Theses and Dissertations

Permanent URI for this communityhttps://hdl.handle.net/20.500.11875/5

Browse

Now showing 1 - 20 of 34

Analytical method development for cyanide antidotes and characterization of a new formulation of dimethyl trisulfide.
(2017-07-07) Hewa Rahinduwage, Chathuranga Chinthana; Petrikovics, Ilona
Cyanide (CN) is one of the most highlighted toxic compounds. It inhibits the cytochrome c oxidase enzyme, which catalyzes oxygen utilization in cells. As the brain and the heart are the main oxygen consumers, the effects of CN are more prominent on these organs. CN is converted into the less toxic thiocyanate in the presence of a sulfur donor, such as DMTS or thiosulfate (TS). In-house analytical methods were developed to determine CN, TS and nitrite (NT) concentrations by ion chromatograph (IC). Two different formulations for DMTS have been prepared for intramuscular (IM) administration. Formulation 1 (DMTS-F1) is a dispersion of DMTS in 15% aqueous polyoxyethylenesorbitan monooleate (poly80) solution. Formulation 2 (DMTS-F2) is a dispersion of DMTS in a mixture of poly80 and sorbitan monooleate (span80) (1:3 w/w). The concentrations of DMTS in F1 is 50 mg/mL and in F2 is 400 mg/mL. The Blood Brain Barrier (BBB) penetration by the two formulated DMTS structures were studied in a BBB model, Parallel Artificial Membrane Permeability Assay (PAMPA). The PAMPA system has two compartments to model the brain side and the blood vessel side of the BBB. Those compartments are separated with a porcine brain lipid-impregnated membrane. The antidote concentrations in the PAMPA samples were determined by HPLC with UV detection. In the first 30 minutes DMTS-F1 showed much higher speed in traveling from the blood to the brain side of the PAMPA. However, after 30 minutes DMTS-F2 showed much higher travel speed to the brain side. The size distribution stability of the two formulations were measured using a dynamic light scattering (DLS) instrument (Zetasizer). For quality measurements, this technique requires an estimate of the viscosity of the liquid. The viscosity of 2.32 cP for DMTS-F1 and 511.00 cP for DMTS-F2 were measured by a dropping ball viscometer. Size distribution studies suggest that the DMTS-F1 stored at 4 ̊C provides much more stable droplet size.
Chemical Vapor Deposition of Transparent Conducting Oxide Nanostructures on Various Substrates for Solar Cell Applications
(2021-07-21) Stephen, Hailey C; Trad, Tarek M
Nanostructured wide band gap transparent conducting oxides are important in the optoelectronic industry. Chemical vapor deposition (CVD) is a simple and effective method for synthesizing high-quality nanostructures from bulk materials. Three areas were investigated during this research: the effects of a ZnO seed layer on ZnO nanowires grown on transparent substrates by CVD, the vapor-liquid-solid synthesis of nanostructures by CVD using graphite to reduce Ga2O3, and a preliminary study of dye-sensitized solar cell design and testing. The ZnO seed layer was shown to improve the vertical alignment and distribution of the synthesized ZnO nanowires on mica, fused quartz, and c-plane sapphire substrates. Scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and room temperature photoluminescence were used to characterize the ZnO nanostructures. Nanoparticles and nanowires were synthesized on Si(100) substrates with a 10-nm catalytic gold layer by varying the reaction conditions. However, these experiments were not always reproducible. The products were analyzed by SEM and EDS to determine the morphology and average chemical composition of the structures, but the small amount of deposition prohibited proper analysis of the crystal phase of the nanostructures by XRD and room temperature photoluminescence with the available instrumentation. Rudimentary dye-sensitized solar cells were fabricated using conductive glass, bulk TiO2, N3 dye (cis-bis(isothiocyanato)bis(2,2′-bipyridyl-4,4′-dicarboxylato)ruthenium(II), and an I-/I3- redox couple electrolyte. These cells produced voltage measurements comparable to literature values for similarly constructed cells, but the measured current was significantly lower than expected.
