The development of biodegradable plastics from sustainable sources is at the forefront of chemical research. One such example is the production of polylactide (PLA) via the ring-opening polymerisation (ROP) of the cyclic ester lactide (LA). Current industrial metal initiators utilised for the ROP of LA do not allow control over the stereochemistry of the resulting product. This thesis will investigate various initiators containing a variety of ligand sets for the ROP of rac-LA. Chapter 1 introduces the ROP of rac-LA, the mechanisms utilised and the methods employed for characterisation of PLA. A review of the current literature of recent developments in the production of PLA via various metal initiators is also included. Chapter 2 reports the development of a series of group (IV) complexes containing various amine tris(phenolate) ligands, where the sterics and electronics have been varied. Such complexes were trialled for the ROP of rac-LA as well as the ROP of trimethylene carbonate (TMC). The ability of such initiators to produce copolymers of rac-LA/TMC and rac-LA/isosorbide was also investigated and discussed. Chapter 3 describes the synthesis of a range of group (IV) complexes containing Salalen ligands. The sterics of the ligands have been varied and the ability of the initiators to initiate the ROP of rac-LA in a stereocontrolled fashion has been investigated. Furthermore, the complexes have been trialled for the degradation of PLA into methyl lactate, an important starting material in the production of LA. Chapter 4 investigates the development of Al(III) Salalen complexes for the ROP of rac-LA, where the sterics and electronics of the ligand have been varied. Kinetic investigations have been carried out to aid the understanding of the polymerisation process. Chapter 5 provides details of the reaction procedures for the synthesis of ligands, complexes and polymers. Kinetic procedures are also reported together with details of the analytical techniques employed.

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Presented herein is the development, optimization and mechanistic investigation of an Fe-catalyzed reaction for the Cα-H oxidation of tertiary aliphatic amines to form amides, and related synthetic reactions. Traditional amide synthesis typically involves nucleophilic substitution, and thus produces stoichiometric waste. The need to develop safer, more efficient methodologies for amide synthesis is well documented. The field of transition metal catalysis has made progress toward meeting this synthetic need by developing a variety of transition metal-catalyzed reactions for the oxidation of primary, secondary and benzylic amines. However, tertiary aliphatic Cα-H amine oxidation had not been developed. Guided by literature precedent, and inspired by cytochrome P450, initial investigations involved the evaluation of Fe-based transition metal catalysts with a variety of mono- and bidentate ligands, oxidants and solvents. Ultimately, the ligands picolinic acid and pyridine, the oxidant tert-butyl peroxybenzoate, and water as additive were identified as key players in this catalytic reaction. Through the systematic evaluation of reaction conditions, the Cα-H oxidation of tripropylamine to form N,N-dipropylpropanamide was optimized to afford 63% yield. The Cα-H oxidation of a variety of other amine substrates, including the complex pharmaceutical amines Lidocaine and Donepezil, were optimized to afford amide product in synthetically useful yields. Preliminary mechanistic investigations revealed water to be the source of the O atom in amide formation. Furthermore, these studies suggested that the amine substrate forms an iminium ion after C-H activation, which then undergoes nucleophilic attack by water to form a hemiaminal intermediate. These results allowed us to hypothesize that other nucleophiles, such as CN-, may be used to attack the iminium ion intermediate and thus afford other products. Using slightly modified reaction conditions, this catalytic system was optimized to perform Cα -H cyanation of dimethylaniline. This finding expanded the utility of the reaction as well as supported the mechanistic hypothesis of the presence of an iminium intermediate. Once the Fe/picolinic acid-catalyzed reaction for the Cα-H oxidation of tertiary aliphatic amines was firmly established, detailed mechanistic investigations were conducted using tripropylamine as substrate. Using in-situ IR spectroscopy, the structure of the resting state of the catalyst was probed. These studies revealed that picolinic acid binds to the Fe center in a 1:1 ratio to produce the catalytically active species. Amine substrate as well as water and pyridine were also found to be coordinated to the Fe center. Furthermore, initial rate kinetics were used to establish the dependence of the reaction rate on the concentration of each reaction component. Through these investigations, the kinetic order in each reagent was established and a rate law determined. Additionally, a primary kinetic isotope effect was observed using deuterated substrate, which implicated C-H bond cleavage as the turnover-limiting step in the catalytic cycle. Finally, Eyring studies and oxidant radical probe reactions were conducted, and implicated a concerted 2e- turnover- limiting step. This finding is in contrast to many mechanisms of Fe-catalyzed oxidation reactions found in the literature and allowed us to propose the unprecedented, detailed mechanistic hypothesis described herein. The research presented here establishes an unprecedented amide synthesis methodology through the use of both simple and complex amines. Because this catalytic reaction selectively oxidizes the Cα-H bonds of amines, a high percentage of atoms in the starting material are incorporated into the amide product, and it thus affords a significant increase in atom economy. The mechanistic work offers unique insight into 2e- Fe-oxidation catalysis, and may serve as a foundation for additional optimization, including industrial scale-up.

