A highly chlorinated xylene promoter for ethylene–propylene copolymerisation over a vanadium catalyst

The regularities of ethylene–propylene copolymerisation over a vanadium oxytrichloride (VOCl₃)–ethylaluminium sesquichloride (EASC) catalytic system in the presence of hexachloro-p-xylene (HCPX), tert-butyl chloride, trichlorotoluene, hexachlorocyclopentadiene, and trichloroacetate were studied. The main kinetic regularities of ethylene–propylene copolymerisation when using HCPX were determined and the kinetic parameters of the process were obtained. It was shown that hexachloro-p-xylene is the most efficient promoter of polymerisation that increases activity of the “vanadium” catalyst severalfold and enhances propylene reactivity in its copolymerisation with ethylene. A number of molecular characteristics and physicochemical parameters were determined for the synthesised samples of ethylene–propylene copolymers. The resulting copolymers have a higher molecular weight and a broad molecular weight distribution and are richer in propylene monomers compared to the copolymers synthesised in the catalytic system without HCPX. Modification of the “vanadium” catalyst yields the copolymer with a more homogeneous structure. Assumptions were made about the mechanism of action of the promoter under study in the VOCl₃–EASC catalytic system.

Hexachloro-p-xylene was found to be an effective promoter of olefin copolymerisation in the presence of vanadium catalyst, which increases the activity severalfold, enhances propylene incorporation in the copolymer, and results in a more homogeneous polymer.     

Developmental expression of nitric oxide synthase in the rat diencephalon with special reference to the thalamic paratenial nucleus

Using immunohistochemistry and in situ hybridization the distribution of nitric oxide synthase (NOS) was investigated in the rat brain during pre- and postnatal development. At E15 weak NOS-like immunoreactivity (NOS-LI) could be seen in the differentiation field of the anterior hypothalamus. At E17 strong NOS-LI was observed in the developing neurons of the hypothalamic paraventricular nucleus, supraoptic nucleus, anterodorsal nucleus and lateral hypothalamic areas. In the thalamic paratenial nucleus a strong NOS-LI was observed in these neurons at E17, E18 and P1 with a weaker intensity at P3, P7, P9 and P15, whereas at P30 and in adult rats no NOS-positive neurons could be detected. NOS expression at E17 and P3 was verified by in situ hybridization. These results suggest that NO may have a developmental role at least in one of the regions studied, the thalamic paratenial nucleus.     

Ultrastructural evidence for the existence of a direct hypothalamic-vagal descending pathway

The ultrastructural changes in the presynaptic nerve terminals in the dorsal vagal nucleus were studied in rats with bilateral electrolytic lesions placed in the dorso-medio-caudal hypothalamic area in the sagittal plane of the dorsomedial nuclei, just behind these nuclei in the P_3,5–P_3,7 interval. On days 3,4 and 5 following placement of the hypothalamic lesions, degeneration of some of the presynaptic profiles in the dorsal vagal nucleus was found in the experimental animals. The data obtained provide evidence for the existence of descending hypothalamic axons terminating in the medulla oblongata on the neurons of the dorsal vagal nucleus. The possible involvement of the descending hypothalamic-vagal nerve pathway in the control of endocrine pancreas is discussed.     

Contrasting effects of P2 receptor agonists on spontaneous contractility of human fallopian tubes with and without acute inflammation.

Two groups of women were used to compare effects of P2 receptor agonists on the contractile activity of isolated human fallopian tubes with and without acute purulent inflammation. A control group included women with uterine tubes without inflammation (n=15). A study group included women, operated for unsuccessful conservative anti-inflammatory treatment of acute purulent tuboovarial formations (group with acute purulent salpingitis, n=16). Division into two groups was done according to pathohistological diagnosis. Spontaneous contractions of the isolated tubes were registered isometrically with electromechanical transducer before and after incubation of the tissues with agonists of P2 receptors-ATP, UTP, 2-methylthio-ATP and alpha,beta-methylene-ATP. In the control group neither of the agonists produced any significant effect on fallopian tube contractility. In the study group, ATP, 2-methylthio-ATP and alpha,beta-methylene-ATP significantly increased the spontaneous contractility of isolated tubes. It is suggested that higher activity of P2 receptor agonists in the uterine tubes with acute purulent inflammation is due to expression of several subtypes of P2 receptors during inflammation.     

Calixarene alpha-ketoacetylenes: versatile platforms for reaction with hydrazine nucleophile

Late stage diversification of calix[4]arenes and thiacalix[4]arenes with heterocycles remains a significant synthetic challenge and hampers further exploitation of the scaffolds. Here we describe the development of a short and facile synthetic route to conformationally diverse novel calix[4]arene and thiacalix[4]arene ynones using a palladium cross coupling approach (5% Pd(ii) + 10% Cu(i)) with benzoyl chloride. Their successful conversion to heterocycles to afford pyrazoles was demonstrated through treatment with hydrazine. Functionalisation is calixarene conformation and linker independent enabling access to a library of structures.

