The growing demand for chemical production combined with the urgent need to mitigate the accelerated climate and environmental changes motivates efforts to create highly efficient and selective catalysts and adsorbents. Zeolites and molecular sieves are a key class of materials for addressing these needs because of their high activity and selectivity with catalytic reactions. Additionally, they can show superior adsorption properties because of their structure and surface polarity that can also give shape selectivity with molecules smaller than ca. 1 nanometer. Further advancements in molecular sieve properties will rely on advancements in preparation methods. To this end, the research results presented here explore synthetic approaches for controlling the framework topology and the heteroatom incorporation within silicate-based molecular sieves by means of the strategic design of their organic structure-directing agents (OSDAs).
\r\n\r\nPart I presents the synthesis of STW-type germanosilicate molecular sieves with high-silica framework compositions and the enrichment of chirality. A chiral OSDA is computationally designed based on the predicted stabilization energy toward the pure-silica STW framework. An improved synthesis route for both enantiomers of the OSDA is developed. The enantiopure OSDA is capable of crystallizing a high-silica STW-type germanosilicate molecular sieve that shows distinct framework compositions from previously reported germanium-rich STW. The enantiomeric enrichment of powdered samples without occluded enantiopure OSDAs is characterized by the dynamical refinement of microcrystal electron diffraction data. The high-silica, enantiomerically enriched STW exhibits the framework stability upon thermal treatment and the enantioselective adsorption of 2-butanol. The results in Part I demonstrate the design strategy of OSDAs for crystallizing stable, enantio-enriched molecular sieves for enantioselective chemical separations and catalysis.
\r\n\r\nIn Part II, the distribution of heteroatoms incorporated within borosilicate molecular sieves is studied with regard to its control by cationic OSDAs. To aid in the characterization of the heteroatom sites within borosilicate molecular sieves, the relationship between the 11B NMR chemical shift and the local geometry of boron within tetrahedrally coordinated silicate frameworks is first investigated. From crystalline borosilicate minerals with highly ordered, tetrahedrally coordinated boron atoms, it is revealed that the chemical shifts from 11B NMR linearly correlate with the local geometric parameters. Further studies on the borosilicate molecular sieves that possess more open space and wider angles suggest that the correlation between the average bond angles and 11B NMR chemical shifts can be employed for the entire class of three-dimensional, crystalline borosilicates. Two structurally similar quaternary ammonium OSDAs with different locations of positive charge are designed and synthesized. MWW-type borosilicate molecular sieves are crystallized by both OSDAs, and the quaternary ammonium moieties in the two OSDAs are found to interact with boron species with significantly different 11B NMR chemical shifts. Using the correlation developed here, the characterization results demonstrate that the heteroatom siting within the molecular sieve framework can be selectively altered by tailoring the OSDA structure in terms of the position of positive charge.
", "doi": "10.7907/d1xj-kn25", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:15139", "collection": "thesis", "collection_id": "15139", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04142023-055704455", "primary_object_url": { "basename": "Faisal Alshafei - PhD Thesis - FINAL V1.pdf", "content": "final", "filesize": 13075550, "license": "other", "mime_type": "application/pdf", "url": "/15139/1/Faisal Alshafei - PhD Thesis - FINAL V1.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Enhancing the Ethylene and Propylene Selectivities in the Methanol-to-Olefins Reaction by Exploiting the Intricate Relationship between Framework Topology and Acidity", "author": [ { "family_name": "Alshafei", "given_name": "Faisal H.", "orcid": "0000-0003-1808-1374", "clpid": "Alshafei-Faisal-H" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Flagan", "given_name": "Richard C.", "orcid": "0000-0001-5690-770X", "clpid": "Flagan-R-C" }, { "family_name": "Manthiram", "given_name": "Karthish", "orcid": "0000-0001-9260-3391", "clpid": "Manthiram-Karthish" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" }, { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis describes and presents results from several related projects within the theme of molecular sieve synthesis and catalysis. The early part of the thesis focuses on understanding the link between cage size/dimension and acidity (i.e., acid site density and strength) in the methanol-to-olefins (MTO) reaction. This relationship between cage size and acidity, once identified and investigated, is exploited in the latter parts of the thesis to rationally design materials that are able to steer the light olefins product distribution toward either more ethylene or propylene in a significant improvement over SAPO-34 (CHA), the commercial catalyst.
\r\n \r\nIn Chapters 2, 44 zeolites and silicoaluminophosphates (SAPOs) belonging to five frameworks (AEI, CHE, LEV, SWY, and ERI) with a wide range of Si/Al=4-31 and Si/(Al+P)=0.04-0.3, are synthesized and characterized using a myriad of techniques. Their MTO behavior is then systematically investigated to rationalize the effect of cage dimensions on the olefins product distribution as a function of acid site density and strength. The results from this study show that changes in acid site density and strength play a secondary role to the dominating influence of cage architecture on product distribution in AEI- and CHA-type molecular sieves. Decreasing the cage size, in going from AEI and CHA to LEV, SWY, and ERI, however, results in substantial changes in the ethylene-to-propylene ratio (E/P) as a function of acidity. These changes are attributed to differences in the identity and concentration of the hydrocarbon-pool (HP) species that form, particularly in early stages of the reaction.
\r\n \r\nIn Chapters 3 and 4, ERI-type molecular sieves (e.g., SSZ-98, UZM-12, ERI-type zeolites, and SAPO-17) are thoroughly investigated as promising methanol-to-ethylene materials due to their narrow cage size. Specifically, numerous ERI-type molecular sieves are synthesized using several organic structure-directing agents (OSDAs) with varied Si/Al or Si/T-atoms ratios. The list of ERI-related materials synthesized and tested in MTO included a new disordered SAPO, denoted as CIT-16P, which upon thermal treatment in air transforms to SAPO-17 (ERI). The reaction results show that decreasing the Si/Al (or increasing the Si/T) ratio, irrespective of other material properties, improves the E/P of ERI-type molecular sieves (E/P=1.1-1.9) over CHA-type molecular sieves (E/P=0.82-0.85) in MTO. Dissolution-extraction experiments reveal that the rapid formation of cyclic intermediates and the shift in their composition toward less-methylated methylbenzenes and methylnaphthalenes are found to be key to enhancing the ethylene selectivity in ERI-type molecular sieves.
\r\n \r\nIn Chapter 5, several SAT-type molecular sieves are investigated as promising methanol-to-propylene catalysts. This effort entails the synthesis of CIT-17, an SAT SAPO-type molecular sieve, which is isostructural to STA-2 (MgAPO-SAT). Following the successful synthesis of CIT-17, the MTO behavior of several SAT-type molecular sieves (MgAPO, CoAPO, and SAPO) are investigated in MTO. The combination of low acidity of CIT-17 and unique structural features of the narrow SAT-cage lead to a catalytic pathway and mechanism that predominantly favors propylene (propylene-to-ethylene ratios (P/E) of 2-4.2; propylene selectivity of 40-50%). Indeed, CIT-17 achieves one of the highest P/E ratio values reported for this class of materials.
", "doi": "10.7907/btcj-w948", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:13614", "collection": "thesis", "collection_id": "13614", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01102020-003449091", "type": "thesis", "title": "Resistance is Futile: Physical Science, Systems Biology and Single-Cell Analysis to Understanding the Plastic and Heterogeneous Nature of Melanoma and Their Role in Non-Genetic Drug Resistance", "author": [ { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" } ], "thesis_advisor": [ { "family_name": "Heath", "given_name": "James R.", "clpid": "Heath-J-R" }, { "family_name": "Baltimore", "given_name": "David L.", "clpid": "Baltimore-D-L" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Wang", "given_name": "Zhen-Gang", "clpid": "Wang-Zhen-Gang" }, { "family_name": "Heath", "given_name": "James R.", "clpid": "Heath-J-R" }, { "family_name": "Baltimore", "given_name": "David L.", "clpid": "Baltimore-D-L" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Melanoma is the most deadly form of skin cancer due to its great metastatic potential. Targeted therapy that inhibits the BRAF-V600E driver mutation has shown impressive initial responses in melanoma patients. However, drug resistance, as the universal phenomenon for any cancer therapy, always limits treatment efficacy and compromises outcomes. As the early-step of resistance development, non-genetic mechanisms enable cancer cells to transition into a drug-resistant state in as early as a few days after drug treatment without alteration of the genome. This early mechanism is, to a large extent, due to the heterogeneous and highly plastic nature of tumor cells. Therefore, it imperative to understand the plastic and heterogeneous nature of the melanoma cells in order to identify combination therapies that can overcome resistance.
\r\n\r\nIn this thesis, we investigate these two fundamental natures of non-genetic drug resistance using BRAF inhibition of BRAF-mutant melanomas as the model system. These melanoma cells undergo multi-step, reversible drug-induced cell-state transitions from the original sensitive phenotype to a drug-resistant one.
\r\n\r\nWe first conducted bulk analysis to characterize the detailed kinetics of the entire transition from drug-sensitive state towards drug-resistant state, revealing expression changes of thousands of genes and extensive chromatin remodeling. A 3-step computational biology approach greatly simplified the complexity and revealed that the whole cell-state transition was controlled by a gene module activated within just the first three days of drug treatment, with the RelA transcription factor driving chromatin remodeling to establish an epigenetic program encoding long-term phenotype changes towards resistance. From there, a detailed mechanism connecting tumor epigenetic plasticity with non-genetic drug resistance was resolved through in-depth molecular biology experiments. The mechanism was validated in clinical patient samples.
\r\n\r\nWe further investigated heterogeneity by moving from bulk cellular studies to single-cell analysis. The single-cell view further revealed that two driving forces from both cell-state interconversions and phenotype-specific drug selection control the cell-state transition dynamics. The single-cell studies also pinpointed the signaling network hub, RelA, as the driver molecule of the initiation of the adaptive transition. These two competing driving forces were further quantitatively modeled via a thermodynamic-inspired surprisal analysis and a modified Fokker-Planck-type kinetic model.
\r\n\r\nFinally, using integrated single-cell proteomic and metabolic technology I developed to characterize the early-stage signaling and metabolic changes upon initial drug responses, we further identified two distinct paths connecting drug-sensitive and drug-tolerant states. Melanoma cells exclusively traverse one of the two paths depending on the level of MITF in the drug-na\u00efve cells. The two trajectories are associated with distinct signaling and metabolic susceptibilities and are independently druggable.
\r\n\r\nIn total, this thesis combines and synergizes various physical science and systems biology approaches together with several unique single-cell technologies and analysis to obtain a deep and comprehensive understanding of non-genetic drug resistance in cancer. The findings from this thesis provide several novel insights into the rational design of effective combination therapy for overcoming the development of resistance in response to cancer treatments.
", "doi": "10.7907/78ZP-Y270", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:11702", "collection": "thesis", "collection_id": "11702", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06072019-032220561", "type": "thesis", "title": "I. Shape Selectivity of Small-pore Molecular Sieves for the Methanol-to-Olefins Reaction and II. Synthesis and Topotactic Transformation of Germanosilicate CIT-13", "author": [ { "family_name": "Kang", "given_name": "Jong Hun", "orcid": "0000-0002-4197-9070", "clpid": "Kang-Jong-Hun" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Rossman", "given_name": "George Robert", "clpid": "Rossman-G-R" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis presents research results from two projects involving molecular sieves. These investigations concern their synthesis, characterization and use as heterogeneous catalysis.
\r\n\r\nIn part I, the shape selectivity in the methanol-to-olefins (MTO) reaction is studied, and a new molecular sieve structure \u2013 MTO reaction selectivity relationship is developed. 17 zeolites and 13 phosphate-based molecular sieves having 14 selected cage-type/small-pore topologies (CHA, AFX, SFW, LEV, ERI, DDR, AEI, RTH, ITE, SAV, LTA, RHO, KFI, and UFI) are synthesized. The MTO reaction is performed using these catalysts at the same reaction conditions.
\r\n\r\nThe reaction results lead to the conclusion that the molecular sieve cage topology is the most important structural factor that primarily determines the olefin product distribution. For example, AEI and CHA are synthesized with four different elemental compositions (zeolite, SAPO, CoAPO, MgAPO). Regardless of differences in elemental compositions, very similar product distribution patterns are observed in each of the isostructural groups of molecular sieves. Additionally, other isostructural pairs of SAPOs and zeolites show similar product distributions.
\r\n\r\nThe reaction results from 14 topologies are grouped into four categories. Category I consists of CHA, AFX, SFW, and other GME-related topologies. Catalysts having these topologies show ethylene-to-propylene ratios close to one. Category II is a group of ERI and LEV which generate more ethylene than propylene. Category III is a group of DDR, AEI, RTH, ITE, and SAV which shows propylene selectivities higher than those of ethylene. Category IV is a group of LTA, RHO, KFI, and UFI which possess LTA-cages. These types of catalysts give high butylene selectivities.
\r\n\r\nThe concept of cage-defining ring and its size is introduced as a reliable geometric indicator on the basis of a hypothetical ellipsoid cage model. The cage-defining ring size can be easily calculated from crystallographic information which is available online. A strong correlation is found between the cage-defining ring sizes and the four categories of reaction behavior.
\r\n\r\nIn part II, an extra-large-pore germanosilicate molecular sieve CIT-13 with 14- and 10-ring pores is synthesized using monoquaternary, methylbenzylimidazolium-derivative OSDAs, and the synthesis conditions are optimized. Fluoride-free synthetic pathways for pure germanosilicate CIT-13 and isomorphous aluminum substitution in synthesis of aluminogermanosilicate CIT-13 are also described. The nature of disorder in the arrangement within CIT-13 framework is discussed, and its physicochemical properties compared to a UTL-type germanosilicate IM-12.
\r\n\r\nA comprehensive network of topotactic transformation and postsynthetic modification pathways starting from germanosilicate CIT-13 (Ge-CIT-13) is described. The moisture-mediated transformation of Ge-CIT-13 into another extra-large-pore CFI-type germanosilicate (Ge-CIT-5) is discovered, and the role of sorbed water in the transformation kinetics studied. The resultant Ge-CIT-5 is the first germanosilicate molecular sieve having a CFI topology, and the corresponding transformation is also the first inter-germanosilicate transformation occurring at room temperature. The microporosity of Ge-CIT-5 matched well with the reference pure-silica CIT-5 synthesized using the sparteine-type OSDA.
\r\n\r\nThe acid-delamination processes of Ge-CIT-13 and Ge-CIT-5 are investigated. Ge-CIT-13 can be transformed into two new frameworks, CIT-14 with 12- and 8-ring pores and CIT-15 with 10-ring pores, on the basis of an ADOR-type topotactic transformation. The inverse sigma transformation of Ge-CIT-13 directly into CIT-14 is also firstly described. The conventional acid-delamination of Ge-CIT-13 does not yield Ge-CIT-5. However, the CIT-15-type material is obtained via the base-delamination pathway from Ge-CIT-5. The postsynthetic alumination of Ge-CIT-13 and Ge-CIT-5 is also achievable.
\r\n", "doi": "10.7907/PG34-B728", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:11033", "collection": "thesis", "collection_id": "11033", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06062018-180959061", "type": "thesis", "title": "Targeted Nanoparticle Delivery of Therapeutics Across the Blood-Brain and Blood-Tumor Barriers to Breast Cancer Brain Metastases", "author": [ { "family_name": "Wyatt", "given_name": "Emily Ann", "orcid": "0000-0002-7534-0582", "clpid": "Wyatt-Emily-Ann" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "clpid": "Shapiro-M-G" }, { "family_name": "Mazmanian", "given_name": "Sarkis K.", "clpid": "Mazmanian-S-K" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Brain metastases of human epidermal growth factor receptor 2 (HER2)-positive breast cancer are presenting an increasing problem in the clinic. While HER2-targeted therapies effectively control systemic disease, their efficacy against brain metastases is hindered by their inability to penetrate the blood-brain and blood-tumor barriers (BBB and BTB). One promising strategy to increase brain penetration of systemic therapeutics is to exploit endogenous transport systems at the BBB to shuttle drugs into the brain. Previous studies showed that gold nanoparticles designed to shed transferrin receptor (TfR)-targeting ligands under acidic conditions encountered during transcytosis of the BBB demonstrated increased accumulation in the brain. The focus of this work was to determine whether therapeutic, TfR-targeted nanoparticles using an improved acid-cleavable chemistry could be used to deliver therapeutically useful amounts of drug to the brain.
\r\n\r\nTo accomplish this goal, a new animal model of HER2-positive breast cancer brain metastasis was developed in an attempt to create a clinically representative, impermeable barrier to standard therapeutics. This new model establishes brain metastases by methods that more closely resemble the human disease, forming whole-body tumors that eventually metastasize to the brain. Brain metastases formed by this new methodology show no response to standard HER2-targeted agents, mimicking the clinical situation.
\r\n\r\nNext, efficacy and brain uptake of TfR-targeted, single-agent therapeutic nanoparticles were investigated in the newly developed model, as well as two common models from the literature. These nanoparticles show significant tumor growth delay and increased accumulation in both brain metastases and healthy brain tissue in all three models, highlighting their therapeutic potential. Additionally, non-BBB-penetrant small molecule and non-targeted nanoparticle therapeutics elicit a substantial antitumor response as well as brain tumor accumulation in the most commonly used literature model. In contrast, the new model and one gaining popularity in the literature provide for a more clinically relevant, impermeable barrier to non-BBB-penetrant agents, indicating that the method used to establish brain metastases can affect efficacy and brain uptake of therapeutics.
", "doi": "10.7907/5qpd-0736", "publication_date": "2018", "thesis_type": "phd", "thesis_year": "2018" }, { "id": "thesis:9903", "collection": "thesis", "collection_id": "9903", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08192016-131948034", "primary_object_url": { "basename": "Ji_Yuewei_2017_thesis_final.pdf", "content": "final", "filesize": 9644883, "license": "other", "mime_type": "application/pdf", "url": "/9903/1/Ji_Yuewei_2017_thesis_final.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Organic Structure Directing Agent Free Synthesis of Small Pore Zeolite Catalysts for the Methanol-to-Olefins Reaction\r ", "author": [ { "family_name": "Ji", "given_name": "Yuewei Lucy", "orcid": "0000-0002-6625-4252", "clpid": "Ji-Yuewei-Lucy" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Rossman", "given_name": "George Robert", "clpid": "Rossman-G-R" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Light olefins, ethylene and propylene, are two of the highest produced petrochemicals globally. The methanol-to-olefins (MTO) reaction is a promising route for making these chemicals from non-petroleum feedstocks such as natural gas and coal that has been successfully commercialized. The catalysts employed for this reaction are typically microporous molecular sieves with Br\u00f8nsted acidity, e.g., zeolites and silicoaluminophosphates, that generally require costly organic structure directing agents (OSDAs) to synthesize.
\r\n\r\nThis thesis explores an alternative, low cost method for synthesizing small pore zeolite catalysts for the MTO reaction without the use of OSDAs. Small pore zeolites are first synthesized in the absence of OSDAs. The resulting high-aluminum materials are then converted into useful catalysts via high temperature (500-800\u00b0C) steam treatments that extract a portion of the framework aluminum, thereby modifying the acid site concentration, pore structure and catalytic behavior of the materials. This synthesis method is demonstrated on three small pore zeolite structures that are prepared without using OSDAs: CHA, RHO and KFI. In the as-synthesized forms, these materials deactivate rapidly when evaluated as catalysts for the MTO reaction due to their high aluminum contents. Upon steam treatment, however, improved catalyst lifetimes and olefin selectivities are observed that are attributed to a decrease in the total Br\u00f8nsted acid site concentration and the creation of mesopores that facilitate transport of reactants and products.
\r\n\r\nImprovements in the activity were observed for all three of the zeolites chosen for investigation with CHA-type zeolites performing best, though differences in olefin selectivities were observed. Poisoning of acid sites located in the mesopores and on external surface of the steamed zeolites did not change the observed product distribution, suggesting that these differences do not arise from secondary reactions of olefins and instead may be attributed to differences in the pore structures.
\r\n\r\nOverall, the successful demonstration of this catalyst preparation method on three different zeolite structures suggests that it may be a useful route for converting any small pore zeolite that can be synthesized without using OSDAs into catalysts that may be useful for reactions like MTO.
\r\n", "doi": "10.7907/Z9MG7MG0", "publication_date": "2017", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:10141", "collection": "thesis", "collection_id": "10141", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04182017-134255198", "primary_object_url": { "basename": "Brand_Stephen_2017.pdf", "content": "final", "filesize": 62579051, "license": "other", "mime_type": "application/pdf", "url": "/10141/1/Brand_Stephen_2017.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "I. Tin Silsesquioxanes as Analogs for the Open and Closed Sites in Tin-Containing Zeotype Beta and II. Enantiomerically Enriched, Polycrystalline Molecular Sieves", "author": [ { "family_name": "Brand", "given_name": "Stephen Kramer", "orcid": "0000-0002-0894-401X", "clpid": "Brand-Stephen-Kramer" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Agapie", "given_name": "Theodor", "clpid": "Agapie-T" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The use of biomass as a resource to produce value-added products has garnered significant interest as a means of reducing reliance on fossil fuels. This task is complicated by the complex, highly functionalized nature of abundant biomass derivatives, such as glucose. Tin-containing zeolite Beta (Sn-Beta) has been investigated as a catalyst for isomerizing aldohexoses into ketohexoses through a Lewis acid mediated hydride shift (1,2-intramolecular hydride shift, 1,2-HS). Recent studies on the reactivities of Lewis base-doped and alkali-exchanged Sn-Beta samples have conclusively demonstrated that the open tin site performs the glucose isomerization reaction. With Lewis base doped Sn-Beta, glucose conversion is almost completely eliminated and product selectivity is shifted predominantly to mannose, formed through a 1,2-intramolecular carbon shift (1,2-CS). To understand the structure-activity relationships between the conditions of the active sites in the zeolite, three molecular models (tin silsesquioxanes) of the tin sites in the zeolite are synthesized. Two tin silsesquioxanes that contain an octahedral tin site with and without an adjacent silanol group are prepared and used as catalysts for the reaction of glucose. The catalyst that contains the adjacent silanol group selectively forms fructose through a 1,2-HS while the catalyst without the silanol group yields mannose through a 1,2-CS. These results provide further evidence for the nature of the active sites in Sn-Beta. A methyl-ligated tin silsesquioxane is experimentally and theoretically examined to examine possible reactivities at the closed site. This compound is an active glucose conversion catalyst that selectively produces mannose, although the rates of reaction are far below those obtained from Sn-Beta. Additionally, a hybrid quantum mechanical/molecular mechanics model is constructed, and the complete catalytic cycle is computationally examined via considering ring-opening, three distinct pathways for each hydride- and carbon-shift reaction, and ring-closing. The combined experimental and computational results suggest that there could be reaction pathways that involve Si-O-Sn cleavage that give much slower reaction rates than the open tin site in Sn-Beta.
