Physical Sciences and Mathematics Commons^™

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Tethered Axial Coordination As A Control Modality In Rhodium(Ii)-Catalyzed Carbene Transfer Reactions, Anthony Dean Abshire

Doctoral Dissertations

Rhodium(II) paddlewheels are versatile carbene transfer catalyst that are broadly applied in insertion reactions, cycloadditions, and ylide transformations. The effects of axial coordination in rhodium(II)-catalyzed carbene transfer reactions are still little understood due to compounding factors that are difficult to isolate. Traditionally, researchers study axial coordination by addition of Lewis base additives. To ensure interaction between the Lewis base and catalyst, high molar equivalents are used. This can also have the undesired effect of hampering the activity of the catalyst and suppressing the yield of the reaction. We have developed ligands with a tethered Lewis base to overcome these issues. …

Polynorbornenes For Advanced Applications And Processes, Xinyi Wang

Doctoral Dissertations

Polynorbornenes have dramatically different properties and various applications depending on their chemical structures. The modular nature of norbornene-based systems provides a facile route toward synthesizing diverse polymeric materials, thus making them ideal materials for systematic structure-property investigations. Herein, their application as gas separation membranes and the correlation between their gas-transport properties and polymer structures will be investigated. Though many valuable correlations between gas-permeability and polynorbornene structure have been studied previously, many of these efforts have focused heavily on designing materials with various chemical structures to achieve high permeabilities. In contrast, the influence of molecular structure on: a) polynorbornene chain packing …

Influence Of Tethered, Axially Coordinated Ligands On Rh(Ii,Ii)-Catalyzed Carbene Transfer Reactions, Cristian E. Zavala

Doctoral Dissertations

Dirhodium (II,II) paddlewheel complexes have become ubiquitous in diazo-mediated carbene transfer reactions. The Rh(II,II)-carbene intermediate is capable of a large variety of transformations such as cyclopropanation, C-H and X-H (O, N, S, Si, B) insertion reactions, cyclopropenations, and ylide transformations. Cyclopropanation reactions resulting in the formation of functionalized cyclopropane structures has always been a major focus in Rh(II,II)-carbene chemistry. Improvements on catalytic performance in cyclopropanations has largely focused on the modification of the bridging ligands and has resulted in Rh(II,II) catalysts that exhibit high reactivity and selectivity in cyclopropanation reactions. However, high enantio- and diastereoselectivity is not easily achieved with …

Chiral Mesogen-Free Liquid Crystalline Polyethers With Sulfonylated Side Chains And Patchy Brush Nanoparticles, Caleb A. Bohannon

Doctoral Dissertations

Ferroelectric liquid crystalline polymers (LCPs) hold promise for various applications driven by low electric fields, e.g., electrocaloric materials, because of the higher molecular motion in the liquid crystalline (LC) state. However, traditional chiral smectic C (SmC*) LCPs exhibit small spontaneous polarizations due to the bulky aromatic mesogens and weak polar groups. This dissertation research is focused on the design of mesogen-free sulfonylated LCPs with a goal of seeking the ferroelectric SmC* phase. Such LCPs are expected to exhibit high polarizations owing to the sulfonyl’s large dipole moment. A series of poly(oxypropylene)s (POPs), with chirality being introduced into either the backbone …

Development Of Stimuli-Responsive Liposomes For Drug Delivery Applications, Jinchao Lou

Doctoral Dissertations

Liposomes are spherical nano-assemblies that are proven to be effective drug delivery vehicles. Due to their unique bilayer structures, they are able to encapsulate both hydrophilic and hydrophobic drugs in their aqueous inner core and membrane bilayers, respectively. While liposomal delivery platforms exbibit numerous advantages, the therapeutic efficacy of these platforms would be enhanced by developing triggered release strategies such that one can tune the timing and location of the cargo release in a controlled manner. In this dissertation, we mainly present the development of stimuli-responsive liposomes targeting different disease-associated metabolites utilizing rationally designed synthetic lipid switches.

