Many different experimental approaches were attempted to achieve carbon-carbon bond formation by nucleic acid template-directed reactions and ribozyme catalysis as potential lipid synthesizing machineries in the RNA world. A novel biomimetic condition for decarboxylative Claisen condensation in polyketide biosynthesis was discovered. The reaction of a malonic acid half oxyester with a Nhydroxysuccinmidyl ester forming reagent resulted in self-condensation to provide the corresponding 1,3-acetonedicarboxylic acid diester in the absence of a divalent metal chelator or a coordinating solvent. The decarboxylative Claisen condensation of malonyl adenosine using a poly-U template in solution or with immobilized poly-U was attempted. Various analytical methods demonstrated that malonyl adenosine underwent an exclusive hydrolysis reaction instead of condensation in the given conditions. Similar results were observed for the reaction of malonyl-CoA with acetyl-CoA on poly-U templates. No evidence for the decarboxylative Claisen condensation was observed by a DNA-templated system although a double helical structure of DNA duplex was proven to facilitate a bimolecular reaction by offering a favorable proximity effect. Therefore, it seems that the unsuccessful condensation resulted not from the bad template effect but from the intrinsic properties of the decarboxylative Claisen condensation reaction itself. Two tRNA molecules loaded with a malonic acid were prepared by ligation of truncated tRNAs with malonylated dinucletides. Our initial attempts to probe carbon-carbon bond formation by subjecting malonylated tRNAs to the in vitro translational machinery were not successful. Novel carbon isosteres of α-amino acids are suggested as a potential source of a more stable and reactive carbanion for future experiments. Isoprenoid conjugates of nucleoside 5??-diphosphates, which were proposed as either an initiator nucleotide or substrate molecule for in vitro selection of prenyl-transferase ribozyme were prepared by one step nucleophilic displacement reactions. A random DNA pool was constructed for selection of a ketosynthase ribozyme. A substrate bearing a biotin tag was prepared by one-step conjugation. Hig-tagged T7 RNA polymerase was expressed and purified for a large scale transcription reaction. In vitro transcription of the random DNA pool with a 5??-thiol modified GMP analogue as an initiator nucleotide produced a thiol-modified random RNA library.

The use of organic compounds as templates to assemble inorganic materials with structures over multiple length scales has received much attention due to the potential applications that can be developed from these materials. Many organisms synthesize organic/inorganic composites with exceptional control over morphology, physical properties, and nanoscale organization of these materials. Materials such as bone, nacre, and silica diatoms are excellent examples of the complex yet highly controllable hierarchically structured materials nature can form at ambient conditions. The ability to mimic these organisms through the design of supramolecular assemblies and use them to direct the growth of hierarchically structured materials has increased significantly in recent years. In this dissertation, block copolypeptide templated inorganic materials were synthesized and characterized using a wide range of analytical techniques. There are three major conclusions from this dissertation. First, the conformation of a polypeptide chain can be used to manipulate the porosity of oxide materials obtained. Second, individual supramolecular objects (vesicles) formed by block copolypeptides can be used as templates to form nanostructured hard materials. Third, polypeptide chemistry and solution conditions can be used to control both the morphology and porosity of the hard materials they assemble. This dissertation also describes preliminary work toward designing the block copolypeptides derivatives for biomimetic inorganic synthesis and gene delivery. This work includes the synthesis of these block copolypeptides derivatives and of the templated oxide materials. Some interesting silica materials such as porous silicas and silica nanocapsules were synthesized using double hydrophilic block copolypeptides derivatives as templates. Also, the preliminary work of using these block copolypeptides derivatives for gene delivery is included and shows these copolypeptide derivatives are potential delivery vehicles.