\r\n\r\nZeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis. Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would enable these materials to perform enantioselective functions. In part II of this thesis, the synthesis of enantiomerically enriched samples of a molecular sieve is reported. Enantiopure organic structure directing agents (OSDAs) are designed with the assistance of computational methods, and used to synthesize enantioenriched, polycrystalline molecular sieve samples of either enantiomer. Computational results correctly predicted which enantiomer is obtained, and enantiomeric enrichment is proven by high-resolution transmission electron microscopy. The enantioenriched and racemic samples of the molecular sieves are tested as adsorbents and heterogeneous catalysts. The enantioenriched molecular sieves show enantioselectivity for the ring opening reaction of epoxides and enantioselective adsorption of 2-butanol (R enantiomer of the molecular sieve shows opposite and approximately equal enantioselectivity from the S enantiomer of the molecular sieve, while the racemic sample of the molecular sieve shows no enantioselectivity).
\r\n", "doi": "10.7907/Z96T0JPX", "publication_date": "2017", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:9894", "collection": "thesis", "collection_id": "9894", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07202016-150438490", "primary_object_url": { "basename": "Marat Orazov PhD Thesis.pdf", "content": "final", "filesize": 4919027, "license": "other", "mime_type": "application/pdf", "url": "/9894/1/Marat Orazov PhD Thesis.pdf", "version": "v9.0.0" }, "type": "thesis", "title": "Development and Characterization of Catalytic Systems for Biomass-Derived Chemical Feedstocks", "author": [ { "family_name": "Orazov", "given_name": "Marat", "orcid": "0000-0003-1621-1331", "clpid": "Orazov-Marat" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Agapie", "given_name": "Theodor", "clpid": "Agapie-T" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Heterogeneous catalysis by Br\u00f8nsted and/or Lewis acid sites isolated within microporous environments is a topic that is perpetually growing in scope and importance. While Br\u00f8nsted acid sites in zeolites have been studied and applied extensively in the petrochemical industry, new opportunities for green processes based on renewable chemical feedstocks call for applications of new microporous materials that possess Lewis acid sites (e.g., zeotypes with framework Sn, Ti, Zr, or Hf). Characterization of such materials and the specific structures of the Lewis acid sites provides insights for rational catalyst design and application.
\r\n\r\nThis work provides experimental evidence for the identities of the active sites in Sn-Beta zeotype for the 1,2-intramolecular hydride shift (1,2-HS) reaction that results in D-glucose isomerization to D-fructose, and for the 1,2-intramolecular carbon shift (1,2-CS) reaction that results in D-glucose isomerization to D-mannose. Specifically, by selective poisoning experiments, the partially-hydrolyzed, \"open\" Sn site is shown to be the active site for the 1,2-HS reaction. The participation of the proximal silanol of such an open Sn site in the 1,2-HS reaction is demonstrated thorough alkali-exchange experiments. Such experiments also reveal that the active site for the 1,2-CS reaction is an open Sn site with a cation-exchanged proximal silanol.
\r\n\r\n1,2-CS catalysts, in general, are shown to also catalyze retro-aldol reactions of hexoses at moderate temperatures (ca. 100 \u00b0C), and to be compatible with microporous 1,2-HS catalysts in tandem catalytic schemes that enable production of alkyl lactates.
\r\n\r\nFinally, the Lewis acidity of framework Zn in zincosilicate microporous materials is demonstrated through probe-molecule infrared spectroscopy. One such material is then shown to catalyze Diels-Alder cycloaddition-dehydration reactions of oxygenated furans and ethylene. To the best of our knowledge, these materials are the first heterogeneous catalysts reported to catalyze the direct formation of terephthalate esters from ethylene and dimethyl 2,5-furandicarboxylate with appreciable selectivity.
\r\n", "doi": "10.7907/Z9X63JZZ", "publication_date": "2017", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:9083", "collection": "thesis", "collection_id": "9083", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08062015-163035886", "primary_object_url": { "basename": "Schmidt thesis v5 proofreader comments.pdf", "content": "final", "filesize": 3880387, "license": "other", "mime_type": "application/pdf", "url": "/9083/1/Schmidt thesis v5 proofreader comments.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Imidazolium-Based Organic Structure Directing Agents for the Synthesis of Microporous Materials", "author": [ { "family_name": "Schmidt", "given_name": "Joel Edward", "orcid": "0000-0002-0039-2863", "clpid": "Schmidt-Joel-Edward" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Rossman", "given_name": "George Robert", "clpid": "Rossman-G-R" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The central theme of this thesis is the use of imidazolium-based organic structure directing agents (OSDAs) in microporous materials synthesis. Imidazoliums are advantageous OSDAs as they are relatively inexpensive and simple to prepare, show robust stability under microporous material synthesis conditions, have led to a wide range of products, and have many permutations in structure that can be explored. The work I present involves the use of mono-, di-, and triquaternary imidazolium-based OSDAs in a wide variety of microporous material syntheses. Much of this work was motivated by successful computational predictions (Chapter 2) that led me to continue to explore these types of OSDAs. Some of the important discoveries with these OSDAs include the following: 1) Experimental evaluation and confirmation of a computational method that predicted a new OSDA for pure-silica STW, a desired framework containing helical pores that was previously very difficult to synthesize. 2) Discovery of a number of new imidazolium OSDAs to synthesize zeolite RTH, a zeolite desired for both the methanol-to-olefins reaction as well as NOX reduction in exhaust gases. This discovery enables the use of RTH for many additional investigations as the previous OSDA used to make this framework was difficult to synthesize, such that no large scale preparations would be practical. 3) The synthesis of pure-silica RTH by topotactic condensation from a layered precursor (denoted CIT-10), that can also be pillared to make a new framework material with an expanded pore system, denoted CIT-11, that can be calcined to form a new microporous material, denoted CIT-12. CIT-10 is also interesting since it is the first layered material to contain 8 membered rings through the layers, making it potentially useful in separations if delamination methods can be developed. 4) The synthesis of a new microporous material, denoted CIT-7 (framework code CSV) that contains a 2-dimensional system of 8 and 10 membered rings with a large cage at channel intersections. This material is especially important since it can be synthesized as a pure-silica framework under low-water, fluoride-mediated synthesis conditions, and as an aluminosilicate material under hydroxide mediated conditions. 5) The synthesis of high-silica heulandite (HEU) by topotactic condensation as well as direct synthesis, demonstrating new, more hydrothermally stable compositions of a previously known framework. 6) The synthesis of germanosilicate and aluminophosphate LTA using a triquaternary OSDA. All of these materials show the diverse range of products that can be formed from OSDAs that can be prepared by straightforward syntheses and have made many of these materials accessible for the first time under facile zeolite synthesis conditions. ", "doi": "10.7907/Z96H4FBM", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9689", "collection": "thesis", "collection_id": "9689", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04282016-162609209", "primary_object_url": { "basename": "Clark_Andrew J_Thesis_04292016_Final.pdf", "content": "final", "filesize": 7462710, "license": "other", "mime_type": "application/pdf", "url": "/9689/1/Clark_Andrew J_Thesis_04292016_Final.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Delivery of Targeted Nanoparticles Across the Blood-Brain Barrier Using a Detachable Targeting Ligand", "author": [ { "family_name": "Clark", "given_name": "Andrew James", "orcid": "0000-0003-4240-7119", "clpid": "Clark-Andrew-James" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Heath", "given_name": "James R.", "clpid": "Heath-J-R" }, { "family_name": "Beauchamp", "given_name": "Jesse L.", "clpid": "Beauchamp-J-L" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "clpid": "Shapiro-M-G" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Chronic diseases of the central nervous system are poorly treated due to the inability of most therapeutics to cross the blood-brain barrier. The blood-brain barrier is an anatomical and physiological barrier that severely restricts solute influx, including most drugs, from the blood to the brain. One promising method to overcome this obstacle is to use endogenous solute influx systems at the blood-brain barrier to transport drugs. Therapeutics designed to enter the brain through transcytosis by binding the transferrin receptor, however, are restricted within endothelial cells. The focus of this work was to develop a method to increase uptake of transferrin-containing nanoparticles into the brain by overcoming these restrictive processes.
\r\n\r\nTo accomplish this goal, nanoparticles were prepared with surface transferrin molecules bound through various liable chemical bonds. These nanoparticles were designed to shed the targeting molecule during transcytosis to allow increased accumulation of nanoparticles within the brain.
\r\n\r\nTransferrin was added to the surface of nanoparticles through either redox or pH sensitive chemistry. First, nanoparticles with transferrin bound through disulfide bonds were prepared. These nanoparticles showed decreased avidity for the transferrin receptor after exposure to reducing agents and increased ability to enter the brain in vivo compared to those lacking the disulfide link.
\r\n \r\nNext, transferrin was attached through a chemical bond that cleaves at mildly acidic pH. Nanoparticles containing a cleavable link between transferrin and gold nanoparticle cores were found to both cross an in vitro model of the blood-brain barrier and accumulate within the brain in significantly higher numbers than similar nanoparticles lacking the cleavable bond. Also, this increased accumulation was not seen when using this same strategy with an antibody to transferrin receptor, indicating that behavior of nanoparticles at the blood-brain barrier varies depending on what type of targeting ligand is used.
\r\n\r\nFinally, polymeric nanoparticles loaded with dopamine and utilizing a superior acid-cleavable targeting chemistry were investigated as a potential treatment for Parkinson\u2019s disease. These nanoparticles were capable of increasing dopamine quantities in the brains of healthy mice, highlighting the therapeutic potential of this design. Overall, this work describes a novel method to increase targeted nanoparticle accumulation in the brain.
\r\n", "doi": "10.7907/Z9WH2MZ6", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9714", "collection": "thesis", "collection_id": "9714", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05092016-155820873", "primary_object_url": { "basename": "DorothyPan_Thesis_Edits2.pdf", "content": "final", "filesize": 20115454, "license": "other", "mime_type": "application/pdf", "url": "/9714/1/DorothyPan_Thesis_Edits2.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Development of a Cationic Mucic Acid Polymer-Based Nanoparticle siRNA Delivery System", "author": [ { "family_name": "Pan", "given_name": "Dorothy Weichi", "orcid": "0000-0003-4066-7750", "clpid": "Pan-Dorothy-Weichi" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Heath", "given_name": "James R.", "clpid": "Heath-J-R" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Campbell", "given_name": "Judith L.", "clpid": "Campbell-J-L" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Cancer chemotherapy has advanced from highly toxic drugs to more targeted treatments in the last 70 years. Chapter 1 opens with an introduction to targeted therapy for cancer. The benefits of using a nanoparticle to deliver therapeutics are discussed. We move on to siRNA in particular, and why it would be advantageous as a therapy. Specific to siRNA delivery are some challenges, such as nuclease degradation, quick clearance from circulation, needing to enter cells, and getting to the cytosol. We propose the development of a nanoparticle delivery system to tackle these challenges so that siRNA can be effective.
\r\n\r\nChapter 2 of this thesis discusses the synthesis and analysis of a cationic mucic acid polymer (cMAP) which condenses siRNA to form a nanoparticle. Various methods to add polyethylene glycol (PEG) for stabilizing the nanoparticle in physiologic solutions, including using a boronic acid binding to diols on mucic acid, forming a copolymer of cMAP with PEG, and creating a triblock with mPEG on both ends of cMAP. The goal of these various pegylation strategies was to increase the circulation time of the siRNA nanoparticle in the bloodstream to allow more of the nanoparticle to reach tumor tissue by the enhanced permeation and retention effect. We found that the triblock mPEG-cMAP-PEGm polymer condensed siRNA to form very stable 30-40 nm particles that circulated for the longest time \u2013 almost 10% of the formulation remained in the bloodstream of mice 1 h after intravenous injection.
\r\n\r\nChapter 3 explores the use of an antibody as a targeting agent for nanoparticles. Some antibodies of the IgG1 subtype are able to recruit natural killer cells that effect antibody dependent cellular cytotoxicity (ADCC) to kill the targeted cell to which the antibody is bound. There is evidence that the ADCC effect remains in antibody-drug conjugates, so we wanted to know whether the ADCC effect is preserved when the antibody is bound to a nanoparticle, which is a much larger and complex entity. We utilized antibodies against epidermal growth factor receptor with similar binding and pharmacokinetics, cetuximab and panitumumab, which differ in that cetuximab is an IgG1 and panitumumab is an IgG2 (which does not cause ADCC). Although a natural killer cell culture model showed that gold nanoparticles with a full antibody targeting agent can elicit target cell lysis, we found that this effect was not preserved in vivo. Whether this is due to the antibody not being accessible to immune cells or whether the natural killer cells are inactivated in a tumor xenograft remains unknown. It is possible that using a full antibody still has value if there are immune functions which are altered in a complex in vivo environment that are intact in an in vitro system, so the value of using a full antibody as a targeting agent versus using an antibody fragment or a protein such as transferrin is still open to further exploration.
\r\n\r\nIn chapter 4, nanoparticle targeting and endosomal escape are further discussed with respect to the cMAP nanoparticle system. A diboronic acid entity, which gives an order of magnitude greater binding (than boronic acid) to cMAP due to the vicinal diols in mucic acid, was synthesized, attached to 5kD or 10kD PEG, and conjugated to either transferrin or cetuximab. A histidine was incorporated into the triblock polymer between cMAP and the PEG blocks to allow for siRNA endosomal escape. Nanoparticle size remained 30-40 nm with a slightly negative ca. -3 mV zeta potential with the triblock polymer containing histidine and when targeting agents were added. Greater mRNA knockdown was seen with the endosomal escape mechanism than without. The nanoparticle formulations were able to knock down the targeted mRNA in vitro. Mixed effects suggesting function were seen in vivo.
\r\n\r\nChapter 5 summarizes the project and provides an outlook on siRNA delivery as well as targeted combination therapies for the future of personalized medicine in cancer treatment.
\r\n", "doi": "10.7907/Z9VM497J ", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:8866", "collection": "thesis", "collection_id": "8866", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05182015-163742452", "primary_object_url": { "basename": "JJ PACHECO PHD THESIS_MAY 2015_Final.pdf", "content": "final", "filesize": 3537043, "license": "other", "mime_type": "application/pdf", "url": "/8866/1/JJ PACHECO PHD THESIS_MAY 2015_Final.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "New Catalysts for the Renewable Production of Monomers for Bioplastics", "author": [ { "family_name": "Pacheco", "given_name": "Joshua Joseph", "clpid": "Pacheco-Joshua-Joseph" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Grubbs", "given_name": "Robert H.", "clpid": "Grubbs-R-H" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Terephthalic acid (PTA) is one of the monomers used for the synthesis of the polyester, polyethylene terephthalate (PET), that is used for the large-scale manufacture of synthetic fibers and plastic bottles. PTA is largely produced from the liquid-phase oxidation of petroleum-derived p-xylene (PX). However, there are now ongoing worldwide efforts exploring alternative routes for producing PTA from renewable, biomass resources.
\r\n\r\nIn this thesis, I present a new route to PTA starting from the biomass-derived platform chemical, 5-hydroxymethylfurfural (HMF). This route utilizes new, selective Diels-Alder-dehydration reactions involving ethylene and is advantageous over the previously proposed Diels-Alder-dehydration route to PTA from HMF via 2,5-dimethylfuran (DMF) since the H2 reduction of HMF to DMF is avoided. Specifically, oxidized derivatives of HMF are reacted as is, or after etherification-esterification with methanol, with ethylene over solid Lewis acid catalysts that do not contain strong Br\u00f8nsted acids in order to synthesize intermediates of PTA and its equally important diester, dimethyl terephthalate (DMT). The partially oxidized HMF, 5-(hydroxymethyl)furoic acid (HMFA) is reacted with high pressure ethylene over a pure-silica molecular sieve catalyst containing framework tin (Sn-Beta) to produce the Diels-Alder-dehydration product, 4-(hydroxymethyl)benzoic acid (HMBA), with ~30% selectivity at ~20% yield. If HMFA is protected with methanol to form methyl 5-(methoxymethyl)furan-2-carboxylate (MMFC), MMFC can react with ethylene in the presence of a pure-silica molecular sieve containing framework zirconium (Zr-Beta) to produce methyl 4-(methoxymethyl)benzenecarboxylate (MMBC) with >70% selectivity at >20% yield. HMBA and MMBC can then be oxidized to produce PTA and DMT, respectively. When Lewis acid containing mesoporous silica (MCM-41) and amorphous silica, or Br\u00f8nsted acid containing zeolites (Al-Beta), are used as catalysts, a significant decrease in selectivity/yield of the Diels-Alder-dehydration product is observed.
\r\n\r\nAn investigation to elucidate the reaction network and side products in the conversion of MMFC to MMBC was performed, and the main side products are found to be methyl 4-formylcyclohexa-1,3-diene-1-carboxylate and the ethylene Diels-Alder adduct of this cyclohexadiene. These products presumably form by a different dehydration pathway of the MMFC/ethylene Diels-Alder adduct and should be included when determining the overall selectivity to PTA or DMT since, like MMBC, these compounds are precursors to PTA or DMT.
\r\n\r\nFundamental physical and chemical information on the ethylene Diels-Alder-dehydration reactions catalyzed by the Lewis acid-containing molecular sieves was obtained. Madon-Boudart experiments using Zr-Beta as catalyst show that the reaction rates are limited by chemical kinetics only (physical transport limitations are not present), all the Zr4+ centers are incorporated into the framework of the molecular sieve, and the whole molecular sieve crystal is accessible for catalysis. Apparent activation energies using Zr-Beta are low, suggesting that the overall activation energy of the system may be determined by a collection of terms and is not the true activation energy of a single chemical step.
\r\n", "doi": "10.7907/Z9N58JBZ", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8855", "collection": "thesis", "collection_id": "8855", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05112015-143241169", "primary_object_url": { "basename": "M_Deimund_Thesis_Corrected.pdf", "content": "final", "filesize": 112843968, "license": "other", "mime_type": "application/pdf", "url": "/8855/11/M_Deimund_Thesis_Corrected.pdf", "version": "v8.0.0" }, "type": "thesis", "title": "I. Nickel-Exchanged Zincosilicate Catalysts for the Oligomerization of Propylene and II. Organic SDA-Free Catalysts for the Methanol-to-Olefins Reaction", "author": [ { "family_name": "Deimund", "given_name": "Mark Austin", "clpid": "Deimund-Mark-Austin" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Nickel-containing catalysts are developed to oligomerize light olefins. Two nickel-containing zincosilicates (Ni-CIT-6 and Ni-Zn-MCM-41) and two nickel-containing aluminosilicates (Ni-HiAl-BEA and Ni-USY) are synthesized as catalysts to oligomerize propylene into C3n (C6 and C9) products. All catalysts oligomerize propylene, with the zincosilicates demonstrating higher average selectivities to C3n products, likely due to the reduced acidity of the Zn heteroatom.
\r\n\r\nTo test whether light alkanes can be incorporated into this oligomerization reaction, a supported homogeneous catalyst is combined with Ni-containing zincosilicates. The homogeneous catalyst is included to provide dehydrogenation/hydrogenation functions. When this tandem catalyst system is evaluated using a propylene/n-butane feed, no significant integration of alkanes are observed.
\r\n\r\nNi-containing zincosilicates are reacted with 1-butene and an equimolar propylene/1-butene mixture to study other olefinic feeds. Further, other divalent metal cations such as Mn2+, Co2+, Cu2+, and Zn2+ are exchanged onto CIT-6 samples to investigate stability and potential use for other reactions. Co-CIT-6 oligomerizes propylene, albeit less effectively than Ni-CIT-6. The other M-CIT-6 samples, while not able to oligomerize light olefins, may be useful for other reactions, such as deNOx.
\r\n\r\nMolecular sieves are synthesized, characterized, and used to catalyze the methanol-to-olefins (MTO) reaction. The Al concentration in SSZ-13 samples is varied to investigate the effect of Al number on MTO reactivity when compared to a SAPO-34 sample with only isolated Si Br\u00f8nsted acid sites. These SSZ-13 samples display reduced transient selectivity behavior and extended reaction lifetimes as Si/Al increases; attributable to fewer paired Al sites. MTO reactivity for the higher Si/Al SSZ-13s resembles the SAPO-34 sample, suggesting that both catalysts owe their stable reaction behavior to isolated Br\u00f8nsted acid sites.
\r\n\r\nZeolites CHA and RHO are prepared without the use of organic structure-directing agents (OSDAs), dealuminated by steam treatments (500\u00b0C-800\u00b0C), and evaluated as catalysts for the MTO reaction. The effects of temperature and steam partial pressure during steaming are investigated. X-ray diffraction (XRD) and Ar physisorption show that steaming causes partial structural collapse of the zeolite, with degradation increasing with steaming temperature. 27Al MAS NMR spectra of steamed materials reveal the presence of tetrahedral, pentacoordinate, and hexacoordinate aluminum.
\r\n\r\nProton forms of as-synthesized CHA (Si/Al=2.4) and RHO (Si/Al=2.8) rapidly deactivate under MTO testing conditions (400\u00b0C, atmospheric pressure). CHA samples steamed at 600\u00b0C performed best among samples tested, showing increased olefin selectivities and catalyst lifetime. Acid washing these steamed samples further improved activity. Reaction results for RHO were similar to CHA, with the RHO sample steamed at 800\u00b0C producing the highest light olefin selectivities. Catalyst lifetime and C2-C3 olefin selectivities increase with increasing reaction temperature for both CHA-type and RHO-type steamed samples.
