DSpace Repository :: Browsing by Author "Brazel, Christopher S."

Browsing by Author "Brazel, Christopher S."

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Advanced solvents for CO2 separation applications
(University of Alabama Libraries, 2016) Flowers, Brian Steven; Bara, J. E.; University of Alabama Tuscaloosa
The objective of this dissertation is to advance the understanding of several novel solvents for CO2 capture and separation applications. Many of the solvents investigated were imidazole based, as these compounds are highly tunable, neutral, and less expensive analogs to imidazolium based ionic liquids (ILs). While much is known about the physical properties of ILs, the physical properties of these neutral compounds have not been researched as thoroughly, and so there is a need to explore these compounds as potential CO2 capture media. It has been further proven that the most effective means of predicting CO2 capture performance in imidazole based compounds is by examining the fractional free volume (FFV) using a molecular simulation program like COSMOTherm. Other non-imidazole based physical solvents were synthesized and compared to commercially available processes. 1,2,3-Trimethyoxypropane (1,2,3 TMP) was found to compare favorably with regard to CO2 absorption and viscosity to the current industry standard for CO2/CH4 pre-combustion separation techniques, Selexol, while being significantly less toxic. Chemical solvents for post-combustion CO2 capture were also investigated. It was determined that changing the substituents on 1-(3-aminopropyl)imidazole increases the CO2 solubility by increasing the basicity of the imidazole ring. The advantages in vapor pressure of these substituted aminopropylimidazole over traditionally used alkanolamines could potentially provide massive operational savings by reducing solvent losses through evaporation and increased solvent life.
The anionic ring-opening polymerization of cyclic imines
(University of Alabama Libraries, 2019) Reisman, Louis; Rupar, Paul A.; University of Alabama Tuscaloosa
One important class of polymers is polyimines. Polyimines have a wide range of applications such as CO2 capture and non-viral gene-transfection. Despite their many applications, the use of these polymers is limited due to difficulties in controlling the polymerization. To increase the feasibility of polyimines in the aforementioned high-value applications, the research in this dissertation focuses on controlled routes to produce linear polyimines using living anionic ring-opening polymerization (AROP). The early work of this dissertation focuses on an AROP route to linear polyethylenimine (LPEI). Due to the insolubility of p(N-sulfonylaziridine)s (i.e. non-2-substituted) in all common solvents, this was achieved using a copolymerization strategy. Utilizing two N-sulfonylaziridines, N-(methanesulfonyl)aziridine (MsAz) and N-(sec-butylsulfonyl)aziridine (sBsAz), with similar reactivities, a soluble random copolymer with narrow molecular weight distributions is produced. Removal of the sulfonyl groups of p(MsAz-r-sBsAz) affords the first example of LPEI by living, controlled AROP. The later work in this dissertation focuses on the AROP of N-sulfonylazetidines in route to linear poly(trimethylenimine) (LPTMI). Initially, the polymerization of N-(methanesulfonyl)azetidine (MsAzet) was investigated. The kinetics of this polymerization were studied, and the reaction found to be first order with respect to monomer and the number of active chain ends remains constant throughout the polymerization. Interestingly, activation occurs at the methanesulfonyl group, leading to polymer branching. This branching precludes p(MsAzet) from being a precursor to LPTMI. By more judicial selection of N-sulfonylazetidine monomers, a living, controlled AROP approach to LPTMI was achieved by copolymerizing two similar N-sulfonylazetidines, N-(p-tolylsulfonyl)azetidine (pTsAzet) and N-(o-tolylsulfonyl)azetidine (oTsAzet), to produce a statistical copolymer. Copolymerization was required as the homopolymers resulting from these monomers were insoluble in all common solvents. The copolymerization is living and controlled, producing polymers with narrow molecular weight distributions. The kinetics of the copolymerization, and the reactivity ratios of the two monomers, were studied and the sulfonyl groups of the polymer were removed to provide the first example of LPTMI by living, controlled AROP. Finally, the high barrier to polymerization of N-sulfonylazetidines was utilized to produce block copolymers, containing no homopolymer impurities, in a closed system in which all monomers are present in solution at the time of initiation.
