Towards practical earth abundant reduction catalysis : design of improved catalysts for manganese catalysed hydrogenation

The authors thank EPSRC (grant code: 1654521) for DTG funding for MBW.Manganese catalysts derived from tridentate P,N,N ligands can be activated easily using weak bases for both ketone and ester hydrogenations. Kinetic studies indicate the ketone hydrogenations are 0th order in acetophenone, positive order in hydrogen and 1st order in catalyst. This implies that the rate determining step of the reaction was the activation of hydrogen. New ligand systems with varying donor strength were studied and it was possible to make the hydrogen activation significantly more efficient; a catalyst displaying around a 3-fold increase in initial Turn-Over Frequencies for the hydrogenation of acetophenone relative to the parent system was discovered as a result of these kinetic investigations. Ester hydrogenations and ketone transfer hydrogenation (isopropanol as reductant) are first order for both the substrate and catalysts. Kinetic studies also gained insight into catalyst stability and identified a working range in which the catalysts is stable throughout the catalytic reaction (and a larger working range where high yields can still be achieved). The new more active catalyst, combining an electron-rich phosphine with an electron-rich pyridine is capable of hydrogenating acetophenone using as little as 0.01 mol% catalyst at 65 oC. In all, protocols for reduction of 21 ketones and 15 esters are described.PostprintPeer reviewe

The contradictory effect of the methoxy-substituent in palladium-catalyzed ethylene/methyl acrylate cooligomerization

Two new nonsymmetric bis(aryl-imino)acenaphthene ligands (Ar,Ar'-BIAN) and one symmetric Ar2-BIAN were studied. The three ligands share the presence of at least one methoxy group on one of the two aryl rings. These ligands were used for the synthesis of neutral and monocationic palladium(II) complexes of general formula [Pd(CH3)Cl(N-N)] and [Pd(CH3)(L)(N-N)][PF6] (N-N = Ar,Ar'-BIAN, Ar2-BIAN; L = CH3CN, dmso). Due to the nonsymmetric nature of the ligands and their coordination to palladium in a nonsymmetric chemical environment, cis and trans isomers are possible for the three series of complexes with Ar,Ar'-BIANs. Both a detailed NMR investigation in solution and the X-ray characterization in solid state point out that the trans isomer is the preferred species for the neutral derivatives, whereas for the cationic compounds a decrease in the stereoselectivity of the coordination is observed. One of the new Ar,Ar'-BIANs differs from an already reported nonsymmetric \uf061-diimine for the replacement, on one aryl ring, of a methyl group with a methoxy susbtituent, thus allowing a comparison of the structural features of the relevant complexes. The monocationic complexes were tested as precatalysts for the ethylene/methyl acrylate copolymerization under mild reaction conditions. Despite the structural similarities observed in solution with the already known precatalysts, the present compounds demonstrated a remarkable decrease in the productivity values associated to a higher affinity for the polar monomer

