Browsing by Author "Bailey, Travis S., committee member"

Now showing 1 - 20 of 20

Open Access
A nanoparticulate-reinforced hyaluronan copolymer hydrogel for intervertebral disc repair
(Colorado State University. Libraries, 2011) Yonemura, Susan S., author; James, Susan P., advisor; Bailey, Travis S., committee member; Kisiday, John D., committee member; Wheeler, Donna L., committee member
Degenerative disc disease (DDD) is an inevitable consequence of aging, commonly resulting in low back pain (LBP). Current clinical treatment options for disc degeneration exist at two extremes: conservative management or extensive surgical intervention. Given the economic impact of lost productivity and disability associated with low back pain, there is significant interest in earlier, less invasive intervention. Biomimetic disc replacement and regenerative therapies offer an attractive alternative strategy for intervertebral disc repair, but materials employed to date have not exhibited a successful combination of mechanical and biological properties to achieve viable solutions. The composite material developed and characterized in this work consisted of a novel hyaluronan-co-poly(ethylene-alt-maleic anhydride) (HA-co-PEMA) hydrogel matrix reinforced with nanoparticulate silica; the hydrogel matrix provided a compliant hydrated matrix conducive to integration with the surrounding tissue while the nanoparticulate reinforcement was manipulated to mimic the mechanical performance of healthy ovine nucleus pulposus (NP) tissue. HA-co-PEMA was formed via an esterification reaction between a hydrophobically-modified HA complex and PEMA, and candidate formulations were characterized by chemical, thermal, and physical means to select an appropriate base hydrogel for the reinforced composite. Three grades of commercially-available fumed silica, varying by degree of hydrophobic surface modification, were evaluated as nanoparticulate reinforcement for the composite materials. Mechanical testing of two reinforced composite formulations (620-R and 720-R) emphasized dynamic shear properties and results were directly compared to ovine nucleus pulposus (NP) tissue. The complex shear modulus (G*) for 620-R ranged from 1.8±0.2 KPa to 2.4±0.3 KPa over the frequency range 0.1 Hz < f < 10 Hz, while G* for 720-R varied from 4.4 ± 0.5 KPa to 6.1 ± 0.6 KPa over the same frequency range. Ovine NP tissue tested using identical methods exhibited G* of 1.7 ± 0.2 KPa at 0.1 Hz up to 3.8 ± 0.5 KPa at 10 Hz. Thus, the complex shear moduli (G*) for 620-R and 720-R effectively bracketed G* for NP over a physiologically-relevant frequency range. Subsequent in vitro cytotoxicity and biocompatibility experiments suggest that the 720-R formulation warrants consideration for future in vivo modeling.
Open Access
Control of polymer network structure and degradation
(Colorado State University. Libraries, 2017) Yaghoubi Rad, Ima, author; Stansbury, Jeffrey W., advisor; Kipper, Matthew J., advisor; James, Susan P., committee member; Bailey, Travis S., committee member
This thesis presents work performed evaluating controlled degradation in polymeric networks via incorporation of nanogels either as precursor or as a component of pseudo-interpenetrating polymeric networks. These polymeric crosslinked nanoparticles have applications in drug/gene delivery, cell imaging, and inert or functional prepolymer nano-fillers, therefore controlling their molecular weight (size) and structural properties are mandatory requirements. In addition to the primary effects of reactant selection on the nanogel formation, the solvent used and the agitation rate can provide additional parameters to control nanogel size. This work also develops a practical understanding of polymer characteristics and degradation kinetics of networks constructed from reactive nanogels with regiospecifically degradable linkages. Analogous non-degradable control structures are also prepared for each experimental condition. Clear, monolithic photopolymers are prepared from 50 wt% solvent-based dispersions of the reactive nanogels. The results of equilibrium swelling, mass loss, and compressive modulus (dry/swollen) demonstrate interplay between hydrophilic/hydrophobic effects, labile linkage location, and the crosslinking density that appears to dominate many of predicted property trends. The introduction of hydrolytically degradable linkages (PLA) into the internal crosslink structure of the nanogel promotes greater hydrophobic character compared to PLA placement in external reactive side chains. Consequently, nanogel-based networks with shorter hydrophilic crosslinker and lower crosslinker concentration show lower mass swelling rate, higher Tg, and lower compressive modulus reduction. Nanogels unlock an immense potential in designing superior alternatives for accepted materials with significantly reduced network heterogeneity compared to conventional hydrogels, which ultimately appoint them as novel candidates for controlled drug delivery and tissue engineering applications. Another part of this work demonstrates the effects of nano-scale pre-crosslinked hydrophobic particles as additive to model labile monomer on hydrolytic degradation. The modification of hydrolytically vulnerable polymers through the intimate integration of secondary networks based on styrenic nanogel structures is intended to reduce or even eliminate hydrolytic degradation potential. Nanogel addition at any level produces reduction in network swelling and mass loss proportional to nanogel content. The flexural modulus and ultimate transverse strength of nanogel-loaded resin monomer (TEGDMA) does not change compared to neat resin homopolymer as one control material in addition to the homopolymer of PEG2000PLADMA, which includes polylactic acid segments in the crosslinks. The use of a monomer-swollen highly crosslinked hydrophobic nanogel offers a versatile platform from which hydrolytic and potentially enzymatic degradation can be suppressed in a variety of applications such as polymer-based dental restoratives while retaining resin formulation, handling and mechanical properties. Some of the most important challenges in processing high performance materials are their high viscosity and limited solubility as a result of high molecular weight, intermolecular interactions, and rigid monomeric structure. Alternatively, high strength thermoset materials formed by ambient photopolymerization are limited in their performance by incomplete, vitrification-limited conversion, and relatively low glass transition temperature. In non-biological applications, significant effort has been focused on improving processing techniques and advanced machinery, and notably trivial attention has been paid to upgrade molecular structure of the resins. On the other hand, in biological applications photocuring is the perfect choice since applying high temperatures is practically impossible. As a result, another objective of this work was to develop an alternative photocurable material with enhanced processability, yet retaining thermal and mechanical properties of conventional resins. The average diameter of these polymeric particles is less than 20 nm with glass transition temperatures greater than 200 °C. These paradoxical properties trace back to molecular-level rearrangements of the same monomeric building blocks used in current thermoplastic/thermoset resins.
Open Access
Development of Lewis pair methodologies for advanced polymer synthesis and application
(Colorado State University. Libraries, 2022) McGraw, Michael Lawrence, author; Chen, Eugene Y.-X., advisor; Bailey, Travis S., committee member; Rappe, Anthony K., committee member; Linden, James C., committee member
This dissertation describes the development of new chemistries related to Lewis pair polymerization methodology with emphasis on chemical selectivity and control. Selectivity is defined as the ability to promote desirable chemistry while simultaneously discouraging unwanted chemistry. Control is defined as the ability to target specific and highly sophisticated products from the outset and the ability to reliably achieve that desired product as a consequence of predictable reaction behavior. The themes contained herein relate to catalysis, mechanism elucidation and application, polymer synthesis, and green chemistry. Chapter 1 introduces LPP and includes sections from my published perspective article Lewis Pair Polymerization: Perspective on a Ten-Year Journey. This chapter includes a brief history of the technique, as well as mechanistic fundamentals and key features of the method. Chapters 2 & 3 describes the LPP of the challenging biorenewable monomer methyl crotonate. Chapter 4 describes the invention of the compounded sequence control (CSC) LPP method. Chapter 5 discusses the application of CSC to the synthesis of more advanced cyclic diblock structures using by utilizing a unique sorbate-based initiation system. Chapter 6 details the mechanism by which the sorbate-based initiation system effects cyclization to produce cyclic polymers with spatial and temporal control. Finally, Chapter 7 offers some conclusions and future directions.