Borafluorenes and polyborafluorenes boron doped varients of fluorene
(University of Alabama Libraries, 2017) Adams, Ian; Rupar, Paul A.; University of Alabama Tuscaloosa
A series of novel boron containing variants of fluorene were synthesized. Boron was incorporated synthetically via lithium halogen exchange and Grignard reaction pathways. Once incorporated, the borafluorene could be polymerized or undergo further functionalization via Yamamoto and Stille coupling reactions. This incorporation of boron into a conjugated system imparted Lewis acidic and electron deficient properties into a conjugated system. It is our hope that this will dope fluorene and create novel n-type semiconductors. A novel polymer of borafluorene, poly(9-borafluorene) (P9BF) was synthesized. HOMO and LUMO levels of P9BF were estimated by cyclic voltammetry. As predicted in prior DFT studies, P9BF has a reduced band gap and a lower lying LUMO compared with polyfluorene. To examine how the HOMO and LUMO levels of borafluorene systems could be tuned, copolymers of 9-borafluorene were synthesized. Four of the copolymers were a series of donor-acceptor (DA) type copolymers. A borafluorene-fluorene (P9BF-OF) copolymer and borafluorene-diketopyrrolopyrrole (P9BF-DPP), as an acceptor-acceptor (AA) copolymer were also synthesized. The series of DA copolymers showed higher energy HOMO and LUMO levels in correlation with the relative donating ability of the donor monomer. P9BF-OF has a reduced LUMO level in comparison with P9BF. P9BF-DPP has a very low band gap (1.8eV), with absorption well into the near-IR region. To examine ways to make borafluorene more air stable, a series of borafluorenes bearing bismethylmethoxyphenyl (BMMP) ligands were investigated. Interestingly, ii bismethylmethoxyphenyl-borafluorene (BMMP-BF) exhibits an exceptionally large Stokes shift of 16000 cm-1. To extend the conjugation and change the Stokes shift, thiophene containing derivatives BMMP-BF-T, BMMP-BF-2T, and BMMP-BF-3T were synthesized. These thiophene containing compounds exhibited anomalous two wavelength fluorescence. During our fluoride titration experiments, we noticed spectral impurities when using tetrabutylammonium fluoride (TBAF) as our fluoride source. Examining this more closely, we found that commercial samples of TBAF were found to absorb light at 295 and 370 nm and fluoresce as 435 nm. This was not expected for analytically pure TBAF, so we concluded that there must be an impurity present in commercial TBAF. The source of this impurity was found to be I3- which occurs from the oxidation of I-.
Determining iron oxide nanoparticle heating efficiency and elucidating local nanoparticle temperature for application in agarose gel-based tumor model
(Elsevier, 2016) Shah, Rhythm R.; Dombrowsky, Alexander R.; Paulson, Abigail L.; Johnson, Margaret P.; Nikles, David E.; Brazel, Christopher S.; University of Alabama Tuscaloosa
Magnetic iron oxide nanoparticles (MNPs) have been developed for magnetic fluid hyperthermia (MFH) cancer therapy, where cancer cells are treated through the heat generated by application of a high frequency magnetic field. This heat has also been proposed as a mechanism to trigger release of chemotherapy agents. In each of these cases, MNPs with optimal heating performance can be used to maximize therapeutic effect while minimizing the required dosage of MNPs. In this study, the heating efficiencies (or specific absorption rate, SAR) of two types of MNPs were evaluated experimentally and then predicted from their magnetic properties. MNPs were also incorporated in the core of poly(ethylene glycol-b-caprolactone) micelles, co-localized with rhodamine B fluorescent dye attached to polycaprolactone to monitor local, nanoscale temperatures during magnetic heating. Despite a relatively high SAR produced by these MNPs, no significant temperature rise beyond that observed in the bulk solution was measured by fluorescence in the core of the magnetic micelles. MNPs were also incorporated into a macro-scale agarose gel system that mimicked a tumor targeted by MNPs and surrounded by healthy tissues. The agarose-based tumor models showed that targeted MNPs can reach hyperthermia temperatures inside a tumor with a sufficient MNP concentration, while causing minimal temperature rise in the healthy tissue surrounding the tumor. (C) 2016 Elsevier B.V. All rights reserved.
Development and characterization of high-performance functionalized membranes for antibody adsorption
(University of Alabama Libraries, 2012) Shethji, Jayraj Kiritbhai; Ritchie, Stephen M. C.; University of Alabama Tuscaloosa
Capacity and selectivity are the major bottlenecks for the development of affinity membrane adsorbers for protein and antibody purification. The focus of this doctoral research is to develop polyethersulfone (PES) microfiltration (MF) membranes containing multiple highly selective poly(styrene-co-hydroxystyrene) grafts mimicking the key dipeptide Phe-132/Tyr-133 motif of ligand protein A to selectively adsorb immunoglobulin G (IgG) under convective flow conditions. This research work consists of two phases. In phase 1, homopolymer and block copolymer grafts were synthesized and characterized in the membrane pores using monomers styrene, ethoxystyrene, and chloromethylstyrene. 1H NMR characterization showed successful incorporation of the sequential stages of graft chemistry, including: polystyrene, poly(chloromethylstyrene), poly(ethoxystyrene), poly(styrene-b-ethoxystyrene), and poly(styrene-b-chloromethylstyrene). A study of monomer reactivity showed that chloromethylstyrene reacted approximately 1.3 times slower than styrene and ethoxystyrene during formation of homopolymers and block copolymers. The ion-exchange capacity of sulfonated functionalized membranes was 4.9 meq/g with as many as 125 repeat units per chain. In phase 2, PES MF membranes tailored with two different graft chemistries including poly(styrene-co-hydroxystyrene) and glycine functionalized poly((styrene-co-hydroxystyrene)-b-chloromethylstyrene) grafts were developed and tested for selective IgG adsorption. 1H NMR characterization confirmed membrane pore functionalization by poly(styrene-co-hydroxystyrene), chloromethylstyrene block addition, and subsequent glycine functionalization of the chloromethyl block. The dynamic binding capacity (DBC) for IgG was as high as 95 mg/ml, more than 9 times as compared to Sartobind® and Ultrabind® membranes and twice as compared to affinity resin. The DBC was independent of flow rate and there was no significant loss (<5%) in capacity at higher linear velocities (230 cm/h) indicating that the transport of IgG to the adsorptive sites is predominantly by convection. Bind and elute experiments showed that there was no significant loss of DBC over a period of five cycles and the average recovery of antibody was >94%. Competitive sorption using membranes containing negatively charged spacer arms showed that the membrane was ~11 times more selective for IgG than BSA. Additionally, the DBC was 22% higher (115 mg/ml) than without spacer arms indicating that the negatively charged spacer arms moved the grafted chains apart and improved the accessibility of IgG to the binding sites.
