Grubbs-Hoveyda type catalysts bearing a dicationic N-heterocyclic carbene for biphasic olefin metathesis reactions in ionic liquids

Abstract The novel dicationic metathesis catalyst [(RuCl 2 (H 2 ITapMe 2 )(=CH-2-(2-PrO)- N-heterocyclic carbene (NHC) ligand was prepared. The reactivity was tested in ring opening metathesis polymerization (ROMP) under biphasic conditions using a nonpolar organic solvent (toluene) and the ionic liquid (IL) 1-butyl-2,3-dimethylimidazolium The structure of Ru-2 was confirmed by single crystal X-ray analysis. 163

Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells

Mechanotransduction via yes-associated protein (YAP) is a central mechanism for decision-making in mouse embryonic stem cells (mESCs). Nuclear localization of YAP is tightly connected to pluripotency and increases the cell division rate (CDR). How the geometry of the extracellular environment influences mechanotransduction, thereby YAP localization, and decision-making of single isolated mESCs is largely unknown. To investigate this relation, we produced well-defined 2D and 2.5D microenvironments and monitored CDR and subcellular YAP localization in single mESCs hence excluding cell–cell interactions. By systematically varying size and shape of the 2D and 2.5D substrates we observed that the geometry of the growth environment affects the CDR. Whereas CDR increases with increasing adhesive area in 2D, CDR is highest in small 2.5D micro-wells. Here, mESCs attach to all four walls and exhibit a cross-shaped cell and nuclear morphology. This observation indicates that changes in cell shape are linked to a high CDR. Inhibition of actomyosin activity abrogate these effects. Correspondingly, nuclear YAP localization decreases in inhibitor treated cells, suggesting a relation between cell shape, intracellular forces, and cell division rate. The simplicity of our system guarantees high standardization and reproducibility for monitoring stem cell reactions and allows addressing a variety of fundamental biological questions on a single cell level

The contribution of musculoskeletal disorders in multimorbidity: Implications for practice and policy

People frequently live for many years with multiple chronic conditions (multimorbidity) that impair health outcomes and are expensive to manage. Multimorbidity has been shown to reduce quality of life and increase mortality. People with multimorbidity also rely more heavily on health and care services and have poorer work outcomes. Musculoskeletal disorders (MSDs) are ubiquitous in multimorbidity because of their high prevalence, shared risk factors, and shared pathogenic processes amongst other long-term conditions. Additionally, these conditions significantly contribute to the total impact of multimorbidity, having been shown to reduce quality of life, increase work disability, and increase treatment burden and healthcare costs. For people living with multimorbidity, MSDs could impair the ability to cope and maintain health and independence, leading to precipitous physical and social decline. Recognition, by health professionals, policymakers, non-profit organisations, and research funders, of the impact of musculoskeletal health in multimorbidity is essential when planning support for people living with multimorbidity

Kontinuierliche Olefinmetathese in zweiphasigen flüssig/flüssig-Systemen unter Verwendung immobilisierter ionischer Flüssigkeiten