The use of magnesium for degradable implants can fill the need for temporary, load bearing, metallic orthopaedic implants without the risks and expense of further surgeries once the bone has healed. Mg is non toxic and biocompatible, but the corrosion rate in the body is too high. The rate will need to be moderated if these implants are to be made clinically useful. A review of common orthopaedic coatings found that the biomimetic calcium phosphate coating process meets the criteria for a good coating. This process was designed for permanent implants, and its corrosion protection properties were unknown on Mg. The research presented here evaluates and optimizes aspects of the corrosion protection of biomimetic coatings in vitro. To accurately identify the corrosion mechanisms of such coatings, the in vitro behaviour of several common simulated body fluids and buffer systems was evaluated. The deposition of biomimetic coatings on Mg was compared to Ti. The effect of common surface treatments on the deposition, composition, and ultimate corrosion protection was identified in order to understand the corrosion properties of these coatings. Following the results, the biomimetic method was modified to optimize the protection by reducing the defects. The corrosion properties of these modified coatings were assessed in vitro. The limitation of the biomimetic coatings was found to be in all cases sensitive to the defects present in the coating. While these could be minimized, they were not eliminated. This led to unfavourable corrosion properties. To solve this problem, a novel treatment was developed to give the biomimetic coatings self-healing properties. This treatment promoted local repair in the coating at the defects, greatly improving the corrosion properties. The in vitro model was increased in complexity by adding first amino acids, then proteins. The corrosion behaviour of the coatings was compared in these solutions to understand the effects of these molecules. The data gathered will help to build a better model of in vivo corrosion, and allow better prediction of the performance of biomimetic coatings for corrosion resistance.

Using both artificial and natural templates, biomimetic micro-structures are fabricated on conventional coating materials (epoxy and silicone elastomers) to mimic both artificial and natural templates through effective pattern transfer processes. The pattern transfer processes use a soft-polymer negative stamp, where the flexibility of the stamp allows for easy conformation to both flat and curved surfaces. Patterns have been successfully transferred as a rigid epoxy to complex surfaces or as a soft elastomer replica of a hydrophobic Trembling Aspen leaf. The hydrophobicity and friction behaviour of the resulting micro-patterned surfaces are systematically investigated, showing that surface patterning can be used as an effective way to improve hydrophobicity while reducing the surface adhesion and friction without a loss of the structural integrity or rigidity typical of epoxy coatings. The relative strength of the micro-pattern was determined through indentation testing in order to support the claim of a robust pattern on the micro-scale that is able to withstand the harsh environment of industrial application or weather exposure. With the well characterized patterned epoxy material fabricated and able to be transferred to many different surfaces, the potential for the patterned surface to act as an icephobic coating was pursued. The robustness of the epoxy material with the unique ability to coat surfaces that are typically unable to possess a micro-structure makes this coating an ideal candidate for large-scale icephobic application. The potential use of a micro-patterned epoxy coating is investigated against comparable surface coatings within an innovative experimental set-up to measure the relative ice-adhesion strength of different substrates. In characterizing the relative shear-force required to remove frozen water droplets from the coating surface at the interface, several variables and factors were explored. The addition of a surface pattern was found to impact the icephobic ability of several materials, where different materials with the same pattern were compared to identify that the surface energy of the substrate influences the icephobic nature of a surface. Moreover, previous studies that relate the water contact angle or hysteresis to ice-adhesion strength are questioned through a preliminary qualitative analysis of ice adhesion strength data. This work demonstrates a potential process for the utilization of biomimetic epoxy micro-patterns as an enhanced hydrophobic and icephobic option for large scale protective coatings.