", "doi": "10.7907/Z9XK8CG9", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8241", "collection": "thesis", "collection_id": "8241", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05192014-100254158", "primary_object_url": { "basename": "Bermejo-Deval_R, 06-13-2014.pdf", "content": "final", "filesize": 5287603, "license": "other", "mime_type": "application/pdf", "url": "/8241/1/Bermejo-Deval_R, 06-13-2014.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Reaction of Glucose Catalyzed by Framework and Extraframework Tin Sites in Zeolite Beta", "author": [ { "family_name": "Bermejo-Deval", "given_name": "Ricardo", "clpid": "Bermejo-Deval-Ricardo" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Agapie", "given_name": "Theodor", "clpid": "Agapie-T" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The isomerization of glucose into fructose is a large-scale reaction for the production of high-fructose corn syrup, and is now being considered as an intermediate step in the possible route of biomass conversion into fuels and chemicals. Recently, it has been shown that a hydrophobic, large pore, silica molecular sieve having the zeolite beta structure and containing framework Sn4+ (Sn-Beta) is able to isomerize glucose into fructose in aqueous media. Here, I have investigated how this catalyst converts glucose to fructose and show that it is analogous to that achieved with metalloenzymes. Specifically, glucose partitions into the molecular sieve in the pyranose form, ring opens to the acyclic form in the presence of the Lewis acid center (framework Sn4+), isomerizes into the acyclic form of fructose and finally ring closes to yield the furanose product. Akin to the metalloenzyme, the isomerization step proceeds by intramolecular hydride transfer from C2 to C1. Extraframework tin oxides located within hydrophobic channels of the molecular sieve that exclude liquid water can also isomerize glucose to fructose in aqueous media, but do so through a base-catalyzed proton abstraction mechanism. Extraframework tin oxide particles located at the external surface of the molecular sieve crystals or on amorphous silica supports are not active in aqueous media but are able to perform the isomerization in methanol by a base-catalyzed proton abstraction mechanism. Post-synthetic exchange of Na+ with Sn-Beta alters the glucose reaction pathway from the 1,2 intramolecular hydrogen shift (isomerization) to produce fructose towards the 1,2 intramolecular carbon shift (epimerization) that forms mannose. Na+ remains exchanged onto silanol groups during reaction in methanol solvent, leading to a near complete shift in selectivity towards glucose epimerization to mannose. In contrast, decationation occurs during reaction in aqueous solutions and gradually increases the reaction selectivity to isomerization at the expense of epimerization. Decationation and concomitant changes in selectivity can be eliminated by addition of NaCl to the aqueous reaction solution. Thus, framework tin sites with a proximal silanol group are the active sites for the 1, 2 intramolecular hydride shift in the isomerization of glucose to fructose, while these sites with Na-exchanged silanol group are the active sites for the 1, 2 intramolecular carbon shift in epimerization of glucose to mannose. ", "doi": "10.7907/6AYX-9086", "publication_date": "2014", "thesis_type": "phd", "thesis_year": "2014" }, { "id": "thesis:7293", "collection": "thesis", "collection_id": "7293", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11282012-141927745", "primary_object_url": { "basename": "Thesis_BhaweYashodhan.pdf", "content": "final", "filesize": 24883515, "license": "other", "mime_type": "application/pdf", "url": "/7293/1/Thesis_BhaweYashodhan.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "I: Solid Materials for Low Temperature Thermochemical Water Splitting. II: Structure-Property Relationships on the Zeolite Catalyzed Conversion of Methanol to Light Olefins", "author": [ { "family_name": "Bhawe", "given_name": "Yashodhan", "clpid": "Bhawe-Yashodhan" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Miller", "given_name": "Thomas F.", "clpid": "Miller-T-F" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis describes two separate projects. The first part of the thesis involves the synthesis of materials for enabling thermochemical water splitting at temperatures below 1000\u00baC, while the second part focuses on the structure-property relationships for the catalytic conversion of methanol-to-olefins.
\r\n\r\nIn the first project, metal oxide clusters are impregnated in a silica support and tested as catalysts for the thermochemical splitting of water at temperatures below 1000\u00baC. These supported catalysts are able to do either the oxidation or reduction half cycle, but not both. Thermodynamic analyses reveal that for most common metal / metal oxide pairs, a thermochemical water splitting cycle can not occur in two steps below 1000\u00baC. Thus, a multi-step thermochemical cycle is developed using Mn3O4 and Na2CO3. This new cycle can be closed at temperatures that do not exceed 850\u00baC. Additionally, three metal spinels (Mn, Fe and Co based) are investigated with three alkali metal carbonates (Li, Na and K) for both thermochemical water splitting and thermochemical CO2 reduction. The manganese, sodium system is found to be the optimal combination for water splitting.
\r\n\r\nThe second project explores the effects that zeolite structure has on the product selectivity in the methanol-to-olefins (MTO) reaction. After first ensuring that literature results on the more common MTO catalysts could be reproduced, the effects of several zeolite structure features on product selectivity are elucidated. Structural features such as channel width and channel eccentricity, cage size (tested on the LEV, CHA and AFX frameworks) and framework composition (tested on the LEV, AEI, CHA and AFX frameworks) are explored. It is found that the product selectivity does not have a strong correlation with channel width and eccentricity. Ethylene selectivity did increase with a reduction in cage size, while propylene selectivity is a maximum with the CHA cage. The most consistent theme noted is that between the aluminosilicates (zeolites) and the silicoaluminophosphates (SAPOs), the effect of temperature on the C3=/C2= is the same (if the aluminosilicate shows an increase in C3=/C2= with an increase in temperature, so does the silicoaluminophosphate, etc.).
", "doi": "10.7907/05FG-JG39", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7498", "collection": "thesis", "collection_id": "7498", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03062013-145838327", "primary_object_url": { "basename": "Wiley PhD Thesis.pdf", "content": "final", "filesize": 77779507, "license": "other", "mime_type": "application/pdf", "url": "/7498/1/Wiley PhD Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Design of Nanoparticles that Cross the Blood-Brain Barrier by Receptor Mediated Transcytosis", "author": [ { "family_name": "Wiley", "given_name": "Devin Thomas", "clpid": "Wiley-Devin-Thomas" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Webster", "given_name": "Paul", "clpid": "Webster-P" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The primary objective of my thesis work is to establish a set of design criteria for nanoparticles whose purpose is to safely and efficiently access the brain after systemic injection. Nanoparticles that can access the brain may be able to deliver therapeutic molecules to the brain that otherwise would be excluded by the blood-brain barrier.
\r\n\r\nE. coli glycoprotein 96 (Ecgp96) is explored as a candidate receptor on the blood-brain barrier that could potentially facilitate nanoparticle-receptor mediated transcytosis into the brain. Results from studies utilizing PET/CT, SPECT/CT, MRI, Xenogen fluorescence imaging, and confocal microscopy conclude that Ecgp96 is observed in the blood-brain barrier endothelial cells, but is not accessible from the blood of adult or neonatal mice under normal, non-pathological conditions.
\r\n\r\nTransferrin receptor is a well-characterized receptor on the blood-brain barrier that is accessible from the blood and known to transcytose transferrin. I focused on this receptor and on synthesizing and characterizing a well-defined set of transferrin containing gold nanoparticles of various sizes and transferrin compositions that would be investigated during in-vivo studies. Nanoparticle sizes were measured by DLS and nanoparticle tracking analysis. Zeta potentials were also measured. Nanoparticle transferrin content was directly measured by labeling transferrin with 64Cu and measuring the nanoparticle associated gamma activity. The nanoparticle binding avidities to mouse transferrin receptors were ranked by a silver enhancement fluorescence-based method using the mouse Neruo2A cell line.
\r\n\r\nEach nanoparticle formulation was systemically injected into mice, and localization in the mouse brain was observed by silver enhancement light microscopy, and TEM. The quantitation of the gold was determined by ICP-MS. Nanoparticles with large amounts of transferrin remain strongly attached to brain endothelial cells, while nanoparticles with less transferrin are capable of both interacting with transferrin receptor on the luminal side of the blood-brain barrier and detaching from transferrin receptor on the brain side of the blood-brain barrier. These results highlight the fact that the nanoparticle avidity must be tuned to maximize the number of nanoparticles exiting the endothelial cells and entering the brain tissue. Lanthanum nitrate perfusion-fixation studies demonstrate that the nanoparticle formulations investigated do not degrade the blood-brain barrier integrity and enter the brain by transferrin receptor-mediated transcytosis. The results from these studies provide initial design criteria for creating nanoparticle therapeutics for delivery to the brain from systemic administrations.
\r\n", "doi": "10.7907/DKRM-S631", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7443", "collection": "thesis", "collection_id": "7443", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01262013-020116009", "primary_object_url": { "basename": "Han Thesis.pdf", "content": "final", "filesize": 52470821, "license": "other", "mime_type": "application/pdf", "url": "/7443/1/Han Thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Development of Targeted, Polymeric Delivery Vehicles for Camptothesin and siRNA Via Boronic Acid-Diol Complexation", "author": [ { "family_name": "Han", "given_name": "Han", "clpid": "Han-Han" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Grubbs", "given_name": "Robert H.", "clpid": "Grubbs-R-H" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Wang", "given_name": "Zhen-Gang", "clpid": "Wang-Zhen-Gang" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Our research lab has developed polymer-based nanoparticle delivery systems for the anticancer drug, camptothecin (CPT), CRLX101; and for the small interfering RNA (siRNA), CALAA-01. CRLX101 has shown great success in both animal studies and clinical trials. However, it is incapable of achieving targeted delivery. CALAA-01 has demonstrated effectiveness in a phase I clinical trial. However, it suffers from its rapid in vivo clearance. To address the issues of targeting in the anticancer drug delivery system and the short circulation time in the siRNA delivery system, we have created a new delivery platform involving the use of boronic acid-diol complexation. This thesis is divided into two parts to discuss CPT delivery and siRNA delivery separately.
\r\n\r\nIn Part I, the targeted delivery of CPT via boronic acid-diol complexation is described. CPT was conjugated to a copolymer of mucic acid and PEG (MAP) and self-assembled into MAP-CPT nanoparticles. The targeting agent, Herceptin antibody was attached to boronic acid (BA), this was then complexed with the diol-containing MAP to form a targeted nanoparticle carrying ca. 60 CPT, with a 40 nm diameter and a slightly negative surface charge. The attachment of a single Herceptin per nanoparticle was sufficient to enhance cellular uptake of nanoparticles into BT-474, a HER2 overexpressing cell line by 70% compared to the non-targeted version. Nude mice bearing BT-474 xenograft tumors treated with targeted MAP-CPT nanoparticles resulted in all mice revealing complete tumor regression.
\r\n\r\nIn Part II, the boronic acid-diol complexation delivery platform is applied for the delivery of siRNA. First, the CALAA-01 delivery system for siRNA was further characterized and optimized. Then, a copolymer of mucic acid and dimethylsuberimidate (MAD) was synthesized and used in condensing the anionic siRNA into nanoparticles. Nanoparticles were stabilized by placing a surface PEG layer through boronic acid-diol complexation. Targeting was achieved by conjugating the distal end of the BA-PEG with a targeting agent, Herceptin antibody. MAD/siRNA nanoparticles effectively entered cells and demonstrated low cellular toxicity. MAD/siRNA nanoparticles stabilized with nitroPBA-PEG resulted in a diameter of 130 nm with a slightly negative surface charge. Pharmacokinetic studies in mice demonstrated improved circulation compared to CALAA-01.
\r\n\r\n", "doi": "10.7907/NWSP-0Y35", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7083", "collection": "thesis", "collection_id": "7083", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05282012-134754737", "primary_object_url": { "basename": "Culic-Viskota_Jelena_2012_thesis.pdf", "content": "final", "filesize": 31966432, "license": "other", "mime_type": "application/pdf", "url": "/7083/1/Culic-Viskota_Jelena_2012_thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Synthesis and Functionalization of Second Harmonic Generation Nanocrystals and Their Application in Biological Imaging", "author": [ { "family_name": "Culic-Viskota", "given_name": "Jelena", "clpid": "Culic-Viskota-Jelena" } ], "thesis_advisor": [ { "family_name": "Fraser", "given_name": "Scott E.", "clpid": "Fraser-S-E" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Fraser", "given_name": "Scott E.", "clpid": "Fraser-S-E" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Pantazis", "given_name": "Periklis", "clpid": "Pantazis-P" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The discovery and use of fluorescent proteins has been of extreme importance in biological imaging of cells, tissues, and organs. In order to address some of the limitations of fluorescent tags, second harmonic generation can be used. Second harmonic generating nanoprobes allow nontoxic, long-term imaging that, with proper functionalization, can be utilized for biological imaging applications. As a proof of principle, commercial tetragonal barium titanate nanoparticles were functionalized to expose surface amine groups, which could be further modified for a plethora of biological applications. Barium titanate nanoparticles were functionalized for selective targeting of tissue sections, biorthogonal linkages and for nonspecific long-term imaging using biocompatible polymers enabling the study of cells as they differentiate during zebrafish development. Since the commercial barium titanate nanoparticles do not have a narrow size distribution, which limits the application of such nanoprobes, synthesis of monodisperse nanocrystals was attempted.
\r\n\r\nZinc oxide nanocrystals were synthesized by solvothermal methods involving the base hydrolysis of zinc salts in the presence of capping ligands. Different synthesis procedures were investigated based on the properties of the prepared nanoparticles. To prevent nanoparticle aggregation and to achieve good dispersion, a capping agent was chosen that provides a tightly bound shell around the nanoparticles. It was observed that the polymerization of PEG molecules with the organic ligands bound to the surface of zinc oxide provided the most adequate coating for the desired size control and dispersion of the nanocrystals. Exploration of the experimental conditions enabled production of variable size hexagonal zinc oxide nanocrystals, which can be used both as SHG probes and as quantum dots.
", "doi": "10.7907/XFXJ-7987", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:7052", "collection": "thesis", "collection_id": "7052", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05182012-134600511", "primary_object_url": { "basename": "Thesis_Final.pdf", "content": "final", "filesize": 10246787, "license": "other", "mime_type": "application/pdf", "url": "/7052/1/Thesis_Final.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Targeting Tumors and the Kidney with siRNA Nanoparticles and Evaluation of Extracellular MicroRNA-based Methodologies to Track Their Activity", "author": [ { "family_name": "Zuckerman", "given_name": "Jonathan Eric", "clpid": "Zuckerman-Jonathan-Eric" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Heath", "given_name": "James R.", "clpid": "Heath-J-R" }, { "family_name": "Baltimore", "given_name": "David L.", "clpid": "Baltimore-D-L" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-A" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The goal of my thesis work is to discover new ways to enable the use of nanoparticle therapeutics to treat human disease. The work presented here touches on several areas in medicine and is united by a common theme: engineering ways to make, use, and evaluate therapeutics that maximize the benefit to the patient and minimize the harm. I have explored three interrelated strategies to achieve my objectives: (1) the use of targeted-nanoparticle-based therapeutics to deliver therapeutic entities to specific sites in the body, (2) the use of a highly specific type of therapeutic, siRNA, and (3) the evaluation of strategies for using extracellular microRNAs to non invasively monitor therapeutic activity and disease response to that activity.
\r\n\r\nIn Chapter 2, I present the first evidence of targeted-nanoparticle delivery of siRNA to solid tumors following systemic administration to patients. My coworkers and I demonstrate both dose-dependent accumulation of the siRNA nanoparticles and evidence of gene knockdown via the canonical RNAi mechanism.
\r\n\r\nChapters 3 \u2013 5 describe the therapeutic potential of targeted nanoparticles (one version used in the clinic and described in Chapter 2) for: (i) targeting ribonucleotide reductase subunit M2 in human melanoma cell lines (Chapter 3), (ii) Herceptin-targeted nanoparticles containing siRNA against Her2 in Her2(+) breast cancer (Chapter 4), and (iii) siRNA targeting the \u201cundruggable\u201d protein N-Ras for N-Ras mutant melanomas (Chapter 5).
\r\n\r\nChapters 6 \u2013 8 focus on the interaction of nanoparticles with the kidney. Chapter 6 explores a previously unknown phenomenon of size-dependent glomerular accumulation of nanoparticles. In Chapter 7, a new mechanism of clearance for polycation-polymer-based nucleic acid delivery systems is demonstrated, based on interactions between polymer components in the nanoparticle and the anionic surface of the renal filtration barrier, explaining the rapid clearance of these siRNA nanoparticle systems. Chapter 8 illustrates targeted-nanoparticle delivery of siRNA to the kidney.
\r\n\r\nIn Chapter 9, I test the hypothesis that analysis of tumor-secreted microRNAs within patient blood samples can be used as real-time markers of drug pharmacodynamics. Specifically, I focus on efforts to characterize microRNA expression patterns following pharmacologic inhibition of the oncogene BRAF in melanoma cells and their secreted exosomes.
", "doi": "10.7907/P4FF-NQ42", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:6245", "collection": "thesis", "collection_id": "6245", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02162011-153857988", "primary_object_url": { "basename": "thesis.pdf", "content": "final", "filesize": 14305814, "license": "other", "mime_type": "application/pdf", "url": "/6245/1/thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Pharmacological Behavior of Systemically Administered Nanoparticles of Defined Properties: Mechanistic Investigations at the Organ, Tissue, and Cellular Levels", "author": [ { "family_name": "Choi", "given_name": "Chung Hang Jonathan", "clpid": "Choi-Chung-Hang-Jonathan" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Brady", "given_name": "John F.", "clpid": "Brady-J-F" }, { "family_name": "Wang", "given_name": "Zhen-Gang", "clpid": "Wang-Zhen-Gang" }, { "family_name": "Webster", "given_name": "Paul", "clpid": "Webster-P" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The objective of this thesis is to establish design rules for nanoparticle properties that enable their in vivo transport to target destinations. Gold nanoparticles containing surface-engrafted polyethylene glycol (PEG) chains are prepared with controlled physicochemical properties (hydrodynamic size, surface charge, targeting ligand density). Upon systemic injection into mice, the transport of nanoparticles is monitored by blood pharmacokinetics as well as distribution at the organ, tissue, and subcellular levels from the same injection in an individual animal.
\r\n\r\nAt a constant, slightly negative surface charge (ca. -10 mV), most PEGylated gold nanoparticles (PEG-AuNPs) deposit in the liver, spleen, and kidney of normal mice 24 hours after injection. Increasing retention in the liver (Kupffer cells) and spleen correlate positively with increasing nanoparticle diameter over the range of 25-165 nm, largely due to phagocytic uptake. Accumulation in the kidney is size-dependent, but shows a maximum uptake at ca. 75 \u00b1 25 nm that also gives the highest deposition in the mesangium (uptake by mesangial cells).
\r\n\r\nTumor-bearing mice received injections of PEG-AuNPs of near-constant size (ca. 75 nm) and surface charge (ca. -10 mV) but with variable amounts of ligands that target cancer cells (0-144 ligands per nanoparticle). Independent of ligand content, nanoparticles accumulate in the tumor by the enhanced permeation and retention effect to the same magnitude, and adjacent to leukocytes. Nanoparticles only enter cancer cells in significant amounts when they contain targeting ligands above a threshold amount (between 18 and 144 ligands per nanoparticle).
\r\n\r\nMechanistic studies from model nanoparticles provide insights for the delivery of therapeutic nanoparticles. Systemic administrations of targeted, cyclodextrin-based, siRNA-containing nanoparticles are investigated in animals and humans (Phase I clinical trial). A fluorescent chemical stain with exposed adamantane molecules for binding into the cyclodextrin cups of the targeted nanoparticles is created, allowing for the examination of tumor tissue sections from animals and patient biopsies. Results from both animal and human tissues reveal intracellular, dose-dependent accumulation of targeted nanoparticles in cancer cells of the tumor.
", "doi": "10.7907/33C2-FY20", "publication_date": "2011", "thesis_type": "phd", "thesis_year": "2011" }, { "id": "thesis:5287", "collection": "thesis", "collection_id": "5287", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09292009-141737581", "primary_object_url": { "basename": "JRC_Thesis_Full.pdf", "content": "final", "filesize": 1815815, "license": "other", "mime_type": "application/pdf", "url": "/5287/1/JRC_Thesis_Full.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "I. Synthesis and Testing of a Supported Shilov Oxidation Catalyst and II. Influence of Structural Features on Zeolite Characterization by Constraint Index Testing", "author": [ { "family_name": "Carpenter", "given_name": "John Reeves, III", "clpid": "Carpenter-John-Reeves" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis is composed of two separate projects invoking the use of heterogeneous catalyst, one focused on catalyst development and another on characterization.
\r\n\r\nThe first project concentrates on the development of a heterogeneous catalyst for alkane oxidation utilizing Shilov chemistry. Three techniques for creating heterogeneous catalyst are compared using Wacker oxidation: supported molten salts, supported aqueous phases (SAP), and ion-exchanged zeolites. From the Wacker oxidation study the supported aqueous phase catalyst was identified as the best potential method for developing a Shilov oxidation catalyst.
\r\n\r\nInitial work focused on oxidation of ethanesulfonate loaded onto the SAP catalyst. Similar turnovers were achieved on the SAP catalyst as have been seen in the homogeneous system. The reaction parameters of liquid loading, oxygen pressure, reactant concentration, copper (II) chloride concentration, and acid addition were investigated. While the SAP catalyst was successful in the oxidation of ethanesulfonate, attempts to perform ethane oxidation in a flow system were not. The loss of chloride ions is believed to lead to the deactivation.
\r\n\r\nThe second project investigates anomalous Constraint Index (CI) results for zeolites containing cages that are relatively larger than their pore opening. The CI test utilizes the competitive cracking of 3-methylpentane and n-hexane to classify structures as having small, medium, or large pores. However, structures like SSZ-23, SSZ-25, SSZ-28 and SSZ-35 with these large cages have CI results consistent with a larger pore classification than the pores in them.