In Chapter 2, …

Behavioral Modulation Of Supramolecular Assemblies Via Covalent And Non-Covalent Interfacial Transformations, Ann Fernandez

Doctoral Dissertations

There are several molecular level mechanisms at the origin of biological functions that serve as inspiration for the development of the “next generation” of materials that display adaptive and interactive properties. However, it will take time for synthetic materials to approach the level of complexity, robustness, and adaptability of biological systems. Although there are switchable platforms that respond via sensitized molecular components, there are currently no examples of materials that truly possess the type of autonomous behavior seen in biological systems. Even though these concepts are common in living organisms, their translation into a synthetic platform remains challenging to this …

Design Of Resposive Oligomeric And Polymeric Interfaces For Sensing And Controlled Release Applications, . Manisha

Doctoral Dissertations

Nature has designed magnificent responsive systems by constructing several interacting molecular level networks for the recognition and propagation of chemical and biochemical information. One of the eminent characteristics of these systems is their capability to quickly transduce molecular scale recognition events into macroscopic or visually observable responses. Inspired by these systems present in nature, we became interested in developing artificial responsive systems with similar capabilities. This dissertation will feature four such systems that employ amphiphilic oligomers and polymers which were chosen as the scaffolds because of their high thermodynamic stability, low critical aggregation concentrations, convenient handles to incorporate functional group …

Development Of Catalysts For The Ring-Opening Polymerization Of Cyclic Esters And The Coordination-Insertion Polymerization Of Olefins, Alicia Doerr

Doctoral Dissertations

Over the past few decades, interest in the design and synthesis of tailorable polymeric materials has grown due to the well documented correlation between structure, property, and function. However, in order to obtain polymers with desired microstructures, well controlled synthetic methods are needed. Therefore, the continued investigation of homogeneous, single-site polymerization catalysts is important to gain a deeper understanding of how systematic modifications of polymerization conditions, ligand scaffold, metal center identity, cocatalyst or activator identity, etc. affect the catalytic activity, selectivity, and/or polymer topology obtained when using these catalysts for the polymerization of a variety of monomers. This dissertation will …

Characterization Techniques And Cation Exchange Membrane For Non-Aqueous Redox Flow Battery, Kun Lou

Doctoral Dissertations

The motivation of this work comes from one of the major problems of emerging non-aqueous flow battery (NAFB) that a separator or membrane which facilitates conductivity and blocks redox species crossover does not exist. Although many aspects of principles can be mirrored from mature fuel cell and aqueous flow battery, it is found that some well-defined membrane properties in aqueous systems such as swelling, transport and interactions are different in non-aqueous solvents to some extent. However, the approach of this work does follow the way perfluorosulfonate ion exchange membrane (PFSA) facilitated development of fuel cell and aqueous flow battery in …

Fine Tuning Rhii Complexes With Tethered, Axial Coordination: Structural Studies And Application To Diazo-Mediated Cyclopropanation Reactions, Derek Cressy

Doctoral Dissertations

The cyclopropane moiety is an attractive synthetic target due to its application in pharmaceuticals and medicinal research. One effective strategy involves the formation of metal carbenoid species from diazo reagents. The carbenoid then reacts with an olefin substrate to generate the cyclopropane ring. Of the metal complexes that can facilitate this reaction, dirhodium(II) paddlewheel complexes are arguably the most prevalent catalysts. This is because modification of the bridging ligands enables control to be exerted over the catalyst’s chemoselectivity and enantioselectivity. Exploiting the axial site as a control element is often overlooked as strongly coordinated Lewis bases inhibit catalysis. Despite this, …

Synthesis, Characterization, And Applications Of Nucleobase-Functionalized Conjugated Polymers, Sina Sabury

Doctoral Dissertations

Understanding the effect of the functional groups at the terminus of the side chains is important for developing conjugated polymers through side chain engineering. Nucleobases, which are known for their multi-functionality, have not been deeply studied as functionality in conjugated polymers due to synthetic challenges. The overarching goal of my dissertation is to design, synthesize, characterize conjugated polymers bearing nucleobase functionality in their side chains and demonstrate their utility in various applications. Stille cross-coupling and direct arylation polymerization are used to synthesize adenine- and thymine-containing conjugated polymers. Monomer design requirements for successful polymerization are studied and conditions that optimize polymerization …

Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta

Doctoral Dissertations

Biologic drugs have gained enormous research attention in recent years as reflected by the development of multiple candidates to the clinical pipelines and an increased percentage of FDA approval. This is reasoned by the fact that biologics have been proven to deliver more predictive and promising benefits for many hard-to-cure diseases by ‘drugging the undruggable’ targets. However, the challenges associated with biologic drug development are multi-fold, viz, poor encapsulation efficacy, systemic instability, low cellular internalization and endosomal escape capability. Thus, it is essential to develop new molecular strategies that can not only address the associated drug delivery challenges, but also …

Providing Insight To Enable The Design Of Tailored, Nano-Structured Polymeric Surfaces And Interfaces, Onome J. Agori-Iwe

Doctoral Dissertations

Methods are presented for modifying polymeric material surfaces using: 1) selective surface segregation in binary branched/linear polymer blends, and 2) surface functionalization with polymer brushes. Using neutron reflectivity, elastic recoil detection, and other complementary techniques, the aim was to identify structure-property relationships and provide fundamental insight into the time evolution and formation of surfaces and interfaces in these materials.

In blends of poly(styrene) (PS) HyperMacs and DendriMacs in a linear deuterated PS (d-PS) matrix, smaller hyperbranched additives (<1E6 g/mol) move slower than their linear analogues. Larger (>1E6 g/mol) and less flexible hyperbranched additives with smaller fractal dimensions move faster than their linear analogues, suggesting that they are less …

Modulating Nanoparticle-Protein Interactions Through Covalent Or Noncovalent Approach For Biomedical Applications, Jingjing Gao

Doctoral Dissertations

Discoveries at the interface of chemistry, biology, and materials science have emerged as a powerful route to impact life science in this century. My research in the Thayumanavan group is focused on problems at this interface. A common theme of all the six projects is the use of modern synthetic organic chemistry to build interesting, novel macromolecules which are chemically rich, to study the molecular self-assembly behavior in solution and then translate to solve problems in the biomedical area. By addressing the design challenge to prepare novel amphiphiles with desired functional groups, controlled molecular weight and the ability to respond …

Protein Detection And Structural Characterization By Mass Spectrometry Using Supramolecular Assemblies And Small Molecules, Bo Zhao

Doctoral Dissertations

Mass spectrometry (MS) has played an increasingly prominent role in proteomics and structure biology because it shows superior capabilities in identification, quantification and structural characterization of proteins. To realize its full potential in protein analysis, significant progress has been made in developing innovative techniques and reagents that can couple to MS detection. This dissertation demonstrates the use of polymeric supramolecular assemblies for enhanced protein detection in complex biological mixtures by MS. An amphiphilic random co-polymer scaffold is developed to form functional supramolecular assemblies for protein/ peptide enrichment. The influences of charge density and functional group pK_a on host-guest interactions …

Providing Molecular Insight For Understanding Anion Exchange Membrane Conductivity, Michael Kwasny

Doctoral Dissertations

Anion exchange membranes (AEMs) are notorious for having both low alkaline stability and poor ion conductivity in fuel cell operation conditions, with solutions to these two challenges often being developed independent of each other. The chemical instability of an AEM is viewed through degradation of the polymer backbone and the cationic species and improving a material’s stability is approached by altering the polymer backbone, the cation, or both. On the other hand, poor ion conductivity is typically addressed by modifying bulk membrane properties such as increasing the ion exchange capacity (IEC), changing the morphology, or increasing the water uptake. These …

Reactive And Stimuli-Responsive Sulfonium-Based Polymer Zwitterions, Cristiam Santa Chalarca

Doctoral Dissertations

This dissertation describes the synthesis and characterization of novel monomers and (co)polymer zwitterions that incorporate trialkylsulfonium cations. The novel materials presented herein constitute a unique type of polymer zwitterions that exhibit salt- and temperature-dependent water solubility as well as inherent reactivity. The behavior of these polymers in aqueous solutions, as nanostructures, and at liquid-liquid interfaces was studied; in all cases, the inherent reactivity of the polymers was harnessed towards the fabrication of novel polymers and soft materials. Following an introductory chapter, Chapter 2 describes the synthesis of sulfonium sulfonate monomers and polymer zwitterions. Both styrenic and methacrylic monomers were synthesized …

Design, Synthesis And Study Of Functional Amphiphilic Polymers And Their Applications, Huan He

