<p> The development of a unified system for the automatic neutron activation analysis of large numbers of samples is described. The realization of the system entailed the automation of a gamma ray spectrometer system by means of a data and control link to a small computer (PDP-15) and the development of a reliable and fast data reduction algorithm suited to the small computer system. A detailed study of the algorithm and the errors associated with it has been included. </p> / Thesis / Master of Science (MSc)

Growth arrest specific (GAS) genes are highly inducible at quiescence (G0) and repressed rapidly in response to mitogens. Aberrant disruption of quiescence can lead to abnormal development and diseases such as cancer, thus, it is important to study the signals and mechanisms responsible for expressions of quiescent specific genes. p20K, a GAS gene whose expression is highly induced in conditions of contact inhibition & hypoxia in chicken embryo fibroblasts (CEF), is studied in this thesis. Preliminary studies demonstrate that p20K activation is dependent on its Quiescence Responsive Unit (QRU), a 48bp promoter region. In addition, the binding sites of a CCAAT/enhancer binding protein (C/EBPβ) and ERK2 on the QRU of p20K promoter overlap with each other regulating the competition between activating (C/EBPβ) and inhibiting (ERK2) of the p20K gene. After culturing CEF with media rich in growth factors (10%FBS), p20K induction is delayed in hypoxia. Moreover, it is the decrease of Phospho-ERK not CHOP level that correlates with p20K inhibition in hypoxia in both 5%CCS and 10%FBS. Western blotting analysis of Hypoxia Inducible Factor 1α (HIF1α) expression indicated that this hypoxia-response factor is induced rapidly and with the same kinetics in CEF subjected to hypoxia cultured in 5%CCS or 10%FBS, indicating that they sense and respond similarly to low oxygen concentrations. These results suggest that p20K induction in hypoxia is caused by growth arrest induced by hypoxia. To further document this process, hypoxia mimicking reagent DMOG, a prolyl-hydroxylase inhibitor that can stabilize HIF in normoxia, was used. Interestingly, p20K expression was highly induced after DMOG treatment in CEF, even if CHOP, an inhibitor of C/EBPβ, was induced in these conditions. Co-Immunoprecipitation results showed that the accumulation of CHOP-C/EBPβ heterodimers was induced during DMOG treatment. Additionally, Proliferation Assay suggested that DMOG treatment significantly inhibited CEF proliferation. Finally, Chromatin Immunoprecipitation Analysis indicated that ERK-2 did not bind to the QRU after DMOG treatment, indicating that ERK-2 dissociation correlates with p20K induction in response to DMOG in CEF. Collectively, these results demonstrate that growth arrest induced by hypoxia or DMOG treatment plays a determinant role in p20K induction. In contrast, CHOP level or CHOP-C/EBPβ heterodimer reduction did not correlate with the induction of p20K. / Thesis / Master of Science (MSc)