Evolution of metal catalyst during CVD synthesis of carbon nanotubes

La découverte révolutionnaire des nanotubes de carbone (CNT) en 1991 a provoqué une intensification des travaux de recherche dans le domaine de la science du carbone. Les propriétés fascinantes de ce matériau offrent une multitude d’applications potentielles, par exemple comme émetteur de champs, conducteur uni-dimensionnel, condensateur haute capacité (“supercap”), fibres de renforcement ou encore comme réservoir d’hydrogène. Malgré d’immenses progrès techniques, l’amélioration des méthodes de synthèse en vue d’une application commerciale est encore au centre des recherches. La technique de dépôt en phase vapeur (CVD) est un candidat prometteur. Dans cette technique, la nucléation et la croissance des CNTs sont induites par la décomposition de gaz carburés (CO, CO2, C2H2, etc.) sur un catalyseur métallique à des températures comprises entre 600°C et 1200°C. La CVD est largement utilisée pour la fabrication à grande échelle de CNTs et beaucoup de progrès ont été faits en ce qui concerne la quantité, les frais de synthèse et la pureté des produits. Toutefois, le mécanisme de croissance des nanotubes par CVD reste peu connu. La diffusion du carbone à travers le catalyseur métallique est souvent considérée comme l’étape déterminante lors de la croissance des CNTs. Les métaux les plus réactifs sont le fer, le cobalt et le nickel, mais leur effet catalytique est dépendant de plusieurs facteurs tels que la nature du précurseur, le substrat utilisé et les gaz de réaction. La nature chimique actuelle du catalyseur actif est très controversée; on ne sait pas par exemple s’il est présent sous forme de métal, de carbure ou en phase mélangée. Jusqu’à présent, très peu d’analyses insitu de l’évolution chimique et morphologique du catalyseur durant le processus CVD ont été faites. Le comportement de catalyseurs à base de nickel, cobalt, chrome ou molybdène a été analysé sous une atmosphère azote/acétylène ou azote/acétylène/ hydrogène à des températures de 600°C et de 750°C. Pour mieux comprendre les propriétés des phases métalliques pendant le processus de synthèse, un diffractomètre à rayons X équipé avec une table chauffante et un système de contrôle atmosphérique a été utilisé pour étudier in-situ l’évolution des revêtements de nitrate métallique. Les échantillons ont été ensuite trempés à différents stades de pyrolyse pour être finalement observés au MEB et MET. Les images au microscope ont montré que le nickel ainsi que le cobalt et le molybdène peuvent agir comme catalyseurs pour la nucléation et la croissance des CNTs, cepandant pas le chrome. La réduction de la taille des grains résultant d’une perte suffisante de volume solide pendant les réactions rédox dans le précurseur catalytique, ainsi que la transformation de ces précurseurs en une phase métallique sont les principales conditions nécessaires à la croissance de CNTs. Les stades de réaction observés pendant la réduction du précurseur ont été mis en relation avec la nucléation et la croissance des nanotubes. La diffusion de carbone à travers les particules métalliques, marquée par un agrandissement des paramètres cellulaires du métal et identifiée sur les diffractogrammes par un déplacement des pics, est observée à chaque fois que des nanotubes de carbone sont générés. Avec le nickel et le cobalt, aucune phase de carbure ne s’est formée. Avec le fer, la décomposition des phases métastables de carbure agit comme une seconde activation de la croissance des nanotubes alors que le molybdène va favoriser la formation de carbures qui vont stopper la croissance des CNTs après 20 minutes. Dans tous les cas, il a été démontré qu’un traitement préliminaire à l’hydrogène favorise la croissance des nanotubes.Die revolutionäre Entdeckung von Kohlenstoff- Nanoröhrchen (CNT) im Jahre 1991 liess die Forschungsarbeiten im Bereich der Kohlenstoffwissenschaft intensivieren. Die faszinierenden Eigenschaften dieses einzigartigen Materials ermöglichten eine Vielzahl von potenziellen Anwendungen wie zum Beispiel als Elektronen Feldemissionsquelle, eindimensionale Konduktoren, Superkapazitäten, Verstärkungsfaden oder Wasserstoffspeicher. Trotz der atemberaubenden technischen Fortschritte bemüht man sich immer noch um die Entwicklung einer Synthesemethode für die kommerzielle Anwendung. Ein vielversprechender Kandidat ist die Technik der chemischen Gasphasenabscheidung (CVD). Die Keimbildung und das Wachstum von CNTs werden induziert durch die Zersetzung von kohlenstoffhaltigen Gasen (CO, CO2, C2H2, usw.) über einem metallischen Katalysator bei Temperaturen zwischen 600°C und 1200°C. CVD ist eine weit verbreitete Technik für die Fabrikation von CNT in grossen Quantitäten und Fortschritte betreffend der Menge, der Synthesekosten und der Reinheit der Produkte, wurden erzielt. Doch das grosse Rätsel der CVD Methode bleibt der Wachstumsmechanismus. Der Hauptreaktionsschritt für das Wachstum von Nanoröhrchen scheint die Diffusion von Kohlenstoff durch den Metallkatalysator zu sein. Die reaktivsten Metalle sind Eisen, Kobalt und Nickel, doch deren katalytische Wirkung ist abhängig von der Art des Ausgangsmaterials, des benutzten Substrates und der Reaktionsgase. Sehr