Development of hydroxypropyl cellulose-filled poly(2-hydroxyethyl methacrylate) semi-interpenetrating networks for drug delivery
(University of Alabama Libraries, 2010) Melnyczuk, John Michael; Brazel, Christopher S.; University of Alabama Tuscaloosa
Cancer is the second leading cause of death in the United States of America and the National Cancer Institute has released a paper stating that the ideal cancer therapy should have an imaging, targeting, reporting, and therapeutic part. The overall project goal is to be able to create a delivery system that can be triggered externally to the body and can release an anticancer agent in a controlled manner. The current project deals specifically with using hydroxypropyl cellulose (HPC) filled poly(2-hydroxyethyl methacrylate) (PHEMA) (HFPG) hydrogel to cause a release of theophylline when the hydrogel is placed at a temperature above the lower critical solution temperature (LCST) of HPC (57 ºC) and to have no release at normal body temperature, 37 ºC. In a series of polymerization reactions, various compositions of hydroxypropyl cellulose (HPC) filled crosslinked PHEMA gels were synthesized by free radical polymerization. The LCST for different average molecular weights, M̅_n, of HPC were found to be 44.8 ºC ± 0.8, 48.7 ºC ± 0.3, and 46.2 ºC ± 0.7 for 80,000, 100,000, and 370,000 M̅_n HPC respectively. A change in concentration of HPC with a M̅_n 80,000 from 0.01 to 0.05 g/mL showed an increase in the LCST from 44.8 ºC ± 0.8 to 46.6 ºC ± 1.0. Changing the media from water to 0.65M sodium chloride change LCST from 46.6 ºC ± 1.0 to 35.4 ºC ± 2.3. The swelling study showed the mesh size was unaffected by synthesis temperature, analytical temperature, and HEMA to HPC ratio, indicating that HPC was pore-filling. Mechanical testing confirmed the results of the swelling study, in that there was no net change in the calculated mesh size with a change in analytical or synthesis temperature by either method. This study showed that HPC did change the mesh size with a change in the HEMA:HPC ratio. Dissolution testing for the release of theophylline from the HFPG hydrogel showed an increased release rate with an increase in analytical temperature was possible. The increase in synthesis temperature increased the release rate. It is shown that an increase in the HEMA:HPC ratio with a decrease in the diffusion coefficient. The HPC collapsed and evolved out of the HFPG and this effect could produce a higher diffusion. Further investigations should be conducted to test the effects of different initiators and crosslinking ratio's on the release of HFPG hydrogels.
Dissolution and processing of cellulosic materials with ionic liquids: fundamentals and applications
(University of Alabama Libraries, 2010) Sun, Ning; Rogers, Robin D.; University of Alabama Tuscaloosa
With the inevitable depletion of petroleum-based resources, there has been an increasing worldwide interest in renewable resources such as biomass. One reason for the current approaches being taken to utilize biomass is the difficulty in processing lignocellulosic materials and the energy needed for separation of the components. The three major components of biomass are covalently bonded together, which makes dissolution and further separation of the three major components difficult and this has been recognized as the grand challenge for biomass utilization. This dissertation describes research efforts in processing of lignocellulosic biomass using ionic liquids (ILs) as solvents. ILs are salts with melting points below 100 oC, which possess many advantage properties. Cellulose composite fibers have been prepared based on IL solution with dispersion of the additives. Wood and bagasse have been completely dissolved in ILs. Partial separation of the components has been obtained using selected reconstitution solvents. High temperature and fast dissolution was found to be an efficient method for both dissolution and separation of biomass components. Biomass composite fibers can be prepared directly from such biomass solutions. With selected catalysts in solution, improved dissolution and separation has been achieved, making the delignification and pulp yield comparable to the kraft pulping process.