Open Access
Development of microsystems for point-of-use microorganism detection
(Colorado State University. Libraries, 2018) Wang, Lei, author; Dandy, David S., advisor; Tobet, Stuart A., committee member; Henry, Chuck S., committee member; Geiss, Brian J., committee member; Bailey, Travis S., committee member; Marchese, Anthony J., committee member
To view the abstract, please see the full text of the document.
Open Access
Disentangle model differences and fluctuation effects in DPD simulations of diblock copolymers
(Colorado State University. Libraries, 2013) Sandhu, Paramvir, author; Wang, Qiang (David), advisor; Bailey, Travis S., committee member; Szamel, Grzegorz, committee member
In the widely used dissipative particle dynamics (DPD) simulations 1, polymers are commonly modeled as discrete Gaussian chains interacting with soft, finite-range repulsions. In the original DPD simulations of microphase separation of diblock copolymer melts by Groot and Madden 2 , the simulation results were compared and found to be consistent with the phase diagram for the "standard model" of continuous Gaussian chains with Dirac δ-function interactions obtained from self-consistent field (SCF) calculations. Since SCF theory is a mean-field theory neglecting system fluctuations/correlations while DPD simulations fully incorporate such effects, the model differences are mixed with the fluctuation/correlation effects in their comparison. Here we report the SCF phase diagram for exactly the same model system as used in DPD simulations. Comparing our phase diagram with that for the standard model highlights the effects of chain discretization and finite-range interactions, while comparing our phase diagram with DPD simulation results unambiguously (without any parameter-fitting) reveal the effects of system fluctuations/correlations neglected in the SCF theory.
Open Access
Fast off-lattice Monte Carlo simulations of phase transitions in block copolymers and liquid crystals
(Colorado State University. Libraries, 2015) Zong, Jing, author; Wang, Qiang, advisor; Bailey, Travis S., committee member; Szamel, Grzegorz, committee member; Watson, A. Ted, committee member
The basic idea of the so-called fast off-lattice Monte Carlo (FOMC) simulations is to perform particle-based Monte Carlo (MC) simulations in continuum with the excluded-volume interactions modeled by soft repulsive potentials that allow particle complete overlapping, where using soft potentials naturally arises from the application of coarse-grained models. This method is particularly suitable for the study of equilibrium properties of soft matter. One apparent advantage of FOMC is that using soft potentials can greatly improve the sampling efficiency in the simulations. Another advantage is that FOMC simulations can be performed in any statistical ensemble, and all the advanced off-lattice MC techniques proposed to date can be readily applied to further improve the sampling efficiency. Moreover, it provides a powerful methodology to directly compare theoretical results with simulation results without any parameter fitting. Last but not least, using FOMC is the only way to study experimentally accessible fluctuation/correlation effects in many-chain systems. This work makes use of FOMC simulations to study phase transitions in block copolymers and liquid crystals. To compare with the simulations results, various theoretical methods are also applied in the research. Chapter 2 is devoted to study the classic yet unsolved problem of fluctuation/correlation effects on the order-disorder transition (ODT) of symmetric diblock copolymer (DBC). In Chapter 3, we highlight the importance of quantitative and parameter-fitting-free comparisons among different models/methods. In Chapter 4, we investigate the effect of system compressibility on the ODT of DBC melts. In Chapter 5, we extend FOMC simulations to study the isotropic-nematic transition of liquid crystals. Finally, in Chapter 6, we briefly summarize all the studies in this dissertation and give some directions to future work.
Open Access
Kinetic and mechanistic studies of supported-nanoparticle heterogeneous catalyst formation in contact with solution
(Colorado State University. Libraries, 2011) Mondloch, Joseph E., author; Finke, Richard G., advisor; Bailey, Travis S., committee member; Ferreira, Eric M., committee member; Prieto, Amy L., committee member; Shores, Matthew P., committee member
This dissertation begins with a comprehensive and critical review of the literature addressing the kinetics and mechanism(s) of supported-nanoparticle heterogeneous catalyst formation. The review chapter that follows makes apparent that routine kinetic monitoring methods, as well as well-defined supported-nanoparticle formation systems, are needed in order to gain fundamental insights into the mechanisms of supported-nanoparticle heterogeneous catalyst formation--a somewhat surprising finding given the long history as well as commercial importance of heterogeneous catalysis. Hence, the research presented within this dissertation is focused on (i) developing a kinetic monitoring method (i.e., in what follows, the cyclohexene reporter reaction method) capable of measuring supported-nanoparticle formation in contact with solution, and (ii) developing a well-defined supported-nanoparticle formation system, also in contact with solution, that is amenable to rigorous mechanistic studies. Development of the cyclohexene reporter reaction has allowed for the rapid and quantitative monitoring of the kinetics of Pt(0)n/Al2O3 and Pt(0)n/TiO2 supported-nanoparticle heterogeneous catalyst formation in contact with solution from H2PtCl6/Al2O3 and H2PtCl6/TiO2 respectively. Importantly, those kinetic studies revealed conditions where the most desirable, chemical-reaction-based, supported-nanoparticle formation conditions are present rather than diffusional-limited kinetic regimes. The largest drawback when utilizing the H2PtCl6 as a supported-precatalyst is its speciation--that is, other solvated Pt-based species form when in contact with solution. Such non-uniform speciation leads to a large variation in the supported-nanoparticle formation kinetics, observations that were obtained through the use of the cyclohexene reporter reaction kinetic monitoring method. Due to the large variability in the formation kinetics associated with the H2PtCl6 precatalyst speciation, synthesized next as a part of this dissertation work was the well-defined, fully characterized, speciation-controlled supported-organometallic precatalyst, Ir(1,5-COD)Cl/γ;-Al2O3. When in contact with acetone, cyclohexene and H2 this supported-precatalyst was found to evolve into a highly active and long-lived Ir(0)~900/γ;-Al2O3 supported-nanoparticle catalyst. The kinetics of Ir(0)~900/γ-Al2O3 formation were successfully followed by the cyclohexene reporter reaction method and found to be well-fit by a two-step mechanism consisting of nucleation (A → B, rate constant k1) followed by autocatalytic surface growth (A + B → 2B, rate constant k2) previously elucidated by Finke and Watzky. More specifically, nucleation was found to occur in solution from Ir(1,5-COD)Cl(solvent), while nanoparticle growth occurs on the γ-Al2O3 support, but in a reaction that involves the Ir(1,5-COD)Cl(solvent) species in solution. Most importantly, the fits to the two-step mechanism suggest that the nine synthetic and mechanistic insights, of nanoparticle formation in solution, should now be applicable to the formation of supported-nanoparticle heterogeneous catalysts in contact with solution. That is, it seems reasonable to expect that these studies will allow a more direct avenue for transferring both the mechanistic and synthetic insights that have resulted from the modern revolution in nanoparticle science to the synthesis of size, shape and compositionally controlled supported-nanoparticle catalysts under the nontraditional, mild and flexible conditions where supported organometallics and other precursors are in contact with solution.