Cyclic Vacuum Cavitation for Cleaning Applications
(2021-07-22) Ariyarathna, Rajamanthree Wedage Udumbara Nethmini; Williams, Darren L
The removal of micron-sized carbon black particles from capillary tubes (outer diameter 1.46 mm, inner diameter 1.12 mm, length 50.00 mm) using cyclic vacuum cavitation (VC) cleaning was investigated. As the first objective of this study, the VC apparatus was constructed. This VC setup allowed video monitoring of the cleaning process. Photographs, video recordings, and gravimetric analysis tests were used to identify the cleaning efficiencies. As the second part, the carbon black powder removal efficiencies were used to compare cyclic VC and ultrasonic cavitation (UC) cleaning. Cyclic VC coupled with deionized (DI) water was able to remove 67 ± 7% of carbon black powder from contaminated capillary tubes. Solutions of 1% sodium lauryl sulfate (SLS) in DI water successfully removed 82 ± 7% of carbon black powder using fifteen vacuum cycles at room temperature. The UC process was unable to flush the carbon black soil from the internal volume of the capillary tubes. The cleaning was more effective with cyclic VC than UC cleaning at given conditions. Raising the temperature, of the liquid increased cavitation and caused better wetting of the carbon black powder at the bottom of the tubes. The optimized VC process parameters (25 vacuum cycles, 1% SLS in DI water, vigorous stirring at 40 °C) removed 99 ± 1% of the carbon black powder. This study showed experimental evidence that cyclic VC is a good cleaning approach for cleaning parts that have deep blind holes.
DEVELOPING METHODS FOR INVESTIGATING DIMETHYL TRISULFIDE IN AQUEOUS SOLUTIONS
(2023-08-01T05:00:00.000Z) Brockhausen, David Duane; Thompson, David E; Gross, Dustin E; Hinze, Meagan E
Dimethyl trisulfide (DMTS) is currently being investigated as an antidotal candidate for cyanide poisoning. DMTS is lost from aqueous solution more rapidly than would be expected given that its boiling point exceeds that of water. Prior investigations have shown that the preferential loss of DMTS from aqueous solutions is reproducible but have not yet provided a scientific explanation for the loss. To lay a foundation for addressing this question, an accelerated evaporation apparatus was assembled that allowed sampling at regular time intervals from an evaporation flask and an attached cold trap. The decrease of DMTS concentrations in these samples was then followed by NMR and HPLC characterization, taking into consideration the susceptibility of DMTS to photolysis and thermolysis induced disproportionation. The rate of DMTS loss in this accelerated evaporation model system greatly exceeds natural rates of disproportionation, strongly suggesting that, under the conditions of accelerated evaporation, the preferential losses of DMTS are due primarily to direct preferential evaporation of DMTS, and with only very small contributions from the evaporation of disproportionation products. Under slower rates of evaporation, the indirect loss of DMTS via disproportionation pathways is expected to be more significant.
Development of bifunctional catalysts containing hydride-relay ligands for CO2 hydrogenation
(2019-04-17) Devi, Nilakshi; Zall, Christopher M.
The research described in this thesis focuses on the synthesis of bifunctional catalysts for hydrogenation of CO2. These catalysts contain redox active phenanthridinium and benzimidazolium groups capable of mediating hydride transfer incorporated within a transition metal phosphine complex. These redox active groups, called “hydride relays,” are NADH-type organic hydride donors that can reversibly accept or donate hydride ions and transfer them to substrates, like CO2. A series of bifunctional ligands, LPhenH, LPhen+, LBI+ and LPhenBI+, were synthesized in which the targeted hydride relays are tethered to a phosphine donor via an ethylene linker so that they can be combined with transition metal ions that have complementary proton acceptor abilities. Ni(II) complexes proved to be too sterically hindered to bind these ligands when used with polydentate phosphine ligands. However, [Ni(LPhenBI+)Br3], a Ni(II) species containing bromide ligands, was synthesized. A crystal structure was obtained for [Ni(LPhenBI+)Br3]: monoclinic, P21/c, a = 18.3574(13), b = 15.8651(8), c = 20.1961(12) Å, β = 106.102 (7)°, R = 0.0709, and RW = 0.1150. Pd(II) complexes using redox active ligands in conjunction with ancillary polydentate phosphine ligands like PP2 [PhP(CH2CH2PPh2)2], and PNHP [HN(CH2CH2PPh2)2] were synthesized. Crystal structures were obtained for the complexes containing phenanthridinium relays, [Pd(PP2)(LPhenH)][BF4]2•(CH3CN)3.25 and [Pd(PP2)(LPhen+)][BF4]3•(CH3CN)3. For [Pd(PP2)(LPhenH)][BF4]2•(CH3CN)3.25: monoclinic, P21/n, a = 11.2927(4), b = 41.743(1), c = 12.9751(4) Å, β = 90.251(3)°, R = 0.0772, and RW = 0.1483 and for [Pd(PP2)(LPhen+)][BF4]3•(CH3CN)3: monoclinic, P21/c, a = 21.822(2), b = 13.632(1), c = 22.575(2) Å, β = 91.116(8)°, R = 0.0632, and RW = 0.1349. Pd0 complexes were also synthesized. A crystal structure was obtained for the complex [Pd0(PP2)(LPhenH)]: triclinic, P-1, a = 11.5406(6), b = 12.6451(6), c = 18.3167(7) Å, α = 79.558(4)°, β = 80.469(4)°, γ = 78.061(4)°, R = 0.0680, and RW = 0.1176. These complexes were also characterized using 1H and 31P NMR spectroscopy. These studies show that the hydride relays can be successfully incorporated in close proximity to the transition metal of tetraphosphine complexes.
Diazaboroles: Experimental Investigations of their Dynamic Covalent Nature and Computational Chemistry
(2017-07-14) Abeysinghe, Janaka Prasad; Gross, Dustin E.
Diazaboroles have interesting optical and electronic properties. They are soluble in many organic solvents, electrochemically active, and thermally stable. The understanding of diazaboroles’ dynamic covalent behavior is important for the synthesis and incorporation in complex molecular architectures like fully p-conjugated, non-collapsible, and shape-persistent macromolecules. The present study involves the influence of solvent on diazaborole formation and its dynamic covalent behavior under various conditions. XRD structural determination was carried out for structural identification of diazaborole; moreover, computational calculations were used to compare experimental and theoretical results. The investigation of the solvent effect on diazaborole formation is important when synthesizing more complex diazaborole based molecular architectures. Therefore, the effect of the solvent on diazaborole formation was investigated and identified that only solvent evaporation time was sufficient to obtain greater diazaborole formation in high boiling solvents. Even though high reaction temperature leads to high diazaborole production, the functional groups of the solvents show less impact on the reaction. The reversibility of diazaborole formation was examined by considering diazaborole transamidation and exchange reactions with different diazaborole substituents. The results illustrate that transamidation reactions of diazaboroles are reversible. Computational calculations reveal the bond angle and bond length deviation of diazaborole isostructures (analogues). Further, electrostatic potential maps disclose the existence of an electron rich phenyl ring in diazaborole. The Gibbs free energy values of diazaborole formation in the solvent phase reveal the reaction favorability of diazaborole formation in some solvents under appropriate conditions.
Effect of Boron Trifluoride on the Transesterification of Boronate Esters
(2017-06-29) Ekanayake, Dulamini; Gross, Dustin E.
Boronate ester-based materials have received interest and found utility in many applications. The preeminent goal of this research is to advance the field of boron-oxygen based porous materials. The formation of these materials has been predominantly facilitated by boron-oxygen dynamic covalent character. In an effort to understand and improve this process, we are investigating the effect of boron trifluoride, a well-known Lewis acid catalyst, on synthesis and exchange of dioxaboroles. From our previous studies, we have observed an increase in reaction rate as well as beneficial side reactions, which have driven the reaction equilibrium to unexpected products from the transesterification of phenyl pinacol boronate ester (PPB) in the presence of boron trifluoride. Initially, we studied the effect of boron trifluoride on the transesterification of different boronate esters (dioxaboroles) with catechol. Then, we synthesized bis boronate ester materials by combining the knowledge learned in the above-described work. Finally, we investigated the Lewis acid-catalyzed (boron trifluoride and para-toluene sulfonic acid) pinacol rearrangement of different diols (pinacol, hydrobenzoin, and benzpinacol). In the presence of boron trifluoride all transesterification reactions of boronate esters with catechol showed an improvement. Additionally, we were able to find a method to isolate catechol boronate ester on the gram scale.