The effects of physiological fluid shear stress on circulating tumor cells
(University of Alabama Libraries, 2018) Triantafillu, Ursula Lea; Kim, Yonghyun; University of Alabama Tuscaloosa
The focus of this dissertation is on the effects of physiological fluid shear stress (FSS) on circulating tumor cells (CTCs). FSS occurs on cells both in vitro and in vivo. FSS is typically considered as a major variable in large scale bioprocessing while FSS is assumed to have a negligible role in bench scale culture. In physiological settings, FSS impacts cells in cancer where local, regional, and distant cancers experience FSS through interstitial, lymphatic, and hematological flow, respectively. CTCs in hematological flow experience the highest FSS and are involved in the transit stage of metastasis. One challenge of metastatic cancer is the lack of secondary tumor detection. Detection of CTCs largely relies on the epithelial cell adhesion molecule (EpCAM). CTC phenotype also includes expression of cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT), which are correlated to increased resistance to chemotherapy. The study of FSS using an in vitro model can provide a better understanding on CTC phenotype expression and drug resistance. FSS was first examined using a baseline study with in vitro cell spheroid culture. Spheroids provide better representation of the stem and tumor cell environment than 2D culture. These cells experience FSS during cell dissociation. Since FSS can detrimentally affect cells, a gentler mechanical platform was developed for dissociation. Furthermore, this method, as well as traditional dissociation methods, was tested to study how FSS affects cell viability and expression. This platform was further used to model breast CTCs as suspension cells under FSS. This metastatic model allowed for testing the effects of FSS on CTC phenotype, and it was found that FSS increased CSC and CTC expression. Since an increase in CSC expression is correlated to increased drug resistance, drug resistance on CTCs under FSS was tested with chemotherapy drugs. It was found that the combination of FSS and drug resistance synergistically increases drug resistance expression in the model CTCs, corroborating clinical reports of CTC drug resistance. Finally, the effects of FSS and drug resistance was tested on estrogen receptor positive (ER+) molecular subtype. Collectively, these studies provide a better understanding on CTC behavior during metastasis.
Experimental and theoretical studies on the electronic properties and dissociation reactions of gas-phase metal oxide nitrate complexes
(University of Alabama Libraries, 2016) Hester, Thomas Hinton; Goebbert, Daniel J.; University of Alabama Tuscaloosa
This dissertation discusses dissociation studies performed on various gas-phase transition and main group metal nitrate anion complexes using a tandem mass spectrometer. The dissociation of these complexes, via consecutive loss of NO2•, results in the formation of multiple metal-oxygen bonds. The dissertation focuses primarily on the metal oxide products in an attempt to gain a better understanding of the nature of metal-oxygen bonds, with an emphasis on the assignment of oxidation states for the atoms in these species. The dissociation behavior for each system was found to be characteristic to the metal in that system. Specifically, the elimination of NO2• results in abstraction of O•− by the metal and formation of a metal-oxygen bond. The formation of this bond can result in oxidation of the metal, reduction of the metal, or show an absence of redox activity for the metal. The main group metals, such as aluminum, gallium, and the pseudo-main group metal zinc, have valences lower in energy than that of the O•− ligand and do not undergo oxidation or reduction upon metal-oxygen bond formation. The oxygen ligand retains the radical and is the reactive site in those systems, illustrated by the observed high degree of dissociation. The late transition metal, copper(II), has a low-lying 3d vacancy that allows metal reduction upon metal-oxygen bond formation. The copper(I) system, with its full 3d valence shows dissociation behavior identical to that of the main group metals. The nickel(II) cation has a nearly degenerate valence to that of the O•− ligand, resulting in dissociation similar to that of the main group metals. The dissociation patterns are similar because the O•− ligands are the primary reactive sites in the nickel system. Metal reduction can occur upon elimination of atomic and molecular oxygen from some complexes. This metal reduction occurs at relatively low energy due to the low-lying 3d vacancies for nickel. There are two instances of electron transfer that result in partial metal and partial ligand reduction, due to the near degeneracy of the valences for the nickel cation and O•− ligand. The unusual, half-integer values for the oxidation state assignments in these two cases introduce a larger unanswered question of, “What do the oxidation states tell us about these types of metal oxide systems?” Early-to-mid transition metals, such as chromium through cobalt, undergo metal oxidation upon metal-oxygen bond formation. These metals have high energy valence occupancies relative to the valence of the O•− ligand. An electron transfers from the metal 3d subshell to the 2p subshell of the oxygen ligand, reducing it to an O2− ligand. Metal reduction can occur for these systems upon elimination of atomic and molecular oxygen, but it occurs at high energy due to the high energy 3d subshell.
Experimental Study on Electrical Conductivity of Imidazolium- Based Ionic Liquids and Their Application to Current Density Simulation
(University of Alabama Libraries, 2021) Nahian, Md Khalid; Reddy, Ramana G.; University of Alabama Tuscaloosa
Over the last few decades, ionic liquids (ILs) have been the focus of considerable research in the field of electrochemistry for their exceptional physio-chemical characteristics. In this study, the electrical conductivity of imidazolium-based ionic liquid was investigated by electrochemical impedance spectroscopy (EIS). Aluminum chloride (AlCl3) was mixed with three different kinds of imidazolium ionic liquids, 1-butyl-3-methylimidazolium chloride (BMIC), 1-ethyl-3-methylimidazolium chloride (EMIC), and 1-hexyl-3-methylimidazolium chloride (HMIC), individually. The electrical conductivity of these chloroaluminates was determined as a function of temperature and molar ratio. For AlCl3:BMIC and AlCl3:EMIC, electrical conductivity decreases with an increase in AlCl3 content, whereas electrical conductivity increases for AlCl3: HMIC with an increase in AlCl3. Electrical conductivity increases with temperature for all three ILs systems. Following this, the effects of titanium tetrachloride (TiCl4) and temperature on the electrical conductivity of ILs systems were studied. In this case, electrical conductivity for all ionic liquid systems increases rises to a certain TiCl4 ratio and then decreases with the additional TiCl4, and electrical conductivity also increases with temperature. Activation energy was also calculated from electrical conductivity data. The obtained AlCl3:BMIC electrical conductivity data was used to simulate the current density and contact resistance for aluminum refining electrochemical cell by ANSYS Fluent. When Al metal matrix composite anode was used, a consistent electrode-electrolyte contact resistance (0.041 m2) was found regardless of applied voltage. But the contact resistance was not consistent with applied potential when Al2020 was chosen as anode.