\r\n\r\nIncomplete hemi-cages on the external surface may provide a nonselective active site that would result in lower CI results. This work looks at this possibility by comparing SSZ-25 and SSZ-35 with ZSM-5 and BEA* that are normally behaving medium- and large-pore structures respectively. The surface is passivated by a dealumination treatment and the CI test is compared on the parent and treated samples. No evidence of activity on the external surface having an influence on the CI test is observed. Several techniques are also used to further investigate accessibility. Finally we observed that for structures with multiple distinct features, different fouling rates in each feature may result in observable changes in the CI value over time.
\r\n", "doi": "10.7907/WGZA-R541", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:5294", "collection": "thesis", "collection_id": "5294", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10082009-183206738", "primary_object_url": { "basename": "Thesis.pdf", "content": "final", "filesize": 4068185, "license": "other", "mime_type": "application/pdf", "url": "/5294/12/Thesis.pdf", "version": "v8.0.0" }, "type": "thesis", "title": "I. Development of Facile Route to Fluoride-Mediated, Pure-Silica Zeolite Thin Films. II. Removal of Structure-Directing Agents from Molecular Sieves via the Use of Photolabile Structure-Directing Agents", "author": [ { "family_name": "Hunt", "given_name": "Heather Kristine", "orcid": "0000-0001-8412-2774", "clpid": "Hunt-Heather-Kristine" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Greer", "given_name": "Julia R.", "clpid": "Greer-J-R" }, { "family_name": "Yan", "given_name": "Yushan", "clpid": "Yan-Yushan" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis consists of two projects related to the development of new routes to zeolite films. In an effort to expand the known library of pure-silica zeolites accessible in planar conformation, Part I details the development of a new synthetic technique, the vapor phase transport of fluoride, to produce pure-silica zeolite films with the LTA, CHA, STT, ITW and \u2013SVR topologies. The films are characterized by X-ray diffraction, field emission scanning electron microscopy, X-ray energy dispersive analyses, and mechanical testing. Such pure-silica zeolite films could be useful in a variety of applications, due to their porosity, crystallinity, and general stability. For example, these materials could be employed as low dielectric constant materials, which are needed for microprocessors as the feature size is continually reduced. Upon investigation of the aforementioned zeolite powders and films, we find that the materials with the LTA topology have the lowest dielectric constant of all the pure-silica zeolites. Additionally, all the zeolites investigated, except STT, give k-values lower than predicted from their structures using the Bruggeman effective medium model, which has been commonly employed and found able to predict dielectric constants of amorphous silicas.
\r\n\r\nThe second part of this thesis presents the development of an alternative method to thermal combustion to remove organics from zeolite pores, which can degrade zeolite films, using a photolabile structure-directing agent that can be removed from the zeolite pore space using UV photolysis. Here, the synthesis, photocleavage, and structure-directing ability of two different photolabile molecules (8,8-dimethyl-2-(2-nitrophenyl)-1,4-dioxa-8-azoniaspiro[4.5]decane hydroxide (P-SDA 1) and 1-(2-nitrobenzyl)-1H-imidazole (P-SDA 2)), are presented and discussed. Cleavage of the photolytic P-SDA 1 is demonstrated in a homogeneous solution, and intercalated into a dealuminated zeolite FAU. The structure-directing ability of P-SDA 1 is evaluated via attempts to synthesize silicate and aluminosilicate zeolites, resulting in the formation of amorphous and layered materials. The structure-directing ability of P-SDA 2 is evaluated via attempts to produce aluminophosphate zeolites, resulting in several unknown crystalline phases, in addition to dense and hydrated phases. Lastly, complete photocleavage of P-SDA 2 within the crystalline, aluminophosphate materials is also demonstrated. \r\n
", "doi": "10.7907/P09Y-2K69", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:5250", "collection": "thesis", "collection_id": "5250", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09042009-115118", "primary_object_url": { "basename": "BMackThesis.pdf", "content": "final", "filesize": 2034398, "license": "other", "mime_type": "application/pdf", "url": "/5250/1/BMackThesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Biodegradable Filaments for Controlled Ophthalmic Drug Delivery", "author": [ { "family_name": "Mack", "given_name": "Brendan Cahill", "clpid": "Mack-Brendan-Cahill" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Kornfield", "given_name": "Julia A.", "clpid": "Kornfield-J-A" }, { "family_name": "Wright", "given_name": "Kenneth", "clpid": "Wright-K" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The focus of this thesis is the wet-spinning, in-vitro characterization, and in-vivo implantation of drug loaded filaments for ophthalmic, controlled-release applications. Filaments of ca. 200-300 micrometers in diameter are comprised of the copolymer poly(d,l-lactide-co-glycolide), with various lactide to glycolide ratios, and either the antibiotic levofloxacin or the steroid dexamethasone. The objective of this work is to develop implantable filaments that can provide long release of drugs in the eye and then dissolve in order to replace eye drops, since poor patient compliance can limit the utility of drops.
\r\n\r\nFilament formation by wet-spinning is examined in Chapter 2. Mass transfer during filament coagulation is experimentally probed. The experimental plan explores the effect of drug on the mass flux of solvent and antisolvent. Drug retention during extrusion is examined in the context of mass transport, as well as solid-state and solution-state thermodynamics. Chapter 3 presents data that show how the composition of the filaments affects the thermal, mechanical, and release properties. By manipulating various aspects of filament formulation (drug content, polymer type, etc.), release rate and mechanical properties can be greatly changed. The development of an in-vivo model (rabbit) to verify in-vitro results is described in Chapter 4. Drug release into the tear film and mechanical stability are determined for one filament using three different implantation techniques. Large exposed sections of filament are necessary for drug release into the tear fluid and filament ends must be secured for in-vivo mechanical stability. In-vivo results correlate well to in-vitro results for both drug release and mechanical life span. A method of combining the properties of different single component filaments through side-by-side multicomponent wet-spinning is described in Chapter 5. Single component properties are maintained by this method, so mechanical and release properties of various monocomponent filaments described in Chapter 3 can be combined into a single filament. This thesis shows that wet-spinning is a versatile method of producing drug loaded filaments with various drug encapsulation and release properties, and that these filaments are well suited for ophthalmic controlled release applications.
\r\n", "doi": "10.7907/NFRZ-BY29", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:2120", "collection": "thesis", "collection_id": "2120", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05262009-145437", "primary_object_url": { "basename": "FinalThesisDocumentIII.pdf", "content": "final", "filesize": 9966032, "license": "other", "mime_type": "application/pdf", "url": "/2120/1/FinalThesisDocumentIII.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "I. Synthesis and Proton Conductivity Studies of Mesostructured Organosilicates and Bitriazole-Polymer Composites. II. Targeted Nanoparticles for siRNA Delivery", "author": [ { "family_name": "Alabi", "given_name": "Christopher Akinleye", "orcid": "0000-0003-2654-018X", "clpid": "Alabi-Christopher-Akinleye" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Grubbs", "given_name": "Robert H.", "clpid": "Grubbs-R-H" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Goddard", "given_name": "William A., III", "clpid": "Goddard-W-A-III" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The underlying theme of the research outlined in both parts of this report is centered on the ability to use synthetic design as a probe to investigate and answer fundamental mechanistic questions in an effort to improve the function of materials employed in energy and biological research. Specifically in the field of energy research, we have designed a new strategy aimed at improving the proton conductivity of organically modified silica-based polymer electrolyte membranes for use in direct methanol fuel cells. Our design involves the incorporation of the desired organic functional group into a siloxane-modified polymerizable surfactant that can be used in mesoporous silicate synthesis. This approach takes advantage of the silicate assembly mechanism, which places surfactants exclusively within the pores of the silicate at high loadings. The desired functional group is revealed upon selective cleavage after hydrothermal silicate synthesis. We have used this approach to synthesize organosilicates with different sized organic groups displaying high organic acid densities and have studied their proton conductivity under fully hydrated conditions. Under these conditions, structural diffusion via a percolated water network is the dominant mechanism of proton transport.
\r\n\r\nWith regards to membranes for use in hydrogen fuel cells that operate best at temperatures above the dew point of water, the need for an alternative to water as the proton conducting medium is desired. Towards this end, we designed a new nitrogen-containing heterocycle (NCH), 4,4-1H-1H-bi-1,2,3-triazole (bitriazole) capable of mimicking water in the solid state and have investigated its ability to conduct protons in the presence of polyethylene oxides under anhydrous conditions. With numerous chemical tools at our disposal, we probed the mechanism of proton conduction and confirmed the bitriazole proton to be the source of anhydrous proton conductivity. Our data suggests structural diffusion as the dominant transport mechanism via synergistic interactions between bitriazole and polyethylene oxides in the polymer-rich region of the composite material that is encapsulated by a crystalline nonconductive bitriazole framework.
\r\n\r\nIn the second part of this report, we shift our focus to the investigation of antibody-mediated targeting, using our well-established cyclodextrin polycation (CDP) nanoparticles containing therapeutic oligonuleotides, to epitopes expressed at the surface of cancer cells as a means of increasing site-specific therapeutic delivery. To do this, we synthesized fragments of anti-CD20 (rituximab) and conjugated them to flexible poly(ethylene glycol) (PEG) linkers with terminal adamantane groups that can interact with the cyclodextrins on the surface of the CDP nanoparticle via the formation of an inclusion complex. With the PEGylated antibody fragments in hand, we investigate, via a B-cell lymphoma model, the binding characteristics of the targeting ligands as well as their effect on the binding, internalization, and efficacy of the targeted CDP-nucleic acid therapeutic nanoparticles.
\r\n", "doi": "10.7907/9SNH-2A91", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:2412", "collection": "thesis", "collection_id": "2412", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06022009-100039", "primary_object_url": { "basename": "RHA_Thesis_Complete.pdf", "content": "final", "filesize": 4095228, "license": "other", "mime_type": "application/pdf", "url": "/2412/7/RHA_Thesis_Complete.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Molecular Sieve Synthesis Using Imidazolium Structure Directing Agents", "author": [ { "family_name": "Archer", "given_name": "Raymond Humphrey", "clpid": "Archer-Raymond-Humphrey" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The synthesis of high-silica molecular sieve SSZ-70 is investigated through a guest/host study of imidazolium structure directing agents (SDAs). The original borosilicate synthesis is extended to pure-silica and aluminosilicate compositions using six imidazolium SDAs. Physical characterization using powder X-ray diffraction (XRD), 29Si solid-state NMR, electron microscopy, thermogravimetric analysis, and nitrogen adsorption shows SSZ-70 to be layered with similarity to MCM-22 (MWW). Aluminum-containing SSZ-70 is evaluated for catalytic activity using the constraint index (CI) test and shows a similar cracking rate to SSZ-25 (MWW structure). Distinct differences in CI as a function of time on stream are observed between MWW and SSZ-70 materials. Additional molecular sieve phases observed in this guest/host study included Theta-1 (TON), ZSM-5 (MFI), ZSM-23 (MTT), ZSM-12 (MTW), Beta, Mordenite (MOR), CIT-5 (CFI), SSZ-16 (AFX), and SSZ-35 (STF).
\r\n\r\nAttempts to synthesize Beta enriched in chiral polymorph A are investigated in a second guest/host study using five chiral imidazolium SDAs. Two SDAs successfully gave Beta, but no enrichment in polymorph A is observed. The remaining SDAs do not direct the formation of any molecular sieve phases. Molecular modeling indicates both SDAs occupy the straight [100]/[010] 12 membered ring (MR) pores of Beta. In this configuration, no chirality could be projected across the [001] fault planes and this offers an explanation for not observing enrichment. Modeling shows careful consideration must be given to efficiently filling the entire void volume when large SDAs are used. Additional molecular sieve phases observed in the guest/host study are EU-1 (EUO) and MOR.
\r\n\r\nFinally, attempts to synthesize novel materials using supramolecular SDAs are described. Supramolecular SDAs are created through adamantyl/beta-cyclodextrin inclusion complex formation. Both 2:1 and 1:1 inclusion complex stoichiometries are attempted. Significant cyclodextrin degradation occurs at temperatures above 90\u00b0C and no structure-directing effect can be attributed to the cyclodextrin. Molecular sieve phases observed in the study are SSZ-16 (AFX), MOR, B-SSZ-13 (CHA), VPI-8 (VET), and SSZ-24 (AFI).
\r\n", "doi": "10.7907/GJT6-1C73", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:2179", "collection": "thesis", "collection_id": "2179", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05272009-144416", "primary_object_url": { "basename": "Thesis_V3.pdf", "content": "final", "filesize": 3615450, "license": "other", "mime_type": "application/pdf", "url": "/2179/1/Thesis_V3.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Proton and Ion Conductivity in Microporous Materials", "author": [ { "family_name": "McKeen", "given_name": "John Charles", "clpid": "McKeen-John-Charles" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Giapis", "given_name": "Konstantinos P.", "clpid": "Giapis-K-P" }, { "family_name": "Yazami", "given_name": "Rachid", "clpid": "Yazami-R" }, { "family_name": "Yan", "given_name": "Yushan", "clpid": "Yan-Yushan" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Two separate but related investigations on proton and ion conductivity in microporous materials are presented. In the first study, the effect of hydroxyl group density on the proton conductivity in a family of sulfonic-acid functionalized microporous materials with the *BEA framework topology is investigated. Pure silica, aryl sulfonic acid-functionalized microporous materials are synthesized with high concentration of hydroxyl groups from tetraethylammonium hydroxide and aluminum-containing gels and by post synthetic modification of zinc containing CIT-6, and they exhibit proton conductivities of ~5*10\u207b\u00b3 S/cm. Pure-silica materials with nearly defect free structures (low hydroxyl group density) are synthesized from tetraethylammonium fluoride containing gels and by post synthetic modification of CIT-6, and exhibit proton conductivities an order of magnitude lower, ~5 x 10\u207b\u2074 S/cm, than the samples with a high \u2013OH density. Propyl sulfonic acid, ethyl phosphoric acid, and carboxylic acid containing pure-silica zeolite beta, MCM-41, and MCM-48 are also prepared and investigated for use as solid proton conductors. Strong acids are necessary for fast proton transport in hydrated systems. The proton conductivities of the functionalized solids decrease accordingly with the strength of the organic acids in solutions, and little difference is observed between microporous and mesoporous solids when functionalized to the same level.
\r\n\r\nIn the second study, the ion conducting properties of the microporous, zincosilicate VPI-9 (Si/Zn = 4.0) containing the alkali cations Li\u207a, Na\u207a, K\u207a, Rb\u207a, and Cs\u207a, and the alkaline earth cations Mg\u00b2\u207a, Ca\u00b2\u207a, and Sr\u00b2\u207a are studied using impedance spectroscopy. Monovalent cation exchanged samples Li- and Na-VPI-9 lose X-ray crystallinity upon vacuum dehydration at 450 \u00b0C, while K-, Rb-, and Cs-VPI-9 remain crystalline and exhibit conductivities of 1.7 x 10\u207b\u2074, 3.5 x 10\u207b\u2074, and 4.9 x 10\u2074 S/cm, respectively, at 450 \u00b0C in vacuum. While K-VPI-9 is less conductive than K-X, Rb- and Cs-VPI-9 are more conductive than corresponding zeolite X samples. Divalent cation exchanged sample Mg-VPI-9 also loses X-ray crystallinity, while Ca-, and Sr-VPI-9 remain crystalline and exhibit conductivities of 2.3 x 10\u207b\u2076 S/cm and 7.7 x 10\u2077 S/cm, respectively, at 450 \u00b0C, greatly exceeding the conductivity of correspondingly divalent exchanged zeolite X materials. Dense, crystalline zincosilicate samples with the compositions K\u2082ZnSixO\u2082(x=1) (x = 2 - 5), Rb\u2082ZnSi\u2085O\u2081\u2082, and Cs\u2082ZnSi\u2085O\u2081\u2082 are also prepared and exhibit much lower conductivities than their microporous counterparts.
\r\n", "doi": "10.7907/N0GH-3B50", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:1503", "collection": "thesis", "collection_id": "1503", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-04252008-104916", "primary_object_url": { "basename": "Eric_Margelefsky-thesis-2008.pdf", "content": "final", "filesize": 970511, "license": "other", "mime_type": "application/pdf", "url": "/1503/24/Eric_Margelefsky-thesis-2008.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Cooperative Catalysis by Bifunctionalized Mesoporous Silica", "author": [ { "family_name": "Margelefsky", "given_name": "Eric Louis", "clpid": "Margelefsky-Eric-Louis" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The objective of my work was to prepare heterogeneous catalysts that can perform cooperative catalysis. Cooperative catalysis occurs when the presence of two or more functional groups provide an acceleration of a chemical reaction beyond what is possible when either of the two species is used independently. New catalytic materials were synthesized by functionalizing mesoporous silica (SBA-15) with two different functional groups with the groups distributed either randomly or arranged into heterodimeric pairs. The dependence of catalytic activity and selectivity on the surface arrangement (random vs. paired, distance between paired species) was investigated for several different condensation reactions.
\r\n\r\nCatalysts featuring both sulfonic acid and thiol groups were investigated for the synthesis of various bisphenols. Paired alkylsulfonic acid/thiol catalysts outperformed randomly-distributed catalysts in the synthesis of bisphenol A and bisphenol Z. The distance between the two groups in the acid/thiol pair was varied and the activity and selectivity were found to diminish rapidly as the acid/thiol distance grows. Paired arylsulfonic acid/thiol catalysts outperformed randomly-distributed catalysts in the synthesis of bisphenol Z, whereas the synthesis of bisphenol A was insensitive to spatial arrangement.
\r\n\r\nThe second reaction investigated was the aldol reaction in order to investigate the possibility of acid/base cooperativity. A catalyst containing alkylsulfonic acid and primary amines grouped into pairs were generated by opening surface sultone rings with ammonia. This material was catalytically inactive in the aldol reaction due to acid/base neutralization, whereas randomly-distributed acid-base materials exhibit good catalytic activity. Primary amine/carboxylic acid cooperativity was also investigated, both with homogeneous amino acids and bifunctional heterogeneous silicas. While amine/acid cooperativity was conclusively demonstrated with the homogeneous catalysts, in the heterogeneous case the cooperativity due to surface silanol groups actually overshadowed the effect of the carboxylic acids.
\r\n\r\nThe results obtained provide evidence that the spatial arrangement of disparate functional groups on the surface of a heterogeneous catalyst can have profound effects on the activity and selectivity of the catalyst.
\r\n", "doi": "10.7907/9FET-BR51", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:695", "collection": "thesis", "collection_id": "695", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-02212007-101608", "primary_object_url": { "basename": "zeidanthesis-PDF.pdf", "content": "final", "filesize": 5631864, "license": "other", "mime_type": "application/pdf", "url": "/695/1/zeidanthesis-PDF.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Design of New Multifunctional Materials", "author": [ { "family_name": "Zeidan", "given_name": "Ryan K.", "clpid": "Zeidan-Ryan-K" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Grubbs", "given_name": "Robert H.", "clpid": "Grubbs-R-H" }, { "family_name": "Gray", "given_name": "Harry B.", "clpid": "Gray-H-B" }, { "family_name": "Peters", "given_name": "Jonas C.", "clpid": "Peters-J-C" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Research in areas of science and technology critical to society, such as energy, medicine, electronics, protective equipment, and consumer goods relies on the ability to create new materials with desirable properties. The diversity in the properties of these materials is enormous. An important factor in the quest for developing exciting new materials is the ability to use synthetic chemistry to prepare new materials starting from a molecular point of view. It is this approach that I use in this work.
\r\n\r\nI have used principles of synthetic organic chemistry to guide the molecular design of materials that contain a variety of functionalities. This thesis describes three types of designed functional materials. First, new heterogeneous catalysts have been prepared that incorporate two organic functional groups in a manner that allows for cooperativity between them in catalyzing organic reactions, giving increases in reaction rates and selectivities. In particular, thiol/sulfonic acid bi-functional mesoporous materials have been prepared that give significant enhancements in reactivity and selectivity towards bisphenol A synthesis. These enhancements arise from interactions between thiol and sulfonic acid sites due to their proximity on the surface of the catalyst. Acid-base bi-functional materials have also been synthesized that exhibit excellent reactivity in the aldol condensation between acetone and 4-nitrobenzaldehyde. These catalysts are particularly important as the acid and base groups are mutually incompatible in solution and provide reactivity not achievable without immobilization on the surface of solids. Second, a method for incorporating traceable and quantifiable labels onto cyclodextrins and cyclodextrin containing polymers has been designed that utilizes the reactivity between the primary alcohols on cyclodextrins and ethylene oxide gas, and allows the cyclodextrins to be labeled for use in animal biodistribution studies. Third, polymers bearing aromatic disulfide groups have been prepared that can be degraded through a dual-trigger mechanism requiring simultaneous photochemical and hydrogen peroxide activation.
", "doi": "10.7907/CK8E-7H82", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:1848", "collection": "thesis", "collection_id": "1848", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05172007-150701", "primary_object_url": { "basename": "Bartlett_Thesis.pdf", "content": "final", "filesize": 14914066, "license": "other", "mime_type": "application/pdf", "url": "/1848/13/Bartlett_Thesis.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "An Engineering Approach to Cancer Therapy Using Systemically Delivered siRNA", "author": [ { "family_name": "Bartlett", "given_name": "Derek William", "clpid": "Bartlett-Derek-William" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Asthagiri", "given_name": "Anand R.", "clpid": "Asthagiri-A-R" }, { "family_name": "Smolke", "given_name": "Christina D.", "clpid": "Smolke-C-D" }, { "family_name": "Rossi", "given_name": "John J.", "clpid": "Rossi-J-J" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The next generation of cancer therapeutics will specifically target processes responsible for the growth and survival of cancer cells. Among the most promising of these molecularly targeted therapeutics are small interfering RNAs (siRNAs). These siRNAs serve as the effectors of RNA interference, a naturally occurring and highly specific mechanism for regulating gene expression through sequence-specific degradation of messenger RNA. While these siRNAs have shown potential in vitro and in preclinical animal models, safe and effective systemic delivery remains one of the greatest challenges hindering their clinical application. This thesis describes an engineering approach to address the challenge of systemic delivery of siRNAs for cancer therapy.
