Systematic review on inhaled corticosteroid monotherapy and its efficacy and safety in longterm treatment of patients with chronic obstructive pulmonary disease (COPD)

--chronic obstructive pulmonary disease,COPD,corticosteroids,systematic review,chronisch obstruktive Lungenerkrankung,COPD,Kortikosteroid,systematischer Review

Movement direction or change in distance? Self- and object-related approach-avoidance motions

Based on the conceptualization of approach as a decrease in distance and avoidance as an increase in distance, we predicted that stimuli with positive valence facilitate behavior for either approaching the stimulus (object as reference point) or for bringing the stimulus closer (self as reference point) and that stimuli with negative valence facilitate behavior for withdrawing from the stimulus or for pushing the stimulus away. In Study 1, we found that motions to and from a computer screen where positive and negative words were presented lead to compatibility effects indicative of an object-related frame of reference. In Study 2, we replicated this finding using social stimuli with different evaluative associations (young vs. old persons). Finally, we present evidence that self vs. object reference points can be induced through instruction and thus lead to opposite compatibility effects even when participants make the same objective motion (Study 3)

Synthesis and reactivity of the first isolated hydrogen-bridged silanol-silanolate anions.

Weitkamp R, Neumann B, Stammler H-G, Hoge B. Synthesis and reactivity of the first isolated hydrogen-bridged silanol-silanolate anions. Angewandte Chemie International Edition. 2020;59(14):5494-5499.We report on the first examples of isolated silanol-silanolate anions, utilizing weakly coordinating phosphazenium counterions. The silanolate anions are synthesized by the reaction of the recently published phosphazenium hydroxide hydrate salt with siloxanes. The silanol-silanolate anions are postulated intermediates in the hydroxide mediated polymerization of aryl and alkyl siloxanes. The silanolate anions are strong nucleophiles due to the weakly coordinating character of the phosphazenium cation, which is perceptible in their activity in polysiloxane depolymerization. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Direct functionalization of white phosphorus with anionic dicarbenes and mesoionic carbenes: facile access to 1,2,3-triphosphol-2-ides

Rottschäfer D, Blomeyer S, Neumann B, Stammler H-G, Ghadwal R. Direct functionalization of white phosphorus with anionic dicarbenes and mesoionic carbenes: facile access to 1,2,3-triphosphol-2-ides. CHEMICAL SCIENCE. 2019;10(48):11078-11085.A series of unique C2P3-ring compounds [(ADC(Ar))P-3] (ADC(Ar) = ArC{(DippN)C}(2); Dipp = 2,6-iPr(2)C(6)H(3); Ar = Ph 4a, 3-MeC(6)H(4)4b, 4-MeC(6)H(4)4c, and 4-Me(2)NC(6)H(4)4d) are readily accessible in an almost quantitative yield by the direct functionalization of white phosphorus (P-4) with appropriate anionic dicarbenes [Li(ADC(Ar))]. The formation of 1,2,3-triphosphol-2-ides (4a-4d) suggests unprecedented [3 + 1] fragmentation of P-4 into P-3(+) and P-. The P-3(+) cation is trapped by the (ADC(Ar))(-) to give 4, while the putative P- anion reacts with additional P-4 to yield the Li3P7 species, a useful reagent in the synthesis of organophosphorus compounds. Remarkably, the P-4 fragmentation is also viable with the related mesoionic carbenes (iMICs(Ar)) (iMIC(Ar) = ArC{(DippN)(2)CCH}, i stands for imidazole-based) giving rise to 4. DFT calculations reveal that both the C3N2 and C2P3-rings of 4 are 6 pi-electron aromatic systems. The natural bonding orbital (NBO) analyses indicate that compounds 4 are mesoionic species featuring a negatively polarized C2P3-ring. The HOMO-3 of 4 is mainly the lone-pair at the central phosphorus atom that undergoes sigma-bond formation with a variety of metal-electrophiles to yield complexes [{(ADC(Ar))P-3}M(CO)(n)] (M = Fe, n = 4, Ar = Ph 5a or 4-Me-C(6)H(4)5b; M = Mo, n = 5, Ar = Ph 6; M = W, n = 5, Ar = 4-Me(2)NC(6)H(4)7)

Dynamical modelling of phenotypes in a genome-wide RNAi live-cell imaging assay.

International audienceBACKGROUND: The combination of time-lapse imaging of live cells with high-throughput perturbation assays is a powerful tool for genetics and cell biology. The Mitocheck project employed this technique to associate thousands of genes with transient biological phenotypes in cell division, cell death and migration. The original analysis of these data proceeded by assigning nuclear morphologies to cells at each time-point using automated image classification, followed by description of population frequencies and temporal distribution of cellular states through event-order maps. One of the choices made by that analysis was not to rely on temporal tracking of the individual cells, due to the relatively low image sampling frequency, and to focus on effects that could be discerned from population-levelbehaviour. RESULTS: Here, we present a variation of this approach that employs explicit modelling by dynamic differential equations of the cellular state populations. Model fitting to the time course data allowed reliable estimation of the penetrance and time of appearance of four types of disruption of the cell cycle: quiescence, mitotic arrest, polynucleation and cell death. Model parameters yielded estimates of the duration of the interphase and mitosis phases. We identified 2190 siRNAs that induced a disruption of the cell cycle at reproducible times, or increased the durations of the interphase or mitosis phases. CONCLUSIONS: We quantified the dynamic effects of the siRNAs and compiled them as a resource that can be used to characterize the role of their target genes in cell death, mitosis and cell cycle regulation. The described population-based modelling method might be applicable to other large-scale cell-based assays with temporal readout when only population-level measures are available