5-Nitrofurans are synthetic antibacterial agents. In general, nitrofurans have been shown to be toxic and mutagenic to cultured mammalian cells and carcinogenic in rodents. The possibility that human exposure to nitrofurans may be causing genetic damage or cancer has stimulated research directed towards elucidating the metabolism and mechanism of action of these compounds. A comprehensive understanding of the molecular basis of nitrofuran action may also be useful for comprehending the mechanism of action of other aryl and heterocyclic nitro compounds. It is known that enzymatic reduction of nitrofurans to reactive but uncharacterized metabolites that damage DNA constitutes an important "activation" step in both bacteria and hypoxic mammalian cells. However, since the known mammalian enzymes having nitroreductase activity are reported to be strongly inhibited by molecular oxygen, the relation of reductive activation to the DNA-damaging effects of nitrofurans in intact animals or in aerobic cultured cells is unclear. In rodents the liver is a major site of nitrofuran reduction in vivo. Net reduction of 5-nitro-2-furaldehyde semicarbazone (nitrofurazone) by rat liver homogenate was found to be relatively insensitive to oxygen when compared to net nitroreduction by milk xanthine oxidase. Intermediates generated in the aerobic nitroreduction bound tightly and probably covalently to protein. The nitroreductase in the rat liver preparation was identified as xanthine oxidoreductase by its apparent MW, substrate specificity and inhibition by allopurinol. Xanthine oxidoreductase is known to function in vivo as xanthine dehydrogenase (D form) which is converted to xanthine oxidase (0 form) during purification and storage. The 0 form is considered to be the major cytosolic nitroreductase and its activity is strongly inhibited by oxygen in vitro. Net nitroreduction by the D form has not been studied previously. In the rat liver preparation the bulk of the aerobic nitroreductase activity was associated with the D form of xanthine oxidoreductase during chromatography on CM cellulose, heat conversion of D form to 0 form and chemical interconversion of D form to 0 form and back to D form. Thus, net reduction of nitrofurazone by xanthine dehydrogenase is considerably less sensitive to inhibition by oxygen than is net nitroreduction by rat liver or milk xanthine oxidase. The ability of xanthine dehydrogenase to reduce nitrofurazone aerobically to highly reactive species in vitro suggests that this enzyme may play a role in a nitroreductive process which contributes to the mutagenic and carcinogenic action of nitrofurans and other nitroheterocyclic and nitroaromatic compounds in vivo. On the other hand, the nitroreductase activity of xanthine dehydrogenase in non-target tissues may, in some cases, decrease the amount of nitrocompound available in target tissues and hence play a "protective" role. / Thesis / Master of Science (MSc)

Spent Nuclear Fuel (SNF) is a by-product of existing nuclear reactors; SNF consists of long-lived radioactive actinides which have an average half-life of several thousand years (e.g. Plutonium-239 with a half-life of 24,000 years, and Americium-243 with a half-life of 7,360 years). Several multinational organizations are making an attempt to extract the energetic value out of these nuclear stockpiles in order to minimize the risk of nuclear proliferation and reduce waste volume. The Inert Matrix Fuel (IMF) concept is being considered as an option to reuse the radioactive actinides present in spent nuclear fuel by means of a transmutation process. Due to the volatile nature of these radioactive actinides, it is expected that the high-temperature conventional processing of IMFs will result in a significant loss of material. This study investigates microwave sintering of inert matrix material (excluding actinide fuel) as an alternative route to conventional processing. It was observed that microwave sintering showed a reduction of 300°C in temperature required for full densification when compared to conventional sintering. The reduction in sintering temperatures did not show any significant variation in the resulting properties (hardness and grain size). While these results satisfy the need for the application, it is important to understand why microwaves enhance the sintering phenomena. It is speculated (by many researchers) that the electric field associated with microwave energy is enhancing flux leading to accelerated densification during microwave sintering. This study has observed a decrease in the activation energy (for sintering 8YZ) with the increase in the magnitude of the applied electric field. / Ph. D.

No description available.

No description available.