\r\n\r\nAnalysis of the kinetics of siRNA-mediated gene silencing reveals that gene inhibition by unmodified siRNAs can last for one week in rapidly dividing cells and up to one month in cells with minimal division. Additionally, chemical modifications to enhance siRNA nuclease stability do not prolong intracellular siRNA activity. These data, when used in combination with results from a mathematical model of siRNA function, demonstrate that dilution from cell division, and not intracellular nuclease stability, is the dominant factor governing the duration of gene inhibition by siRNAs.
\r\n\r\nCyclodextrin-containing polycations (CDP) can self-assemble with siRNAs to form nanoparticles with desirable properties for systemic application. Characterization of these nanoparticles demonstrates that they can contain several thousand siRNAs, protect the siRNA payload from nuclease degradation, and be modified with transferrin targeting ligands that show multivalent binding to cell surface receptors.
\r\n\r\nMultimodality in vivo imaging with positron emission tomography (PET) and bioluminescent imaging (BLI) is used to monitor the biodistribution and function of the siRNA nanoparticles after intravenous administration in live mice. Attachment of targeting ligands to the surface of the nanoparticles enhances gene inhibition within the tumor, although the biodistribution and tumor localization are not dependent on the amount of targeting ligand. The targeting ligand likely serves to augment nanoparticle uptake by the tumor cells. When the siRNA nanoparticles are used to deliver therapeutic siRNAs to achieve tumor growth inhibition in disseminated and subcutaneous murine cancer models, schedule-dependent anti-tumor effects are observed.
", "doi": "10.7907/TS5S-FD74", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:3692", "collection": "thesis", "collection_id": "3692", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09222005-123557", "primary_object_url": { "basename": "thesis.pdf", "content": "final", "filesize": 11991748, "license": "other", "mime_type": "application/pdf", "url": "/3692/1/thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Intracellular Considerations in the Development of Non-Viral Nucleic Acid Delivery Systems for Systemic Administration", "author": [ { "family_name": "Mishra", "given_name": "Swaroop", "clpid": "Mishra-Swaroop" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Asthagiri", "given_name": "Anand R.", "clpid": "Asthagiri-A-R" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Webster", "given_name": "Paul", "clpid": "Webster-P" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Non-viral nucleic acid delivery systems must condense nucleic acids into small particles, confer protection from degrading factors in serum and in cells, achieve uptake to targeted cells, direct nucleic acids to appropriate intracellular destinations, release this cargo to permit its action, and exhibit minimal toxicity. The nature of synthetic vectors allows for facile addition of new features, but these modifications can affect performance in unanticipated ways. The effective combination of functional components necessitates a systems approach, where the materials design simultaneously considers the functional environment of and the various barriers to delivery. This thesis facilitates and promotes a systems approach by undertaking development of an improved mechanistic understanding of non-viral gene transfer in vitro, emphasizing elucidation of delivery vehicles\u2019 interactions with and behavior within cells. Special attention is given to the gene delivery behavior of cyclodextrin-containing polycations.
\r\n\r\nSimple modifications to delivery systems can have unanticipated consequences. In Chapter 2, it is shown that greater distance between toxicity-reducing cyclodextrin moieties and amidine charge centers increases both the transfection efficiency and toxicity of a polycationic vector. Chapter 3 shows data demonstrating that modification with poly(ethylene glycol) for extracellular salt-stabilization alters non-viral gene delivery particles\u2019 intracellular trafficking and resulting gene expression. Taken together, the results reveal that non-viral gene delivery vehicles behave as assembled, multifunctional systems.
\r\n\r\npH-buffering components exhibit complex behavior in non-viral gene delivery. In Chapter 4, the intracellular activity of such components is quantified using confocal microscopy. Analysis of chloroquine and its chemical analogues demonstrates in Chapter 5 that chloroquine improves non-viral gene transfer through pH-buffering as well as through enhanced nucleic acid unpackaging and its own interactions with nucleic acids. Chapter 6 gives results that characterize delivery behavior of analogous vectors with and without pH-buffering capacity and show that factors beyond buffering activity contribute to improved transfection efficiency. Collectively, these results emphasize consideration of new system components\u2019 effects on all functions of a non-viral gene delivery system.
\r\n\r\nA systems approach requires comprehensive consideration of the gene delivery process. Chapter 7 reviews current understanding of intracellular barriers to non-viral gene delivery, and Chapter 8 offers recommendations for future work.
\r\n", "doi": "10.7907/7MP8-JJ24", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:2723", "collection": "thesis", "collection_id": "2723", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06252004-101813", "primary_object_url": { "basename": "JFM_Thesis_Complete.pdf", "content": "final", "filesize": 2117681, "license": "other", "mime_type": "application/pdf", "url": "/2723/1/JFM_Thesis_Complete.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Methods for Collection and Processing of Gene Expression Data", "author": [ { "family_name": "Murphy", "given_name": "John Frank", "clpid": "Murphy-John-Frank" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Asthagiri", "given_name": "Anand R.", "orcid": "0000-0002-4925-7523", "clpid": "Asthagiri-A-R" }, { "family_name": "Wold", "given_name": "Barbara J.", "orcid": "0000-0003-3235-8130", "clpid": "Wold-B-J" }, { "family_name": "Tirrell", "given_name": "David A.", "orcid": "0000-0003-3175-4596", "clpid": "Tirrell-D-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Examination of the transcriptional messages encoded in the manifold of mRNA molecules within a cell is a central task of molecular biology and functional genomics. This examination can be broken down into two parts: collection of gene expression data, and analyses of those data. Here, a new method for collecting gene expression data, and two new methods for analyzing those data are presented.
\r\n\r\nA new method for quantifying gene expression denoted as the Mass-spectrometric Analysis of Gene Expression (MAGE) is developed. MAGE relies on novel conjugates of DNA oligonucleotide 30-mers; each unique sequence is conjugated via photolabile linker to an N-substituted glycine oligomer (peptoid) of unique mass. Deuterated bromoacetic acid is incorporated into some peptoids yielding two chemically identical probe conjugates of different molecular weights for each nucleic acid sequence of interest. Mixtures of these probes, along with 3' adjacent biotin-labeled oligonucleotides, are used to interrogate a target mixture of cDNA. Following hybridization, the two adjacent probes are ligated to enhance the specificity of the identification, and to enable the use of a biotin-affinity column for removal of confounding peptoid tags. The resulting mixture is exposed to longwave ultraviolet light to release the peptoid tags, that are quantified using MALDI-TOF mass spectrometry using the isotopically labeled peptoids as internal standards. These individual components of MAGE are demonstrated.
\r\n\r\nA strategy for simplification and visualizing of high-dimensional gene expression data, as well as a strategy for inferring the presence of clusters within those data, is formulated and implemented. In order to visualize high-dimensional gene expression data, principle components analysis is used with subsequent mapping of the data onto an orthogonal set of basis functions known as Andrews curves. This analysis method is demonstrated by visualizing of breast cancer tumor data and yeast sporulation data. In order to cluster gene expression data, the expectation-maximization algorithm is employed to optimize the parameters of a mixture model of Lorentzian distributions. The difference between Lorentzian and Gaussian mixture models is first demonstrated with artificial data, and then applied to yeast sporulation data. The results indicate that mixtures of Lorentzian distributions may have significant utility for gene expression analysis.
\r\n\r\nThe tools demonstrated here offer unique advantages when compared to the current suite of experimental and analytical tools employed by investigators of functional genomics.
\r\n", "doi": "10.7907/8p8e-2147", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:2052", "collection": "thesis", "collection_id": "2052", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05252005-114817", "primary_object_url": { "basename": "heidel_thesis.pdf", "content": "final", "filesize": 4815091, "license": "other", "mime_type": "application/pdf", "url": "/2052/1/heidel_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Targeted, Systemic Non-Viral Delivery of Small Interfering RNA in vivo", "author": [ { "family_name": "Heidel", "given_name": "Jeremy David", "clpid": "Heidel-Jeremy-David" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Asthagiri", "given_name": "Anand R.", "clpid": "Asthagiri-A-R" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Rossi", "given_name": "John J.", "clpid": "Rossi-J-J" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Armed with the complete sequence of the human genome and an ever-increasing array of biological techniques, researchers continue to learn more about the genetic basis of diseases. For two decades, scientists and physicians have been developing therapeutic strategies for treating many diseases at the genetic level, creating the field of \"gene therapy.\" For those diseases caused by loss-of-function mutations in a specific gene, delivery of a wild-type copy of that gene to affected cells can reduce or eliminate the disease phenotype. Viruses, having evolved to be extremely effective at delivering nucleic acids (i.e., their own genes for viral production) to cells, have been modified to include therapeutic genes of interest. While such viral gene therapy vectors are the most efficient vectors developed, concerns about their safety and immunogenicity have prompted many to investigate non-viral vector alternatives. Cationic polymers and lipids have emerged as leading non-viral vector materials. Our laboratory has developed a class of cyclodextrin-containing polycations (CDPs) that condense DNA into complexes that can be endocytosed by cells, achieve expression of their genetic payload in those cells, and may be modified to target particular cell types within an animal.
\r\n\r\nIn the past five years, scientists have discovered a new mechanism for the reduction of gene expression in mammalian cells via sequence-specific cleavage of a particular messenger RNA (mRNA); this phenomenon is known as RNA interference (RNAi). Since RNAi is triggered by nucleic acids (small interfering RNA (siRNA) duplexes), I hypothesized that CDPs may be suitable vectors for the delivery of siRNA. In my thesis work, the safety of synthetic siRNA duplexes is examined both in cultured cells and in vivo. Using a number of different siRNA sequences, two different strains of mice, and three different methods of administration, I fail to observe any cytokine (IL-12 or IFN-a) responses, morphological changes, or alterations in complete blood counts (CBCs) or liver enzyme levels.
\r\n\r\nThe ability of CDP to serve as a delivery vehicle for siRNA is also explored. I demonstrate that CDP/siRNA complexes can be formed that are small enough to be endocytosed, can be modified to ensure stability in physiological fluid, and protect the siRNA payload from serum nuclease degradation. Finally, down-regulation of specific target genes, including genes implicated in disease, is shown in vitro and in mice. An endogenous reporter gene (luciferase) in the livers of transgenic mice is down-regulated by galactosylated CDP/siRNA formulations that target hepatocytes. The level of a chimeric oncogene, EWS-Fli1, is reduced by polyplex formulations in cultured Ewing\u2019s sarcoma cells and by transferrin-targeted formulations in tumor-bearing mice; this in vivo down-regulation corresponds to an inhibition of tumor growth. These results suggest that CDP-containing siRNA formulations have the potential for development into therapeutics.
", "doi": "10.7907/F5AX-3Y24", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:1753", "collection": "thesis", "collection_id": "1753", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05122005-144223", "primary_object_url": { "basename": "Thesisfinal2.pdf", "content": "final", "filesize": 3190119, "license": "other", "mime_type": "application/pdf", "url": "/1753/1/Thesisfinal2.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "A New Strategy for Synthesizing Zeolites and Zeolite-Like Materials", "author": [ { "family_name": "Lee", "given_name": "Hyunjoo", "orcid": "0000-0002-4538-9086", "clpid": "Lee-Hyunjoo" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Zeolite and molecular sieve materials are broadly used as ion-exchangers, adsorbents and catalysts in the chemical industry. Zeolites are typically synthesized by using organic molecules as structure-directing agents (SDA). The SDA should be removed from the pore cavity of the zeolite framework to create microporous void space before the zeolite can be used for further purposes. Porous zeolites have been prepared by calcination, or extraction in very limited cases. However, calcination has several undesired aspects mainly resulted from a high temperature. A combustion-free methodology is developed in this work by using a new concept for the SDAs. An organic molecule that can be easily cleaved into smaller fragments and subsequently recombined into the original molecule by simple treatments can be used as a 'recyclable SDA'. That is, after synthesizing a zeolite using this type of organic molecule as the SDA, the molecule can be fragmented in the pore cavity, and its fragments removed due to their smaller size. The recovered fragments are then recombined into the original SDAs, which can be used for further zeolite syntheses. The cyclic ketal molecule, 8,8-dimethyl-1,4-dioxa-8-azaspiro[4,5]decane, is used here to prove this new methodology. The ketal is fragmented into its corresponding ketone and diol molecules after structure-directing the synthesis of the zeolite, ZSM-5. The fragments are successfully removed by ion-exchange, and the prepared porous ZSM-5 shows equivalent porosity, catalytic activity and shape selectivity as conventional ZSM-5. In some cases, the SDA can be so tightly packed inside the pore cavity that the small reagent molecules required for fragmentation by acid hydrolysis have no access to the pore cavity. Therefore, the original methodology was expanded to provide a solution for this problem by utilizing two different kinds of organic molecules, a SDA and a pore-filling agent (PFA), during the zeolite syntheses. The removal of the PFA by simple extraction generates the necessary space inside the pore cavity for agents necessary for the hydrolysis to transport into the zeolite. Using this methodology, ZSM-5, ZSM-12, VPI-8 and MOR are successfully synthesized with various ketal SDAs whose hydrolysis depends on the hydrophilicity and pore connectivity of the synthesized zeolites.", "doi": "10.7907/N5NX-2T83", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:2006", "collection": "thesis", "collection_id": "2006", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05242005-230657", "primary_object_url": { "basename": "FrontMatter.pdf", "content": "final", "filesize": 391273, "license": "other", "mime_type": "application/pdf", "url": "/2006/2/FrontMatter.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "I. Synthesis, Characterization, and Base Catalysis of Novel Zeolite Supported Super-Basic Materials. II. Oxidative Dehydrogenation of Ethane Over Reduced Heteropolyanion Catalysts", "author": [ { "family_name": "Galownia", "given_name": "Jonathan Michael", "clpid": "Galownia-Jonathan-Michael" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis is composed of two separate and unrelated projects. The first part of this thesis outlines an investigation into the synthesis and characterization of a novel zeolite supported super-base capable of carbon-carbon olefin addition to alkyl aromatics. A zeolite supported basic material capable of such reactions would benefit many fine chemical syntheses, as well as vastly improve the economics associated with production of the high performance thermoplastic polyester polyethylene naphthalate.
\r\n\r\nThe thermal decomposition of alkali\u2014metal azides impregnated in zeolite X is investigated as a novel route to the synthesis of a zeolite supported super-base. Impregnation of the alkali\u2014metal azide precursor is shown to result in azide species occluded within the pores of the zeolite support by using high speed, solid-state 23Na MAS and 2D MQMAS NMR, FTIR, and TGA characterization methods. Addition of alkali\u2014metal azides to the zeolite results in redistribution of the extra-lattice cations in the zeolite framework. Thermal decomposition of impregnated azide species produces further cation redistribution, but no neutral metallic clusters are detected by high speed, solid-state 23Na MAS NMR following thermal activation of the materials. Instead, it is possible that inactive ionic clusters are formed. The thermally activated materials do not promote base catalysis for the isomerization of 1-butene, the ethylation of toluene and o-xylene, and the alkenylation of o-xylene with 1,3-butadiene to produce 5-ortho-tolyl-pent-2-ene (5-OTP). The lack of catalytic activity in the materials is attributed to failure of the materials to form neutral metallic clusters during thermal treatment, possibly due to preferential formation of NMR silent ionic clusters. The formation of neutral metallic clusters is found to be insensitive to synthesis technique and activation procedure. It is concluded that the impregnation of alkali\u2014metal azides in zeolite X does not provide a reliable precursor for the formation of zeolite supported super-basic materials.
\r\n\r\nThe second part of this thesis describes the oxidative dehydrogenation of ethane over partially reduced heteropolyanions. Niobium and pyridine exchanged salts of phosphomolybdic (NbPMo12Pyr) and phosphovanadomolybdic (NbPMo11VPyr) acids are investigated as catalyst precursors to prepare materials for catalyzing the oxidative dehydrogenation of ethane to ethylene and acetic acid at atmospheric pressure. The effects of feed composition, steam flow, temperature, and precursor composition on catalytic activity and selectivity are presented for both ethane and ethylene oxidation. Production of ethylene and acetic acid from ethane using the catalytic materials exceeds that reported in the literature for Mo-V-Nb-Ox systems under atmospheric or elevated pressure. Production of acetic acid from ethylene is also greater than that observed for Mo-V-Nb-Ox systems. Addition of vanadium reduces catalytic activity and selectivity to both ethylene and acetic acid while niobium is essential for the formation of acetic acid from ethane. Other metals such as antimony, iron, and gallium do not provide the same beneficial effect as niobium. Molybdenum in close proximity to niobium is the active site for ethane activation while niobium is directly involved in the transformation of ethylene to acetic acid. A balance of niobium and protonated pyridine is required to produce an active catalyst. Water is found to aid in desorption of acetic acid, thereby limiting deep oxidation to carbon oxides. A reaction scheme is proposed for the production of acetic acid from ethane over the catalytic materials.
", "doi": "10.7907/QZ7V-5W65", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:1202", "collection": "thesis", "collection_id": "1202", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-03302005-120327", "primary_object_url": { "basename": "Popielarski_Final_Submitted_Thesis.pdf", "content": "final", "filesize": 7067218, "license": "other", "mime_type": "application/pdf", "url": "/1202/1/Popielarski_Final_Submitted_Thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "I. Structural Effects of Carbohydrate-Containing Polycations on Gene Delivery. II. Development of a Nanoparticle-Based Model Delivery System to Guide the Rational Design of Gene Delivery to the Liver\r ", "author": [ { "family_name": "Popielarski", "given_name": "Stephen R.", "clpid": "Popielarski-Stephen-R" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Asthagiri", "given_name": "Anand R.", "clpid": "Asthagiri-A-R" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Grubbs", "given_name": "Robert H.", "clpid": "Grubbs-R-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Linear cationic beta-cyclodextrin (b-CD)-based polymers can bind with plasmid DNA to form colloid-sized composite particles that transfect cultured cells. In the first part of this thesis, synthetic variations of the b-CD structure are used to probe structure-function gene delivery properties. The type of cyclodextrin and its functionalization are investigated by synthesizing numerous 3A,3B-dideoxy-3A,3B-diamino-b- and g-CD monomers, which are polymerized with dimethyl suberimidate to yield amidine-based polycations. The nature of the spacer between the CD-ring and the primary amines of each monomer is found to influence both molecular weight and polydispersity of the polycations. When complexed with plasmid DNA, polycations with longer alkyl regions between the CD and the charge centers show increased transfection efficiency and toxicity in BHK-21 cells. More hydrophilic spacers resulted in lower toxicity, and g-CD-based polycations were less toxic than otherwise identical b-CD-based polycations.
\r\n\r\nIn the second part of this thesis, a model delivery system is developed that can mimic the size and surface properties of the cyclodextrin-based gene-delivery particles, and this system is used to define design constraints that should be applied to next generation gene delivery particles targeted to the liver. Gal-50 and Gal-140 are galactosylated 50 nm and 140 nm nanoparticles that have the same surface galactose density, while MeO-50 and MeO-140 are methoxy-terminated 50 nm and 140 nm nanoparticles. All four particles have the same surface charge and resist aggregation in serum.
\r\n\r\nIn freshly isolated hepatocytes, Gal-50 nanoparticles are taken up to a greater extent than are MeO-50, but both 50 nm beads are taken up to a much greater extent than are either of the 140 nm nanoparticles. TEM and immunohistochemistry confirm that Gal-140 nanoparticles are primarily internalized by Kupffer cells, though isolated examples of a few Gal-140 in hepatocytes can also be found. On the other hand, Gal-50 nanoparticles are overwhelmingly found in vesicles throughout the cytoplasm of hepatocytes, with only isolated examples of Kupffer cell uptake. As such, it is clear that slightly anionic, galactose-PEGylated nanoparticles should be about 50 nm in diameter to preferentially target hepatocytes while they should be about 140 nm in diameter to selectively target Kupffer cells.
", "doi": "10.7907/rskv-rf12", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:2039", "collection": "thesis", "collection_id": "2039", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05252004-102344", "primary_object_url": { "basename": "aw_master.pdf", "content": "final", "filesize": 3377734, "license": "other", "mime_type": "application/pdf", "url": "/2039/1/aw_master.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "I. Synthesis, Characterization, and Base Catalysis of Organic-Functionalized Molecular Sieves. II. Selective Oxidation of Ethane via Heteropolyanion-Containing Solid Catalysts", "author": [ { "family_name": "Wight", "given_name": "Andrea Palmisano", "clpid": "Wight-Andrea-Palmisano" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Gavalas", "given_name": "George R.", "clpid": "Gavalas-G-R" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis is composed of two separate and unrelated projects. The first project examines the preparation of functional groups that can serve as immobilized bases in molecular sieves. Many heterogeneous, base catalysts are not able to promote diverse reaction types that require strong bases as catalysts. Additionally, some of the stronger solid base catalysts are sensitive to carbon dioxide and moisture in air and therefore are not easily suitable for recycling. Organic-functionalized molecular sieves possess an organic moiety within the pore space of a molecular sieve by incorporation of an organosilane directly into the synthesis gel of the molecular sieve. Previous work reported by Davis and co-workers demonstrated the incorporation of an acid site in zeolite Beta (*BEA type) and its use in shape-selective acid catalysis.
\r\n\r\nHere, a phosphonium functionality is prepared from halogen-containing alkyl groups in *BEA to allow the incorporation of a strong base (OH-) within the molecular sieve for base catalysis. Characterization of the phosphonium-containing material prepared is accomplished. Shape-selective chemical reactions and ion-exchanges are presented, and the results of these experiments suggest that the functional groups are located within the molecular sieve pore space, although the exact structure of these moieties is not conclusively obtained.