Open Access
Ligand and reaction development in the Rhodium(III)-catalyzed C-H activation-mediated synthesis of n-heterocycles
(Colorado State University. Libraries, 2013) Hyster, Todd K., author; Rovis, Tomislav, advisor; Finke, Richard G., committee member; Chen, Eugene Y.-X., committee member; Bailey, Travis S., committee member; Kanatous, Shane B., committee member
Described herein are the development of new directing groups and new ligands for Rh(III)- catalyzed, multi-component synthesis of nitrogen containing heterocycles. The amide directing group was found to be an effective coupling partner for the synthesis of isoquinolones. Mechanistic experiments suggested the possibility to activated alkenyl C-H bonds for the synthesis of pyridones. During these studies, development of a new cyclopentadienyl ligand (Cpt) for C-H activation allowed for enhanced regioselectivity in the alkyne insertion event. Oxime directing groups were found to provide pyridines when coupled with alkynes. Again the Cpt ligand impacted the alkyne migratory insertion event. This ligand is also effective in controlling the migratory insertion of alkenes in the synthesis of dihydroisoquinolones. An enantioselective synthesis of dihydroisoquinolones was discovered using a strept(avidin)-based artificial metalloenzyme providing enhanced reactivity, regioselectivity, and enantioselectivity. This artificial metalloenzyme is also effective for controlling the enantioselective synthesis of γ-lactams from diazo compounds and benzamides.
Open Access
Low-temperature oxidizing plasma surface modification and composite polymer thin-film fabrication techniques for tailoring the composition and behavior of polymer surfaces
(Colorado State University. Libraries, 2014) Tompkins, Brendan D., author; Fisher, Ellen R., advisor; Henry, Charles S., committee member; Bailey, Travis S., committee member; Szamel, Grzegorz, committee member; James, Susan P., committee member
This dissertation examines methods for modifying the composition and behavior of polymer material surfaces. This is accomplished using (1) low-temperature low-density oxidizing plasmas to etch and implant new functionality on polymers, and (2) plasma enhanced chemical vapor deposition (PECVD) techniques to fabricate composite polymer materials. Emphases are placed on the structure of modified polymer surfaces, the evolution of polymer surfaces after treatment, and the species responsible for modifying polymers during plasma processing. H2O vapor plasma modification of high-density polyethylene (HDPE), low-density polyethylene (LDPE), polypropylene (PP), polystyrene (PS), polycarbonate (PC), and 75A polyurethane (PU) was examined to further our understanding of polymer surface reorganization leading to hydrophobic recovery. Water contact angles (wCA) measurements showed that PP and PS were the most susceptible to hydrophobic recovery, while PC and HDPE were the most stable. X-ray photoelectron spectroscopy (XPS) revealed a significant quantity of polar functional groups on the surface of all treated polymer samples. Shifts in the C1s binding energies (BE) with sample age were measured on PP and PS, revealing that surface reorganization was responsible for hydrophobic recovery on these materials. Differential scanning calorimetry (DSC) was used to rule out the intrinsic thermal properties as the cause of reorganization and hydrophobic recovery on HDPE, LDPE, and PP. The different contributions that polymer cross-linking and chain scission mechanisms make to polymer aging effects are considered. The H2O plasma treatment technique was extended to the modification of 0.2 µm and 3.0 µm track-etched polycarbonate (PC-TE) and track-etched polyethylene terephthalate (PET-TE) membranes with the goal of permanently increasing the hydrophilicity of the membrane surfaces. Contact angle measurements on freshly treated and aged samples confirmed the wettability of the membrane surfaces was significantly improved by plasma treatment. XPS and SEM analyses revealed increased oxygen incorporation onto the surface of the membranes, without any damage to the surface or pore structure. Contact angle measurements on a membrane treated in a stacked assembly suggest the plasma effectively modified the entire pore cross section. Plasma treatment also increased water flux through the membranes, with results from plasma modified membranes matching those from commercially available hydrophilic membranes (treated with wetting agent). Mechanisms for the observed modification are discussed in terms of OH and O radicals implanting oxygen functionality into the polymers. Oxidizing plasma systems (O2, CO2, H2O vapor, and formic acid vapor) were used to modify track-etched polycarbonate membranes and explore the mechanisms and species responsible for etching polycarbonate during plasma processing. Etch rates were measured using scanning electron microscopy; modified polycarbonate surfaces were further characterized using x-ray photoelectron spectroscopy and water contact angles. Etch rates and surface characterization results were combined with optical emission spectroscopy data used to identify gas-phase species and their relative densities. Although the oxide functionalities implanted by each plasma system were similar, the H2O vapor and formic acid vapor plasmas yielded the lowest contact angles after treatment. The CO2, H2O vapor, and formic acid vapor plasma-modified surfaces were, however, found to be similarly stable one month after treatment. Overall, etch rate correlated directly to the relative gas-phase density of atomic oxygen and, to a lesser extent, hydroxyl radicals. PECVD of acetic acid vapor (CH3COOH) was used to deposit films on PC-TE and silicon wafer substrates. The CH3COOH films were characterized using XPS, wCA, and SEM. This modification technique resulted in continuous deposition and self-limiting deposition of a-CxOyHz films on Si wafers and PC-TE, respectively. The self-limiting deposition on PC-TE revealed that resulting films have minimal impact on 3D PC structures. This technique would allow for more precise fabrication of patterned or nano-textured PC. PECVD is used to synthesize hydrocarbon/fluorocarbon thin films with compositional gradients by continuously changing the ratio of gases in a C3F8/H2 plasma. The films are characterized using variable angle spectroscopic ellipsometry (VASE), Fourier transform infrared spectroscopy (FTIR), XPS, wCA, and SEM. These methods revealed that shifting spectroscopic signals can be used to characterize organization in the deposited film. Using these methods, along with gas-phase diagnostics, film chemistry and the underlying deposition mechanisms are elucidated, leading to a model that accurately predicts film thickness.