Current fossil fuels (Coal and Petroleum) based economy is not sustainable in the long run because of its dwindling resources, and increasing concerns of climate change due to excessive carbon dioxide (CO2) emission. To mitigate CO2 emission and climate change, scientists across the world have been looking for clean and sustainable energy sources. Among them hydrogen gas (H2) could be more promising because it is the most clean fuel and can be produced from cheap source (water) which is renewable and abundant. Nevertheless, the bottleneck for hydrogen economy is lying in the cost of hydrogen production from water. Still there are no any efficient systems developed which can deliver hydrogen from water in economically viable way. Meanwhile, recent research on old molecule ammonia-borane (H3N•BH3, AB) as hydrogen source has increased the hope towards the hydrogen economy, however, catalytic recycling (or efficient regeneration) of AB from the dehydrogenated product polyborazylene (PB or BNHx) is the biggest hurdle which prevents use of AB as practical hydrogen storage material. Therefore, it is imperative to understand the dehydrogenation pathways of ammonia-borane (or related amine-boranes) which lead to polymeric or oligomeric product(s). On the other hand, methane (CH4) is abundant (mostly untamed) but cleaner fuel than its higher hydrocarbon analogs. To develop highly efficient catalytic systems to transform CH4 into methanol (gas to liquid) is of paramount importance in the field of catalysis and it could revolutionize the petrochemical industry. Therefore, to activate CH4, it is crucial to understand its binding interaction with metal center of a molecular catalyst under homogenous condition. However, these interactions are too weak and hence σ–methane complexes are very elusive. In this context, σ-H2 and σ-borane complexes bear some similarities in σ-bond coordination (and four coordinated boranes are isoelectronic with methane) could be considered as good models to study σ-methane complexes. Studying the H−H and B−H bond activation in H2 and amine-boranes, respectively, would provide fundamental insights into methane activation and its subsequent functionalization. Moreover, the proposed methanol economy by Nobel laureate George Olah seems more promising because methanol can be produced from CH4 (CO2 as well). This in turn will gradually reduce the amount of two powerful greenhouse gases from the earth’s atmosphere. Thus, efficient and economic production of methanol from CH4 and CO2 is one of most challenging problems of today in the field of catalysis and regarded as the holy grails. Furthermore, very recently formic acid (HCOOH) is envisaged as a promising reversible hydrogen storage material because it releases H2 and CO2 in the presence of a suitable and efficient catalyst or vice versa under ambient conditions. Objective of the research work: Taking the account of the above facts, the research work in this thesis is mostly confined to utilize electrophilic Ru(II)-complexes for activation of small molecules such as ammonia-borane (H3N•BH3) [and related amine-borane (Me2HN•BH3)], hydrogen (H2), methane (CH4), formic acid (HCOOH) and carbon dioxide (CO2) and investigation of their mechanistic pathways using NMR spectroscopy under homogeneous conditions. Though these molecules are small, they have huge impacts on chemical industries (energy sector and chemical synthesis: drugs/natural products) and environment [CO2 and CH4 are potent green house gases] as well. However, they are relatively inert molecules, especially CH4 and CO2, and impose very tough challenges to activate and functionalize them into useful products under ambient conditions. The partial oxidation of the strong C−H bond in CH4 for its transformation into methanol under relatively mild condition using an organometallic catalyst is considered as a holy grail in the field of catalysis which is mentioned earlier. More importantly, to develop better and highly efficient homogeneous catalytic systems for the activation of these molecules, it is imperative to understand the mechanistic pathways using well defined homogeneous metal complexes. Thus, an understanding of the interaction of these inert molecules with metal center is obligatory. In this context, discovery of a σ-complex of H2 gave remarkable insights into H−H bond activation pathways and its implications in catalytic hydrogenation reactions. Subsequently, σ-borane complexes of amine-boranes were discovered and found to be relatively more stable because of stronger M−H−B interaction and hence act as good models to study the M−H−C interaction of elusive σ-methane complex. On the other hand, HCOOH, a promising