\r\n\r\nThe second part of this thesis examines the use of niobium- and pyridine-exchanged heteropolyanions as catalyst precursors for the selective oxidation of light alkanes with dioxygen. The versatility of many oxidation catalysts is limited, thereby restricting potential usefulness. Alkenes, typically used as feedstock, are becoming costly as their demand for use in many other industrial processes increases. The use of light alkanes as reactants for selective oxidation would allow one to take advantage of an under-utilized and relatively inexpensive feedstock for selective oxidation.
\r\n\r\nNiobium- and pyridine-exchanged heteropolyanions (HPAs) have been shown to produce highly active and selective catalysts for the oxidation of propane and n-butane to acrylic acid and maleic acid, respectively, by Davis and co-workers. Specifically, molybdophosphoric acid and molybdovanadophosphoric acid were exchanged with niobium oxalate and pyridine to produce the exchanged HPAs (denoted NbPMo12pyr and NbPMo11Vpyr, respectively). Preliminary work in these studies indicates that the exchanged HPAs may also be effective for the oxidation of ethane to acetic acid. The application of this catalyst system to the selective oxidation of ethane to acetic acid and ethylene is explored here.
\r\n\r\nThe exchanged heteropolyanions give higher ethane conversion at elevated pressures (230 psig and 280oC) but better yields at atmospheric pressure and 380oC. Variations of steam flow rates or reaction temperatures are not observed to improve acetic acid space-time-yield (STY). Lower gas-hourly-space-velocity (GHSV) causes the ethylene and acetic acid to over-oxidize to COx. The maximum STY of acetic acid using NbPMo12pyr is 0.021 mmol/min/g catalyst at 380oC, 0 psig, and flows of 16: 8: 16: 20 mL/min of ethane: oxygen: helium: steam.
\r\n\r\nAt elevated pressure (230 psig) the addition of vanadium into the Keggin ion precursor is shown to decrease conversion (from 6.0% to 2.2%) but improve selectivity to ethylene (from 23.2% to 46.8%). The formation of acetic acid is not affected (0.002 mmol/min/g catalyst). At atmospheric pressure the addition of vanadium into the Keggin precursor does have a favorable affect on the acetic acid formation. NbPMo11Vpyr is shown to have a maximum acetic acid production of 0.062 mmol/min/g catalyst at 380oC, 0 psig, and flows of 16: 8: 16: 20 mL/min of ethane: oxygen: helium: steam.
\r\n\r\nThe addition of both Nb and pyridine to the HPA is crucial for active catalyst formation, for reactions both at atmospheric pressure and 230 psig. Substitution of other metals for Nb does not yield materials that give significant ethane conversion.
\r\n\r\nHigher ethane/oxygen ratios increase the selectivity to acetic acid over NbPMo12pyr at atmospheric pressure. The oxidation of ethylene over NbPMo12pyr is accomplished, and the results indicate that acetic acid is formed from ethylene during the oxidation of ethane. D2O is substituted as the source of steam, and the observation that acetic acid contains deuterium shows that the steam in the feed is involved in its formation.
\r\n\r\nThe data obtained from NbPMo11Vpyr suggest that this precursor can give a catalyst that is active and selective for producing ethylene and acetic acid from ethane and dioxygen. Further experimentation is necessary to optimize performance.
", "doi": "10.7907/DCKV-0007", "publication_date": "2004", "thesis_type": "phd", "thesis_year": "2004" }, { "id": "thesis:5495", "collection": "thesis", "collection_id": "5495", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01062010-084034470", "primary_object_url": { "basename": "Piccione_pm_2002.pdf", "content": "final", "filesize": 8240658, "license": "other", "mime_type": "application/pdf", "url": "/5495/1/Piccione_pm_2002.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Thermodynamics of Formation of Molecular Sieves", "author": [ { "family_name": "Piccione", "given_name": "Patrick Manuel", "clpid": "Piccione-Patrick-Manuel" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Gavalas", "given_name": "George R.", "orcid": "0000-0003-1468-6835", "clpid": "Gavalas-G-R" }, { "family_name": "Navrotsky", "given_name": "Alexandra", "orcid": "0000-0002-3260-0364", "clpid": "Navrotsky-Alexandra" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Molecular sieves, porous, crystalline frameworks with pore sizes of molecular dimensions, are of great industrial importance as detergents, catalysts and absorbants. Despite their technological importance, the syntheses of these materials are still not well understood and typically rely on extensive series of trials to produce new framework structures.
\r\n\r\nThermodynamic investigations are undertaken to better understand the energetic differences amongst molecular sieve frameworks and the mechanisms and interactions important in molecular sieve self-assembly. The enthalpies relative to quartz at 298.15 K are determined by high-temperature solution calorimetry for a collection of calcined pure-silica molecular sieves with diverse structural features. Si0_2 molecular sieves are shown to be only modestly (6.8-14.4 kJ/mol) metastable with respect to quartz. A strong linear correlation between enthalpy and molar volume is observed, implying that the overall packing quality determines the relative enthalpies of Si0_2 molecular sieves. Silanol (Si-O-H) defect sites lead to an additional destabilization of no more than 2.4 kJ/mol. The entropies of four pure-silica molecular sieves spanning the entire range of molar volumes available to Si0_2 frameworks are determined by the integration of heat capacity measurements from 5 to 400 K. The entropies of these structures are almost identical (3.2-4.2 J\u2219K^(-1)\u2219mol^(-1) above quartz), hence the empty pore volume and cages do not contribute appreciably to the vibrational density of states. The enthalpy and entropy data are combined to calculate the Gibbs free energies of transition from quartz to eight other silica polymorphs, including four molecular sieves as well as silica glass. At typical synthesis conditions, the available thermal energy is RT = 3.5 kJ/mol. The molecular sieve Gibbs free energies are only slightly larger than RT at 5.5-12.6 kJ/mol above quartz and lie in the same energetic region as the amorphous precursors used for molecular sieve preparation. There are therefore no significant thermodynamic barriers to transformations among silica polymorphs. Thus the role of SDA in molecular sieve syntheses is not the stabilization of otherwise very unstable phases.
\r\n\r\nInteraction enthalpies between inorganic frameworks and organic SDAs are measured by HF solution calorimetry for six molecular sieve/SDA pairs. The enthalpies are only moderately exothermic (-1.1 to -5.9 kJ/mol SiO_2), as expected if the predominant interactions are van der Waals contacts between the hydrophobic silica frameworks and the hydrocarbon portions of the SDAs. Interaction entropies can be estimated for three framework/SDA pairs, and, when used in combination with the interaction enthalpies, allow the calculation of the Gibbs free energies of interaction between these three inorganic/organic pairs. The latter values range from -2.0 to -5.4 kJ/mol SiO_2, smaller in magnitude than twice the available thermal energy at molecular sieve synthesis temperatures. This energy range is comparable to the range observed for the molecular sieve frameworks alone, showing that energetics of both the frameworks and of the molecular sieve/SDA interactions must be considered in order to adequately describe molecular sieve synthesis. The energetics of the synthesis of molecular sieves (considering all components present in the synthesis mixture) are examined here and also reveal small differences between various molecular sieve/SDA combinations. The energetic contribution of the effective dilution experienced by the SDA upon occlusion is similar in magnitude to the other energetic effects. The strong selectivity of organic SDAs experimentally observed in the face of the comparatively small energetic differences suggests that kinetic factors dominate in molecular sieve preparation.
", "doi": "10.7907/TQVE-FW28", "publication_date": "2002", "thesis_type": "phd", "thesis_year": "2002" }, { "id": "thesis:6376", "collection": "thesis", "collection_id": "6376", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05052011-134334164", "primary_object_url": { "basename": "Sundaresan_v_2002.pdf", "content": "final", "filesize": 78961721, "license": "other", "mime_type": "application/pdf", "url": "/6376/1/Sundaresan_v_2002.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Selective Molecular Recognition in Imprinted Polymeric Adsorbents and in Biological Macromolecules", "author": [ { "family_name": "Sundaresan", "given_name": "Vidyasankar", "clpid": "Sundaresan-Vidyasankar" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Kornfield", "given_name": "Julia A.", "orcid": "0000-0001-6746-8634", "clpid": "Kornfield-J-A" }, { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" }, { "family_name": "Tirrell", "given_name": "David A.", "orcid": "0000-0003-3175-4596", "clpid": "Tirrell-D-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis describes the synthesis and use of molecularly imprinted polymeric adsorbents for use in ligand-exchange chromatographic separations of structurally similar substrates. A general model of stereo selectivity is also described, which can be applied both to chromatographic adsorbents and to biological receptors.
\r\n\r\nCrosslinking polymerization of trimethylolpropane trimethacrylate (TRIM), under controlled conditions yields macroporous polymers bearing surface-accessible unpolymerized methacrylate residues. These residues have been utilized for copolymerization with different functional monomers to obtain composite polymer matrices with surface coatings of functional polymer chains. Surface modification has been carried out by molecular imprinting, using ternary Cu^(2+) complexes of [N-(4-vinylbenzyl)imino]diacetate and bisimidazole templates, with ethylene glycol dimethacrylate as comonomer. Selectivity characteristics similar to bulk-copolymerized polymers have been observed. The physicochemical characteristics of these functional polymer matrices have been evaluated by ^(13)C NMR, X-ray photoelectron spectroscopy, IR spectroscopy, and scanning electron microscopy.
\r\n\r\nThe ability of molecular imprinting to impart enantioselectivity to polymeric adsorbents has been studied using Cu^(2+) complexes of the achiral monomer [N-(4-vinylbenzyl)imino]diacetate and \u03b1-amino acids. Crosslinking polymerization with ethylene glycol dimethacrylate as the comonomer yields polymeric adsorbents capable of enantioresolutions of underivatized \u03b1-amino acids. Chromatographic adsorbents have been prepared by grafting the imprinted polymer on to silica particles. The observed enantioselectivity increases corresponding to the size of the side chain of the amino acid used as template, with the best enantioresolutions being obtained for materials imprinted against phenylalanine (~1.65 for D,L-phenylalanine enantioresolution). Adsorbents imprinted for alanine show negligible enantioselectivity. Cross-selectivity patterns towards non-template amino acids have been investigated, and the ability of an amino acid imprinted material to resolve analogous chiral amines has been demonstrated.
\r\n\r\nThe mechanisms underlying enantioselectivity in imprinted polymers are discussed in terms of the three-point interaction model. This model has been extended to a stereocenter-recognition (SR) model for substrates with multiple stereocenters. For N stereocenters in a linear chain, it has been demonstrated that a minimum of N + 2 interactions need to be distributed over all stereocenters, such that three effective interactions exist per stereocenter. The general applicability of the SR model is demonstrated for biological ligand-receptor interactions, by reinterpreting several previous experimental observations.
", "doi": "10.7907/jvev-x884", "publication_date": "2002", "thesis_type": "phd", "thesis_year": "2002" }, { "id": "thesis:17029", "collection": "thesis", "collection_id": "17029", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02262025-185839420", "primary_object_url": { "basename": "Main_RM_2002.pdf", "content": "final", "filesize": 15188630, "license": "other", "mime_type": "application/pdf", "url": "/17029/1/Main_RM_2002.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Studies Towards the Development of New Catalysts for Methane Conversion", "author": [ { "family_name": "Main", "given_name": "Rebekah Mary", "clpid": "Main-Rebekah-Mary" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "In efforts to develop new catalysts for the partial oxidation of methane to\r\nmethanol, studies were focused on developing supported aqueous phase (SAP) catalysts\r\nfor this chemistry. The work can be separated into two main projects. First, steps were\r\ntaken to prepare an organometallic SAP catalyst. A water-soluble sulfonated Pt diimine\r\nspecies has been prepared and supported on controlled-pore glass. The compound was\r\ncharacterized by solid state 13C CP-MAS NMR, and observations were made on the\r\ncompounds behavior. This work is carried out in collaboration with research into\r\nhomogeneous organometallic catalysts, and progress in this area is dependent on the\r\ndevelopment of successful homogeneous catalysts. The second project involves using\r\nplatinum/copper salt catalyst for the hydroxylation of alkanes, where dioxygen is the\r\nultimate oxidant. Several homogeneous reactions were carried out to investigate the\r\nreactivity of this catalyst system in solution. The catalysts were found to successfully\r\nhydroxylate sulfonated alkanes as well as ethane and methane, all with multiple platinum\r\nturnovers. Product characterizations were carried out using 1H NMR and GC/MS.\r\nEfforts were also begun to develop a SAP catalyst with the Pt/Cu system, modeled after\r\nthe SAP Pd/Cu Wacker oxidation catalyst.", "doi": "10.7907/xxcm-zd60", "publication_date": "2002", "thesis_type": "masters", "thesis_year": "2002" }, { "id": "thesis:6184", "collection": "thesis", "collection_id": "6184", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11192010-081828575", "primary_object_url": { "basename": "Hwang_sj_2001.pdf", "content": "final", "filesize": 7869336, "license": "other", "mime_type": "application/pdf", "url": "/6184/1/Hwang_sj_2001.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Rational Design of a New Class of Cyclodextrin-Containing Polymers for Gene Delivery", "author": [ { "family_name": "Hwang", "given_name": "Suzie Jean", "orcid": "0000-0003-1443-4996", "clpid": "Hwang-Suzie-Jean" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Farbstein", "given_name": "Mark", "clpid": "Farbstein-M" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" }, { "family_name": "Tirrell", "given_name": "David A.", "orcid": "0000-0003-3175-4596", "clpid": "Tirrell-D-A" }, { "family_name": "Triche", "given_name": "Timothy", "clpid": "Triche-T" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The transfer of gene therapy from an academic exercise to a clinical setting demands the development of an efficient, biocompatible gene delivery vector. Current non-viral systems suffer from toxicity, low transfection efficiency, and in vivo instability. In this work, a new class of polymers was designed to address these issues. Linear, polyamidine, \u03b2-cyclodextrin (\u03b2CD)-containing polymers (\u03b2CDPs) are synthesized by polymerizing difunctionalized cyclodextrins with other difunctionalized comonomers. The inclusion of \u03b2CD in the backbone of the polyamidine polymers decreases the IC\u2085\u2080s by three orders of magnitude, resulting in a polymer with very low in vitro and in vivo toxicity. The cationic \u03b2CDPs are able to self-assemble with and condense DNA into small particles (100-150 nm in diameter). When formulated at a positive charge, the complexes are readily internalized by nearly all exposed cultured cells.
\r\n\r\nThe transgene expression from the delivered complexes was increased by fine-tuning the \u03b2CDP structure for optimum reporter gene activity and by modifying the polymer to enhance endosomal release. The function of the \u03b2CDPs was found to be highly dependent on the polymer structure; changes in position of the amidine charge centers by a few angstroms resulted in transfection and toxicity differences of one order of magnitude. The highest transfection is achieved with the \u03b2CDP6 polymer, that contains a 2 methylene spacer between the cyclodextrin and amidine group and a 6 methylene spacer between adjacent amidine functionalities. The conjugation of a pH-sensitive moiety, histidine, to \u03b2CDP6 endgroups also increases transgene expression by 20-fold without a change in polymer toxicity. Flow cytometry and confocal microscopy experiments with fluorescently-Iabeled DNA suggest that histidylation of \u03b2CDP6 enhances transfection by buffering the endosomal pH, thereby delaying lysosomal degradation and allowing for more endosome release.
\r\n\r\nThe \u03b2CDP-based particles (\u03b2CD-polyplexes) were modified for in vivo stability by using the ability of cyclodextrins to form inclusion complexes with hydrophobic guest molecules. Various compounds were conjugated to adamantane, a molecule that has a high cyclodextrin association constant. The adamantane conjugates, when added to preformed \u03b2CD-polyplexes, are able to self-assemble with the \u03b2CD-polyplexes without disrupting the polymer/DNA binding interactions. Using this method, \u03b2CD-polyplexes were modified with adamantane-polyethylene glycol (PEG) conjugates. The PEGylated particles were salt stabilized in a PEG length-dependent manner. In a second example, modification of \u03b2CD-polyplexes with anionic peptide-adamantane conjugates prevented non-specific cellular uptake in cultured cells. The assembly of the three components, DNA, \u03b2CDP, and adamantane-based modifer, results in a particle with the potential for achieving systemic, in vivo gene delivery. Finally, a small molecule, fluorescein, was conjugated to adamantane and co-delivered with \u03b2CD-polyplexes to cultured cells, thus demonstrating the possibility for therapeutic pouches of small molecule and gene-drugs.
", "doi": "10.7907/jvc2-6q78", "publication_date": "2001", "thesis_type": "phd", "thesis_year": "2001" }, { "id": "thesis:4492", "collection": "thesis", "collection_id": "4492", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-11102005-135122", "primary_object_url": { "basename": "Luo_l_2001.pdf", "content": "final", "filesize": 12298676, "license": "other", "mime_type": "application/pdf", "url": "/4492/1/Luo_l_2001.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Partial Oxidation of Propane Over Vanadium-Containing Zeolite Catalysts", "author": [ { "family_name": "Luo", "given_name": "Lin", "clpid": "Luo-Lin" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Gavalas", "given_name": "George R.", "orcid": "0000-0003-1468-6835", "clpid": "Gavalas-G-R" }, { "family_name": "Flagan", "given_name": "Richard C.", "orcid": "0000-0001-5690-770X", "clpid": "Flagan-R-C" }, { "family_name": "Labinger", "given_name": "Jay A.", "orcid": "0000-0002-1942-9232", "clpid": "Labinger-J-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Over the past few decades, significant efforts have been devoted to the development of new catalysts and processes for the partial oxidation of cheap and abundant light alkanes directly into oxygenates and olefins. One of the main challenges in the partial oxidation of light alkanes is that they are usually less reactive than the desired products, and further oxidation to total oxidation products, COx, is thermodynamically favored. With a few exceptions, e.g., partial oxidation of n-butane to malefic anhydride by V-P-O and a oxidation of propane to acrylonitrile by V-Al-Sb, catalysts investigated for the partial oxidation of light alkanes consist of complicated elemental compositions of metal oxides that have less than desirable catalytic behavior.
\r\n\r\nCompared to the traditional bulk metal oxides where the active sites selective for partial oxidation of hydrocarbons are usually lattice oxygens, small metal oxide clusters that do not have lattice energies are anticipated to offer oxygen with a lower energetic barrier. Thus, by using metal oxide clusters, the reaction temperature for oxidation of hydrocarbons may possibly be lowered and total oxidation reduced. Zeolites have been shown to be able to provide an excellent matrix for stabilizing metal oxide clusters. Here, a new approach is investigated for the partial oxidation of propane that combines the tunable advantages of zeolites with possibility of high reactivity of metal oxide clusters by using zeolite supported metal oxide clusters as catalysts.
\r\n\r\nVarious methods are employed to synthesize zeolite supported small metal oxide clusters, including ion-exchange-hydrolysis, liquid phase impregnation, vapor phase impregnation, and post-synthesis modification methods. Vanadium is used as the transition metal of interest and is combined with zeolite L, beta and SSZ-33. Vanadium oxide clusters are successfully incorporated inside zeolites and they have remarkably lower reduction temperatures than the bulk metal oxide. These zeolite based catalysts are studied for propane oxidation. The influence of the locations of the vanadium, the acidity of the zeolite matrix, the hydrophobicity of the zeolite framework and the addition of a second metal(Mo and Sb) are discussed. It is found that vanadium oxide cluster catalysts (VxOy/zeolite L, VxOy/zeolite beta, V-Sb/zeolite beta, V-Mo/zeolite beta) are not particularly selective for the partial oxidation of propane at the reaction conditions investigated (contact time 2 s, reaction temperature 350-450\u00b0C, feed gas molar ratio C3H8:O2:H2O:He=4:2:4:5), and most of the vanadium-containing zeolite beta catalysts are as active as V2O5 (as suggested by the turnover frequency).
\r\n\r\nA considerable amount of acetic acid is produced with vanadyl ion-exchanged zeolite beta (VO-H-beta), with a selectivity to acetic acid of 21.1% at propane conversion 1.62% (350\u00b0C). It appears that more valuable oxygenates, e.g., acrylic acid, may have been produced in the reaction and overoxidized to COx, since feeding acrylic acid into this VO-H-beta reaction system at 350\u00b0C results in complete oxidation of the acid to CO\u2093. Motivated by these data, the reaction pathways for propane and propylene oxidation are investigated on this catalyst. For comparison, reaction pathways are also studied with a \"Mitsubishi\" type catalyst, Mo1V0.3Te0.23Nb0.120x, one of the best catalysts for propane partial oxidation to acrylic acid. With VO-H-beta, propylene is the primary product of propane oxidation and acetic acid is a sequential oxidation product of the formed propylene possibly through an acetone intermediate. Mo1V0.3Te0.23Nb0.120x also gives propylene as the primary product of propane oxidation and the propylene thus formed further oxidizes to acrylic acid and acetone. Reactions of individual oxygenate compounds, e.g., propanal, acrolein, etc., suggest a need to further suppress the total oxidation and to improve allylic oxidation feature for the zeolite based catalysts.