"Catalysts are involved at some stage in the manufacture process of virtually all commercially produced chemical product. Among the materials used as catalysts, metal oxides are one of the most used due to their versatility and wide range of physical properties. Identifying the principles of surface to adsorbate charge transfer is key to a better understanding of metal oxide materials as both catalysts and gas sensors. Using density functional theory (DFT), we modeled the adsorption of small molecules over stoichiometric and reduced metal oxide surfaces of group IV metals and quantify the effect of electron transfer upon adsorption. We found that charge transfer only occurs during the adsorption process of an adsorbate more electronegative than the surface. We also found a correlation between the work function of the metal oxide, and the ionic adsorption of the oxygen molecule. Mixed phase rutile/anatase catalysts show increased reactivity compared with the pure phases alone. However, the mechanism causing this effect is not fully understood. Using DFT and the +U correction we calculated the bands offsets between the phases taking into account the effect of the interface. We found rutile to have both higher conduction and valence band offsets than anatase, leading to an accumulation of electrons in the anatase phase accompanied by hole accumulation in the rutile phase. We also probed the electronic structure of our heterostructure and found a gap state caused by electrons localized in undercoordinated Ti atoms which were present within the interfacial region. Interfaces between bulk materials and between exposed surfaces both showed electron trapping at undercoordinated sites. Finally, we studied the effect of the size of gold nanoparticles in the catalytic properties of gold decorated titania surfaces. We found that the adsorption energy of several intermediates reactives in the CO oxidation and water gas shift reaction does not change with the size of the nanoparticles. In conclusion, the factor that affects the reactivity of the system is the density of undercoodinated gold atoms on the interface perimeter."