Open Access
Membrane adsorbers and novel affinity peptides for recombinant protein purification
(Colorado State University. Libraries, 2015) Weaver, Justin, author; Wickramasinghne, S. Ranil, advisor; Qian, Xianghong, committee member; Carlson, Jon O., committee member; Bailey, Travis S., committee member
The purification of recombinant proteins for use as pharmaceutically active ingredients represents one of the largest costs of drug development and production. Of the different classes of recombinant protein therapeutics monoclonal antibodies represent the largest percentage of protein therapeutics currently on the market with even more in clinical development. The work presented in this thesis describes the evaluation of both commercial and newly designed anion exchange and hydrophobic interaction (HIC) membrane adsorbers as well as identification of novel affinity peptides for the purification of recombinant proteins, specifically monoclonal antibodies. Commercially available anion-exchange membrane adsorbers were evaluated for their potential to remove impurities commonly present at low concentration in recombinant protein solutions expressed in mammalian cell culture. These so-called trace impurities include virus, host cell proteins, and DNA; these impurities are of particular concern because they are highly immunogenic at very low concentrations. Ionic strength and pH were shown to be the dominant factors affecting impurity binding on quaternary amine (Q) membranes indicating these ligands interact with the impurities primarily through electrostatic interactions. It is likely impurity interactions with primary amine ligands involved not only electrostatic but hydrogen bonding interactions which stabilized impurity-ligand interactions enabling greater removal at a broader range of solution pH and ionic strength conditions. Binding of host cell proteins with a broad range of isoelectric points was also demonstrated using the primary amine ligand as compared to the Q ligands. The effect of solution pH, ionic strength, flow rate, and the presence of competing anionic species was investigated. In addition to commercially available anion-exchange membrane adsorbers novel anion-exchange membranes, developed by Dr. Bharat Bhut and Prof. Scott Husson at Clemson University, were evaluated for binding capacity and virus removal. Regenerated cellulose microfiltration membranes were modified with a negatively-charged quaternary amine polymer, systematically varying the polymer chain density and length. IgG and DNA binding capacity, as well as minute virus of mice removal, was evaluated as a function of polymer chain density and length. It was shown that IgG binding capacity increased with polymer chain density indicating IgG access to binding sites was not a limiting factor. Similarly, high polymer chain density and longer polymerization time (translating to longer polymer chain length) resulted in higher DNA binding and virus removal again indicating ligand accessibility was not an issue even with large solutes such as virus. Environmentally-responsive hydrophobic interaction membranes were also developed in the Wickramasinghe lab and evaluated for protein binding capacity and recovery. Three-dimensional polymer brushes were grafted from 0.45 µm pore size regenerated cellulose membrane surfaces. The dynamic binding capacity of human IgG was greater than current commercially available hydrophobic interaction membranes with comparable recoveries. Affinity purification using novel small peptides was also explored as an antibody purification tool. Several heptapeptide affinity ligands were identified that bound specifically to the Fc region of IgG. These peptides have similar function to Staphylococcus Aureus Protein A, which is used extensively as an affinity purification ligand for monoclonal antibodies in the pharmaceutical industry. A large library of seven amino acid-long peptides was screened via M13 Phage Display for specific binding to the Fc, or constant region, of human IgG antibody. After initial identification, specificity of binding only to IgG was demonstrated through subsequent competitive ELISA assays. Though the affinity peptides were initially screened against human IgG₄ Fc, binding to a larger subset of human and non-human antibodies was shown indicating the peptides were binding to highly conserved regions on the antibodies. Because Protein A has some limitations in industrial process applications, these novel heptapeptides may provide an alternative solution for affinity purification of monoclonal antibodies.
Open Access
Organopolymerization of multifunctional γ-butyrolactones
(Colorado State University. Libraries, 2018) Tang, Jing, author; Chen, Eugene Y.-X., advisor; Szamel, Grzegorz, committee member; Miyake, Garret M., committee member; Bailey, Travis S., committee member; Belfiore, Laurence A., committee member
The complexity of polymerizations increases drastically as the functionality of monomers increases, which brings about challenges for elucidation of polymerization mechanisms, establishing control of the polymerization, and characterization of the resulting polymer structures. On the other hand, the increased multifunctionality in monomers and polymers offers new opportunities to create polymers with unique structures and interesting properties. The research described in this dissertation demonstrates both challenges and advantages that multifunctionality brings into the polymerization and polymer structures. The first successful polymerization of the naturally occurring, OH-containing, tri-functional monomer Tulipalin B (βHMBL) was achieved by utilizing N-heterocyclic carbene and phosphazene superbase catalysts. Owing to its presence of both the reactive exocyclic double bond and hydroxyl group, the resulting P βHMBL is a branched vinyl–ether lactone copolymer structure with six different types of substructural units. The results reveal multiple types of reaction pathways and their mechanistic crossovers involved in the polymerization, including conjugate Michael and oxa-Michael additions, proton transfer processes, as well as ene-type dehydration reactions, enabled by proton transfer. The reactions of other less complicated multifunctional γ-butyrolactone-based monomers under same conditions was also studied to help uncover the polymerization mechanism, including the polymerization of bifunctional (endocyclic double bond, lactone ring) dihydrofuran-2(3H)-one (FO), 3-methylfuran-2(5H)-one (3-MFO), and 5-methylfuran-2(5H)-one (5-MFO), as well as trifunctional (endocyclic or exocyclic double bond, lactone ring, hydroxyl group) 3-(hydroxymethyl) furan-2(5H) one (3-HMFO). The polymerization of the parent FO leads to a vinyl-addition polymer, while the predominant trimerization and dimerization are observed in the reaction involving the two methyl substituted derivatives, 3-MFO and 5-MFO. The polymerization of trifunctional 3-HMFO gives a poly(vinyl–ether lactone) copolymer structure, via two different types of base activation mechanisms and a combination of Michael and ox-Michael additions and proton transfer processes. This thesis work also investigates how different initiation and termination chain ends of poly(γ butyrolactone) (PγBL) affect the materials properties, including thermal stability, thermal transitions, thermal recyclability, hydrolytic degradation, and dynamic mechanical behavior. Four different chain end-capped polymers with similar molecular weights have been synthesized. The termination chain end showed a large effect on polymer decomposition temperature and hydrolytic degradation. Overall, by chain-end capping, linear PγBL behaves much like cyclic PγBL in those properties sensitive to the chain ends.