Doctoral Dissertations

Amphiphilic homopolymers with high densities of functional groups are synthetically challenging. Thiol-yne nucleophilic click reactions have been investigated to introduce multiple functional groups in polymers with high density. An electron deficient alkyne group bearing methacrylate monomer was polymerized using reversible addition−fragmentation chain-transfer (RAFT) polymerization. Subsequently, the electron deficient alkyne group on polymer side chain was readily reacted with a thiol reagent using triethylamine (TEA) as the organocatalyst. This reaction was found to be very efficient under mild conditions. The resultant homopolymer bearing thiol vinyl ether functional groups could perform a second thiol addition with a stronger base, such as triazabicyclodecene(TBD), …

Modification Of 2d Materials Utilizing Functional Polymer Interfacial Layers, Ryan Selhorst

Doctoral Dissertations

This dissertation describes the modification of 2D transition metal dichalcogenides (TMDCs). These materials exhibit unique electronic properties, ranging from metallic to insulating, and can transport either electrons (n-type) or holes (p-type). Polymers containing electronically-active moieties offer a path to control the electronic properties of a 2D material without altering the inherent structure of the semiconductor. This dissertation focuses on the synthesis of polymers bearing chalcogen-rich or zwitterionic moieties to alter the electronic and solution properties of 2D materials. Chapter 2 describes polymers containing sulfur-rich tetrathiafulvalene (TTF) and their effects as electroactive coatings on the TMDC molybdenum disulfide (MoS₂). …

Design And Self-Assembly Of Responsive Scaffolds For Food And Sensing Applications, Uma Sridhar

Doctoral Dissertations

Developing an understanding of how molecules, materials and complex systems contribute to biological functions is important since the interpretation of such mechanisms paves the way to further the development of materials that replicate natural functions or impart the observed properties to synthetic materials. The self-assembly of stimuli-responsive scaffolds based on micelles, liposomes, hydrogels and thin films has been of considerable interest. These systems need to be endowed with certain design features which influence the self-assembly and the responsiveness of the scaffold when subjected to external stimuli which could be physical, chemical or biological in nature. This kind of insight is …

Amphiphilic Assemblies With Responsive Characteristics At Surfaces And Interfaces, Piyachai Khomein

Doctoral Dissertations

Amphiphilic self-assembly has gained a lot of interest in both academic and industrial fields. Amphiphiles have a unique ability to self-assemble in water, providing a range of nanosized materials of various morphologies. Many efforts have been dedicated to developing responsive amphiphilic assemblies by introducing responsive characteristics into the amphiphile building blocks. Responsive assemblies have been utilized in many promising applications such as targeted drug delivery systems, smart sensors, and electronic devices. Here, we reported four different types of responsive assemblies created via the incorporation of different responsive groups either at the material’s surface or interface. To achieve the responsive characteristics …

The Benefit Of Precise Chemical Shift And Concentration Referencing In Nmr Applications, Ming Huang

Doctoral Dissertations

“In Nuclear Magnetic Resonance (NMR) spectroscopy, the chemical shift and intensity of NMR signals provide critical information about a sample's molecular structure, reaction conditions, and material properties. For the precise determination of structures and properties, it is critical to know sample or reaction conditions such as temperature, pH, concentration, or absolute amount of material. Chemical-shift and signal-intensity calibrations play a key role for extracting the maximum amount of information from NMR experiments. In this dissertation, internal and external reference standards are used to calibrate NMR spectra with respect to chemical shift and signal intensity. Sealed capillary tubes filled with specific …

Impact Of Chemical Doping On The Thermoelectric Charge Transport Of Organic Semiconductors, Connor J. Boyle

Doctoral Dissertations

The thermoelectric properties of organic semiconductors allow them to directly convert heat into electricity without the use of moving parts and to directly convert electricity into heat without the use of working fluids. These properties offer opportunities for the generation of electricity from non-conventional or renewable sources of heat and for refrigeration without the risk of leaking harmful working fluids at any length scale down to the nanoscale. Since organic materials are lightweight, flexible, and made from abundant resources, these opportunities could one day become affordable for widespread use and could be expanded to include specialized and otherwise difficult to …

Study Of Self-Assembly And Stimuli Responsive Behavior In Polymeric And Dendritic Amphiphiles, Poornima Rangadurai