Functional ionic liquids for use in pharmaceutical applications
(University of Alabama Libraries, 2010) Hough, Whitney Lauren; Rogers, Robin D.; University of Alabama Tuscaloosa
For years, the pharmaceutical industry has relied heavily on crystalline active pharmaceutical ingredients (APIs) that can be approved by the Federal Drug Administration (FDA) as neutral compounds, salts, or solvates of said neutral compounds and salts. Yet, the solid crystalline form can have unexpected and unfavorable effects on properties such as solubility, bioavailability, efficacy, etc., due to different polymorphic forms of the API. A drug can be present in multiple forms and interconvert between forms during isolation, manufacturing, storage, and transport of the end product. These unwelcome problems could be alleviated or even eliminated by the formation of a liquid drug, which possesses no crystal structure. Unfortunately, research in this area has been limited to solubilization of solid drugs into various drug delivery vehicles such as emulsions, suspensions, and liposomes. However, it is possible for a drug to crystallize from these vehicles during the manufacturing, storage, and transportation. Thus, a new method to liquefy pharmaceuticals, thereby reducing problems associated with the solid-state, is needed. A potential solution is the use of ionic liquids (IL), defined as salts that melt below 100 °C. Since ILs are salts it is possible to combine a pharmaceutical ion with any desired counter ion, thereby, providing a level of tunablity that is not possible with current techniques. This IL modular strategy was the basis for the research discussed here, in which APIs with known problems were combined with GRAS (generally regarded as safe) compounds or FDA-approved APIs, which resulted in ILs displaying dual biological functionality. This strategy was successful in producing a wide range of ILs, all containing at least one pharmaceutically active ion. The physical property set for these synthesized ILs was varied, as it is difficult to predict how two ionic organic compounds will interact. However, common trends regarding melting point depression, thermal stability, and solubility were determined. The most exciting results were exhibited during the biological testing, as several of the synthesized ILs demonstrated improved biological activity over the precursor ions. Additionally, the drug mechanism, at a cellular level, was found to be modified when contained within an IL. This indicates that ILs behavior differently in the body than simple halide containing salts. Overall, the obtained results signify that ILs can serve as pharmaceuticals, in which these liquid salts eliminate problems associated with the solid-state and displayed to synergistic physical and biological properties.
Functionalized membranes for membrane chromatography
(University of Alabama Libraries, 2011) Shethji, Jayraj Kiritbhai; Ritchie, Stephen M. C.; University of Alabama Tuscaloosa
The focus of this thesis is synthesis and quantification of homopolymer and block copolymer grafts and understanding controlled polymer growth. The homopolymer and block copolymer grafts were synthesized through sequential cationic polymerization of styrene and substituted styrene monomers chloromethylstyrene (CMS) and 4-ethoxystyrene (ES) in the pores of microfiltration polyethersulfone (PES) membrane. Polymer growth aspects like kinetics of reaction, amount of monomer reacted, ion-exchange capacity (IEC), and graft length were studied with respect to initiator contact time and monomer feed concentration. Functionalization of the microfiltration membrane was achieved by a two step procedure. The first step was to introduce sulfonic acid initiator sites by mild sulfonation with 0.5N H2SO4. This was followed by cycling through each type of monomer solution (styrene and substituted styrenes). Successful introduction of homopolymer and block copolymer grafts was confirmed by material balances on the monomer/toluene permeate solutions. Analytical techniques used for quantification of polymer grafting include UV-Visible spectroscopy, gas chromatography and atomic absorption. The functionalized membrane showed a steep decrease in membrane permeability compared to the raw membrane indicating the presence of polymeric chains in the membrane flow path. Functionalized membranes prepared by this method have as many as 125 repeat units per chain. Given the initiator concentration, this equates to an IEC of 4.9 meq/g, indicating high dynamic and equilibrium binding capacity. Pseudo-first-order kinetic expression correlated well with the experimental data for each monomer reacted. At lower initiator surface density, graft length and IEC were impacted by both monomer feed concentration and initiator contact time. However, for higher initiator surface density, monomer feed concentration parameter dominates. Block copolymer formation is the first step to synthesizing an analog of the phenylalanine/tyrosine dipeptide structure in protein A, which is shown in literature for selective adsorption of immunoglobulin G (IgG). This work will lead to further development of functionalized membranes as membrane adsorbers for high throughput production of monoclonal antibodies for new cancer therapies. In addition, it will lead to discoveries in sequential polymerization to generate customized structures and design of synthetic affinity ligands.