Open Access
Part one: The formal total synthesis of dehydrogliotoxin and the first synthesis of an epidiselenodiketopiperazine and Part two: Towards the total synthesis of the tetrapetalones
(Colorado State University. Libraries, 2013) McMahon, Travis Chandler, author; Wood, John L., advisor; Kennan, Alan J., committee member; Ferreira, Eric M., committee member; Bailey, Travis S., committee member; Crick, Dean C., committee member
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), affects approximately one third of the global population and is associated with nearly two million deaths annually. Although there are known cures for TB, current treatment plans suffer due to length, usually taking 6-9 months to complete. Additionally, developing countries lack the infrastructure and resources necessary to both efficiently diagnose and treat patients. Of particular concern are an increasing number of strains of TB that are becoming resistant to the current drug regimens, which has been a result of patients beginning, but not completing their treatment. In light of these facts it is clear there is a continuing need to develop simplified and shorter treatments for TB, and with the increasing prevalence of resistant strains, chemically unique targets should be investigated. As part of a collaborative effort with the Hung group at the Broad Institute, we identified two related epidithiodiketopiperazine (ETP) natural products, gliotoxin and dehydrogliotoxin, as potential candidates for exploration as anti-TB agents. We initially targeted a synthesis of dehydrogliotoxin, as it had also never been tested against MTB, whereas gliotoxin was known to be active. Additionally, as dehydrogliotoxin was the simpler of the two compounds, we believed it could be synthesized more rapidly and also be more amenable to derivatization to form structural analogs. The synthetic studies towards dehydrogliotoxin culminated in a formal total synthesis that featured a key two step amidation-intramolecular ring-closure. With access to dehydrogliotoxin we were able to test it against MTB and found its activity to be comparable to gliotoxin. We next turned our attention to the synthesis of structural analogs in hopes of identifying a compound that could potentially be used as an anti-TB therapeutic. In that regard, we targeted a compound wherein the disulfide region of the natural product was replaced with a diselenide. As an epidiselenodiketopiperazine (ESeP) had never been synthesized before, we initially explored the installation of this functional group in a model system. These synthetic efforts resulted in the synthesis of an ESeP, both from a simple diketopiperazine and directly from an ETP. Additionally, in these model systems, the ESeP exhibited comparable activity towards MTB as the ETP. Tetrapetalone A was isolated in 2003 by Hirota and coworkers from a culture filtrate of Streptomyces sp. USF-4727. The related compounds tetrapetalones B, C, and D were isolated from the same Streptomyces strain in 2004. We became interested in this family of natural products due to their interesting structural features and the synthetic challenge they present. Salient features of the tetrapetalones include a tetracyclic core containing a tetramic acid, a seven-membered ring possessing a trisubstituted double bond, a p-quinol, and a five-membered ring with a pendant β-rhodinose. Several strategies towards the synthesis of the tetrapetalones have been explored. In our initial approach we hoped to form the seven-membered ring of the natural product through nucleophilic attack of the aromatic ring onto a pendant palladium π-allyl species. While exploring this process, we found that the desired seven-membered product was not formed, instead we isolated a product containing a five-membered ring, the result of attack at the wrong position of the palladium π-allyl species. Attempts to bias the substrate towards formation of the desired seven-membered ring through a transannular palladium π-allyl approach proved unfruitful. Our current route features a Friedel-Crafts acylation to form the seven-membered ring containing the trisubstituted double bond. The precursor for this approach was built up rapidly from simple starting materials, and the desired Friedel-Crafts reaction proceeds smoothly. Furthermore, we have implemented a C-H oxidation protocol to install a synthetic handle, which can ultimately be converted to an alkyne that we envision can be transformed into the five-membered ring bearing the sugar moiety in order to finish the natural product. Concurrent to the approaches described above, we have also targeted the related natural product, ansaetherone, which was isolated from the same Streptomyces strain as the tetrapetalones and is proposed to be a biosynthetic precursor to the family. The ultimate goal in this approach was to develop a synthesis of ansaetherone and explore methods to convert it to one of the members of the tetrapetalones in a biomimetic fashion. Our proposed synthesis included a key tandem enyne-cross metathesis to form the eleven-membered ring present in the natural product. Although this synthesis is still in its infancy, we have accessed a compound that is a few synthetic steps away from the precursor to explore the key step. We are currently exploring an improved synthesis of this intermediate and ways to elaborate it to the natural product.
Open Access
Photo-induced electron transfer in cu(i) bis-phenanthroline based assemblies. Part I: Chromophore-acceptor diads. Part II: Donor-chromophore-acceptor triads
(Colorado State University. Libraries, 2013) Lazorski, Megan, author; Elliott, C. Michael, advisor; Shores, Matthew P., committee member; Chen, Eugene, committee member; Bailey, Travis S., committee member; Sites, James R., committee member
The photophysical behavior of [Cu(I)P2] (P=2,9-disubstituted-1,10-phenanthroline ligands) in donor-chromophore-acceptor (D-C-A) triads and chromophore-acceptor (C-A) diads is a complex and fascinating area of under developed, yet fundamental, electron transfer chemistry. In metal polypyridyl D-C-A and C-A triads/diads, metal polypyridyl chromophores (C) in which the polypyridyl ligands are covalently linked to acceptor (A) and/or donor (D) moieties, photo-excitation of the chromophore initiates a series of electron transfer events that result in the formation of a charge separated (CS)/charge transfer (CT) state, respectively. The majority of high-performing metal polypyridyl D-C-A/C-A complexes, on which [Cu(I)P2] D-C-A/C-A research is based, incorporate ruthenium (as [Ru(II)L3] where L=polypyridyl ligand) or other rare, expensive, and sometimes toxic metals such as osmium, rhenium and platinum. Although [Ru(II)L3] D-C-A/C-A's have historically set the benchmark for metal polypyridyl D-C-A/C-A performance, it is clear that these complexes are not a practical choice if D-C-A's or C-A's were incorporated into a device for large scale production. However, bisphenanthroline complexes of copper, a much more earth abundant, cheaper and less toxic metal, exhibit very similar photophysical properties to [Ru(II)L3] and have thus gained recognition as promising new materials for D-C-A/C-A triad/diad construction. In order to understand the electron transfer (ET) events occurring in [Cu(I)P2] D-C-A/C-A triads/diads, a complex must be synthesized that is capable of forming a CS with high quantum efficiency (Φcs/ct) and a long CS/CT lifetime (τcs/ct). Therefore, the intent of the research reported herein is to synthesize novel, yet functional heteroleptic [Cu(I)P2] D-C-A/C-A triads/diads and study their fundamental, photo-initiated electron transfer chemistry, specifically the formation of a CS/CT state. Many challenges, which are not present for [Ru(II)L3], make the design and synthesis of [Cu(I)P2] D-C-A/C-A assemblies an art in itself. Therefore, a significant amount of effort was spent on fabricating ligand architectures that (1) are appended with acceptor and/or donor moieties capable of being reduced/oxidized resulting in the formation of a CS/CT, (2) are able to be easily modified so the amount of energy stored in the CS/CT can be tuned, (3) favor the self-assembly of [Cu(I)P2] complexes, (4) are able to facilitate processes that maximize the Φcs/ct. Once the ligands were obtained, the complexation equilibria behavior of these [Cu(I)P2] triads and diads were studied. Despite efforts to design ligand architectures that favor heteroleptic formation, the thermodynamic driving force for heteroleptic D-C-A triad formation is less favor-able than expected. Thus, mixing stoichiometric quantities of D, C and A results in a statistical mixture of C-A, C-D and D-C-A products. Furthermore, since the ligands are labile and will re-arrange to the most thermodynamically stable configuration of products when these complexes are dissolved, isolation of the D-C-A product is impossible. However, recent advances in ligand design have shown promise for resolving this on-going issue. Despite having a mixture of products with the D-C-A, the electron transfer processes of the [Cu(I)P2] D-C-A triads and C-A diads were investigated. Using Transient Absorption (TA) laser spectroscopy, the CT state in the constructed C-A diads and the CS state in the D-C-A triads were detected and the lifetimes were determined. However, it was found that those lifetimes could be modulated to a small degree by solvent in the C-A diads (c.a. 6x longer in polar solvents), and drastically via the application of a magnetic field in D-C-A triads (c.a. 60x longer). The ability to modulate the lifetimes enabled the deconvolution of the effects due to the C-A diad vs D-C-A triad in the statistical product mixtures. Although the response in a magnetic field was a somewhat expected result, as similar effects occur in the [Ru(II)L3 D-C-A/C-A's, the magnitude of change in the lifetime and the quantum efficiency offers new insight into the electron transfer events that occur in the CS/CT formation process for [Cu(I)P2] D-C-A/C-A complexes.