umstritten ist die aktuelle chemische Beschaffenheit des aktiven Katalysators, zum Beispiel ob er als Metall, Karbid oder als gemischte Phase vorliegt. Bis jetzt wurden nur sehr wenige in-situ Analysen der chemischen und morphologischen Evolution des Katalysators während des CVD Prozesses durchgeführt. Diese Doktorarbeit befasst sich mit der Evolution von nickel-, kobalt-, chrom- und molybdänbasierenden Katalysatoren unter Stickstoff/Acetylen und Stickstoff/Acetylen/Wasserstoff Atmosphäre bei 600°C und 750°C. Um die Eigenschaften von metallischen Phasen während des Syntheseablaufs aufzuklären, wurde ein Röntgendiffraktometer mit einem Heiztisch und einem Atmosphärenkontrollsystem ausgestattet, welches das in-situ Studium der Evolution von Metallnitrat-Filmen ermöglicht. Die Proben wurden dafür bei verschiedenen Pyrolysezeiten abgeschreckt und im REM und TEM untersucht. Die Mikroskopiebilder zeigen, dass Nickel sowie Kobalt und Molybdän unter typischen Nanoröhrchen Synthesebedingungen als Katalysatoren für CNTs Keimbildung und Wachstum agieren können, jedoch nicht Chrom. Korngrössenreduktion, resultierend aus dem ausreichenden Festkörpervolumenverlust während der Redox Reaktion im katalytischen Ausgangsmaterial, und die Transformation des Ausgangsmaterials zu einer metallischen Phase sind die Hauptvoraussetzungen für das CNT Wachstum. Die beobachteten Reaktionsabschnitte während der Reduktion des Ausgangsmaterials werden in Verbindung gebracht mit der Keimbildung und dem Wachstum von Nanoröhrchen. Kohlenstoffdiffusion durch die metallischen Partikel, angezeigt durch eine Vergrösserung der Zellparameter des Metalls und identifiziert in Diffraktogramme als Peak- Verschiebung, wurde beobachtet wann immer CNTs gebildet wurden. Im Nickel- und Kobaltsystem wurden keine Karbidphasen entdeckt. Doch im Vergleich zum Eisensystem, wo die Zerlegung von metastabilem Karbid als zweiter Schub von Nanoröhrchen Bildung dient, wird das CNT Wachstum im Molybdänsystem nach der Bildung von Karbiden nach 20 Minuten gestoppt. In jedem Fall begünstigt eine Vorbehandlung mit Wasserstoff die Nanoröhrchen Bildung.The revolutionary discovery of carbon nanotubes (CNT) in 1991 led to intense research activities in the domain of carbon science. The fascinating properties of these unique material has opened a great number of potential applications e.g. as electron field emitters, one-dimensional conductors, supercapacitors, reinforcing fibres or hydrogen storage. Despite these stunning technical progresses there is still much struggle in the development of a synthesis method suitable for commercial applications. A leading candidate is the chemical vapour deposition (CVD) technique. Nucleation and growth of CNTs are induced by the decomposition of carbon-containing gases (CO, CO2, C2H2, etc) over a metallic catalyst at temperatures between 600°C and 1200°. CVD is a widely used technique to generate CNTs in large quantities and much progress has been made from the point of view of the yield, the synthesis costs or the purity of the products. But the great conundrum of CVD process remains the growth mechanism. A key reaction step for nanotube growth seems to be diffusion of carbon through the metal catalyst and the most active metals are iron, cobalt and nickel but their catalytic action depends on the type of precursor, the type of substrate and of the reactive gases used. Highly controversial is the actual chemical nature of the active catalyst e.g. if it is present as metal, carbide or as mixed phase. So far few investigations of the chemical and morphological evolution of the catalyst during CVD process have been performed. This thesis focuses on the evolution of nickel-, cobalt-, chromium- and molybdenum-based catalysts under a nitrogen/acetylene and a nitrogen/acetylene/ hydrogen atmosphere at 600°C and 750°C. In order to elucidate the nature of the catalyst during synthesis runs an X-ray diffractometer equipped with a heating stage and an atmosphere controlling system was used to study in-situ the evolution of metal nitrate films. Samples quenched after different pyrolysis time were investigated by SEM and TEM. The microscopic images showed that nickel, cobalt and molybdenum can act under typical nanotube synthesis conditions as catalyst for CNT nucleation and growth, but not chromium. Grain size reduction resulting from a sufficient solid volume loss during redox reactions in the catalyst precursor and the transformation of these precursors to a metallic phase are the main requirements for nanotube growth. The reaction sequences observed during the reduction of the precursor are put in relation with the nucleation and growth of nanotubes. Diffusion of carbon through the metal particle, indicated by an increase of metal cell parameters identified in diffractograms as peak shifts, was observed whenever carbon nanotubes were generated. In the nickel and cobalt system no carbide phases were detected. In contrast to the iron system, where the break-down of metastable carbides act as a second boost of nanotube formation, the appearance of carbides in the molybdenum system after 20 minutes stops further carbon nanotube growth. In any case hydrogen pre-treatment promotes nanotube growth