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Made available in DSpace on 2014-06-11T19:29:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-27Bitstream added on 2014-06-13T19:17:22Z : No. of bitstreams: 1 wong_a_me_araiq.pdf: 4048206 bytes, checksum: cdc95008c64d5a92757cafbd9ad5ad6c (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Eletrodos quimicamente modificados à base de pasta de carbono foram construídos para determinação de captopril, empregando catalisadores biomiméticos em potencial da enzima P450. O complexo que permitiu obter os resultados mais satisfatórios foi o bis(piridil)ftalocianinaferro (II) [Fe(dipy)Pc]. O sensor proposto foi avaliado em batelada e em sistema de análise por injeção em fluxo (FIA), e as condições de análise foram devidamente otimizadas empregando a amperometria. Em batelada obtiveram-se os melhores resultados aplicando potencial de 0,175 V vs Ag|AgCl(KClsat) e usando solução tampão TRIS 0,1 mol L-1 como eletrólito em pH 8,0. Nestas condições observou-se uma faixa linear de resposta para o sensor entre 25 e 165 μmol L-1; com uma sensibilidade de 2.315(±61) μA L mol-1 e um limite de detecção e quantificação de 0,9 e 3,1 μmol L-1, respectivamente. Em sistema em fluxo, os melhores resultados foram obtidos aplicando potencial de 0,100 V vs Ag|AgCl (KClsat) em solução carregadora de tampão TRIS 0,1 mol L-1 e pH 8.0, com volume de amostra injetado de 75 μL e vazão de 1,4 mL min-1. A faixa linear de resposta obtida no sistema em fluxo (FIA) foi entre 5,0 x 10-5 e 2,5 x 10-2 mol L-1, com uma sensibilidade de 210(±1) μA L mol-1 e uma reprodutibilidade menor que 4%, avaliado pelo valor do desvio padrão médio relativo (R.S.D.) para sete injeções consecutivas de solução padrão de captopril 2,5 x 10-3 mol L-1. A biomimeticidade do sensor foi estudada, assim como a seletividade e seus possíveis interferentes. O sensor biomimético foi aplicado na análise de formulações comerciais, amostras biológicas e ambientais (águas de rios e esgoto). Os resultados obtidos quando comparados com o método oficial de análise baseado na cromatografia líquida de alta eficiência (HPLC), mostraram boa eficiência do sensor desenvolvido na quantificação do captopril / Chemically modified electrodes based on carbon paste were constructed for determination of captopril, catalysts employing biomimetic of the P450 enzyme. The compound that allowed to obtain the most satisfying results was the iron (II) phthalocyanine bis(pyridine) complex [Fe(dipy)Pc]. The proposed sensor was evaluated in batch system and flow injection analysis (FIA) and the analysis conditions were properly optimized employing amperometry. In batch experiments were obtaining the best results by applying a potential of 0,175 V vs Ag | AgCl (KClsat) and using 0.1 mol L-1 TRIS buffer at pH 8.0, the electrolyte. These conditions was observed under the linear response range for the sensor between 25 and 165 μmol L-1, with a sensitivity of 2315 (± 61) μA L mol-1 and quantification and detection limits of 0.9 and 3.1 μmol L-1, respectively . In the flow system the best results were obtained at the potential of 0,1 V vs. Ag | AgCl (KClsat) in carrier solution of 0.1 mol L-1 TRIS buffer at pH 8.0, with the injected sample volume of 75 mL and flow rate of 1.4 mL min-1. The linear response range obtained in the FIA system was between 5.0 x 10-5 and 2.5 x 10-2 mol L-1, with a sensitivity of 210 (± 1) μA L mol L-1 and the reproducibility value lower than 4 %, calculated the relative standard deviation (RSD) for seven consecutive injections of standard solution of captopril 2.5 x 10-3 mol L-1. The biomimetic characteristics of the sensor was studied and the selectivity and possible interfering. The biomimetic sensor has been applied to analysis of commercial formulations, biological and environmental samples (river water and sewage). The results compared with the official method of analysis based on high performance liquid chromatography (HPLC) showed the good efficiency of this sensor is developed quantification of captopril

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第17541号 / 工博第3700号 / 新制||工||1563(附属図書館) / 30307 / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 清水 芳久, 教授 田中 宏明, 教授 米田 稔 / 学位規則第4条第1項該当

Indiana University-Purdue University Indianapolis (IUPUI) / The pancreas is a vital organ that secretes key metabolic hormones and digestive enzymes. In pancreatic ductal adenocarcinoma (PDAC), one of the leading causes of cancer-related death in the world, limited advances in diagnosis or therapies have been made over decades. Key features of PDAC progression include an elevated matrix sti ness and an increased deposition of extracellular matrices (ECM), such as hyaluronic acid (HA). Understanding how cells interact with components in the tumor microenvironment (TME) as PDAC progresses can assist in developing diagnostic tools and therapeutic treatment options. In recent years, hydrogels have proven to be an excellent platform for studying cell-cell and cell-matrix interactions. Utilizing chemically modi ed and naturally derived materials, hydrogel networks can be formed to encompass not only the components, but also the physicochemical properties of the dynamic TME. In this work, a dynamic hydrogel system that integrates multiple click chemistries was developed for tuning matrix physicochemical properties in a manner similar to the temporally increased matrix sti ness and depositions of HA. Subsequently, these dynamic hydrogels were used to investigate how matrix sti ening and increased HA presentation might a ect survival of PDAC cells and their response to chemotherapeutics.