Cycloaddition Reactions of the Diphosphenyl Complex (η5-C5Me5)(CO)2Fe-P=P-Mes* (Mes* = 2,4,6-tBu3C6H2) with Hexafluoroacetone. X-Ray Structure Analyses of (η5-C5Me5)(CO) Fe P(=PMes*)OC(CF3)2CO and (η5-C5Me5)(CO)2FePP(Mes*)OC(CF3)2

Weber L, Buchwald S, Lentz D, Preugschat D, Stammler H-G, Neumann B. Cycloaddition Reactions of the Diphosphenyl Complex (η5-C5Me5)(CO)2Fe-P=P-Mes* (Mes* = 2,4,6-tBu3C6H2) with Hexafluoroacetone. X-Ray Structure Analyses of (η5-C5Me5)(CO) Fe P(=PMes*)OC(CF3)2CO and (η5-C5Me5)(CO)2FePP(Mes*)OC(CF3)2. Organometallics. 1992;11(7):2351-2353.The diphosphenyl complex (eta-5-C5Me5)-(CO)2Fe-P=P-Mes* (Mes* = 2,4,6-tBu3C6H2) undergoes a [3 + 2] dipolar cycloaddition with hexafluoroacetone to give the metalla heterocycle (eta-5-C5Me5)(CO)-Fe-P(=PMes*)OC(CF3)2C(O) with a remarkably short Fe-P bond (2.084 (4) angstrom) and an exocyclic P=P bond. When stored in solution at -40-degrees-C, this complex partly rearranges to the metalated 1-oxa-2,3-diphosphetane (eta-5-C5Me5)(CO)2Fe-P-P(Mes*)OC(CF3)2. The molecular structures of both isomers were elucidated by single-crystal X-ray analyses

Aryl-Aryl Interactions in (aryl-perhalogenated) 1,2-Diaryldisilanes.

Mitzel NW, Linnemannstöns M, Schwabedissen J, Neumann B, Stammler H-G, Berger R. Aryl-Aryl Interactions in (aryl-perhalogenated) 1,2-Diaryldisilanes. Chemistry. 2020;26(10):2169-2173.Three 1,2-diaryltetramethyldisilanes X5C6-(SiMe2)2-C6X5 with two C6H5, C6F5 or C6Cl5 groups were studied concerning the im-por-tan-ce of London dispersion driven interactions between their aryl groups. They were prepared from 1,2-di-chlo-rotetra-methyl-disi-la-ne by salt elimination. Their structures were determi-ned in the solid state by X-ray diffraction and for free molecules by gas elec-tron-diffraction. The solid-state struc-tures of the fluori-nated and chlo-rinated derivatives are domi-na-ted by aryl-aryl inter-actions. Unex-pectedly, Cl5C6-(SiMe2)2-C6Cl5 exists exclusive-ly as eclipsed syn-conformer in the gas phase with strongly distor-ted Si-C6Cl5 units due to strong intramo-le-cular interactions. In contrast, F5C6-(SiMe2)2-C6F5 reveals wea-ker inter-actions. The contributions to the total interaction energy was analyzed by SAPT calculations. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

FUNCTIONALIZED SILICON-COMPOUNDS WITH OMEGA-TETRAMETHYL AND OMEGA-PENTAMETHYLCYCLOPENTADIENYLALKYL LIGANDS - MOLECULAR-COMPONENTS FOR THE PREPARATION OF METALLIC POLYMERS