This work reveals the development of a novel, supported catalytic system for continuous olefin metathesis reactions. The concept enables to combine the advantages of both homogeneous as well as heterogeneous catalytic processes and is based on the combination of functionalized monolithic support materials and tailored, ionic ruthenium alkylidene complexes. The porosity of these monoliths can be adjusted with high precision and reproducibility. Adequate choice of the monomers and crosslinkers, their ratio towards each other, as well as their relative percentage in the total polymerization mixture enables the preparation of monoliths with convincing form stability. These monoliths allow for a high reactant throughput (this means high flow rates are applicable), hence without giving too high back pressures (< 20 bar). The monoliths surface is functionalized by grafting an ionic monomer onto it, thereby taking advantage of the living character of the ROMP (ring-opening metathesis polymerization) reaction used for its preparation. For these reasons, ROMP-derived monoliths are outstandingly well-suited to be used as support materials in continuously operated biphasic liquid-liquid catalysis reactions. The ionic moieties facilitate/enable to attach and to fix films of ionic liquids with adjustable thickness. In fact, these films of ionic liquids represent the actual stationary phases for the performed metathesis reactions under biphasic liquid-liquid conditions. Novel ionic ruthenium alkylidene complexes were dissolved in the ionic liquid and are due to ionic interactions immobilized within this phase. The substrates intended to be used in metathesis reactions were first dissolved in a nonpolar, organic solvent and were then simply flushed through the monolith, which was loaded with catalyst immobilized in the ionic liquid. The metathesis reaction is rendered possible by diffusion of the reactants to the catalytically active Ru-complex immobilized in the stationary phase. Diffusion of the products back into the mobile phase guarantees for the transport of the desired compounds out of the monolithic support. Besides the benefit of low catalyst leaching, the fact, that a biphasic liquid-liquid system is used definitely widens the range of potentially accessible substrates. Moreover, the facile recycling of the monolithic support by flushing with, e.g., methanol, represents an additional advantage. The simple recharging process with fresh catalyst dissolved in the ionic liquid allows restoring the catalytic system within a rather short period of time.In der vorliegenden Arbeit wird die Entwicklung eines neuartigen, geträgerten Katalysesystems für kontinuierliche Olefinmetathese-Reaktionen vorgestellt. Das Konzept vereinbart Vorteile der heterogenen sowie der homogenen Katalyse und basiert auf der Kombination funktionalisierter, monolithischer Trägermaterialien mit neuartigen, ionischen Ruthenium-Alkylidenkomplexen. Die Porenstruktur polymerer Monolithe lässt sich präzise und reproduzierbar einstellen. Durch geeignete Wahl der verwendeten Monomere und Quervernetzer, sowie deren Verhältnis zueinander und deren relativen Anteil an der Gesamtmasse des Polymerisationsansatzes können Monolithe mit hoher Formstabilität hergestellt werden. Diese ermöglichen einen großen Reaktantendurchsatz (d.h. es können hohe Flussraten angelegt werden), ohne dass sich dabei ein allzu hoher Gegendruck (p < 20 bar) einstellt. Die gewählte Herstellungsmethode bietet ein weiteres Argument dafür, weshalb polymere Monolithe geeignete Trägermaterialien für das im Folgenden vorgestellte Katalysekonzept darstellen. Monolithe können mittels Ring-öffnender Metathesepolymerisation (ROMP) synthetisiert werden. Unter Ausnutzung des lebenden Charakters dieser Polymerisationsart kann die monolithische Oberfläche auf einfache Weise funktionalisiert werden, was z.B. durch das Pfropfen ionischer Monomere erzielt werden kann. Monolithe eignen sich daher hervorragend als Trägermaterialien für kontinuierlich betriebene Flüssigphasen-Reaktionen. Die ionischen Gruppen erleichtern bzw. ermöglichen die Aufbringung und Fixierung ionischer Flüssigkeiten (engl. ionic liquids (ILs)) mit beliebig einstellbarer Filmdicke. Diese IL-Phase stellt die eigentliche stationäre Phase für die durchgeführten zweiphasigen flüssig-flüssig Reaktionen dar. Neu entwickelte, ionische Ruthenium-Alkylidenkomplexe werden in der ionischen Flüssigkeit gelöst und durch ionische Wechselwirkungen in dieser Phase immobilisiert. Die Substrate für die durchgeführten Olefinmetathesereaktionen werden in einem unpolaren, organischen Lösungsmittel aufgenommen und durch den, mit Katalysator beladenen Monolithen gepumpt. Diffusion der Edukte aus der mobilen Phase in die stationäre Phase ermöglicht dort die Umsetzung mit dem ionischen Katalysator. Diffusion der Produkte zurück in die mobile Phase garantiert dagegen deren Abtransport aus dem Monolithen. Neben dem augenscheinlichen Nutzen einer geringen Katalysatorauswaschung und damit geringen Produktkontamination ermöglicht ein zweiphasiges flüssig-flüssig System die Verwendung einer großen Vielzahl an potentiell verfügbaren Substraten. Ein weiterer Vorteil liegt in der einfachen Entfernung der mobilen Phase und dem darin enthaltenen, inaktiven Katalysator, was durch Spülen des Monolithen mit Methanol erzielt werden kann. Durch einen einfachen Wiederbeladungsprozess ist das monolith-geträgerte Katalysatorsystem bereits nach kurzer Zeit für den erneuten Einsatz in kontinuierlich durchgeführten Metathesereaktionen verwendbar