A Complex Regulatory Network Coordinating Cell Cycles During C. elegans Development Is Revealed by a Genome-Wide RNAi Screen

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development

Detailed Multi-dimensional Modeling of Direct Internal Reforming Solid Oxide Fuel Cells

Fuel flexibility is a significant advantage of solid oxide fuel cells (SOFCs) and can be attributed to their high operating temperature. Here we consider a direct internal reforming solid oxide fuel cell setup in which a separate fuel reformer is not required. We construct a multidimensional, detailed model of a planar solid oxide fuel cell, where mass transport in the fuel channel is modeled using the Stefan-Maxwell model, whereas the mass transport within the porous electrodes is simulated using the Dusty-Gas model. The resulting highly nonlinear model is built into COMSOL Multiphysics, a commercial computational fluid dynamics software, and is validated against experimental data from the literature. A number of parametric studies is performed to obtain insights on the direct internal reforming solid oxide fuel cell system behavior and efficiency, to aid the design procedure. It is shown that internal reforming results in temperature drop close to the inlet and that the direct internal reforming solid oxide fuel cell performance can be enhanced by increasing the operating temperature. It is also observed that decreases in the inlet temperature result in smoother temperature profiles and in the formation of reduced thermal gradients. Furthermore, the direct internal reforming solid oxide fuel cell performance was found to be affected by the thickness of the electrochemically-active anode catalyst layer, although not always substantially, due to the counter-balancing behavior of the activation and ohmic overpotentials

synthesis biological evaluation and molecular docking studies of new amides of 4 chlorothiocolchicine as anticancer agents

Abstract Colchicine belongs to a large group of microtubule polymerization inhibitors. Although the anti-cancer activity of colchicine and its derivatives has been established, none of them has found commercial application in cancer treatment due to side effects. Therefore, we designed and synthesized a series of six triple-modified 4-chlorothiocolchicine analogues with amide moieties and one urea derivative. These novel derivatives were tested against several different cancer cell lines (A549, MCF-7, LoVo, LoVo/DX) and primary acute lymphoblastic leukemia (ALL) cells and they showed activity in the nanomolar range. The obtained IC50 values for novel derivatives were lower than those obtained for unmodified colchicine and common anticancer drugs such as doxorubicin and cisplatin. Further studies of colchicine and selected analogues were undertaken to indicate that they induced apoptotic cell death in ALL-5 cells. We also performed in silico studies to predict binding modes of the 4-chlorothiocolchicine derivatives to different β tubulin isotypes. The results indicate that select triple-modified 4-chlorothiocolchicine derivatives represent highly promising novel cancer chemotherapeutics

Computational Investigations of Catalyzed Organic Reactions: Carbocatalysis, Biocatalysis, Metal and Organo Catalysis

This thesis comprises most of the computational results obtained during the three year Chemistry Ph.D course, during which the research activity mainly focused on investigating catalyzed reaction mechanisms. Catalysis is a vast phenomenon and this dissertation does not presume to cover its extent, nor to be a mere list of computational investigations. The purpose is to stress out that computational organic chemistry is a tool to be exploited to explain how and why some reactions prefer to cover one path rather than another by interpreting computation outcomes. Among the immense world of catalysts, the activity of carbon nanoparticles, enzymes, metal complex and proline in catalyzed organic reactions were investigated. Commercially available software for molecular computations were used to carry out the investigations. The thesis is divided in few parts; the former (Part I) provides some insights into the computational methods used during the PhD activity where Quantum-Mechanics (QM), Molecular-Mechanics (MM) and hybrid QM/MM methods are briefly described. Parts II-V gather the results obtained during the PhD activity. In Part II, two examples of carbo-catalyzed reactions are reported, while Part III and IV collect the computational evidences achieved by analysing the reaction mechanism of enzymatic and metal- (or organo-) catalyzed reactions respectively. The last Part (V) includes two, among the many, side works that were carried out during the PhD course. A résumé of the computational results is reported in Part VI