EXPLORING NOVEL CATALYSTS FOR THE CHEMICAL VAPOR DEPOSITION SYNTHESIS, AND CHARACTERIZATION OF ZINC AND GALLIUM OXIDE NANOSTRUCTURES
(2023-08-01T05:00:00.000Z) Oyegoke, Jamal; Trad, Tarek M; Thompson, David E; Hobbs, Christopher E
Zinc oxide (ZnO) possesses a non-centrosymmetric structure, which imparts it with piezoelectric properties, rendering it appealing for various technological applications involving nanostructured ZnO. In this investigation, the growth of ZnO surface structures was examined using Magnetite-Catalyzed Chemical Vapor Deposition (CVD). The CVD technique offered control over reaction time, enabling precise growth of ZnO structures. Incorporating catalytic layers of magnetite nanoparticles promoted nucleation and facilitated the development of a distinct morphology resembling interconnected microsized flakes as observed through scanning electron microscopy (SEM). Also in this study, the impact of pressure on the morphology and photoluminescence properties of ZnO nanostructures synthesized through chemical vapor deposition (CVD) was explored. X-ray diffraction (XRD) analysis revealed changes in crystalline quality, size, and orientation of ZnO nanostructures at different pressure conditions. Scanning Electron Microscopy (SEM) showed distinct morphologies, such as hexagonal rods and randomly arranged nanowires. X-ray fluorescence (XRF) analysis provided information about the elemental composition, and photoluminescence measurements indicated excitonic and defect-related emissions. These findings demonstrate the significance of pressure in shaping the characteristics of ZnO nanostructures for potential nanodevice applications. Lastly, the synthesis of Ga2O3 nanostructures using chemical vapor deposition (CVD) was explored. The growth mechanism involved metal adsorption on gold droplets on a heated substrate, followed by v oxygen integration into the nanowire's crystal lattice. X-ray diffraction confirmed specific lattice planes and orientations in the nanowires, with preferential alignment along the c-axis direction. SEM images showed well-controlled and uniform growth, with an average thickness of 65 nanometers. The β-Ga2O3 nanowires also demonstrated optical emission properties within the visible range.
Identification and characterization of non-flammable azeotropic mixtures for precision cleaning
(2017-04-18) Perry, Jacob; Williams, Darren L.; Gross, Dustin E.; Thompson, David E.
The goal of this thesis is to provide methods that can be used to search for new azeotropes with specific desired properties, and methods to characterize these new azeotropes. All azeotrope possibilities that were examined in this study were low-boiling azeotropes composed of non-aqueous solvents, and the desired properties were for the azeotropes to be non-flammable and have good solvency against hydrocarbon grease. In this study, azeotropes were formed for use in cleaning applications, specifically vapor degreasing. For cleaning applications, the most important quality of the azeotrope is solvency. However, in a vapor degreaser flammability is an issue. To obtain the desired solvency in an azeotrope, the Hansen Solubility Parameters (HSPs) were used to decide what solvents were good candidates. However, the solvents that were found from this search were flammable. In an attempt to get the desired properties, the solvents were paired with non-flammable solvents that had similar boiling points to obtain a blend with good solvency and no flammability. Then, these pairs were mixed and distilled to identify whether the pairs formed low-boiling azeotropes. The resulting azeotropes were characterized by obtaining their boiling point, flash point, thermal expansion coefficient, surface tension, density, viscosity and composition. The boiling points were obtained from the distillation process. The flash points were found using a modified ASTM D56 method. Thermal expansion coefficients were obtained through the dependence of the density on temperature. The surface tension and density were obtained using a DuNouy ring tensiometer. Viscosity was found using a ball drop viscometer. Finally, the composition was found using Raman spectroscopy. All these standard procedures can be found in the appendix. A solubility parameter-based model for predicting azeotropic behavior in binary mixtures was explored as an extension of the results of this thesis work. The goal of this model is to predict the likelihood that a given pair of solvents will form a low-boiling azeotrope. Such a model would save time in the laboratory, reduce personnel exposure, and reduce waste by steering the researchers away from unpromising mixtures that are unlikely to form azeotropes.