Open Access
Polymeric films, emulsions, and nanofibers for medical applications
(Colorado State University. Libraries, 2018) Yapor, Janet Pamela, author; Reynolds, Melissa M., advisor; Bailey, Travis S., committee member; Li, Yan V., committee member; Van Orden, Alan, committee member
Natural polymers such as cellulose and proteinaceous materials including hair or animal tissue have been used since prehistory. Their use was appropriate until they no longer met the criteria for the intended applications. For example, for implantable materials, the requirements would include materials with higher rigidity or slower degradation than naturally-occurring polymers. For this reason, scientists have invented new materials that are able to emulate or have similar properties as physiological tissue. New materials with a wide range of physical and chemical properties have been tailored to meet the highly diversified demands of modern technologies such as polyurethanes (PU) used for coatings, adhesives, fiber, foams, and thermoplastic elastomers. However, some of these have been derived from petroleum sources, which is a finite resource and its extraction causes environmental contamination. Furthermore, the synthesis of polymeric materials prepared from renewable resources and without the use of external catalysts has been an evolving field in materials science. Polymers such as polyesters have been developed with the goal of decreasing the use of petroleum sources. In addition, synthetic polymers can be tailored to mimic physiological responses. One method for the functionalization of these materials is through the addition of nitric oxide (NO) by the formation of S-nitrosothiol groups. NO is a relevant endogenous free radical that has important physiological roles such as vasodilation, cell proliferation, angiogenesis, and broad-spectrum antibacterial activity. Various NO-releasing platforms have been developed with morphologies that range from viscous liquids and emulsions to films. The synthesis of NO-releasing polyesters with potential applications in wound healing is discussed in this dissertation. Copolymers were prepared via bulk polycondensation with monomeric units including citric acid, maleic acid, and 1,8-octanediol. The first generation of materials required additional conjugation steps in order to add sulfhydryl groups, which were added using carbodiimide chemistry to couple cysteamine or ethyl cysteinate pendant groups. For the second generation of materials, the use of a sulfhydryl-containing monomer, thiomalic acid, eliminated the need for additional conjugation steps. The polyesters were formed using thiomalic acid and 1,8-octanediol alone, and with citric or maleic acid. The increased tensile mechanical properties of the second generation of polyesters yielded materials with Young's moduli similar to that of soft biological tissues such as meniscus, ligament and tendon. The results expanded the potential applications for such polyesters suggesting that the materials could be used as implantable devices or as scaffolds for tissue engineering. An issue with implantable devices arises from the fibrous encapsulation of the device, which is a physiological response referred to as the foreign body response that can be mitigated by NO. Furthermore, an NO-releasing emulsion with additives such as vitamin E and hyaluronic acid was developed, and its NO release profile was studied. In addition to polymer applications, emulation of physiological activities includes materials that can elicit a response when exposed to a variety of chemical or physical environments. Polydiactelyenes (PDAs) are a class of conjugated polymers that have been studied for their potential applications as sensors that detect biological, chemical and thermal changes in the surroundings. These polymers exhibit a chromatic response from blue to red when exposed to various stimuli. PDA nanofibers were prepared via elecrospinning with matrix polymers such as poly(ethylene oxide) and PU.
Open Access
Polysaccharide-based nanostructures for growth factor delivery and mesenchymal stem cell activation
(Colorado State University. Libraries, 2011) Almodovar Montanez, Jorge Luis, author; Kipper, Matt J., advisor; Bailey, Travis S., committee member; Kisiday, John D., committee member; Prasad, Ashok, committee member
Mesenchymal stem cells (MSCs) are very promising in tissue engineering and regenerative medicine because of their ability to differentiate into different type of cells including bone and cartilage. MSCs differentiation can be modulated using both chemical (i.e. proteins) and physical cues (ie. topography). This thesis presents work performed evaluating polysaccharide-based nanostructures for growth factor delivery and MSCs activation. Different polysaccharide-based nanostructures were developed and characterized including polyelectrolyte multilayers (PEMs) and electrospun nanofibers. On flat gold-coated glass surfaces, PEMs were constructed using the polycations chitosan and N,N,N -trimethyl chitosan, and the polyanions hyaluronan, chondroitin sulfate, and heparin. An exhaustive spectroscopic study was performed on all of the PEMs pairs to investigate the effects of polyelectrolyte charge density on thickness, swelling, composition, and ion-pairing. The results demonstrated that hydrophilicity and swelling are reduced when one polyelectrolyte is strong and the other is weak, while ion pairing is increased. The stability of adsorbed proteins to PEMs was also investigated using IR spectroscopy. Construction of PEMs and adsorption of basic fibroblast growth factor (FGF-2) was evaluated on heparin chitosan PEMs constructed on gold-coated glass, tissue culture polystyrene (TCPS), and titanium. In vitro testing of the FGF-2-loaded PEM constructed on TCPS and titanium was performed using ovine bone marrow-derived MSCs. It was noted that FGF-2 activity is enhanced, with regards to MSCs proliferation, when delivered from PEMs compared to delivery in solution. Chitosan nanofibers were successfully electrospun from a trifluoroacetic acid and dichloromethane solution. A new technique was developed to modify electrospun chitosan nanofibers with polyelectrolyte multilayers using N,N,N -trimethyl chitosan and heparin. Controlled release of bioactive FGF-2, complexed with heparin-chitosan polyelectrolyte complex nanoparticles, from electrospun chitosan nanofiber mats was achieved with zero order kinetics over a period of 27 days. When the nanofibers are further modified with a single PEM bilayer (PEM, composed of N,N,N -trimethyl chitosan and heparin), the release is completely prevented. The mitogenic activity of the released FGF-2 was also evaluated, with respect to the proliferation of ovine bone marrow-derived MSCs. The effect on osteogenic differentiation of bone marrow-derived ovine and equine MSCs seeded on electrospun chitosan nanofibers versus flat TCPS was investigated. The effect of dexamethasone on osteogenic differentiation was also investigated. We found that we can successfully grow and maintain both equine and ovine MSCs on electrospun chitosan nanofibers. Also, both MSCs exhibit higher differentiation markers (alkaline phosphatase activity) when cultured on chitosan nanofibers compared to flat TCPS surfaces. This work demonstrates new systems for stabilizing and controlling the delivery of heparin-binding growth factors for the activation of bone marrow-derived MSCs, using polysaccharide-based nanomaterials. These novel materials have potential applications in musculoskeletal tissue regeneration.
Open Access
Seepage-induced consolidation test mine tailings
(Colorado State University. Libraries, 2017) Tian, Zhengguang, author; Bareither, Christopher A., advisor; Scalia, Joseph, advisor; Bailey, Travis S., committee member
The objectives of this research were to design, construct, and evaluated the seepage induced consolidation testing (SICT) apparatus. Design of the SICT apparatus was based on existing apparatus at the University of Colorado-Boulder and University of British Columbia. Three materials were evaluated by the SICT and the odometer test to validate apparatus functionality: kaolin clay, fine synthetic tailings (FST), and average synthetic tailings (AST). This study consisted of the following tasks: (i) design and construction of the SICT apparatus; (ii) evaluation of geotechnical characteristics of kaolin clay, FST, and AST; (iii) conducting SICTs on kaolin clay, FST, and AST to determine the compressibility and hydraulic conductivity constitutive relationships; (iv) evaluation and comparison of the constitutive relationships of these materials with two constitutive models based on data from SICT; (v) conducting odometer tests on the same three materials to compare with results from the SICT; and (vi) evaluation of the effects of slurry composition on consolidation behavior (i.e., void ratio versus effective stress, e-σ', and hydraulic conductivity versus void ratio, k-e). The results of tasks i-vi support that the SICT apparatus constructed at Colorado State University (CSU) was reliable and repeatable based on benchmark tests conducted on kaolin clay. Constitutive relationship models generated from possible permutations of the seepage test and step loading test that comprise the SICT show a strong correlation. These models are compared to a composite model that combines all seepage and loading phases for a given SICT. The two models yield similar constitutive model parameters. Consolidation behavior (e-σ' and e-k) of kaolin clay, FST and AST show a wide range of behavior due to the different material grain size distributions.