Impact of magnetic field parameters and iron oxide nanoparticle properties on heat generation for use in magnetic hyperthermia
(Elsevier, 2015) Shah, Rhythm R.; Davis, Todd P.; Gover, Amanda L.; Nikles, David E.; Brazel, Christopher S.; University of Alabama Tuscaloosa
Heating of nanoparticles (NPs) using an AC magnetic field depends on several factors, and optimization of these parameters can improve the efficiency of heat generation for effective cancer therapy while administering a low NP treatment dose. This study investigated magnetic field strength and frequency, NP size, NP concentration, and solution viscosity as important parameters that impact the heating efficiency of iron oxide NPs with magnetite (Fe3O4) and maghemite (gamma-Fe2O3) crystal structures. Heating efficiencies were determined for each experimental setting, with specific absorption rates (SARs) ranging from 3.7 to 325.9 W/g Fe. Magnetic heating was conducted on iron oxide NPs synthesized in our laboratories (with average core sizes of 8, 11, 13, and 18 nm), as well as commercially-available iron oxides (with average core sizes of 8, 9, and 16 nm). The experimental magnetic coil system made it possible to isolate the effect of magnetic field parameters and independently study the effect on heat generation. The highest SAR values were found for the 18 am synthesized particles and the maghemite nanopowder. Magnetic field strengths were applied in the range of 15.1-47.7 kA/m, with field frequencies ranging from 123 to 430 kHz. The best heating was observed for the highest field strengths and frequencies tested, with results following trends predicted by the Rosensweig equation. An increase in solution viscosity led to lower heating rates in nanoparticle solutions, which can have significant implications for the application of magnetic fluid hyperthermia in vivo. (C) 2015 Elsevier B.V. All rights reserved.
The localization and behavior of fluorescently tagged magnetic nanoparticles in biological systems
(University of Alabama Libraries, 2009) Sewell, Mary Kathryn; Brazel, Christopher S.; University of Alabama Tuscaloosa
A novel combination cancer therapy platform incorporating chemotherapy and hyperthermia is proposed. Magnetic nanoparticles are included as a way to achieve the hyperthermia treatment, as well as for use as a platform for targeting, imaging, or other therapeutic moieties. Cobalt ferrite (CoFe₂O₄) magnetic nanoparticles (MNPs) were synthesized and tagged with the fluorescent dye rhodamine for tracking in biological systems. The MNP solutions were characterized to determine average diameters of the nanoparticles. Results indicate that sample age, solvent, and concentration can affect the diameters of MNP agglomerates as measured by dynamic light scattering. Older and more concentrated samples, which also tend to be less stable, showed larger MNP sizes than newer and less concentrated samples. Rhodamine-tagged MNPs showed smaller diameters than untagged MNPs at the same concentrations. For MNP in HeLa cell localization studies, the rhodamine-tagged MNPs showed uptake and localization in the cytoplasm of the cells. Partition coefficients, or the ratios of MNP concentrations inside the cells to the extracellular concentration, were shown to increase during the first 6 h of incubation time, with values reaching as high as 3.805, indicating favorable uptake of the MNPs. After 24 h, a smaller ratio of internalized MNPs was seen due to cytotoxic properties of the high concentration of MNPs used in those experiments. Toxicity studies showed that at concentrations below approximately 0.025 mg/mL, both rhodamine-tagged and untagged CoFe₂O₄ MNPs have little effect on cell viability. MNP localization and toxicity studies were also carried out on a model organism, C. elegans worms, with an indication that rhodamine-tagged CoFe₂O₄ MNPs were non-toxic to worms over a period of 12 days. Localization of the MNPs within the worms was inconclusive due to indistinguishable autofluorescence of the C. elegans and the rhodamine fluorescence of tagged MNPs. Further work is needed to characterize the CoFe₂O₄ MNPs for use in the cancer treatment platform.
Magnetic heating of Fe3O4 nanoparticles and magnetic micelles for a magnetothermally-triggered drug delivery system for cancer therapy
(University of Alabama Libraries, 2012) Bennett, James Brandon; Brazel, Christopher S.; University of Alabama Tuscaloosa
Magnetic nanoparticles, MNPs, combined with stimuli-responsive polymers show potential to enhance the efficacy of cancer therapy in multifunctional nanoscale drug delivery systems. This project investigates the use of iron oxide nanoparticles (magnetite) to generate heat, via an applied magnetic field, to stimulate drug release of doxorubicin from an RGD-peptide targeted thermo-sensitive poly (ethylene glycol)-b-poly (caprolactone) micelle. Fe_3 O_4; nanoparticles custom synthesized at UA show the ability to heat to temperatures adequate for melting a semi-crystalline poly (caprolactone) micelle core. Investigations into parameters effecting magnetic heating of Fe_3 O_4 included studying the effects of magnetic field strength, H, and frequency, f. The results showed magnetic heating of the MNPs could induce hyperthermic temperatures. Specific absorption rates (SAR) for the MNPs were in the range of previously reported magnetite SARs, and followed the relationship with magnetic field strength predicted by the Rosensweig equation. The internal energy change in magnetic micelles was larger than that observed for MNPs in hexane when heated by an AC magnetic field. Drug release studies using triamterene- and doxorubicin- loaded micelles show a temperature-dependent acceleration of drug release at temperatures above 42 °C, the melting point of poly (caprolactone), as well as the possibility of magnetic induction hyperthermia-activated release.