IN VITRO AND IN VIVO EFFICACY COMPARISON OF THREE CYANIDE ANTIDOTE CANDIDATES AND FLUORESCENT METHOD DEVELOPMENT FOR MEASURING THE SELECTED CYANIDE ANTIDOTE DIMETHYL TRISULFIDE AT LOW CONCENTRATIONS
(2018-04-11) Gaspe Ralalage, Ramesha Dilhani; Petrikovics, Ilona
Cyanide (CN) is a toxic molecule that inhibits oxygen utilization by cells. Thiosulfate converts CN- into the less toxic thiocyanate (SCN-), a reaction that is catalyzed by rhodanese (Rh). The comparison of sulfur donor (SD) efficacy (in vitro) and antidotal efficacy (in vivo) of different SDs (SD1, SD2 and SD3) is described in the first part. The in vitro SD efficacy was monitored by quantifying the formation of SCN- with and without Rh at physiological pH (7.4) and the optimum pH for Rh (8.6). The in vitro SD efficacy without Rh at pH 7.4 and with Rh at both pH values varies in the order of SD1 > SD2 > SD3. The in vivo antidotal efficacies were expressed and compared using the antidotal potency ratios (APR) (APR= CN LD50 with antidote/CN LD50 without antidote). Mice were injected with CN and SD1 and the APR value was calculated. The antidotal efficacy varies in the order of SD2 > SD1 > SD3. The in vitro SD efficacy values and in vivo antidotal efficacy values were different due to several pharmacokinetic reasons. In the second part, a fluorescent method to detect low concentrations of DMTS (below 1 µg/mL) in blood samples is described. DMTS is a sulfane sulfur type CN antidote. Sulfane sulfur probe (SSP4) is a probe that selectively binds with sulfane sulfurs. Upon the reaction of SSP4 and DMTS, a fluorescent product is expected. The mixture of SSP4 and DMTS was scanned to determine its excitation and emission characteristics using a fluorescence spectrophotometer. The fluorescent product yielded from the reaction between SSP4 and DMTS exhibited peak absorbance at 280 nm and peak emission at 309 nm. A calibration curve was obtained at λex/λem=280/309 nm for fluorescence intensity vs. DMTS concentrations (R2=0.9935). The mixture of SSP4 and DMTS/ACN was then analyzed using an HPLC-fluorescence experiment with λex/λem=280/309 nm. A fluorescent peak with a retention time of 11.1 minutes showed good linear correlation with DTMS concentration in simple aqueous solutions of DMTS (R2=0.993), and in DMTS-spiked blood (R2=0.9995).
In Vivo and In Vitro Characterization of Different Dimethyl Trisulfide Formulations
(2020-07-09) Rios, ChristianThomas; Petrikovics, Ilona
Cyanide is a toxic cytochrome c oxidase inhibitor that prevents the production of ATP, which consequently results in lactic acidosis, histotoxic hypoxia, and death. Dimethyl trisulfide (DMTS) is a promising sulfur donor (SD) type cyanide antidote that can react with cyanide to form the less toxic thiocyanate. These studies provide more insight into the characterization and biological effects for a newly formulated FF-DMTS compared to Poly80-DMTS. The first objective was to determine the optimal pH for rhodanese activity. This was determined by observing the SD efficiencies of DMTS and thiosulfate, without rhodanese and comparing that to their activity in the presence of rhodanese at a pH of 7.4, 8.6, and 10.5. Post-reaction, the DMTS (3.5mM) was seen to be over 40x less concentrated than its TS counterpart (150mM), yet exceeds thiosulfate SD ability, supporting the idea that DMTS is a more efficient SD. Secondly, the in vitro blood brain barrier penetrability was determined using a Parallel Artificial Membrane Permeability Assay system. It was determined that the Poly80-DMTS (Papp =11.8x10-6 cm/s) penetrated the blood brain barrier more than the FF-DMTS (Papp=7.46x10-6 cm/s), although the Poly80-DMTS (tlag=6.42 min.) had a lag time over 3x longer than FF-DMTS (tlag=2.00 min.). Thirdly, when analyzing the formation of methemoglobin by DMTS in vivo, FF-DMTS produced more methemoglobin than Poly80-DMTS. The highest examined doses of both formulations, however, produced less than 30% methemoglobin, which is the percentage that would induce methemoglobinemia and require medical assistance. Lastly, when observing the particle size distribution of the two formulations using the Zetasizer Nano, the particle size of FF-DMTS was almost 3.5x higher than that of the Poly80-DMTS. This can potentially be used to explain the slower blood brain barrier penetrability of FF-DMTS. The information obtained from these studies will be used for further characterization of DMTS as a cyanide antidote. Understanding how DMTS behaves in the body will give insight into developing an alternative cyanide therapeutic agent. The information from these studies, will contribute to the development of an intramuscular injector kit, which can potentially decrease the lives lost to cyanide intoxication.