hydrogen storage material and its efficient catalytic dehydrogenation/decarboxylation and CO2 hydrogenation back to HCOOH using well defined homogeneous catalysts could lead to a sustainable energy cycle. Therefore, it is quite significant to understand the mechanistic pathways of formic acid dehydrogenation/decarboxylation and carbon dioxide reduction to formic acid for the development of next generation efficient catalysts. Chapter highlights: Keeping all these in view, we carried out thorough studies on the activation of these small molecules by electrophilic Ru(II)-complexes. This thesis provides useful insights and perspective on the detailed investigation of mechanistic pathways for the activation of small molecules such as H3N•BH3 [and Me2HN•BH3], H2, CH4, HCOOH and CO2 using electrophilic Ru(II)-complexes under homogeneous conditions using NMR spectroscopy. In Chapter 1 we provide brief overview of small molecule activation using organometallic complexes. This chapter presents pertinent and latest results from literature on the significance of small molecule activation. Although there are several small molecules which need our attention, however, we have focused mainly on H3N•BH3 [and Me2HN•BH3], H2, CH4, HCOOH and CO2. In Chapter 2, we present detailed investigation of mechanistic pathways of B−H bond activation of H3N•BH3 and Me2HN•BH3 using electrophilic [RuCl(dppe)2][OTf] complex using NMR spectroscopy as a model for methane activation. In these reactions, using variable temperature (VT) 1H, 31P{1H} and 11B NMR spectroscopy we detected several intermediates en route to the final products at room temperature including a σ-borane complex. On the basis of elaborative studies using NMR spectroscopy, we have established the complete mechanistic pathways for dehydrogenation of H3N•BH3/Me2HN•BH3 and formation of B−H bond activated/cleaved products along with several Ru-hydride and Ru-(dihydrogen) complexes. Keeping the B−H bond activation of amine-boranes in view as a model for methane activation, we attempted to activate methane using [RuCl(dppe)2][OTf] complex. In addition, [Ru(OTf)(dppe)2][OTf] complex having better electrophilicity than [RuCl(dppe)2][OTf], was synthesized and characterized. The [Ru(OTf)(dppe)2][OTf] complex has highly labile triflate bound to Ru-metal and therefore its reactivity studies toward H2 and CH4 were carried out where H2 activation was successfully achieved, however, no any spectroscopic evidence was found for C−H bond activation of CH4. The Chapter 3 describes the synthesis and characterization of several Ru-Me complexes such as trans-[Ru(Me)Cl(dppe)2], [Ru(Me)(dppe)2][OTf], trans-[Ru(Me)(L)(dppe)2][OTf] (L = CH3CN, tBuNC, tBuCN, H2) with an aim to trap corresponding σ-methane intermediate at low temperature. However, interestingly, we observed spontaneous but gradual methane elimination and orthometalation of [Ru(Me)(dppe)2][OTf] complex at room temperature. We thoroughly investigated mechanistic details of methane elimination and orthometalation of [Ru(Me)(dppe)2][OTf] using VT NMR spectroscopy, NOESY and DFT calculations. Furthermore, H2 activation was confirmed unambiguously by [Ru(Me)(dppe)2][OTf] and Ru-orthometalated complexes using NMR spectroscopy under ambient conditions. An effort was also made to activate methane using Ruorthometalated complex in pressurized condition of methane in a pressure stable NMR tube. Moreover, preliminary studies on protonation reaction of [Ru(Me)(dppe)2][OTf] using VT NMR spectroscopy to trap σ-methane at low temperature was carried out which provided us some useful information on dynamics between proton and Ru-Me species. The Chapter 4 provides useful insights into the mechanistic pathways of dehydrogenation/decarboxylation of formic acid using [RuCl(dppe)2][OTf]. Catalytic dehydrogenation of HCOOH using [RuCl(dppe)2][OTf] was observed in presence of Hunig base (proton sponge). In addition, a complex [Ru(CF3COO)(dppe)2][OTf] was synthesized and characterized using NMR spectroscopy, and found to readily dehydrogenate HCOOH. Moreover, preliminary results on transfer hydrogenation of CO2 into formamide using [RuCl(dppe)2][OTf] as a precatalyst and tert-butyl amine-borane (tBuH2N•BH3) as secondary hydrogen source was confirmed using 13C NMR spectroscopy. The mechanisms were proposed for HCOOH dehydrogenation and transfer hydrogenation of CO2 based on our NMR spectroscopic studies. Furthermore, a few test reactions of transfer hydrogenation of selected alkenes such as cyclooctene, acrylonitrile, 1-hexene using [RuCl(dppe)2][OTf] as pre-catalyst and tert-butyl amine-borane (tBuH2N•BH3) as secondary hydrogen source showed quantitative conversion to hydrogenated products.