Doctoral Dissertations

Natural processes are intricately detailed and able to convert molecular-level events into macroscopic or visually observable properties. This is made possible through multiple interactions at the molecular level, signaling due to covalent and non-covalent interactions, and supramolecular networks that rely on dynamic, non-equilibrium structures. Detailing processes in this manner is the current quest for material science research and designing materials for this purpose is usually via a key process known as self-assembly. Self-assembly is a process in which a material with varied components organizes itself into a particular pattern due to various specific inter and intra molecular interactions. By understanding …

Formulation And Characterization Of Lipogels As A Tunable Delivery Scaffold, Celia Homyak

Doctoral Dissertations

Nanomedicines within the clinic commonly utilize lipid-based scaffolds due to their aqueous assembly and non-covalent dual-guest loading capabilities. Nevertheless, poor stability in vivo and premature guest release remains a challenge with these systems. Polymeric nanomaterials are a popular alternative due to their good stability in vivo with controllable guest release. A caveat to polymeric scaffolds though, is the excess synthetic effort involved for non-covalent dual-drug encapsulation. Benefit lies in harnessing advantages of lipid and polymeric materials via lipid-polymer hybrid scaffold. Such materials have promise due to their dual-encapsulation and dual-stimuli-sensitive characteristics. The need to better understand these materials led us …

Design And Synthesis Of Stimuli-Responsive Polymeric Nanogels Towards Therapeutic Translation, Mallory R. Gordon

Doctoral Dissertations

In the application of delivery of therapeutics, nanostructures of various composition have been employed due to their capacity to act as a host for lipophilic payloads. Advances in the synthetic preparation, size, morphology, and chemical or physical characteristics of polymers have impacted their development and versatility. A detailed understanding of polymeric nanoparticle host-guest properties is crucial to their practical translation to specific delivery applications. Further, these features must be highly tailorable to overcome biological barriers, stably encapsulate their therapeutic contexts, and exhibit payload release selectively in the target environment. In this dissertation, we aim to rationally design polymeric nano-scale assemblies …

Light-Harvesting And Light-Responsive Materials For Optoelectronic And Biological Applications, Youngju Bae

Doctoral Dissertations

In photodynamic therapy, several critical standards are required of photosensitizers including high singlet oxygen quantum yield, biocompatibility in dark, and long term photochemical stability. In addition, current PDT systems lack active targeting strategies to tumor cells, and instead mainly rely on the natural distribution of PS in the body following injection and application of near-infrared light treatment in the tumor region. This thesis describes a series of BODIPY-based molecules that were designed, synthesized and studied as photosensitizers with high singlet oxygen generation capacity through utilizing the heavy atom effect. Additionally, aqueous solubility and active targeting capability were introduced by photosensitizer …

Part I: Design, Synthesis, And Studies Of Novel Age-Inhibitors And Age-Breakers; Part Ii: Novel Synthetic Methods For Organofluorine Compound, Jatin Mehta

Doctoral Dissertations

"Novel small molecule inhibitors and breakers of advanced glycation end-products (AGEs) have been synthesized and their in vitro inhibitory activities have been studied by ¹³C NMR, fluorescence, and UV-visible spectroscopy. We have demonstrated that these AGE-inhibitors and AGE-breakers were found to be more effective in their sequestration of AGE intermediates, such as dehydroascorbate (DHA) than the state-of-the art phenacylthiazolium bromide (PTB)-based AGE-inhibitors and AGE-breakers. Citric acid and other polyphenolic antioxidants have substantial AGE inhibitory effects in the D-glucose/leucine or benzylamine Maillard reaction model systems, and thus they are suitable as dietary additives for ameliorating AGE-induced complications.

Organofluorine compounds have …

Design And Synthesis Of Analogs Of Myo-Inositol, Serine, And Cysteine To Enable Chemical Biology Studies, Tanei J. Ricks

Doctoral Dissertations

Phosphorylated myo-inositol compounds including inositol phosphates (InsPs) as well as the phosphatidylinositol polyphosphate lipids (PIP_ns) are critical biomolecules that regulate many of the most important biological processes and pathways. They are aberrant in many disease states due to their regulatory function. The same is true of the phospholipid phosphatidylserine (PS) which can serve as a marker to begin apoptosis. However, the full scope of activities of these structures is not clear, particularly since techniques that enable global detection and analysis of the production of these compounds spatially and temporally are lacking. With all of these obstacles in …