INVESTIGATING THE BACTERICIDAL EFFICACY OF MAGNETIC METAL FERRITE NANOPARTICLES SYNTHESIZED BY NON-HYDROLYTIC COPRECIPITATION
(2023-05-01T05:00:00.000Z) Johnson, Morgan; Trad, Tarek M; Haines, Donovan C; Zall, Christopher M
New methods of combating bacterial infections must constantly be explored due to the efficiency of the evolution of antibiotic resistance. Nanoparticles can be paired with current antibacterial agents to increase susceptibility. Bare cobalt ferrite and silverdoped ferrite nanoparticles as well as those capped with caprylic acid were synthesized using a previously reported novel non-hydrolytic coprecipitation method. The particles were characterized using FTIR to verify the capping agent and XRD to corroborate that the magnetic spinel ferrite crystal phase was achieved. DLS and TEM provided information about hydrodynamic particle diameter and physical particle morphology, respectively. All particles were tested against broth cultures of Bacillus licheniformis, Erwinia carotovora, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Streptococcus pneumoniae. Infrared spectra of all capped particles verified the presence of caprylic acid in both the precursor and nanoparticle material. Diffractograms showed Miller indices corresponding to known magnetite phases. DLS size-characterization of CoFe2O4 caprylate and bare particles indicated hydrodynamic diameters of approximately 100 nm and 401.6 nm, respectively. Silverdoped ferrite caprylate and bare particles had hydrodynamic diameters of 50.7 nm and 220.6 nm. TEM micrographs of CoFe2O4 caprylate indicated a spherical monodisperse morphology with a diameter of 3.8 ± 0.8 nm. EDS studies indicated only slight silver incorporation in the silver-doped ferrite nanoparticles, while cobalt ferrite particles showed a ratio of 2.4:1 of iron to cobalt. Biological broth testing had varying levels of success with the ethanol control groups often overshadowing possible particle results. Fluorescence testing also had limited success due to light absorption from the particles. Plate counting assays provided the most conclusive results despite not being as delineated as broth culture assays with both silver-doped ferrite caprylate and bare silver-doped ferrite nanoparticles being effective at inhibition of E. coli, P. aeruginosa, S. enterica, S. aureus, S. pneumoniae. Silver-doped ferrite caprylate exhibited a rescue effect for B. licheniformis and E. carotovora with bare silver-doped ferrite exhibiting significant inhibition. Overall, silver-doped ferrite had better inhibitory results than cobalt ferrite, likely due to the presence of silver.