Late stage diversification of calix[4]arenes and thiacalix[4]arenes with heterocycles remains a significant synthetic challenge and hampers further exploitation of the scaffolds.     

Understanding the role of physicians within the managerial structure of Russian hospitals

This article examines the role of physicians within the managerial structure of Russian hospitals. A comparative qualitative methodology with a structured assessment framework is used to conduct case studies that allow for international comparison. The research is exploratory in nature and comprises 63 individual interviews and 49 focus groups with key informants in 15 hospitals, complemented by document analysis. The material was collected between February and April 2017 in five different regions of the Russian Federation. The results reveal three major problems of hospital management in the Russian Federation. First, hospitals exhibit a leaky system of coordination with a lack of structures for horizontal exchange of information within the hospitals (meso-level). Second, at the macro-level, the governance system includes implementation gaps, lacking mechanisms for coordination between hospitals that may reinforce existing inequalities in service provision. Third, there is little evidence of a learning culture, and consequently, a risk that the same mistakes could be made repeatedly. We argue for a new approach to governing hospitals that can guide implementation of structures and processes that allow systematic and coherent coordination within and among Russian hospitals, based on modern approaches to accountability and organisational learning.     

Targeted near-IR hybrid magnetic nanoparticles for in vivo cancer therapy and imaging

We report the use of immuno-targeted gold–iron oxide hybrid nanoparticles for laser-assisted therapy and for MRI-based imaging as demonstrated in xenograft colorectal cancer tumor model. Immuno-targeted gold–iron oxide nanoparticles selectively accumulate in SW1222 xenograft tumors as compared to the accumulation in non-antigen-expressing tumor xenografts. Effective photothermal treatment using near-IR laser irradiation (808 nm, 5 W cm^? 2) application is shown where > 65% of the antigen-expressing tumor cells presented corrupt extracellular matrix and cytoplasmic acidophilia suggesting effectiveness of nanoparticle-assisted thermal therapy. Cell killing was confirmed by hematoxylin and eosin (H&E) histological staining where scar-like structure containing collagen bundles was observed in the treatment group. Further, systemically injected HNPs were shown to be effective T₂ magnetic resonance (MR) imaging contrast agents, localized and detected at the antigen-expressing xenograft tumors. These findings suggest that the new class of bio-conjugated HNPs exhibits great potential for dual-therapy and diagnostics (theranostics) applications.From the Clinical EditorThis team reports the successful use of immuno-targeted gold-iron oxide hybrid nanoparticles for both laser-assisted therapy and MRI-based imaging in a xenograft colorectal cancer tumor model, demonstrating strong potentials for dual applications in cancer diagnosis and therapy.     

Acetonitrile and benzonitrile as versatile amino sources in copper-catalyzed mild electrochemical C–H amidation reactions

A mild, efficient electrochemical approach to the site-selective direct C–H amidation of benzene and its derivatives with acetonitrile and benzonitrile has been developed. It has been shown that joint electrochemical oxidation of various arenes in the presence of a copper salt as a catalyst and nitriles leads to the formation of N-phenylacetamide from benzene and N-benzylacetamides from benzyl derivatives (up to 78% yield). A favorable feature of the process is mild conditions (room temperature, ambient pressure, no strong oxidants) that meet the criteria of green chemistry.

Different pathways of C–H transformation depending on the substrate nature and oxidation potential.