", "doi": "10.7907/ce5g-3606", "publication_date": "2001", "thesis_type": "phd", "thesis_year": "2001" }, { "id": "thesis:4576", "collection": "thesis", "collection_id": "4576", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-11152005-152437", "primary_object_url": { "basename": "Jones_c_1999.pdf", "content": "final", "filesize": 8608188, "license": "other", "mime_type": "application/pdf", "url": "/4576/1/Jones_c_1999.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Organic-functionalized molecular sieves (OFMS'S): A new class of materials", "author": [ { "family_name": "Jones", "given_name": "Christopher W.", "clpid": "Jones-C-W" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Gavalas", "given_name": "George R.", "clpid": "Gavalas-G-R" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Throughout the last two decades, there has been a tremendous interest and growth in molecular sieve science. In particular, substantial attention has been paid to the development of new molecular sieves for catalytic applications, as molecular sieves have the unique ability to promote reactions in a shape-selective manner. To increase the variety of reactions that can be catalyzed by molecular sieves, recent efforts have focused on generating new types of active sites in molecular sieves by incorporating transition metals into the silicate framework or by supporting metal-based species within the micropores. Despite this, there are still many chemistries that can not be carried out over molecular sieve catalysts where significant benefit could be gained if the reaction were to be accomplished in a shape-selective manner. To address this problem, I have prepared a new class of molecular sieves that contain intracrystalline organic functionalities [denoted organic-functionalized molecular sieves (OFMS's)]. Previous attempts to synthesize silicate-based molecular sieves with organic functionalities within the micropores have focused on grafting organic groups onto preformed zeolites. However, this is not a viable route to the production of OFMS's that can function as shape-selective catalysts, as the organic groups preferentially functionalize the external crystal surface. Here, the problems with this approach are circumvented by preparing OFMS's by direct synthesis.\n\nAttempts to synthesize OFMS's directly both in the presence and absence of organic structure-directing agents (SDA's) are described. Pure-silica beta zeolites containing a variety of intracrystalline organic groups are synthesized using tetraethyl ammonium fluoride (TEAF) as the SDA. Porosity is generated by removing the occluded TEAF by solvent-extraction techniques. Following extraction, the exposed organic functionalities are further altered by chemical techniques, e.g., amines to imines, phenethyl groups to phenethylsulfonic acid groups. The ability to perform shape-selective acid catalysis (phenethylsulfonic acid) and shape-selective formation of imines from amines indicates that the organic moieties reside largely in the micropores of the molecular sieve. Several preparation variables have an impact on the nature of the resulting OFMS's, the most of important of which are the synthetic method, silicon source, and extraction method. The effects of these synthetic factors on the crystal size and morphology, porosity and hydrophobicity of the products are discussed.", "doi": "10.7907/6xz1-hh23", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:2736", "collection": "thesis", "collection_id": "2736", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06272005-135319", "primary_object_url": { "basename": "Katz_a_1999.pdf", "content": "final", "filesize": 8450134, "license": "other", "mime_type": "application/pdf", "url": "/2736/1/Katz_a_1999.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "The synthesis and characterization of molecularly imprinted materials", "author": [ { "family_name": "Katz", "given_name": "Alexander", "clpid": "Katz-A" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Current advances in chemical protection strategies, analytical methods such as solid-state NMR and EPR spectroscopies and biological catalysis make it an ideal time to reinvestigate molecular imprinting as a viable method for the synthesis of catalysts for small molecule transformations. In the past, imprinting has been pursued mainly as a method for creating separation media for dealing with issues of adsorption/separation of small molecules. In a few instances, these materials have also been investigated as catalysts. Most imprinted systems to-date have employed non-covalent interactions to achieve functional group positioning, and this type of an approach can lead to other undesired effects such as binding site heterogeneity (as shown in this thesis for one particular system that employs self-assembly to achieve imprinting). Site heterogeneities can be extremely detrimental for selective catalysis. The objective of this work is to determine the origins of site heterogeneity and attempt to overcome these issues in order to synthesize new catalysts via molecular imprinting.\n\nTo gain further insight into the causes responsible for site heterogeneity in imprinted materials, the nature of molecular recognition in an imprinted polymer that is known to exhibit strong binding site heterogeneity is investigated. The system is formed by the self-assembly of a binding monomer and an imprint through non-covalent interactions. Based on observations of bulk phase separation in the system investigated, an alternative mechanism for molecular recognition in the imprinted polymer is proposed. This mechanism involves remaining, occluded imprint molecules that provide for binding via imprint-imprint intermolecular interactions. Support for this mechanism is provided from polymers prepared using a combination of imprint and mimic, which remains covalently bound in the polymer and is shown to increase the rebinding of imprint while not significantly affecting the binding of the opposite enantiomer of the imprint. Elucidation of this mechanism provides insight into the nature of site heterogeneity in imprinted polymer systems.\n\nBased on the findings from the self-assembly system, a new molecular imprinting approach is developed that utilizes the controlled distance method. In this approach, silica is used for the inert crosslinking framework instead of an organic polymer due to its significantly greater mechanical rigidity (300 times more rigid and not susceptible to swelling in organic media). Instead of non-covalent interactions as the driving force for functional group positioning, covalent interactions are used. The method positions several amine functionalities (up to three demonstrated), within the three-dimensional porous structure of silica. This imprinting process is characterized by FTIR and solid state NMR spectroscopies. The imprinted silicas show microporosity specifically resulting from the imprinting process, with the amount of microporosity added consistent with the extent of imprint removal. The imprinted amines which reside in the microporous void space are able to bind molecules such as benzoic acid and acetylacetone and also perform shape-selective catalysis. To ascertain the degree of control over functional group positioning with this imprinting approach, fluorescence measurements with a pyrenebutyric acid probe molecule were performed on the imprinted silicas. The results demonstrate that the imprinting process employed gives local functional group ordering for the case of three amines per site and gives well-isolated functional groups for the case of one amine per site. The imprinted silicas thus provide a foundation from which further investigations towards elucidating quantitative distance information between imprinted functionalities in these materials can be developed.", "doi": "10.7907/w71z-hn73", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:17072", "collection": "thesis", "collection_id": "17072", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03192025-175557925", "primary_object_url": { "basename": "Wagner_PA_1999.pdf", "content": "final", "filesize": 70820925, "license": "other", "mime_type": "application/pdf", "url": "/17072/1/Wagner_PA_1999.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Structural Investigation of Zeolites", "author": [ { "family_name": "Wagner", "given_name": "Paul A.", "clpid": "Wagner-Paul-A" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" }, { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Microporous materials (including zeolites) that contain molecular-sized pores and\r\ncavities have found wide-spread use in industry as molecular sieves for chemical separations,\r\nas ion-exchangers for detergents and as heterogeneous, shape-selective catalysts. The number\r\nof unique molecular sieve structures discovered over the past few decades has burgeoned and\r\ncurrently is over 121.
\r\n\r\nKnowledge of the crystal structure of these microporous solids can provide important\r\ninsights into their properties that can ultimately lead to the design of desirable materials.\r\nHowever, the structure solution of microporous materials can be challenging because they tend\r\nto form as micron or submicron sized crystals that are too small for single crystal X-ray\r\nanalysis. Thus, the objective of this work is to develop and apply new techniques for solving\r\nthe structures of microporous materials that tend to form micro- and nanocrystals and to utilize\r\nthese structural investigations to gain a more thorough understanding of the zeolite/ organic\r\nstructure directing agent (SDA) interactions that lead to the observed zeolite phase selectivity in\r\ntheir synthesis.
\r\n\r\nIn the absence of single crystal data, structure solution and refinement have typically\r\nrequired the use of powder X-ray data. The difficulty in solving crystal structures from\r\npowder X-ray data is that the three dimensions of information available in a single crystal data\r\nset are collapsed into one dimension (d-spacing) in a powder X-ray data set. If the reflections\r\nin the powder X-ray data are significantly overlapping then solving the crystal structure from\r\nthis data can be extremely difficult. Several techniques are applied here for solving\r\nmicroporous crystal structures from powder X-ray data.
\r\n\r\nThe structure solution of CIT-5 (California Institute of Technology Number 5), a new\r\nhigh-silica molecular sieve synthesized under hydrothermal conditions in the presence of\r\nN(16) methylsparteinium and lithium cations, is obtained though an iterative process of model\r\nbuilding and comparison of the simulated powder X-ray data with the experimental powder X-ray\r\ndata. Rietveld refinement of the synchrotron powder X-ray data supports the symmetry and\r\nspace group assignment for the structure as Pmn21(No.31) with refined unit cell parameters of\r\na=l3.6738(8) \u00c5, b=S.0216(3) \u00c5 and c=25.4883(7) \u00c5 (V=1750.1 \u00c53) and confirms that CIT-5\r\nis the first ordered zeolite to contain one-dimensional extra-large pores circumscribed by\r\n14 tetrahedral-atoms (14 MR).
\r\n\r\nComputational techniques for solving the structures of microcrystals from powder Xray\r\ndata are continuing to increase in sophistication and capability. The crystal structures of\r\ntwo high-silica molecular sieves, SSZ-44 and SSZ-35, are solved using Fourier recycling and\r\nrepresents the first application of this new computational technique for solving novel high-silica\r\nzeolite structures from powder X-ray data. Both materials contain unusual 1-dimensional\r\npores circumscribed by 10 and 18 membered-rings, and are the first high-silica zeolites found\r\nthat possess pores containing greater than 14 membered-rings.
\r\n\r\nElectron diffraction data, obtained from a transmission electron microscope (TEM),\r\nhas inherent advantages over X-ray data for analyzing small crystals due to the stronger\r\ninteraction between the electron beam and matter compared to X-rays. This stronger\r\ninteraction allows a single crystal diffraction data set to be obtained from much smaller\r\ncrystals. Provided that the interaction of the incident electron beam with the crystal is\r\nnearly kinematical direct methods can be used as a powerful tool for obtaining the phase\r\ninformation required to solve the crystal structure.
\r\n\r\nThe development of electron diffraction methods for solving the structure of\r\nnanocrystals is described and the application of this technique to solve the structure of a\r\nlarge-pore, high-silica zeolite, SSZ-48, that contains an occluded organic structure directing\r\nagent is presented. The structure is confirmed by electron diffraction refinement and by\r\nhigh resolution transmission electron microscopy and is found to contain a one-dimensional\r\npore system circumscribed by 12 tetrahedral atoms (12 MR). SSZ-48 is the most complex\r\nthree-dimensional material to be solved at atomic resolution using electron diffraction\r\nmethods and illustrates the power of electron diffraction data for resolving the structures of\r\nmaterials that form crystals too small for standard single crystal X-ray analysis.
\r\n\r\nThese investigations into the structural details of micro- and nanocrystalline\r\nmicroporous materials can be utilized to gain a more thorough understanding of the zeolite/\r\norganic structure directing agent (SDA) interactions that lead to the observed zeolite\r\nsynthesis phase selectivity. Two studies are conducted to probe the relationship between\r\nthe organic structure directing agent and the zeolite framework that is formed from its use.
\r\n\r\nThe first study probes the interaction between the CIT-5 framework and the N(l)-\r\nmethyl-\u03b1-isosparteine SDA I that is found to be a more effective structure directing agent\r\nfor CIT-5 than the diastereomer N(l6)-methylsparteinium II originally used to direct this\r\nnew high-silica zeolite. Molecular modeling calculations reveal that I is capable of forming\r\na greater number of van der Waals interactions with the framework than II thereby\r\nproviding a greater degree of stabilization for the CIT-5 structure as compared to II.
\r\n\r\nFinally, a study into the guest/host interactions between three new zeolite\r\nstructures, SSZ-35, SSZ-36 and SSZ-39 and the 37 organic structure directing agents that\r\nare capable of directing for these zeolites is presented. The size and shape of the organic\r\nSDAs presented in this study are designed in order to obtain novel, open framework\r\nzeolites. The design effort focused on synthesizing large rigid spheroidal SDAs that will\r\npreclude the crystallization of the commonly observed clathrates and straight I-dimensional\r\nchannel system zeolites that result when either small or rigid elongated molecules are\r\nemployed as SDAs. Computational calculations of the organic/inorganic energy of\r\ninteractions provided significant insights into the observed zeolite phase selectivity by the\r\norganic SDAs. The molecular modeling investigations presented here highlight the\r\npotential for developing a rational route to the design of desirable zeolite frameworks.
", "doi": "10.7907/t8qz-qa09", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:117", "collection": "thesis", "collection_id": "117", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-01102008-150302", "primary_object_url": { "basename": "Khodabandeh_s_1997.pdf", "content": "final", "filesize": 6345664, "license": "other", "mime_type": "application/pdf", "url": "/117/1/Khodabandeh_s_1997.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Synthesis of Alkaline-earth Zeolites", "author": [ { "family_name": "Khodabandeh", "given_name": "Shervin", "clpid": "Khodabandeh-Shervin" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Gavalas", "given_name": "George R.", "clpid": "Gavalas-G-R" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Gavalas", "given_name": "George R.", "clpid": "Gavalas-G-R" }, { "family_name": "Giapis", "given_name": "Konstantinos P.", "clpid": "Giapis-K-P" }, { "family_name": "Rossman", "given_name": "George Robert", "clpid": "Rossman-G-R" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Zeolite molecular sieves have found extensive applications in ion-exchange, separation and catalytic processes, particularly in the chemical and petroleum industries. Currently, the state-of-the-art in synthesis of high-silica zeolites involves the use of complex organic molecules to direct the formation of zeolitic materials with novel pore structures. While efforts towards preparation of new zeolites using organic molecules as structure-directing agents continues, synthesis of calcium and other alkaline-earth zeolites has not received much attention since the inception of the systematic investigation of zeolite synthesis some 35 years ago. Of the approximate 50 natural zeolites discovered to date, over 20% have eluded synthesis and another 10% have proven exceedingly difficult to synthesize at typical hydrothermal conditions. The overwhelming majority of these zeolites are calcium-dominant. The difficulty encountered in the synthesis of these alkaline-earth zeolites is in direct contrast to their natural occurrence as alteration products of volcanic glasses. Thus, the objective of this work is developing practical methodolgies for the synthesis of alkaline-earth zeolites.
\r\n\r\nHydrothermal transformation of perlite (a natural rhyolitic glass) to calcium zeolites is investigated as a first step towards developing synthesis procedures for the preparation of calcium and other alkaline-earth zeolites from pure starting reagents. In particular, synthetic analogues of the calcium zeolites gismondine, heulandite and epistilbite are obtained as alteration products of perlite glass reacting with calcium-containing solutions. The influence of the solution phase species and their concentrations, the pH and the temperature on the distribution of the zeolite products obtained are discussed. It is observed that the crystallization of heulandite from perlite is preceded by the transient formation of a gismondine-type zeolite most similar to the synthetic zeolite P1. This information is exploited to devise methodology for the preparation of zeolite P1 from pure starting reagents and its subsequent conversion to calcium and other alkaline-earth zeolites upon treatment with solutions containing alkaline-earth cations. Thus, a novel approach for the synthesis of alkaline-earth zeolites based on the hydrothermal conversion of zeolite P1 is developed. Details of the synthesis procedures are enumerated for the preparation of alkaline-earth zeolites CIT-3 (HEU), CIT-4 (BRE), epistilbite (EPI), harmotome (PHI), and yugawaralite (YUG). Transformation of zeolite P1 to alkaline-earth zeolites is governed by factors such as the Si/Al ratio of the starting P1 material, the composition of the solution phase and the presence or absence of seed crystals. The effects of these factors on the products obtained, i.e., phase selectivity, are discussed.
", "doi": "10.7907/35dq-qn66", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:4493", "collection": "thesis", "collection_id": "4493", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-11102005-141042", "primary_object_url": { "basename": "Yan_y_1997.pdf", "content": "final", "filesize": 17311051, "license": "other", "mime_type": "application/pdf", "url": "/4493/1/Yan_y_1997.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Preparation of zeolite ZSM-5 membranes", "author": [ { "family_name": "Yan", "given_name": "Yushan", "clpid": "Yan-Yushan" } ], "thesis_advisor": [ { "family_name": "Gavalas", "given_name": "George R.", "clpid": "Gavalas-G-R" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Gavalas", "given_name": "George R.", "clpid": "Gavalas-G-R" }, { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Giapis", "given_name": "Konstantinos P.", "clpid": "Giapis-K-P" }, { "family_name": "Wang", "given_name": "Zhen-Gang", "clpid": "Wang-Zhen-Gang" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document.\r\n\r\nZeolite ZSM-5 membranes were prepared on porous [...] disks by in-situ crystallization using a clear solution of optimized composition [...]. During the synthesis, the disk was fixed horizontally at the air-liquid interface and a continuous polycrystalline zeolite film of about 10 \u00b5m thickness formed on the bottom surface of disk. Extensive experimentation was carried out to find the optimal composition. Pure gas permeation measurements of the most successful preparation yielded hydrogen:isobutane and n-butane:isobutane ratios of 151 and 18 at room temperature and 54 and 31 at 185\u00b0C, respectively.\r\n\r\nElectron probe microanalysis of the cross section of a membrane prepared on a bare alumina disk revealed a layer of crystalline or amorphous silica extending 80 \u00b5m inside the pores of the support. It is believed that this internal layer adds resistance to permeation and degrades selectivity. To limit the excessive penetration of siliceous species into the support pores, a diffusion barrier was introduced into the pores of the support prior to zeolite crystallization by impregnating the disk with a 1:1 molar mixture of furfuryl alcohol and tetraethylorthosilicate, polymerizing the mixture retained in the disk, and carbonizing the resulting polymer. Following carbonization, a partial carbon burnoff was carried out to generate a carbon-free region near the surface of the support. Membranes synthesized using barriers have n-butane flux and n-butane:isobutane selectivity 2.7 x [...] and 45 at 185\u00b0C which are, respectively, about 1.6 and 4 times as large as those of membranes prepared without the use of barriers.\r\n\r\nThe n-butane:isobutane selectivity of ZSM-5 membranes was substantially improved (e.g. 322 vs. 45 at 185\u00b0C) by a post-synthetic coking treatment which was accomplished by impregnating the membranes with liquid 1,3,5-triisopropylbenzene (TIPB) for 24 hours at room temperature and then calcining them in air at 500\u00b0C for 2 hours. Calcination at 500\u00b0C for up to 30 hours does not destroy the high n-butane:isobutane selectivity. Thermogravimetric analysis experiments suggest that microdefects in the zeolite membranes were selectively eliminated by the TIPB coking treatment while the intracrystalline pore space of the ZSM-5 was not affected.\r\n\r\nA model of surface-induced nucleation, crystal growth, and crystal adhesion was proposed for the aforementioned heterogeneous hydrothermal synthesis system. During the synthesis, aluminosilicates in the aged solution interact favorably with and travel toward the [...] surface, resulting in concentration and nucleation in the vicinity of the surface. Some of the nuclei become attached to the surface and grow into a zeolite film while others settle and produce loose zeolite crystals at the bottom of the autoclave. The nutrients for crystal growth is supplied by active gel particles and the synthesis solution. Surface -OH groups on the substrate appear important for crystal adhesion via condensation. As for zeolite membrane formation on a surface of certain area, the location and orientation of the surface as well as the amount of synthesis liquid accessible to the surface are critical for the quality of the zeolite membrane.\r\n", "doi": "10.7907/05FZ-JS07", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:17086", "collection": "thesis", "collection_id": "17086", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03212025-215725447", "type": "thesis", "title": "I. The Use of Spherosiloxanes as Molecular Building Blocks for Material and Thin Films. II. A Method of Using SC-Cut Quartz Oscillators for Chemical Sensing", "author": [ { "family_name": "Nagel", "given_name": "John Frederick", "clpid": "Nagel-John-Frederick" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Flagan", "given_name": "Richard C.", "orcid": "0000-0001-5690-770X", "clpid": "Flagan-R-C" }, { "family_name": "Gavalas", "given_name": "George R.", "orcid": "0000-0003-1468-6835", "clpid": "Gavalas-G-R" }, { "family_name": "Giapis", "given_name": "Konstantinos P.", "orcid": "0000-0002-7393-298X", "clpid": "Giapis-K-P" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The ability to prepare a priori ordered materials of a desired structure is a long\r\nstanding goal in materials research. Recently, there has been great interest in the use of\r\nwell-defined molecular precursors that can, in principle, be combined in a regular way\r\nwithout degradation to produce ordered materials. This process has been dubbed \"lego-chemistry.\"\r\nThis work examines the use of spherosiloxanes, a family of polyhedral silicate\r\ncage molecules, as molecular building blocks for the synthesis of bulk microporous\r\nmaterials and microporous thin films.
\r\n\r\nThe process for synthesizing and functionalizing the spherosiloxanes with a variety\r\nof reactive functional ligands is presented. The reactive molecules are characterized\r\nusing a suite of analytical and spectroscopic techniques. In order to achieve some degree\r\nof control over the condensation process, a binary reaction mechanism utilizing nonhydrolytic\r\nreaction conditions is proposed for the production of bulk materials. Experimental\r\nresults from the non-hydrolytic condensation of spherosiloxanes are presented.\r\nThe effects of adding various catalysts to the reaction mixture are described. A multinuclear\r\nsolution NMR study was performed on monomeric silicate analogues of the\r\nspherosiloxanes in order to elucidate the non-hydrolytic reaction pathways. It is found\r\nthat under the conditions of interest ligand exchange predominates over condensation.
\r\n\r\nA reaction scheme and growth mechanism for the production of a microporous\r\nthin film from spherosiloxane precursors is presented and discussed. It is speculated that\r\nsuch an ordered film could function as a framework for the production of a molecular electronic\r\ndevice. The first important steps in this scheme, namely the condensation behavior\r\nof spherosiloxanes on the Si (100) - (2x1) reconstructed surface, are explored through a\r\nvariety of surface characterization techniques. In particular, low temperature STM is used\r\nto record the nature of the species condensed on the surface. An image of a single isolated\r\n(CH3O)8Si8O12 is recorded and its position and orientation are discussed in the context of the reaction scheme. A HREELS/TPD study of the spherosiloxanes on the same surface is\r\nperformed and the results discussed.
\r\n\r\nA new technique for chemical sensing is proposed and is based on the recently\r\ndeveloped SC-cut quartz oscillator used in conjunction with the analytical technique\r\nknown as thermal programmed desorption (TPD). This technique is developed in order to\r\naddress the need to develop new sensing techniques that are sensitive, selective and cost\r\nefficient, for application to the rising threats of terrorism and pollution present today. The\r\ntechnique utilizes two vibrational modes of the crystal, one very sensitive and one relatively\r\ninsensitive to changes in temperature, that are monitored throughout the experiment.\r\nThe two mode sensing allows in principle for the simultaneous monitoring of the mass and\r\ntemperature of the sensor.