Magnetic Heating of Iron Oxide Nanoparticles and Magnetic Micelles for Cancer Therapy
(IEEE, 2013) Glover, Amanda L.; Bennett, James B.; Pritchett, Jeremy S.; Nikles, Sarah M.; Nikles, David E.; Nikles, Jacqueline A.; Brazel, Christopher S.; University of Alabama Tuscaloosa; University of Alabama Birmingham
The inclusion of magnetic nanoparticles into block copolymer micelles was studied towards the development of a targeted, magnetically triggered drug delivery system for cancer therapy. Herein, we report the synthesis of magnetic nanoparticles and poly( ethylene glycol-b-caprolactone) block copolymers, and experimental verification of magnetic heating of the nanoparticles, self-assembly of the block copolymers to form magnetic micelles, and thermally-enhanced drug release. The semicrystalline core of the micelles melted at temperatures just above physiological conditions, indicating that they could be used to release a chemotherapy agent from a thermoresponsive polymer system. The magnetic nanoparticles were shown to heat effectively in high frequency magnetic fields ranging from 30-70 kA/m. Magnetic micelles also showed heating properties, that when combined with a chemotherapeutic agent and a targeting ligand could be developed for localized, triggered drug delivery. During the magnetic heating experiments, a time lag was observed in the temperature profile for magnetic micelles, likely due to the heat of fusion of melting of polycaprolactone micelle cores before bulk solution temperatures increased. Doxorubicin, incorporated into the micelles, released faster when the micelles were heated above the core melting point.
Multifunctional iron oxide nanoparticles for biomedical applications
(University of Alabama Libraries, 2014) Xu, Yaolin; Bao, Yuping; University of Alabama Tuscaloosa
This dissertation focuses on the preparation of multifunctional nanoparticles through the integration of iron oxide nanoparticles with other desired moieties. Iron oxide nanoparticles have been widely explored in localized therapy, targeted delivery, and magnetic resonance imaging. However, inaccessible MRI instruments for most research labs and lack of targeting ligands limits the further exploration of iron oxide nanoparticles in routine tumor diagnosis and efficient therapy. Therefore, the preparation of dual-imaging or targeted nanoparticles is highly desirable. In our studies, fluorescent gold nanoclusters or anti&ndashdisialoganglioside&ndashGD2 monoclonal antibodies are integrated onto iron oxide nanoparticle surfaces. The gold nanoclusters provide additional fluorescent imaging capability, which can be easily accessed in common research labs. The conjugation of cancer cell&ndashtargeting antibodies allows for specific localization of nanoparticles. Indeed, these are the two central themes of this dissertation. To prepare multifunctional nanoparticles, high&ndashquality iron oxide nanoparticles were first synthesized in organic solvents following a modified &ldquoheat&ndashup&rdquo method. During synthesis, a modification was made by introducing a co&ndashsurfactant (trioctylphosphine oxide&ndashTOPO). TOPO facilitated the subsequent ligand exchange process because it weakly bound to nanoparticle surfaces and prevented the formation of densely&ndashpacked surfactant coatings. As a result, hydrophilic molecules (such as polyacrylic acid, polyethylenimine, glutathione and dopamine) were capable of replacing the original ligands, yielding water&ndashsoluble iron oxide nanoparticles. In addition to water solubility, dopamine coatings offered nanoparticles additional conjugation capability upon surface oxidization. These surface&ndashoxidized nanoparticles can directly conjugate with amine and/or thiol group&ndashcontained molecules through Michael addition and/or Schiff base formation. Using this conjugation strategy, dual&ndashimaging nanoparticles were prepared by integrating dopamine&ndashcoated nanoparticles with protein (such as bovine serum albumin, trypsin and lysozyme) &ndash encapsulated fluorescent gold nanoclusters. All integrated nanoparticles maintained their functionalities and structural integrity in biological environments. Furthermore, effects of protein characteristics on the photo&ndashchemical properties of gold nanoclusters and integrated nanoparticles were systematically examined. Similarly, cancer cell&ndashtargeting molecules (e.g. anti&ndashGD2 monoclonal antibodies) were conjugated onto dopamine&ndashcoated nanoparticles. After conjugation, antibodies retained their high targeting specificity, suggested by our cellular targeting studies. More promisingly, conjugated nanoparticles were capable of transporting into cytosols, which opens up new possibilities in cancer&ndashcuring drug loading and targeted therapy. Besides these already&ndashpublished works, we have studied the biological responses of human monocytes to different surface&ndashcharged iron oxide nanoparticles (manuscript in preparation). For dual&ndashimaging nanoparticles, their stability and bio&ndashimaging potential will be evaluated in phorbol myristate acetate (PMA)&ndashtreated monocytes using differential interference contrast (DIC) and confocal microscopy.
