Physical Sciences and Mathematics Commons^™

Development Of Copper-Catalyzed Suzuki-Miyaura Coupling Using Alkylboron Reagents And Nickel-Catalyzed Alkene Dicarbofunctionalization Reactions, Prakash Basnet

Chemistry and Chemical Biology ETDs

This thesis is divided into two parts. The first part deals with the development of copper-catalyzed Suzuki-Miyaura coupling of alkylboron reagents for the first time. In the second part, we will discuss the development of novel nickel-catalyzed alkene dicarbofunctionalization reactions.

Part I. Cross-coupling reactions are versatile tools to form new carbon-carbon bonds and are widely used in the synthesis of various drug molecules, natural products and materials. However, these reactions are typically catalyzed by palladium, an expensive and rare metal which makes the reaction unsustainable in long-terms. Additionally, palladium-catalyzed cross-coupling reactions with alkylorganometallic reagents suffer from side reactions due to …

Development Of Functional Chemical Probes For The Study Of Viscosity, Fe(Ii), And Ferroptosis And Photo-Triggered Drug Delivery, Yongyi Wei

Chemistry and Chemical Biology ETDs

Small molecule probes are useful tools for the study of biology. In particular, the dye derived fluorescence probes enable to spatiotemporally monitor the events of analytes of interest. The noninvasive feature is particularly attractive for the biological studies in live cells. The challenge is to develop chemical probes capable of detection of the analyte of interest with high specificity.

Toward this end, my Ph. D. study centers on the development of novel chemical probes for the study and understanding of the alternation of important cellar contents and substances and their functions and relationship between normal and disease states. In the …

Synthesis, Characterization And Application Of Structurally Diverse Poly(Chalcogenylene Vinylene)S, Zhen Zhang

Chemistry and Chemical Biology ETDs

Conjugated polymers have found widespread applications in flexible and printable electronic devices, among which poly(thienylene vinylene) (PTV) displays outstanding optoelectronic properties and promising applications. However, further studies of its structure-property-function relationship have been greatly impeded mainly due to the synthetic difficulty of generating new structures beyond its rudimentary form.

To further investigate this class of material, I have developed a facile methodology for the preparation of structurally diverse poly(chalcogenylene vinylene)s (PCVs) through a combination of acyclic diene metathesis (ADMET) polymerization and post-polymerization modification techniques. Specifically, a series of halogenated and cross-conjugated PCVs have been designed and synthesized, followed by complete …

Developing More Specific Mirna Biogenesis Inhibitors To Get Effective Regulation Of Mirnas, Umesh Bhattarai

Chemistry and Chemical Biology ETDs

MicroRNAs (miRNAs) are short (~ 22 nucleotides long) noncoding RNAs that regulate gene expression post-transcriptionally. They control the expression of various genes that are crucial for cellular function, development and human diseases. Tools to regulate the level and function of miRNAs facilitate the studies of their functions and have therapeutic applications. In my thesis, I developed a newly customizable miRNA biogenesis inhibitor to regulate miRNAs.

Antisense oligonucleotides (ASOs) have been used to regulate miRNA through controlling their production or function. Although commonly used due to the fact that they are easy to design, several limitations exist for ASOs including serious …

Regulating Mirna Biogenesis By Small Molecules, Hao Yan

Chemistry and Chemical Biology ETDs

MiRNAs are key cellular regulators and their dysregulation is associated with many human diseases. The development of miRNA inhibitors has significant implications for the therapy of diseases associated with aberrant miRNA expression. It also provides chemical tools for studying miRNA function. This dissertation focuses on the development of small-molecule based miRNA inhibitors targeting miRNA biogenesis.

The dissertation consists of four chapters. In Chapter 1, the biogenesis of miRNA was first introduced, followed by the explanation of miRNA function in health and disease. Then the approaches used for regulating miRNA were reviewed. Finally, the difficulties with miRNA regulation were summarized.

One …

Catalytic Functionalization Of Organoaluminum Reagents And Olefins By Cross-Coupling With Copper And Nickel, Bijay Shrestha

Chemistry and Chemical Biology ETDs

This thesis is divided into two parts. The first part focuses on the Cu-catalyzed cross-coupling of organoaluminum reagents with organohalides. One of the most powerful tools for the construction of C-C bonds is cross-coupling. But, this reaction is predominantly catalyzed by Pd, a rare and expensive transition metal, which inevitably makes the process unsustainable in the long-term. Furthermore, Pd-catalyzed cross-coupling also shows low tolerance for alkyl and heteroaryl substrates because of β-hydride elimination and catalyst deactivation, respectively. Although these issues remain largely solved by using sterically hindered and electron-rich ligands, however making these types of ligands is synthetically challenging and …

Development Of Mof@Polymer Composite Materials Through Bottom-Up Self-Assembly Techniques, Roberto C. Arbulu