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As society continues to develop, demand for energy is destined to increase. Energy production and consumption are responsible for a majority of greenhouse gas emissions that cause climate change, biodiversity loss, and can generate toxic waste. Today, much of our energy demands are met via nonrenewable resources, particularly by the combustion of fossil fuels. In order to correct recent fluxes of manmade species into the geochemical cycles, we must transition to alternate forms of energy production and consumption that do not imbalance the environment. The transition to a solar hydrogen economy is attractive because it utilizes sunlight and water—virtually unlimited resources, to produce hydrogen fuel and gaseous oxygen as a by-product. Efficient and affordable catalytic systems are necessary to establish a solar-hydrogen economy. Industrial nitrogen fixation plants require an immense amount of energy for maintaining operations aimed at the production of ammonia, an essential chemical for society. Further development of catalytic materials may serve to facilitate the process under less taxing conditions.Nature has resulted in the evolution of a wide variety of enyzmes to catalytically carry out chemical reactions. Billions of years of evolution have resulted in the incorporation of metals readily available in the environment. Enzymes may provide inspiration for the design of novel catalytic systems utilizing abundant elements to result in efficient and affordable materials. To this breath, to understand the structure and function of enzymes of interest, particularly the active sites of metalloenzymes. A useful tool is the comparison of native systems to molecular model complexes. It is thus imperative to synthesize and characterize model complexes that are both structurally and functionally relevant. Of interest to this work are the oxygen-evolving complex (OEC) of photosystem II and the iron-molybdenum cofactor (FeMoco) of molybdenum dependent nitrogenase enzymes. Model complexes of these active sites have been widely investigated, however, OEC and FeMoco model complexes generally fall into one category or the other: structural or functional models. The aim of this work is to synthesize and study synthetic multinuclear metallocomplexes to model the structure and function of the OEC and FeMoco. The lessons learned from these systems could contribute to the understanding and design of catalysts and help progress toward viable catalysts. Presented here is the synthesis and characterization of a series of OEC structural models with hemicubane geometry, derived from self-assembled precursor fragments. In chapter 2, a series of Ca-Mn clusters, with the ligand 2-pyridinemethoxide (Py-CH2O), have been prepared with varying degrees of topological similarity to the CaMn4 oxygen evolving complex (OEC) of photosystem II. Through variation of reagent stoichiometry, Mn4, CaMn3, CaMn5, Ca2Mn4, and Ca4Mn3 clusters are prepared via self-assembled precursor fragments and fully characterized. All products feature a hemicubane motif (a heterocubane structure minus one corner metal ion) with Mn or Ca atoms bridged by oxygen, while containing water-accessible metal coordination sites. In chapter 3, the catalytic activation of water as a substrate in the oxidative degradation of stable propylene carbonate into CO2 is discussed. The propensity of these clusters to activate water in this oxidation reaction is correlated with increasing topological similarity to the OEC. In chapter 4, a series of analogous molecules have been explored with the incorporation of calcium, cobalt, and iron metal centers. Preliminary studies indicate the ability to perform water oxidation by a calcium complex with redox-active ligands. The synthesis, characterization, and electrocatalytic water activation chemistry will be discussed. Chapter 5 focuses on the synthesis and characterization of a [FeII(NR2)2]2CS3 complex, resulting from the activation of CS2 by an FeI(NR2)3 precursor species. This work is an extension of attempts toward achieving a synthetic central carbide included within a synthetic Fe-S cluster, which previously resulted in the activation of CS2 by a reduced FeI(NR2)3 species to obtain {[Fe(NR2)2]2CS2}[K(18-crown-6)1.5]2, where a bridging CS2 group assumes a bent geometry. Understanding the electronic structure and magnetic properties of this model complex is relevant towards the design and development of catalysts used in the production of ammonia via industrial nitrogen fixation. Presented in chapter 6 is the discovery of a layered Fe-S material that consists of alternating sheets of an Fe-S layer and a potassium layer. The crystallographic structure suggests the inclusion of periodic carbon atoms with in the Fe-S layer, although these sites may also be modeled with partial Fe occupancy. X-ray diffraction methods (single crystal and powder diffraction) and X-ray photoelectron spectroscopy were employed to investigate the composition of this material. / Chemistry