Open Access
The development of novel N-heterocyclic carbenes for asymmetric C-C bond forming reactions
(Colorado State University. Libraries, 2012) DiRocco, Daniel A., author; Rovis, Tomislav, advisor; Williams, Robert M., committee member; Finke, Richard G., committee member; Bailey, Travis S., committee member; Chatterjee, Delphi, committee member
A variety of novel N-heterocyclic carbenes have been developed as organocatalysts for highly efficient and selective intermolecular C-C bond forming reactions. Problems associated with attaining high selectivity while retaining high efficiency in asymmetric intermolecular acyl anion pathways have been resolved through non-traditional manipulation of the catalyst architecture. In the context of the asymmetric intermolecular Stetter reaction, a new series of fluorinated triazolium salt pre-catalysts have been developed that catalyze the highly enantioselective coupling of hetaryl aldehydes and nitroalkenes. Stereoelectronic effects in the ground state suggest that conformation of the catalyst plays a role in determining selectivity. DFT calculations provide evidence for an electrostatic interaction between the fluorine-induced dipole and the electrophiles as the source of increased selectivity. The scope of the asymmetric intermolecular Stetter reaction of nitroalkenes has been further expanded to incorporate α,β-unsaturated aldehydes as partners. Mechanistic studies point to the initial proton-transfer event leading to generation of the acyl-anion equivalent as being turnover limiting. With this knowledge, an additive has been introduced that effectively increases the rate of proton transfer leading to substantially shorter reaction times and dramatically lower catalyst loadings. Further catalyst development has led to the realization of another mode of catalyst control, using the C-F bond as an additional source of substrate differentiation. This complementary fluorinated catalyst architecture substantially increases the reactivity of enolizable aldehydes in the asymmetric intermolecular Stetter reaction of nitrostyrenes, and for the first time allows for their inclusion in this transformation. An asymmetric aza-benzoin reaction of aliphatic aldehydes and N-Boc imines has been developed after identifying an extremely selective amino-indanol derived catalyst scaffold and mild reaction conditions. The direct enantioselective acylation of amines has been realized using a dual catalysis manifold, incorporating a photoactive metal complex as a catalyst to activate amines toward acyl-anion addition and a chiral NHC catalyst. This methodology has led to the isolation and full characterization of a series of aza-Breslow intermediates by X-ray crystallography. Studies of these intermediates provide crucial information about the fundamental reactivity of the Breslow intermediate and show that it is not only a catalyst resting state in these transformation but its generation is also reversible in the presence of a weak acid.
Open Access
Tuning interfacial biomolecule interactions with massively parallel nanopore arrays
(Colorado State University. Libraries, 2021) Wang, Dafu, author; Kipper, Matt J., advisor; Snow, Chris D., advisor; Bailey, Travis S., committee member; Stasevich, Tim J., committee member
This project studied interfacial interactions of macromolecules with nanoporous materials, with an ultimate goal of exploiting these interactions in functional biomaterials. We quantified interaction forces and energies for guest molecules threaded into the pores of protein crystals via nano-mechanical atomic force microscopy (AFM) pulling experiments. We demonstrated that both double-stranded DNA and poly(ethylene glycol) are rapidly absorbed within porous protein crystals, where they presumably bind to the inner "wall" surfaces of the protein crystal nanopores. These "guest" molecules can be retrieved from the "host" crystal by chemically modified AFM tips, enabling precise measurements of the adhesion forces and interaction energies. Based on these experiments, machine learning approaches were developed to classify hundreds of thousands of individual force-distance curves obtained in the AFM experiments. Furthermore, we showed that the interactions between protein crystal "hosts" and "guest" macromolecules can be used to modulate cell behavior, by presenting cell adhesion ligands tethered to different lengths of macromolecules that thereby modulate the maximum traction force cells can apply before rupturing bonds tethering the adhesion ligand to the porous protein crystal interior. This method affords the opportunity to create biomaterials that store an internal reservoir of cell-specific signals that can be presented to independently modulate the behavior of different cell populations in a single material. In the first chapter, some recent advancements, and methodologies of measuring interfacial biomolecule interactions are reviewed and compared. The reviewed technics include atomic force microscopy, fluorescence recovery after photobleaching, the total internal reflection fluorescence, confocal microscopy, and optical tweezers. Furthermore, this chapter interduces the application of machine learning to assist the interfacial biomolecule interaction studies, especially the AFM measurements. This chapter further prospects of the future of interfacial biomolecule interactions studies. In the second chapter, the methodologies of probing and observing the surface of highly porous Camphylobacter Jejuni formed protein crystals (CJ protein crystals) by high-resolution AFM are introduced. Throughout this chapter, the morphologies of CJ protein crystals are comprehensively investigated by AFM and have been discussed in this chapter. In the third chapter, for the first time, the interactions of DNA with porous protein crystals are quantitatively measured by high-resolution AFM and chemical force microscopy. The surface structure of protein crystals with unusually large pores was observed in liquid via high-resolution AFM. Force-distance (F-D) curves were also obtained using AFM tips modified to present or capture DNA. The interactions of DNA molecules with protein crystals to be quantitatively studied while revealing the morphology of the protein crystal surface in detail, in buffer, reveals how a new protein-based biomaterial can be used to bind DNA guest molecules. In the fourth chapter, strategies of machine learning are introduced which pioneered the use of machine learning to classify and cluster the interaction patterns between DNA and protein crystals, enabling us to process thousands of F-D curves collected by AFM. Finally, in the fifth chapter, we quantitatively measure and take advantage of the interaction between poly(ethylene glycol) (PEG)-arginine-glycine-aspartic acid (RGD) complex and nanoporous protein crystals to understand how non-covalent surface presentation of peptide adhesion ligands can influence cell behavior. Through AFM, F-D curves of interactions between PEG-RGD and host protein crystals were obtained for the first time. Furthermore, a strategy is developed that enables us to design surfaces that non-covalently present multiple different ligands to cells with tunable adhesive strength for each ligand, and with an internal reservoir to replenish the precisely defined crystalline surface.
