Purkinje cell (PC) morphology and expression of the main glial glutamate transporter—excitatory amino acid transporter 1 (EAAT1). Reactive BG induced by chronic optogenetic stimulation presented increased GFAP immunoreactivity, increased thickness and decreased length of its processes. Oral memantine (~90 mg/kg/day for 4 days) prevented thickening of the processes (1.57 to 1.81 vs. 1.62 μm) and strongly antagonized light-induced reduction in their average length (186.0 to 150.8 vs. 171.9 μm). Memantine also prevented the loss of the key glial glutamate transporter EAAT1 on BG. Finally, memantine reduced the loss of PC (4.2 ± 0.2 to 3.2 ± 0.2 vs. 4.1 ± 0.3 cells per 100 μm of the PC layer). These results identify memantine as potential neuroprotective therapeutics for cerebellar ataxias.     

A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.