New materials for optical sensing of explosives copolymers containing 2-vinyl-4,6-diamino-1,3,5-triazine and co-crystals of electron rich aromatic molecules and 1,3-dinitrobenzene
(University of Alabama Libraries, 2013) McNeil, Steven Keith; Nikles, David E.; University of Alabama Tuscaloosa
This dissertation focuses on the development of electron rich polymers with an affinity for nitroaromatics. Thin polymer films of the electron rich polymers could be applied in an optical waveguide sensor to detect nitroaromatics by changes in the optical properties of the polymer thin films. Charge transfer complexes between electron rich aromatic reagents and electron deficient nitroaromatics were produced providing an understanding of the intermolecular interactions between the electron donor and electron acceptor. Electron rich copolymers were synthesized with 2-vinyl-4,6-diamino-1,3,5-triazine (VDAT) using a published literature procedure. The polymerization procedure was extended to a variety of electron rich monomers, resulting in the production of a number of electron rich copolymers. Thin films of the copolymers were spin coated and their optical properties were characterized by spectroscopic ellipsometry before and after exposure to a nitroaromatic vapor. The exposure to the nitroaromatic vapor allowed the formation of complexes with the electron rich copolymers and the nitroaromatic molecules, creating a change in the optical properties of the polymer films. This refractive index change after exposure to a nitroaromatic demonstrated the possibility of these films to be applied in an optical waveguide sensor for explosive detection. Co-crystals were grown between electron rich donors and the electron deficient 1,3-dinitrobenzene by the slow evaporation method. When the electron donor solution and electron acceptor solution were combined in a crystallization dish, significant color changes were observed. The interaction between the electron donor and electron acceptor were characterized using analytical techniques.
Novel imidazole and ionic liquid-based platforms as media for co2 capture applications
(University of Alabama Libraries, 2014) Shannon, Matthew Samuel; Bara, J. E.; University of Alabama Tuscaloosa
The objective of this extensive research project was to investigate imidazoles as potential solvents for acid gas removal applications. Imidazoles are integral starting materials and neutral analogs for the synthesis and production of imidazolium-based ionic liquids (ILs) and virtually have not been explored as candidates for novel, CO₂ capture media. N-functionalized imidazoles also provide a similar platform as seen in ILs as tunable structures that govern physical and chemical properties leading towards lower volatilities, lower viscosities, higher CO₂uptake, etc. Physical properties (including density, viscosity, and gas solubilities) of N-functionalized imidazoles were recorded providing an initial database for comparisons to commercially-available organic solvents and imidazolium-based ILs. These results show that some novel N-functionalized imidazoles contend with common organic solvents for CO₂ separations in terms of dynamic processing properties (i.e. viscosity and CO₂ uptake). Imidazoles and ILs also provide a non-volatile media in which fugitive emissions and evaporative losses during solvent regeneration are reduced significantly. Chemical simulations and calculations via COSMOtherm software were also employed to rapidly predict thermophysical properties of these imidazoles and ILs, providing a means of screening of such novel solvents to be optimized for CO₂ separation processes. In the concluding chapters of this dissertation, continued research with the N-functionalized imidazole platform are noted, including areas of hybrid solvents, multiply-substituted, isomeric compounds, and imidazole-based polymeric media for acid scavenging (CO₂, SO₂, etc).
A Novel Process of Low Temperature Electrodeposition of Ti-Al Alloys Using Ionic Liquid Electrolytes
(University of Alabama Libraries, 2025) Nahian, Md Khalid; Reddy, Ramana G.
This study investigated the species concentration profile and electrical conductivity of the aluminum chloride (AlCl3) and 1-butyl-3-methylimidazolium chloride (BMIC) ionic liquid (IL) mixture, and its application in titanium (Ti)-aluminum (Al) electrodeposition. The species concentration profile was developed at 25°C as a function of AlCl3 mole fraction (X(AlCl3)), and the electrical conductivity of the IL was measured over a temperature range from 70°C to 110°C and X(AlCl3)= 0 to 0.67. Ti-Al alloys were electrodeposited using this IL, with anode as the source of Ti and IL electrolyte as the source of Al. The AlCl3:BMIC electrolyte was maintained at a 2:1 molar ratio (X(AlCl3) = 0.67), as this composition provided the highest concentration of Al2Cl7-, responsible for both Ti and Al deposition.Initial electrodeposition experiments were conducted in a 50 mL electrochemical cell using a single anode-single cathode configuration. These experiments focused on optimizing key deposition parameters, including deposition time under an argon (Ar) atmosphere, temperature, and applied potential under vacuum atmosphere. The results showed that the vacuum atmosphere significantly improved cathode current density compared to Ar. However, in both Ar and vacuum conditions, a passivation layer was formed on the anode, identified as TiCl3, which hindered the redox reactions and thus reduced the cathode current density.Scale-up experiments were then conducted in a 600 mL electrochemical cell with a single anode-single cathode configuration, using the parameters optimized from the 50 mL electrochemical cell setup. The impact of electrode distance was investigated, revealing that reducing the distance between electrodes improved current density by facilitating more efficient ion transport. The effect of stirring speed was also explored, and higher stirring speeds were found to enhance current density by improving ion mobility and reducing concentration polarization.Finally, experiments with three anodes and two cathodes were conducted in a 1000 mL electrochemical cell to assess the feasibility of Ti-Al electrodeposition using AlCl3:BMIC IL at a larger scale. These experiments confirmed the scalability of the Ti-Al electrodeposition process, with optimized parameters. The study highlights the significance of optimizing process parameters to effectively scale up the Ti-Al electrodeposition process for industrial applications.

Browsing by Author "Brazel, Christopher S."

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