Open Access
Understanding the molecular-level chemistry of H2O plasmas and the effects of surface modification and deposition on a selection of oxide substrates
(Colorado State University. Libraries, 2011) Trevino, Kristina J., author; Fisher, Ellen R., advisor; Elliott, C. Michael, committee member; Henry, Charles S., committee member; Prieto, Amy L., committee member; Bailey, Travis S., committee member
This dissertation first examines electrical discharges used to study wastewater samples for contaminant detection and abatement. The abatement process of contaminants in liquid discharges is relatively unstable; thus, to help elucidate the sources of instability, the gas phase constituents of plasmas formed from artificially-contaminated water samples were examined using optical emission spectroscopy (OES) and mass spectrometry (MS). Two different water samples contaminated with differing concentrations of either methanol (MeOH) or methyl tert-butyl ether (MTBE) were used to follow breakdown mechanisms. Emission from CO* was used to monitor the contaminant and for molecular breakdown confirmation through actinometric OES as it can only arise from the carbon-based contaminant in either system. Detection limits for each compound were as low as 0.01 ppm at a range of varying plasma parameters. MS data revealed plasma molecular breakdown and little evidence for fragment recombination to form larger molecules. MS data for the two contaminated H2O samples suggest the primary plasma species are CHx, C2Hx, CH2O, CO, C4Hx, and C3HxO and their corresponding ions. From this study, the detection and decomposition of organic molecules in water was accomplished for the first time with an ICP system. Detection was achieved at concentrations as low as 0.01 ppm, and molecular decomposition was seen at a variety of plasma parameters. This dissertation also explores the vibrational (θV), rotational (θR) and translational (θT) temperatures for a range of diatomic species in different plasma systems. Specifically we have investigated four molecules; OH in plasmas formed from H2O (g), tetraethyl orthosilicate (TEOS), NH3/O2 mixtures, and CH3OH; NH formed in plasmas created from NH3 and NH3/O2 mixtures; SiH radicals in SiH4, SiH4/Ar, Si2H6 and Si2H6/Ar plasmas; and CH in plasmas formed from mixtures of CH4/Ar. These species were probed with both laser induced fluorescence (LIF) and OES. For the majority of the plasma species studied, θV are much higher than θR and θT. This suggests that more energy is partitioned into the vibrational degrees of freedom in our plasmas. The θR reported are significantly lower in all the plasma systems studied and this is a result of radical equilibration to the plasma gas temperature. θT values show two characteristics; (1) they are less than the θV and higher than the θR and (2) show varying trends with plasma parameters. Radical energetics were examined through comparison of θR, θT, and θV, yielding significant insight on the partitioning of internal and kinetic energies in plasmas. Correlations between energy partitioning results and corresponding radical surface scattering coefficients obtained using our imaging of radicals interacting with surfaces (IRIS) technique are also presented. Another aspect of plasma process chemistry, namely surface modification via plasma treatment, was investigated through characterization of metal oxides (SiOxNy, nat-SiO2, and dep-SiO2) following their exposure to a range of plasma discharges. Here, emphasis was placed on the surface wettability, surface charge, and isoelectric point (IEP). The results demonstrate that 100% Ar, H2O, and NH3 plasma treatments cause changes in surface charge, wettability, and IEP values for all treated surfaces. Observed variations in these values depend primarily on the specific mechanism for surface functionalization with each plasma treatment. Ar plasmas tend to create surface radical sites, H2O plasmas yield surface-bound OH, and NH3 plasmas lead to the incorporation of nitrate functional groups. The wettability, surface charge, IEP values, chemical composition, and surface damage of the substrates were analyzed using contact angle goniometry (CA), x-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). Although the permanence of these modifications varied with substrate, lasting between one week and one month, these results highlight the utility of IEP measurements for characterizing plasma treated surfaces and suggest the possibility that plasmas may provide a valuable means of controlling surface charge and wettability of metal oxides. The incorporation of functional groups on the surface of Zeolite X was also examined as an additional form of plasma surface modification. The intention of these studies was to (1) alter the surface functionality by simple plasmas treatments, as characterized by XPS data; (2) change the hydrophilic nature of the zeolite to be more hydrophobic with flurocarbon plasmas; (3) gain total surface area functionality with our new rotating drum reactor; and (4) ensure that damage was not occurring to the zeolite structure, as evidenced by SEM images. Results showed the incorporation of different surface functionality was accomplished with all plasma systems studied (CF4, C2F6, C3F8), the zeolite structure was not damaged by the plasma, and the potential for altering the entire surface area of these porous materials exists. The final portion of this dissertation addresses aspects of work designed to understand the adhesion behavior of amorphous carbon nitride (a-CNx) films deposited from a CH3CN and BrCN plasmas. In particular, films obtained from CH3CH plasmas stayed intact whereas BrCN plasmas produced films that delaminated upon their exposure to atmosphere. These results have been attributed to humidity, film stress, hydrocarbon species, and the Br content in the film. The major contributions to this work made here center on the chemical composition and binding environments of the deposited films as measured by XPS, which are shown to be critical in understanding the mechanical properties of a-CNx films.
Embargo
Zwitterionic polymeric nanoparticles for drug delivery
(Colorado State University. Libraries, 2024) Lee, Jeonghun, author; Herrera-Alonso, Margarita, advisor; Bailey, Travis S., committee member; Popat, Ketul C., committee member; Peebles, Christie, committee member
Bottlebrush block copolymers, characterized by their densely grafted side chains stemming from a highly persistent backbone, offer unique advantages for drug delivery, including enhanced micellar stability, reduced critical micelle concentration, and controlled surface topography, setting them apart from traditional linear polymers. This dissertation focuses on zwitterionic bottlebrush block copolymers (ZBCPs) composed of poly(D, L-lactide) (PLA) and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) side chains, synthesized via a combination of ring-opening and controlled radical polymerization using a grafting-from approach. ZBCPs were self-assembled into uniform spherical micelles and nanoparticles through direct dissolution and rapid mixing methods, and these self-assembled nanostructures were systematically evaluated. Compared to non-ionic PEG micelles (standard), zwitterionic bottlebrush micelles (ZBM) demonstrated superior stability under high salt conditions, elevated temperatures cycles, and in the presence of fetal bovine serum, whereas kinetically assembled nanoparticles (ZBNP) exhibited greater drug loading capacity. Both ZBM and ZBNP also showed excellent hemocompatibility, with ZBM displaying exceptional redispersibility in the absence of cryoprotectants. In parallel, this dissertation investigates boronic acid-functionalized zwitterionic polymers for drug delivery. A linear ABC-type amphiphilic copolymer containing poly(3-aminophenylboronic acid) as the central block was synthesized and compared to its non-functional counterpart. The boronic acid-containing nanoparticles exhibited pH- and oxidation-responsive behavior, enabling controlled drug release. Expanding this concept to a bottlebrush architecture, boronic acid-functionalized bottlebrush triblock copolymers were developed to further enhance nanoparticle performance. The inclusion of a boronic acid interlayer in the bottlebrushes significantly improved redispersibility of drug-loaded nanoparticles while maintaining high drug loading capacity, superior stability, and excellent hemocompatibility. This dissertation provides fundamental insights into solution-based self-assembled nanostructures derived from ZBCPs and boronic acid-functionalized polymers, establishing them as promising advanced drug delivery platforms. These systems offer tunable release kinetics, robust colloidal stability in harsh biological environments, excellent hemocompatibility, and superior redispersibility, thereby enhancing their translational potential in the field of nanomedicine.