Stereospecific Ring-Opening Metathesis Polymerization (ROMP) of Norbornene and Tetracyclododecene by Mo and W Initiators

We report the synthesis of >98% cis,isotactic and cis,syndiotactic polynorbornene (poly(NBE)) and poly(endo,anti-tetracyclododecene) (poly(TCD)). Cis,isotactic poly(NBE) and poly(TCD) were prepared employing Mo-based biphenolate imido alkylidene initiators, Mo(NR)(CHCMe[subscript 2]Ph)(Biphen) (Biphen = e.g., 3,3′-(t-Bu)[subscript 2]-5,5′-6,6′-(CH[subscript 3])[subscript 4]-1,1′-biphenyl-2,2′-diolate), while cis,syndiotactic poly(NBE) and poly(TCD) were prepared employing W-based imido or oxo monoaryloxide pyrrolide (MAP) initiators, W(X)(CHR′)(Pyrrolide)(OTer) (X = NR or O; OTer = a 2,6-terphenoxide). Addition of 1-hexene or coordinating solvents such as THF do not decrease the stereospecificity of the polymerization. Cis,iso and cis,syndio dyads can be distinguished through examination of [superscript 1]H and [superscript 13]C NMR spectra of the two polymers in a mixture. The polymers were hydrogenated to give isotactic and syndiotactic H-poly(NBE) and H-poly(TCD).United States. Department of Energy (grant DE-FG0286ER13564

Proof of Tacticity of Stereoregular ROMP Polymers through Post Polymerization Modification

Partial bromination or epoxidation has been used to prove the tacticities of several stereoregular polymers made through ROMP methods with well-defined Mo or W initiators.Tacticities were proven for cis,isotactic and cis,syndiotactic poly(norbornene), poly(3-methyl-3-phenylcyclopropene), and poly(endo,anti-tetracyclododecene). Various limitations can prevent application of these proofs in general to stereoregular polymers prepared through ROMP.United States. Department of Energy (DE-FG02-86ER13564

Grubbs–Hoveyda type catalysts bearing a dicationic N-heterocyclic carbene for biphasic olefin metathesis reactions in ionic liquids

The novel dicationic metathesis catalyst [(RuCl2(H2ITapMe2)(=CH–2-(2-PrO)-C6H4))2+ (OTf−)2] (Ru-2, H2ITapMe2 = 1,3-bis(2’,6’-dimethyl-4’-trimethylammoniumphenyl)-4,5-dihydroimidazol-2-ylidene, OTf− = CF3SO3−) based on a dicationic N-heterocyclic carbene (NHC) ligand was prepared. The reactivity was tested in ring opening metathesis polymerization (ROMP) under biphasic conditions using a nonpolar organic solvent (toluene) and the ionic liquid (IL) 1-butyl-2,3-dimethylimidazolium tetrafluoroborate [BDMIM+][BF4−]. The structure of Ru-2 was confirmed by single crystal X-ray analysis

Stereospecific Ring-Opening Metathesis Polymerization (ROMP) of endo-Dicyclopentadiene by Molybdenum and Tungsten Catalysts

United States. Department of Energy (DE-FG02-86ER13564