The search for an alternative clean and renewable energy source has become an urgent matter. One such energy-saving technology is a fuel cell; it uses fuel as the source of energy to produce electricity directly and the byproducts formed are not as voluminous and environmentally harmful. The conventional low temperature fuel cells use hydrogen as the fuel which is produced from conventional fuels via reforming. However, developing reformers for hydrocarbon fuels requires AN understanding of the fundamental mechanisms and kinetics studies. In this study, simple hydrocarbon fuel, namely methane, in external reforming or internal reforming within a solid oxide fuel cell has been studied because of its importance and with the hope that it will ultimately lead to an understanding of reforming of higher hydrocarbons, such as logistic fuels like JP-8. For this purpose, methane was used the starting point and building block for the progressive understanding of reforming of complex hydrocarbons. Methane steam reforming (MSR), CH4 + 2H2O = CO2 + 4H2 is, in fact, the most common method of producing commercial bulk hydrogen along with the hydrogen used in ammonia plants. United States alone produces 9 million tons of hydrogen per year. The overall MSR reaction CH4 + 2H2O = CO2 + 4H2 is in fact composed of two reactions, the water gas shift reaction, CO + H2O = CO2 + H2, which has recently been investigated by a former Ph.D. student in our group, Caitlin Callaghan. Here, the first reaction CH4 + H2O = CO + 3H2, i.e., methane reforming, is analyzed using a reaction route network approach to obtain the overall methane steam reforming network and kinetics. Kinetics providing detailed information of elementary reaction steps for this system, namely micro-kinetics, has not yet been fully addressed. Employing the theory of Reaction Route Network Theory, recently developed by Fishtik and Datta, and using the Unity Bond Index-Quadratic Exponential Potential (UBI-QEP) method of Shustorovich to predict elementary step kinetics coupled with transition-state theory, a detailed microkinetic model of steam and dry reforming of methane has been developed for Rh(111) and Ni(111) in this thesis. While there is extensive literature on it, the standard reference on the mechanism and kinetics of MSR is that of Xu and Froment, who proposed a 13 step mechanism. Based on the assumption of rate limiting steps for these overall reactions, Xu and Froment derived rate expressions for overall kinetics with fitted parameters. Here a more detailed micro-kinetic model of steam reforming of methane has been developed by adding 3 steps pertinent to carbon formation on the catalyst to Xu and Froment's mechanism. The complete set as well as the dominant reaction routes has been identified. This was accomplished first by enumerating the list of reaction routes and drawing this network. A program was written in Maple and was used to assist in creating the list of full routes, empty routes and intermediate nodes. This program reduces the amount of repetitive work that was needed in an earlier Matlab program when computing the list. After drawing the complete reaction network it was than converted into an equivalent electrical circuit and Multisim analysis was performed. Further, the resistances of various reaction steps were compared. From the reduced graph, it was determined that reaction steps pertaining to desorption of carbon dioxide, i.e., step s4, and intermediate methylene forming intermediate methylidyne, s11, are the rate limiting steps. Further, through simulation with Multisim, it was determined that in fact only 2 overall reactions are needed. Adding a third overall reaction results in a nodal balance error. A rate expression was developed based on assuming the above two rate determining steps, with remaining steps at pseudo equilibrium along with the quasi-steady state approximation. The rate expression however produced a substantial error in conversion when compared to the overall microkinetic model. In addition to computing the micro-kinetic model, experimental work for methane steam reforming was conducted. A steam to carbon ratio of 2:1 was fed to the packed bed reactor, where experimental conversion data were obtained. These data points for Ni and Rh catalyst were plotted against the model to see how well the simulation predicted the experimental results. Reasonable agreement was obtained.

by Leung Yiu Chung. / "2000 July." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 98-102). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Enzymes catalyze specific reactions in almost all cellular processes, including DNA replication and repair, transcription, translation, signal transduction and energy production. Therefore, extensive efforts are underway to understand the functions and mechanisms of these processes. The potential contribution of the conformational dynamics of enzymes to their high catalytic power has received particular attention in the last decades. Studies indicate that protein dynamics are involved in substrate binding and product release; however, the role of dynamics in catalysis is still controversial. Here, we investigate the substrate-dependent dynamic properties of the Escherichia coli AlkB protein, and the role of a specific dynamic transition in the efficiency of the catalytic reaction cycle. AlkB is an iron/2-oxoglutarate (Fe(II)/2OG) dependent dioxygenase, which removes certain cytotoxic alkyl lesions from DNA and RNA bases that are not repaired by other known mechanisms. Using Fe(II) as a cofactor and 2OG and molecular oxygen as co-substrates, AlkB catalyzes a multistep redox reaction in which first, 2OG is oxidized yielding succinate, carbon dioxide and a reactive oxyferryl (Fe(IV)=O) intermediate; second, the alkylated base is hydroxylated by the Fe(IV)=O intermediate, and third, the hydroxylated base spontaneously resolves upon release from the enzyme. Our fluorescence and NMR spectroscopic data demonstrate that a microsecond-tomillisecond timescale conformational transition in the nucleotide recognition lid (NRL) of AlkB regulates the correct sequential order of substrate binding, i.e. Fe(II) and 2OG first, followed by the DNA substrate. By combining isothermal titration calorimetry with NMR, we show that less than 20% of the residues in AlkB become ordered during this conformational transition, indicating that this conformational change is mostly localized to the NRL, while the conformation of the dioxygenase core is minimally altered. In mutant AlkB variants that perturb the dynamics of this transition, 2OG is oxidized generating the Fe(IV)=O intermediate; however, the reaction cycle cannot be completed due to the premature release of the alkylated DNA substrate, leading to uncoupled turnover of 2OG. These data demonstrate that the conformational dynamics control the catalytic efficiency of AlkB. Our results further extend the view on the role of protein dynamics in substrate binding or product release by emphasizing the importance of protein dynamics for coupling sequential sub-reactions in a complex multistep reaction cycle. This finding illustrates a striking example of the relation between protein dynamics and overall enzyme efficiency.