\r\n\r\nA system for evaluating the performance of this sensor is designed and built, and\r\nincludes an automated data acquisition and control system. The sensor is tested using a\r\nvariety of chemically selective coatings and analytes. The structure and morphology of\r\nthe coating used is shown to have a significant effect on the oscillation behavior of the\r\ncrystal used. TPD experiments are performed with the sensor in order to evaluate its characteristics.\r\nIn nearly all cases, it is impossible to discern any desorption signal during the\r\nTPD experiment. A dual mode analysis that is used to deconvolute the temperature and\r\nmass responses of the sensor fails to distinguish any desorption signals except from a very\r\nheavily loaded sample, i.e., water on a polyethyleneimine coated crystal where bulk\r\nabsorption occurs. A TPD experiment is performed on a hydrated, PEI coated crystal\r\nusing a Cahn microbalance, and a relationship between the mass loading and frequency\r\nchange is determined for this system. These values are used to calculate the frequency\r\nresponse for a typical coating where only surface adsorption occurs, and the result is\r\nbelow the minimum detection level of the system. Based on these data, it is determined\r\nthat the SC-cut sensor fails to show the sensitivity necessary for application as a practical\r\nsensor device.
", "doi": "10.7907/wkz6-jt81", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:30", "collection": "thesis", "collection_id": "30", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-01042008-112721", "primary_object_url": { "basename": "Lewis_je_1996.pdf", "content": "final", "filesize": 6527501, "license": "other", "mime_type": "application/pdf", "url": "/30/1/Lewis_je_1996.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Characterization and permeation studies on oriented single-crystal ferrierite membranes", "author": [ { "family_name": "Lewis", "given_name": "John Edwin", "clpid": "Lewis-J-Ed" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document.\r\n\r\nSingle-crystals (up to 650 x 550 x 20 [...]) of highly silicious ferrierite (Si-FER, 1), suitable for single-crystal X-ray investigations, are synthesized under organothermal conditions. The structures of the as-synthesized (1a) and the calcined (1b) Si-FER are determined at room temperature. Both structures are refined in the orthorhombic space group Pnnm (No.58, standard setting) with a = 743.0(1), b = 1409.2(2), c = 1882.0(2)pm, V = 1970.5(4)[...], Z = 1,R = 0.041 (la) and a = 741.8(1), b = 1407.0(2), c = 1871.3(2) pm, V = 1953.1(5)[...], Z = 1, R = 0.037 (lb). The structure solution when combined with chemical analysis and [...] and [...] MAS NMR, give a unit cell content of [...] (x = 0 - 1, py = pyridine, ap = 1-amino-n-propane) and [...] for 1a and 1b, respectively. The structure of 1a shows only weak host-guest interactions between the [...] framework and the occluded, orientationally disordered pyridine molecules by means of relatively long organic-to-framework distances,d[...] [...] 354(2) pm. [...] MAS NMR spectra from the organic-containing Si-FER 1a and the organic-free form 1b are in good agreement with the crystallographic results in that they conform to the well-known linear relationship between the cosine expression of the T-O-T angles and the chemical shift of the respective tetrahedral sites (T-sites). A new modification of this relationship is presented here and offers an improved linear correlation between the X-ray and NMR data for 1a and 1b, as well as for other high-silica microporous materials. Application of this new correlation to denser SiO2 compounds is discussed.\r\n\r\nSelected individual crystals of the calcined Si-FER are mounted in a membrane configuration so that only the 10-membered ring channels (5.4 [...] x 5.4 [...] x 4.2 [...]) or the 8-membered ring channels (4.6 [...] x 3.7 [...] x 3.0 [...]) are accessible for gas molecule permeation. The first examples of transport exclusively through 8- or 10-membered ring channel systems are reported and obtained through crystal orientation in the membrane. A series of adsorption experiments are conducted in order to assist the selection of suitable probe molecules and evaluate the role of adsorption in the permeation process for the single-crystal membranes. Methane, n-butane, isobutane and nitrogen probe molecules are used to study intracrystalline sorption and transport effects for different crystal orientations, pressures and temperatures. Both pure gas selectivities and mixed gas separation factors are reported. A mixed gas separation factor of n-butane/isobutane = 116 for the 10-membered ring orientation of the crystal at 383 K and a transmembrane pressure difference of 1.01 x [...] Pa is found using this technique. In addition, molecular sieving is observed for the 8-membered ring orientation of the crystal since methane, but not butane, transport is observed for this crystal orientation.\r\n", "doi": "10.7907/jcyz-xr37", "publication_date": "1996", "thesis_type": "phd", "thesis_year": "1996" }, { "id": "thesis:4972", "collection": "thesis", "collection_id": "4972", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-12122007-111327", "primary_object_url": { "basename": "Dartt_cb_1996.pdf", "content": "final", "filesize": 6583349, "license": "other", "mime_type": "application/pdf", "url": "/4972/1/Dartt_cb_1996.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Synthesis and characterization of titanium-containing molecular sieves", "author": [ { "family_name": "Dartt", "given_name": "Christopher Bruce", "clpid": "Dartt-Christopher-Bruce" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Gavalas", "given_name": "George R.", "clpid": "Gavalas-G-R" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Zones", "given_name": "Stacey I.", "clpid": "Zones-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The use of zeolites and molecular sieves as catalysts for important organic reactions is reviewed. One emerging area of particular interest is the use of titanium-containing molecular sieves as partial oxidation catalysts and is chosen for further study.\r\n\r\nIn order to elucidate the relationships between the physicochemical properties of titanium-containing molecular sieves and their ability to act as partial oxidation catalysts, titanium-containing pure-silica ZSM-5 (TS-1) materials are synthesized using different methods. The activities of the titanium-containing catalysts for the oxidation of alkanes, alkenes, and phenol at temperatures below 100 [degrees]C using aqueous hydrogen peroxide H2O2 as the oxidant are reported. The relationships between the physicochemical and catalytic properties of these titanium silicates are discussed. The effects of added aluminum and sodium on the catalytic activity of TS-1 are described. The addition of sodium during the synthesis of TS-1 is detrimental to the catalytic activity while sodium incorporation into pre-formed TS-1 is not. The framework substitution of aluminum for silicon appears to decrease the amount of framework titanium.\r\n\r\nThe relationships between catalytic performance and physicochemical properties that are controlled through synthetic methods are further investigated using a series of titanium-containing molecular sieves. Titanium-containing pure-silica ZSM-5 (TS- 1), pure-silica ZSM-48 (Ti-ZSM-48) and zeolite beta (Ti-Al-beta) are synthesized and characterized by X-ray powder diffraction (XRD), elemental analysis, physical adsorption of N2, Fourier transform infrared (FT-IR), FT-Raman, and diffuse reflectance ultraviolet (DR-UV) spectroscopies. TS-1 is synthesized by five different methods. All materials are evaluated for their ability to oxidize 1-hexene and n-octane using aqueous H2O2 as the oxidant. The relationships between the physicochemical and catalytic properties of these titanium-containing zeolites are discussed. TS-1 samples synthesized at high pH are catalytically active and framework titanium is shown to be necessary for olefin epoxidation and alkane hydroxylation to occur. The existence of anatase in active TS-1 samples results in decreased hydrogen peroxide efficiencies in the epoxidation reaction. TS-1 produced at pH=7.4 and Ti-ZSM-48 each contain anatase and are not active. Ti-beta is found to contain framework titanium and be free of anatase. However, at the conditions used in this study these samples are not able to activate 1-hexene or n-octane.\r\n\r\nIn attempts to prepare large pore titanium-containing molecular sieves, postsynthetic incorporation of titanium in the borosilicate SSZ-33 and the direct synthesis of an aluminum-free titanium-containing zeolite Beta (Ti-Beta) are reported. These materials are characterized by XRD, FT-IR, FT-Raman, and DR-UV spectroscopies. The molecular sieves are shown to catalyze the epoxidation of various olefins using aqueous hydrogen peroxide as the oxidant. The physicochemical properties as found by the characterization methods are correlated to the catalytic data and the results compared to a high quality sample of TS-1. The modified SSZ-33 samples contain titanium primarily in the form of isolated tetrahedrally coordinated Ti atoms, although some extra-framework Ti is observed by Raman and DR-UV spectroscopies. Ti-Beta samples show no evidence of extra-framework titanium. For the epoxidation of cis-cyclooctene, the Ti-Beta catalysts give quantitative conversion to epoxide, and both the Ti-Beta and Ti-SSZ-33 catalysts are able to epoxidize substrates too large to be oxidized by TS-1.\r\n", "doi": "10.7907/0pnv-rt94", "publication_date": "1996", "thesis_type": "phd", "thesis_year": "1996" }, { "id": "thesis:17089", "collection": "thesis", "collection_id": "17089", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03242025-182317095", "primary_object_url": { "basename": "Seidel_PR_1996.pdf", "content": "final", "filesize": 22105514, "license": "other", "mime_type": "application/pdf", "url": "/17089/1/Seidel_PR_1996.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Direct Decomposition of Nitric Oxide by Copper Containing ZSM-5", "author": [ { "family_name": "Seidel", "given_name": "Peter Robert", "clpid": "Seidel-Peter-Robert" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Currently there is an enormous demand for nitric oxide decomposition catalysts and hydrocarbon-based selective catalytic reduction catalysts to eliminate NO. The incorporation of copper atoms into the pores of ZSM-5\r\nhas endowed this solid with the catalytic ability for the direct decomposition of NO to N2 and O2. This report describes the synthesis, characterization, ion-exchange, and reactivity of several ZSM-5 samples prepared by various methods. ZSM-5 is prepared using TPA and also by template-free synthesis methods. Ion-exchange was performed using copper acetate and a copper ethylene complex. Reaction studies include determining rates and turnover frequencies for certain ZSM-5 samples. It was found that ion-exchange with copper ethylene almost doubled the copper weight percent and the reaction rate compared to samples exchanged with copper acetate, however, the turnover frequencies were similar.
", "doi": "10.7907/ab1s-x455", "publication_date": "1996", "thesis_type": "masters", "thesis_year": "1996" }, { "id": "thesis:2631", "collection": "thesis", "collection_id": "2631", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06172005-085103", "primary_object_url": { "basename": "Lobo_rf_1995.pdf", "content": "final", "filesize": 7848477, "license": "other", "mime_type": "application/pdf", "url": "/2631/1/Lobo_rf_1995.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "The Synthesis and Characterization of Novel High-Silica Zeolites", "author": [ { "family_name": "Lobo", "given_name": "Raul Francisco", "clpid": "Lobo-Raul-Francisco" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" }, { "family_name": "Gavalas", "given_name": "George R.", "orcid": "0000-0003-1468-6835", "clpid": "Gavalas-G-R" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The synthesis and characterization of high-silica molecular sieves is reviewed using molecular recognition phenomena and structure-direction as the unifying themes. A comparative analysis between the synthesis conditions employed and the zeolite structures formed is carried out starting with the synthesis of clathradils or 0-dimensional zeolites, and extending to one-dimensional, multi-dimensional zeosils. The review finishes with the analysis of the combined effects of heteroatoms (Al, B and Zn) and organic structure-directing agents in zeolite product selectivity and thermodynamic stability.\r\n\r\nStructure-direction phenomena is further investigated using the synthesis and characterization of the pure-silica zeolite SSZ-24, prepared using the chiral molecule N(16)methylsparteinium hydroxide as the structure-directing agent. The material is characterized using X-ray powder diffraction (XRD), scanning electron microscopy (SEM), solid-state NMR spectroscopy, fourier transform IR spectroscopy (FTIR) and physical adsorption experiments. The B-substituted SSZ-24 prepared here is the first example where the isomorphous substitution of B for Si in the SSZ-24 framework is accomplished during synthesis using sodium borate as the source of B. The B can be easily substituted by Al. The Al-substituted SSZ-24 is an active catalyst for the cracking of alkanes and may be potentially useful in refinery and chemical processes.\r\n\r\nThe structure solutions and a detailed structural characterizations of the disordered zeolites SSZ-26 and SSZ-33 is presented. These two materials are the first synthetic zeolites with intersecting open 10- and 12-ring pore systems. SSZ-26 and SSZ-33 are expected to show a combination of reaction activity, selectivity and stability unique among known zeolites. SSZ-26 and SSZ-33 may be very useful for catalytic applications in the petrochemical and refining industries. The feasibility of synthesizing a zeolite whose pore structure has been designed a priori is demonstrated with the zeolite SSZ-26 and its structure-directing agent.\r\n\r\nThe synthesis of a new borosilicate, CIT-1, is described. The proposed structure of CIT-1 is confirmed by a Rietveld refinement of the synchrotron XRD pattern. CIT-1 is demonstrated to be an ordered polymorph of the SSZ-33 zeolites. The catalytic properties of CIT-1 are compared to the catalytic properties of known high-silica zeolites (ZSM-5 and zeolite beta) and CIT-1 is shown to be a very active catalyst for the cracking of n-butane. The synthesis of CIT-1 supports the idea that the chiral polymorph A of zeolite beta can be synthesized using the appropriate structure-directing agent.\r\n\r\nA combination of molecular modeling and 1H MAS NMR spectroscopy are used to characterize the interactions of structure-directing agents with the zeolite framework. The results indicate that to simulate correctly the energetic interaction and motional properties of structure-directing agents in zeolites, short-range and long-range forces, water molecules, silanol groups and defects need to be considered simultaneously.\r\n", "doi": "10.7907/01DX-QC48", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" }, { "id": "thesis:4054", "collection": "thesis", "collection_id": "4054", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-10122007-103304", "primary_object_url": { "basename": "Khouw_cb_1995.pdf", "content": "final", "filesize": 4929571, "license": "other", "mime_type": "application/pdf", "url": "/4054/1/Khouw_cb_1995.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Partial oxidation of hydrocarbons using titanium containing molecular sieves", "author": [ { "family_name": "Khouw", "given_name": "Charles B.", "clpid": "Khouw-C-B" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document.\r\n\r\nThe objective of this work is to investigate the reaction mechanism of alkane activation on titanium containing, aluminum-free ZSM-5 (TS-1) and to elucidate the relationships between the physicochemical properties of the catalyst and its reactivity. Samples of TS-1 have been synthesized using different methods. The activities of these catalysts for the oxidation of alkanes, alkenes and phenol at temperatures below 100 [...] using aqueous [...] as oxidant are reported and compared to those from other titanium containing materials, e.g., anatase and an amorphous [...] coprecipitate.\r\n\r\nComparisons between the activities of TS-1 and [...] coprecipitate for alkane oxidation and alkene epoxidation using non-aqueous [...] indicate that the absence of water is crucial for the catalytic activity of silica-supported titanium oxide. Due to the hydrophobicity of TS-1, the concentration of water surrounding the titanium is maintained at low value so that aqueous [...] can be used as oxidant on this catalyst.\r\n\r\nIssues of mechanism of the alkane oxidation on TS-1 are investigated by analyzing the stereoselectivity pattern of cis- and trans-1,3-dimethylcyclopentane, the \"radical clock\" rearrangement of ethyl- and isopropylcyclopropane and the effect of oxidants on the catalytic activity of TS-1. The stereoselective reaction pattern of cis- and trans-1,3-dimethylcyclopentane indicates that radicals are formed during alkane oxyfunctionalization with TS-1. The presence of stereos crambling without any \"radical clock\"\r\nrearrangement during alkane oxidation on TS-1 reveals that the radicals formed may have a very short life-time or their movements are restricted such that no rearrangement can occur. A proposal for the mechanism of alkane oxidation on TS-1 is given and compared to a mechanism suggested for alkene epoxidation on TS-1 and the [...] coprecipitate. Alkyl hydroperoxides are active as oxidants for alkene epoxidation on the [...] coprecipitate but not for alkane oxidation reactions on both TS-1 and the [...] coprecipitate. A plausible explanation for the above results is provided.\r\n\r\nThe presence of alkali metal ions in the synthesis mixture of TS-1 completely eliminates the catalytic activity of this material. However, the catalytic activity can be restored by washing the solid with acid solution prior to catalytic testing. The washing removes [...] ions from silanol groups adjacent to the framework titanium active centers. Thus, it is postulated that a silanol group in the neighborhood of the titanium atom is a necessary feature for catalytic activity. The acid treatment may be useful in overcoming the problems of synthesizing TS-1 from reagents that contain alkali metal ions, e.g., TPAOH solutions. More importantly, this treatment opens the possibility of synthesizing other titanium containing silicate structures that require the presence of alkali metal ions in the synthesis mixture for their formation.\r\n\r\n", "doi": "10.7907/9dyq-m742", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" }, { "id": "thesis:4491", "collection": "thesis", "collection_id": "4491", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-11102005-104907", "primary_object_url": { "basename": "Burkett_sl_1995.pdf", "content": "final", "filesize": 6122314, "license": "other", "mime_type": "application/pdf", "url": "/4491/1/Burkett_sl_1995.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Mechanisms of structure direction in zeolite synthesis", "author": [ { "family_name": "Burkett", "given_name": "Sandra Louise", "clpid": "Burkett-Sandra-Louise" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The mechanisms by which the geometries of organic structure-directing agents are translated into the product pore architectures in the synthesis of pure-silica and aluminosilicate zeolites are investigated by numerous spectroscopic techniques and variations in synthesis gel composition. For the tetrapropylammonium- and 1,6-hexanediamine-mediated syntheses of pure-silica ZSM-5 (Si-ZSM-5), 1H-29Si CP MAS NMR is performed between the protons of the organic species and the silicon atoms of the zeolite framework precursors in a deuterated synthesis medium to probe the interactions between the organic and inorganic components. The origin of structural specificity in the synthesis of pure-silica zeolites in the presence of structure-directing agents is attributed to the formation of favorable intermolecular van der Waals interactions within inorganic-organic composite species that form the key components in zeolite self-assembly. Investigation of the 1H-29Si CP MAS NMR profiles of silicate gels containing tetraalkylammonium cations that do not induce the formation of a crystalline zeolite product suggest the significance of hydrophobic hydration of the organic component in the formation of the inorganic-organic composite structures that is essential to the synthesis of pure-silica zeolites. For the syntheses of the hexagonal (EMT) and cubic (FAU) polymorphs of the aluminosilicate zeolite faujasite in the presence of 18-crown-6 and 15-crown-5, respectively, a combination of NMR and vibrational spectroscopic techniques and variations in the synthesis compositions are used to elucidate the structure-directing roles of the crown ethers. Sodium/crown ether complexes facilitate and direct the assembly of sodium-templated extended aluminosilicate structures via ion-dipole interactions to form the EMT and FAU products. Thus, for the synthesis of Si-ZSM-5 and the synthesis of EMT and FAU, two different mechanisms of structure direction and self-assembly via the formation of extended inorganic or inorganic-organic composite species are proposed.", "doi": "10.7907/t6kk-w159", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" }, { "id": "thesis:7712", "collection": "thesis", "collection_id": "7712", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05152013-113928711", "type": "thesis", "title": "The Design and Synthesis of a True, Heterogeneous, Asymmetric Catalyst", "author": [ { "family_name": "Wan", "given_name": "Kam To", "clpid": "Wan-Kam-To" } ], "thesis_advisor": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" } ], "thesis_committee": [ { "family_name": "Davis", "given_name": "Mark E.", "clpid": "Davis-M-E" }, { "family_name": "Gray", "given_name": "Harry B.", "clpid": "Gray-H-B" }, { "family_name": "Anson", "given_name": "Fred C.", "clpid": "Anson-F-C" }, { "family_name": "McKoy", "given_name": "Basil Vincent", "clpid": "McKoy-B-V" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This work describes the design and synthesis of a true, heterogeneous,\r\nasymmetric catalyst. The catalyst consists of a thin film that resides on a high-surface-\r\narea hydrophilic solid and is composed of a chiral, hydrophilic\r\norganometallic complex dissolved in ethylene glycol. Reactions of prochiral\r\norganic reactants take place predominantly at the ethylene glycol-bulk organic\r\ninterface.
\r\n\r\nThe synthesis of this new heterogeneous catalyst is accomplished in a\r\nseries of designed steps. A novel, water-soluble, tetrasulfonated 2,2'-bis\r\n(diphenylphosphino)-1,1'-binaphthyl (BINAP-4S0_3Na) is synthesized by\r\ndirect sulfonation of 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP).\r\nThe rhodium (I) complex of BINAP-4SO_3Na is prepared and is shown to be\r\nthe first homogeneous catalyst to perform asymmetric reductions of prochiral\r\n2-acetamidoacrylic acids in neat water with enantioselectivities as high as\r\nthose obtained in non-aqueous solvents. The ruthenium (II) complex,\r\n[Ru(BINAP-4SO_3Na)(benzene)Cl]Cl is also synthesized and exhibits a broader\r\nsubstrate specificity as well as higher enantioselectivities for the homogeneous\r\nasymmetric reduction of prochiral 2-acylamino acid precursors in water.\r\nAquation of the ruthenium-chloro bond in water is found to be detrimental to\r\nthe enantioselectivity with some substrates. Replacement of water by ethylene\r\nglycol results in the same high e.e's as those found in neat methanol. The\r\nruthenium complex is impregnated onto a controlled pore-size glass CPG-240 by the incipient wetness technique. Anhydrous ethylene glycol is used as the\r\nimmobilizing agent in this heterogeneous catalyst, and a non-polar 1:1\r\nmixture of chloroform and cyclohexane is employed as the organic phase.
\r\n\r\nAsymmetric reduction of 2-(6'-methoxy-2'-naphthyl)acrylic acid to the\r\nnon-steroidal anti-inflammatory agent, naproxen, is accomplished with this\r\nheterogeneous catalyst at a third of the rate observed in homogeneous\r\nsolution with an e.e. of 96% at a reaction temperature of 3\u00b0C and 1,400 psig of\r\nhydrogen. No leaching of the ruthenium complex into the bulk organic phase\r\nis found at a detection limit of 32 ppb. Recycling of the catalyst is possible\r\nwithout any loss in enantioselectivity. Long-term stability of this new\r\nheterogeneous catalyst is proven by a self-assembly test. That is, under the\r\nreaction conditions, the individual components of the present catalytic system\r\nself-assemble into the supported-catalyst configuration.
\r\n\r\nThe strategies outlined here for the design and synthesis of this new\r\nheterogeneous catalyst are general, and can hopefully be applied to the\r\ndevelopment of other heterogeneous, asymmetric catalysts.
\r\n", "doi": "10.7907/6m3g-3y70", "publication_date": "1994", "thesis_type": "phd", "thesis_year": "1994" } ]