Direct functionalization of C–H bonds is one of the most popular tools in organic synthesis and allows formation of complex molecules from structurally simple starting substrates in one step.¹ The direct functionalization of carbon–hydrogen bonds catalyzed by transition metals is currently one of the main ways of constructing carbon–element bonds (C–N, C–C, C–P, C–R_fetc.).² Catalysed by transition metals, C–N bond building reactions are of particular importance in biology, pharmaceuticals and materials science.³ There are many examples of C–N bond formation reactions using organic (pseudo) halides such as aryl iodides, bromides, chlorides, triflates and sulfonates, that react with amines or their precursors. Ullmann and Goldberg were the first to report on the N-arylation of aryl halides using a copper mediator,⁴ and later Pd, Cu and Rh catalyzed C–N bond formation with suitable ligands was developed (Scheme 1, reaction 1).⁵Open in a separate windowScheme 1Strategies for the synthesis of N-arylamides and N-benzylamides.However, as a rule, such catalytic reactions have limited practical application due to the requirements for stoichiometric amounts of reagents and harsh reaction conditions (high temperature, high pressure, excess amount of strong oxidants, etc.). In addition these reactions involve strong chemical oxidants that are expensive, reduce the atomic economy of the process and lead to the formation of by-products. To address those limitations, reactions of C–H functionalization catalysed by transition metals by means of electrochemical oxidation⁶ and photoelectrochemistry⁷ have been developed relatively recently.Electrocatalytic approaches have been shown to be effective methods for building C–P, C–C, C–R_f and C–N bonds.⁸ In particular, the synthesis of N-arylamides is of particular interest for organic chemists, since amides are important structural frameworks presented in natural products, biological compounds, pharmaceuticals and synthetic materials.⁹ Therefore, the search for the new methods to synthesize N-arylamides, including electrochemical approach, is of current interest. The synthesis of N-arylamides could be more accessible while using nitriles as amidation agents instead of amides.It is known that certain alkanes can be oxidized at sufficiently high electrode potentials in acetonitrile with functionalization of C(sp³)–H bonds. Koch and Miller studied the electrochemical acetamidation reaction of adamantanes in acetonitrile at a platinum anode.¹⁰ The anodic oxidation of adamantine was performed potentiostatically producing N-(1-adamanty1)acetonitrilium ions as the major product. Further aqueous work-up was leading to the formation of 1-adamantylacetamide in 65–90% yields.Ji group developed an efficient and practical methodology for the synthesis of N-arylamides via copper catalyzed amidation of diaryliodonium salts with nitriles (Scheme 1, reaction 2).¹¹N-Arylated amides were obtained in moderate to good yields (up to 88%) and various substituted aryl nitriles and aliphatic nitriles could be applied in this reaction.Ley and coworkers reported on the preparation of benzyl amides from a number of aromatic hydrocarbons by a stable and continuous flow anodic oxidation using Bu₄NPF₆ as electrolyte and Brønsted acid additives (Scheme 1, reaction 3).¹² The amide derivatives of various para-, meta- and ortho-substituted benzene derivatives were obtained in good yields (64%). However the continuous flow electrolysis could not be carried out in pure acetonitrile and limited to certain substrates.In Vecchio group the series of acetamides was obtained in high yields under solvent- and catalyst-free conditions using isopropenyl acetate as reagent for acetylation of amines.¹³ Although this protocol is not suitable for unsubstituted arenes.Just recently Shen and Lambert reported on electrophotocatalytic convert benzylic C–H bonds to acetamides with the use of hard-to-find and expensive trisaminocyclopropenium (TAC) ion as catalyst (Scheme 1, reaction 4).¹⁴ The protocol is compatible with many functional groups and was demonstrated on complex substrates although no examples of aromatic ring amidation reaction were provided.Anodic oxidation of 1-(trifluoromethyl)benzene in dry acetonitrile/Bu₄NBF₄ under constant potential conditions leading to 2-(trifluoromethyl) acetanilide was proposed by Barba et al.¹⁵ No other substrates were demonstrated in this protocol.Inspired by the literature data in this area we report on the optimized conditions of the cross-coupling reaction between unsubstituted arenes (e.g. benzene) and different nitriles. Relying on the previously obtained experience of Cu-catalyzed electrochemical amination reactions,^8g copper acetate salt was chosen as a catalyst. Thus, electrooxidation of benzene in MeCN in the presence of catalytic amount of copper acetate leaded to the formation of acetanilide as only product with a yield of 70% (

Presynaptic gating of postsynaptically expressed plasticity at mature thalamocortical synapses

Thalamocortical (TC) projections provide the major pathway for ascending sensory information to the mammalian neocortex. Arrays of these projections form synaptic inputs on thalamorecipient neurons, thus contributing to the formation of receptive fields (RFs) in sensory cortices. Experience-dependent plasticity of RFs persists throughout an organism's life span but in adults requires activation of cholinergic inputs to the cortex. In contrast, synaptic plasticity at TC projections is limited to the early postnatal period. This disconnect led to the widespread belief that TC synapses are the principal site of RF plasticity only in neonatal sensory cortices, but that they lose this plasticity upon maturation. Here, we tested an alternative hypothesis that mature TC projections do not lose synaptic plasticity but rather acquire gating mechanisms that prevent the induction of synaptic plasticity. Using whole-cell recordings and direct measures of postsynaptic and presynaptic activity (two-photon glutamate uncaging and two-photon imaging of the FM 1-43 assay, respectively) at individual synapses in acute mouse brain slices that contain the auditory thalamus and cortex, we determined that long-term depression (LTD) persists at mature TC synapses but is gated presynaptically. Cholinergic activation releases presynaptic gating through M(1) muscarinic receptors that downregulate adenosine inhibition of neurotransmitter release acting through A(1) adenosine receptors. Once presynaptic gating is released, mature TC synapses can express LTD postsynaptically through group I metabotropic glutamate receptors. These results indicate that synaptic plasticity at TC synapses is preserved throughout the life span and, therefore, may be a cellular substrate of RF plasticity in both neonate and mature animals.