Enzymes are desirable catalysts as they may exhibit high activity, high selectivity, and may be easily engineered. Additionally, enzymes can be mass-produced recombinantly making them a potentially less expensive option than their organic or inorganic counterparts. As a result, they are being used more in industrial applications making their relevance ubiquitous. In this work, various engineering approaches were developed to control the activity and selectivity of enzymes for multi-step catalysis. Unlike nature, many industrial processes require multiple steps to produce the desired product, which is both timely and expensive. Through the use of enzymes, biosynthesis can be used to develop efficient multi-step catalytic cascades. The majority of this work focused on engineering a hyperthermophilic enzyme from the aldo-keto reductase (AKR) superfamily, alcohol dehydrogenase D (AdhD) from Pyrococcus furiosus, to develop approaches to control activity and selectivity. As the AKR superfamily contains many unifying characteristics, such as a conserved catalytic tetrad, (α/β)8-barrel quaternary fold, conserved cofactor binding pocket, and varying substrate loops, the approaches developed here can be applied to many enzymes. AKR members participate in a broad range of redox reactions, such as those involving aldehydes, hydrocarbons, xenobiotics, and many more, and are necessary in physiological processes in all living systems, making these enzymes industrially relevant. AdhD in particular can oxidize alcohols or reduce aldehydes/ketones in the presence of NAD(P)(H). Furthermore, the tools utilized here are modular and can be used to develop pathways with enzymes from different superfamilies’ to expand their current capabilities. In our initial engineering efforts, AdhD cofactor selectivity was broadened or reversed through site directed mutations or insertions in substrate loop B, on the back side of the cofactor binding pocket. To further examine how substrate loops affect cofactor selectivity, allosteric control was added to AdhD through the insertion of a calcium-dependent repeat-in-toxin domain from Bordetella pertussis. Through the chimeric protein, β-AdhD, we demonstrated that the addition of calcium shifts cofactor selectivity in real-time, reminiscent of a protein dimmer. Our next focus shifted towards unnatural amino acid incorporation to add an extra level of selectivity to AdhD. This was done by merging the properties of AdhD and an organic catalyst, TEMPO, for selective alcohol oxidation. We also demonstrated the ability to impart enzymatic selectivity onto an organic catalyst. This was done both in solution and in AdhD hydrogels for added functionality. The next study focused on increasing catalytic efficiency while retaining AdhD structure by engineering the microenvironment of AdhD with supercharged superfolder GFP (sfGFP). The complex interplay between salt, pH, and protein charge was studied and it was determined that catalysis is a function of protein charge, which can affect apparent local ionic strength. The final study focused on utilizing the previous tools examined to engineer substrate channeling in a multi-step cascade with hexokinase II (HK2), sfGFP, and glucose-6-phosphate dehydrogenase (G6PD). In conclusion, we have utilized a myriad of tools to develop engineering approaches to regulate AdhD activity and selectivity. These tools were then extended to engineer substrate channeling in a three-enzyme system. These approaches are modular and provide a foundation for the development of multi-step catalytic cascades.