Strong bond activation mediated by pincer ligated transiton-metal complexes has been the subject of intense study in recent years, due to its potential involvement in catalytic transformations. This dissertation has focused on the net heterolytic cleavage of B-H and B-B bonds across the N-Pd bond in a cationic (PNP)Pd fragment, the C-H oxidative addition to a (PNP)Ir center and the recent results on the C-H and C-O oxidative addition in reactions of aryl carboxylates with the (PNP)Rh fragment. Transition metal carbene and carbyne complexes are of great interest because of their role in a wide variety of catalytic reactions. Our work has resulted in the isolation of a rhodium(I) difluorocarbene. Reaction of the rhodium difluorocarbene complex with a silylium salt led to the C-F bond cleavage and the formation of a terminal fluorocarbyne complex. Reductive elimination is a critical step of cross coupling reactions. In order to examine the effect of the pincer ligand on the reductive elimination reactions from Rh(III), the first pi-accepting PNP ligand bearing pyrrolyl substituents was prepared and installed onto the rhodium center. Arylhalide (halide = Br, I) oxidative addition was achieved in the presence of donor ligands such as acetonitrile to form stable six-coordinate Rh(III) compounds. The C-O reductive elimination reactions in this system were also explored.

Chapter 2 of the thesis describes a highly efficient in situ method for the reduction of amides to aldehydes and aryl O-carbamates to phenols and other transformations involving hydrozirconations. The method, as a three-component-type reaction, involves in situ generation of the Schwartz reagent (Cp2Zr(H)Cl) from Cp2ZrCl2 and the reductant, LiAlH(O-t-Bu)3, and immediate reaction with a substrate. Substrates include aliphatic and aromatic tertiary amides which are reduced to aldehydes, aryl O-carbamates which are reduced to phenols, and alkynes which undergo other transformations via hydrozirconation. Compared to prior methods, this method has advantage in that reagents are inexpensive and stable, reaction times are short, and reaction temperatures are generally conveniently at room temperature. The use of the in situ method described herein instead of the requirement for the synthesis of the commercially available Schwartz reagent is estimated to provide more than 50% reduction in cost. Chapter 3 of the thesis describes the discovery and development of efficient and regioselective Ru-catalyzed amide-directed C-H, C-N, C-O activation/C-C bond forming reactions, ester-directed C-O activation/C-C bond forming reaction, and amide-directed C-O activation/hydrodemethoxylation reactions under a simple RuH2(CO)(PPh3)3/toluene catalytic system. Of these, the amide-directed C-H activation/cross coupling reaction proceeds well but uniquely on furan 3-amide substrates while the ester-directed C-O activation is effective on the 2-MeO-1-naphthoic acid methyl ester. On the other hand, the amide-directed C-N and C-O activation/coupling reactions are broadly applicable on benzamides and naphthamides. All of these achievements of directed C-H, C-N, C-O activation/coupling reactions complement and may supercede the DoM (directed ortho metalation)-cross coupling strategy, and establish the catalytic base-free DoM-cross coupling process at non-cryogenic temperature as a convenient, economical and green alternative. The new catalytic amide-directed ortho-hydrodemethoxylation reaction has potential value in links to aromatic electrophilic substitution and DoM chemistries. Furthermore, a new borylation reaction via Ru-catalyzed amide-directed C-H activation/C-B bond forming process is also reported herein. / Thesis (Ph.D, Chemistry) -- Queen's University, 2010-12-21 11:12:35.564

As fossil fuel resources become more and more scarce, attention has been turned to alternative sources of fuels and energy. One promising prospect is the conversion of methane (natural gas) to methanol, which requires an initial activation of a C-H bond and subsequent formation of a C-O bond. The most well studied methodologies for both C-H activation and C-O bond formation involve oxidation of the metal center. Metal complexes with facile access to oxidation states separated by four charge units, required for two subsequent oxidations, are rare. Non-oxidative methods to perform C-H bond activation or C-O bond formation must be pursued in order for methane to methanol to become a viable strategy. In this dissertation studies on redox and non-redox methods for both C-H activation and C-O bond formation are discussed. In the early chapters C-O bond formation in the form of reductive functionalization is modeled. Polypyridine ligated rhodium complexes were studied computationally to determine the properties that would promote reductive functionalization. These principles were then tested by designing an experimental complex that could form C-O bonds. This complex was then shown to also work in acidic media, a critical aspect for product stabilization. In the later chapters, non-oxidative C-H activation is discussed with Ir complexes. Both sigma bond metathesis and concerted metalation deprotonation were investigated. For the former, the mechanism for an experimentally known complex was elucidated and for the latter the controlling factors for a proposed catalyst were explored.