Chemistry and Chemical Biology ETDs

MOF-based mixed matrix membranes (MMMs) are a promising new class of MOF/polymer composite materials. Currently, fabrication of MMMs is based on top-down methods with limited control over MOF positioning, integration, or morphology. This work focuses on the growth of well-defined one-dimensional (1-D) MOF nanostructures within the pores of a nanoporous polymer template, either commercially available or through the self-assembly of block co-polymers having tailor-designed surface functionalities. Studies were conducted using zeolitic imidazole framework-8 (ZIF-8) and polycarbonate track etched (PCTE) membranes, which demonstrated the feasibility of the outlined approach, and revealed the formation of distinct super- and nanostructures with controlled morphologies …

Copper-Catalyzed Direct And Tandem Couplings, And Mechanistic Studies, Surendra Thapa

Chemistry and Chemical Biology ETDs

Cross-coupling reactions are exceptionally powerful tools to construct carbon-carbon (C-C) bonds. These reactions are widely used to synthesize natural products, polymers, agrochemical, organic materials and pharmaceutical compounds. However, these reactions are typically catalyzed by Palladium. Although these reactions are widely utilized and well developed, the use of noble metals like Pd raises a question about its long-term sustainability. We believe copper can be one of the best alternatives to palladium as it is more abundant, less expensive and less toxic. In addition, Pd-catalyzed transformations usually suffer from β-hydride elimination to afford undesired olefin and rearranged products, when it comes …

Detection Of Salen-Type Tracers For Subterranean Fluid Flow Monitoring Using Surface-Enhanced Raman Spectroscopy, Jenny C. Sanchez

Chemistry and Chemical Biology ETDs

A series of hydrocarbon and aqueous soluble salen-type ligands have been synthesized and characterized by electronic and vibrational spectroscopy. Aqueous soluble salen-type ligands were complexed to a metal and investigated as potential underground fluid flow tracers using Surface-Enhanced Raman Spectroscopy (SERS) as the analytical technique. Vibrational spectra obtained from SERS was shown to have enhanced the spectral signal for these complexes in low concentrations though did not show significant differences between the free ligands and their metal complexes. This research has shown that, with some structural modifications, salen-type ligands can be effective candidates as subterranean fluid flow tracers when SERS …

Development Of New Useful Methods For Aldehyde Synthesis And Its Application In Synthesis, He Huang

Chemistry and Chemical Biology ETDs

Development of sustainable synthetic technologies for molecular construction is an important but formidably challenging task in modern organic synthesis. Aldehyde synthesis represents a long-standing interest in synthesis because of the synthetic utility. Classic methods for aldehyde synthesis have the drawbacks of the use of harsh reaction conditions, poor atom-economy and multi-step operation, and production of stoichiometric amount of chemical wastes. The state-of-the-art strategies employ transition metal complexes as catalysts to promote formylation reactions. The concerns of catalyst cost, operation complexity and poor functional group tolerance demands more efficient synthetic technologies. My Ph.D. study focuses on design of conceptually novel catalytic …

Bioinformatics- And Phylogenetics-Guided Approaches To Understanding Sequence-Function Relationships Of Type Ii Polyketide Biosynthetic Gene Clusters, Han Bich Nguyen

Chemistry and Chemical Biology ETDs

Type II polyketides (PK-II) has made up a class of natural products that are structurally diverse and are clinically useful due to their wide-range of bioactivity. The work described in this dissertation focuses on developing approaches to facilitate our understanding of sequence-function relationships of PK-II biosynthetic gene clusters (BGCs). We have systematically summarized the previous characterizations of enzymes involved in the core structure biosynthesis, which have set a foundation for our developments of approaches to discover organisms harboring novel enzymes responsible for novel PK-II molecules. We have successfully developed bioinformatics tools to globally mine the PK-II BGCs in the NCBI …

An Integrated Approach To Studying And Engineering Bacterial Type Ii Polyketide Core Structure Biosynthesis, Xuechen Zhu

Chemistry and Chemical Biology ETDs

Natural products including alkaloids, phenylpropanoids, polyketides, terpenoids and antibiotics provide abundant resources for drugs and drug leads. Type II polyketides (PK-IIs) are a large array of aromatic polyketides that have exhibited various bioactivities including anti-tumor, anti-cancer, anti-fungal and anti-bacteria. Based on the lengths of carbon chains and the cyclization patterns in their core structures, most bacterial PK-IIs have been classified into 6 typical classes: benzoisochromanequinone (BIQ), anthracycline (ANT), angucycline (ANG), tetracycline (TET), tetracenomycin (TCM) and pentangular (PEN). Bioengineering for diversification of PK-II core structures will generate libraries of bioactivities, which can serve the drug discovery in this family of compounds. …

Systematic Size Control In The Synthesis Of Zero-Valent Iron Nanoparticles, Grant C. Bleier

Chemistry and Chemical Biology ETDs

A novel synthetic method for the production of highly magnetic, low size-dispersity nanoparticles through reversible magnetic agglomeration is introduced and studied in detail. Initially, a weakly coordinating surfactant (3-octadecyl-2,4-pentanedione) is employed to produce a wide range of nanoparticle sizes ranging from 8 to 20 nm in diameter. The kinetics faced in these reactions by cheap and widely available iron complex precursors can be avoided in this method with the introduction of thermodynamic control, which occurs in the form of a magnetic precipitation event that essentially halts nanoparticle growth. Utilizing this synthetic method, the length of the alkyl chain on the …