<p>It is well-known that f-block elements can exhibit coordination modes which surpass those of the transition metals. With uranyl and uranium bis(imido) complexes a strong preference is shown for the oxo or imido ligands in the <i>trans-</i> position; a phenomenon which is known as the inverse trans- influence which is unique to high valent actinides. However, when a third imido is added to the complex, a decrease in bond order occurs and this preference is diminished. Through the synthesis of several novel coordination complexes of tris(2,6-diisopropylphenyl)imido uranium [U(NDipp)₃] with a variety of ligands, we were able to analyze the energy differentials between bonding modes in both the solution and solid state. Furthermore, density functional theory calculations were employed to model the energetic preferences between these geometries. The combination of analyses gives rise to the observation that the orientation of the imido substituents is fluxional depending on the rigidity of the supporting ligands, and oftentimes exhibits low energetic barriers for the formation of different conformers.</p> <p> Uranium tris(imido) species bearing <i>trans</i>-imidos are desirable synthons as they can be used to mimic reactivity of more complicated uranium oxide polymeric systems. Such systems are advantageous as they are easily soluble in organic solvents, making them amenable to standard characterization methods and ligand substitution strategies. Our group has previously shown that uranium tris(imidos), easily synthesized from [(^MesPDI^Me)U(THF)]₂ and various azides, feature axial imido substituents exhibiting differing bond characteristics than the adjacent equatorial imido substituent. The aim of this work is to show that multiple analogues of mixed imido products can be formed from either the aforementioned dimer or stable tris(imido) synthons by exploiting reactivity differences between the axial and equatorial positions. </p> Presented herein are novel copper-​catalyzed ring opening reactions of cyclopropanols and various electrophiles to synthesize a variety of beta-​functionalized ketones. The reactions feature mild conditions and tolerates a wide selection of functional groups leading to complex products which can be used in the synthesis of bioactive molecules.

In the last decade photoredox catalysis has emerged as an important new tool for organic chemists. The especially mild conditions and the broad range of reactions accessible using this methodology had a beneficial effect on the exploitation of radical reactions on otherwise labile substrates. Herein we report our work in this fast developing area and our efforts into the double functionalisation of styrenoid double bonds. We disclosed a new methodology for the room temperature photoredox catalysed alkoxy- and amino-arylation of styrenes using diaryl iodonium tetrafluoroborates and diazonium salts as aryl radical precursors. This methodology allows the successful regioselective coupling of three disparate components together and can be expanded to a wide range of alcohol nucleophiles, nitriles and water in moderate to good yields. The mild conditions employed permit the effective reaction of electron-rich styrenes and the tolerance of halogen functionalities, thus opening the possibility to further molecular elaboration. We then moved to explore the possibility of oxymethylnitrilation of styrenes and of the sysnthesis of heterocyclic cores via internal trapping with a nucleophile. Pleasingly, we were able to develop a mild and general methodology for the methylnitrilation of styrenes using simple and cheap bromoacetonitrile and photoredox catalysis. Furthermore, the synthesis of tetrahydrofuran and dihydrofuran cores was achieved in a single step, allowing us to synthesise tricyclic cores, maintaining functionisable handles such as halogens and ester groups. Finally, we decided to explore the possibility to add an azide functionality. After extensive optimisation, we were pleased to discover reaction conditions allowing for a switchable reactivity: under light irradiation we could perform an azidation reaction followed by addition of a nucleophile of choice; excluding the light from the reaction conditions, we could perform a double azidation reaction. The mild reaction conditions ensured the previously observed tolerance of functional groups; furthermore, we used a more sustainable copper-based photoredox catalyst.