Jutzi P, Heidemann T, Neumann B, Stammler H-G. Funktionalisierte Siliciumverbindungen mit [omega]-Tetramethyl- und [omega]-Pentamethylcyclopentadienylalkyl-Liganden: Molekulare Bausteine zur Darstellung von Metall-haltigen Polymeren. Journal of Organometallic Chemistry. 1994;472(1-2):27-38.Peralkylierte Cyclopentadien-Systeme des Typs Me5C5(CH2)3Si(Me)mY3-m, die über eine Alkyliden-Spacergruppe mit einer funktionalisierten Silan-Einheit verknüpft sind, sind auf zwei verschiedenen Wegen synthetisiert worden. Als Beispiel für den ersten Weg wird die Synthese des Disiloxans [Me5C5CH2)3Si(Me)2]2O (2) beschrieben, welches ausgehend von der Iodverbindung [I(CH2)3Si(Me)2]2O (1) durch Umsetzung mit Me5C5K dargestellt werden kann. Das Trichlorsilan Me5C5(CH2)3SiCl3 (4), als Synthesebeispiel für den zweiten Weg, ist über Hydrosilylierung von 1-Prop-2-enyl-1,2,3,4,5-pentamethylcyclopenta-2,4-dien (3) zugänglich. Beide Synthesewege sind auch zur Darstellung der teilweise alkylierten Cyclopentadiensysteme des Typs Me4HC5(CH2)3Si(Me)mY3-m geeignet. So führen die Umsetzungen der [omega]-Iodalkyl-triethoxysilane I(CH2)nSi(OEt)3 (n = 1, 2, 3) mit Me4HC5K zu den entsprechenden [omega]-(Tetramethylcyclopentadienyl)alkyl-triethoxysilanen 5–7. Verbindungen 5–7 liegen als Isomerengemische vor; das Verhältnis zwischen den Isomeren, die ein allylständiges oder ein vinylständiges Wasserstoffatom am Cyclopentadienring aufweisen, ist abhängig von der Spacerlänge. Isomerengemische der 4-(Tetramethylcyclopentadienyl)butyl-silane des Typs Me4HC5(CH2)4Si(Me)mCl3-m (m = 1, 2, 3) (8–10) mit ausschließlich allyiständigem Wasserstoffatom am Cyclopentadienring können durch Hydrositylierung von 1-But-3-enyl-2,3,4,5-tetramethyleyclopentadien dargestellt werden. Die am Siliciumatom funktionalisierten Verbindungen 2 und 4–10 können weiter derivatisiert werden. An ausgewählten Beispielen wird die Hydrolyse, die Alkoholyse, die reduktive Kupplung, die Heterogenisierung und die Polykondensationsreaktion näher untersucht. So erhält man das Silanol 12 und das Disiloxan 13, die Alkoxysilane 14–17, das Disilan 18 und die funktionalisierten Kieselgele 19–20. Verbindungen 2, 4–10 und 12–20 dienen als “Pool” zur Darstellung von Übergangsmetall-Derivaten. Beispielsweise wird die Dicarbonyl—Cobalt-Verbindung 21 durch Umsetzung von 8 mit Co2(CO)8 gebildet. Reaktion von 16 mit K und FeCl2 liefert das Ferrocen-Derivat 22. Die [eta]4-gebundenen Pt(II)- und Pd(II)-Komplexe 23–27 können durch Umsetzung der funktionalisierten Si---O-Verbindungen 2, 13, und 19–20 mit [PtCl2(Ethylen)]2 oder PdCl2(PhCN)2 erhalten werden.Peralkylated cyclopentadiene systems of the type Me5C5(CH2)3Si(Me)mY3-m, which possess cyclopentadiene units connected with a functionalized silane fragment by an alkylidene spacer group, are prepared via two routes. As an example of the first route, the disiloxane [Me5C5(CH2)3Si(Me)2]2O (2) has been synthesized from the corresponding iodo compound [I(CH2)3Si(Me)2]2O (1) by reaction with Me5C5K. The trichlorosilane Me5C5(CH2)3SiCl3 (4), as an example of a compound prepared via the second route, has been isolated after hydrosilylation of 1-prop-2-enyl-1,2,3,4,5-pentamethylcyclopenta-2,4-diene (3) with HSiCl3. Both synthetic methods are also suitable for the preparation of partly alkylated cyclopentadiene systems of the type Me4HC5(CH2)nSi(Me)mY3-m. Thus the omega-iodoalkyltriethoxysilanes I(CH2)nSi(OEt)3 (n = 1, 2, 3) react with Me4HC5K to give the corresponding omega-(tetramethyl-cyclopentadienyl)alkyl-triethoxysilanes 5-7. Compounds 5-7 consist of a mixture of isomers; the ratio between isomers having an allylic or vinylic hydrogen atom at the cyclopentadiene ring depends on the spacer length. Isomeric mixtures of the 4-(tetramethyl-cyclopentadienyl)butyl-silanes of the type Me4HC5(CH2)4Si(Me)mCl3-m (M = 1, 2, 3) (8-10) with an allylic hydrogen atom at the cyclopentadiene ring have been prepared by hydrosilylation of 1-but-3-enyl-2,3,4,5-tetramethylcyclopentadiene. The silane fragment in the alkylated cyclopentadiene systems 2 and 4-10 can be modified further. As examples hydrolysis, alcoholysis, reductive coupling, heterogenisation and polycondensation reactions are described. Following theses procedures the corresponding silanol 12 and disiloxane 13 have been prepared as well as the alkoxysilanes 14-17, the disilane 18 and the functionalized silicagels 19 and 20. Compounds 2, 4-10 and 12-20 serve as a ''pool'' for the preparation of transition metal complexes. The dicarbonyl cobalt compound 21 has been synthesized by reaction of 8 with CO2(CO)8. Reaction of 16 with K and FeCl2 gives the corresponding ferrocene derivative 22. The eta4-bound Pt(II) and Pd(II)-complexes 23-27 have been prepared by reaction of the functionalized Si-O-compounds 2, 13, and 19-20 with [PtCl2(Ethylen)]2 and PdCl2(PhCN)2, respectively