INVESTIGATING THE INTERACTION OF ALBUMIN WITH THE CYANIDE (CN) ANTIDOTE CANDIDATE POLY- 80 FORMULATED DIMETHYL TRISULFIDE (DMTS) AND CEFUROXIME, A COMMON ANTIBIOTIC AS A COMPARISON
(2023-08-01T05:00:00.000Z) Herath, Herath; Petrikovics, Ilona; Thompson, David E; Trad, Tarek M
Finding a new Cyanide (CN) antidote is a great milestone in toxicology. Nithiodote™ and Cyanokit® are the two current CN antidotes used in the USA. Due to some of their limitations, there was a need to develop an effective intramuscular (IM) antidote to treat CN intoxication. The small lipophilic compound Dimethyl trisulfide (DMTS) has been proposed as a novel CN antidote. Protein binding and membrane binding are important aspects of drug development as they influence the bioavailability of a drug. The well-known Protein Equilibrium Dialysis (PED) method was used for the protein binding characterization for two molecules: the CN antidote candidate Poly-80 formulated Dimethyl trisulfide (DMTS),(Poly80-DMTS) and the antibiotic Cefuroxime. In this study, the Parallel Artificial Membrane Permeability Assay (PAMPA) method was employed for the protein binding and penetration studies. The moles in the donor cells and the acceptor cells for both drugs were determined using High Performance Liquid Chromatography (HPLC) method calibrated for the specific PED setup in PION PAMPA Buffers both in the presence and absence of Albumin. In PAMPA studies with Poly80-DMTS, the presence of Albumin decreased the membrane penetration by factor 1.27 and enhanced the membrane retention by factor 1.20. This suggests that DMTS has an affinity for binding to Albumin and the DMTS-Albumin complex is less capable of traveling through the artificial membrane. More experimental conditions are being investigated in the ongoing studies. In PED studies with Poly80-DMTS, the percentage of DMTS transferred to the acceptor plate in the absence of Albumin was about 1.5 times greater than the percentage transferred when Albumin was present. This also suggests that DMTS has significant affinity for binding to Albumin. In PED studies with Cefuroxime, the percentage of Cefuroxime B and Cefuroxime A transferred to the acceptor plate was lowered by a factor of 1.6, when Albumin was present in the donor plate, suggesting that Cefuroxime also has significant binding affinity to Albumin. DMTS shows better in vitro and in vivo antidotal character than any of the current CN antidotes. Presently DMTS is on the way to the FDA approval for being established as a therapeutic agent to treat CN intoxication. Clinical trials and metabolism studies are listed as to be done experiments.
Investigation of Diazaborole Formation and Diazaborole-Linked Macrocycles with EthylHexyl Ester Substituents
Nguyen, Thao N.; Gross, Dustin E.
Boron-containing polymers and macrocycles are currently an exciting field of study due to their wide variety of potential applications. The exploration of the dynamic covalent behavior of 2-phenyl-1,3,2-benzodiazaborole (DAB) under different solvent and temperature conditions may provide insight into the synthesis of larger diazaborole-based frameworks. The effects of solvent and temperature on the condensation of DAB were explored. The results showed that the DAB product formed faster in DMSO than in toluene. However, DAB formation showed higher percent conversion in toluene. In addition, Raman spectroscopy was used for in situ reaction monitoring of DAB formation. By using a calibration curve, we found that the formation of DAB in chloroform at 50 °C can achieve up to 68% conversion. However, the use of Raman spectroscopy for reaction monitoring of DAB formation was limited by solubility and by the baseline noise. Furthermore, our research group is investigating the use of diazaboroles as the active linking unit in shape-persistent macrocycles. The present study describes the continuing efforts towards improving the solubility of monomers, oligomeric intermediates, and macrocyclic products. Ethylhexyl ester functional groups were installed on the monomer to improve solubility. The results illustrated that although the presence of branched 2-ethylhexyl ester had a positive effect on solubility of the monomer, the side chain interactions were not strong enough to overcome the pi-stacking forces of the macrocycles. The poor solubility of the co-reactant benzene-1,4-diboronic acid (BDBA) is a limiting factor for the formation of the macrocycle product. To overcome this issue, we investigated the use of BDBA-based esters instead of BDBA. The results revealed that the reactions between BDBA-based esters with various di- and tetraamines in chloroform at room temperature were slow and intramolecular reactions to form the macrocycle could not compete with the stability of the BDBA-based esters.
INVESTIGATION OF OLIGO(BENZOXAZABOROLE)S DERIVED FROM ALKYLLINKED BIS(AMINOPHENOL)S
(2021-05-01T05:00:00.000Z) Muthumali, Ahangama Munasingahge Thusharika; Gross, Dustin E
Boronate ester-based materials have gained significant research interest and utility because of their ability to be formed through dynamic covalent bonds (DCBs). This reversible nature has been shown to organize molecular building blocks into the most thermodynamically stable structures such as linear polymers, nanotubes, macrocycles, and covalent organic frameworks (COFs). Previously, we reported the synthesis of simple boronate ester derivatives, benzoxazaboroles, using 2-(alkylamino)phenols and diboronic acids. However, the synthesis of benzoxazaboroles derived from bis(aminophenol)s is less explored. There is a possibility to yield macrocycles along with the linear polymers due to the ditopic functionality of the starting materials and an equilibrium between ring and chain structures may exist. In this research, we have synthesized investigated oligo(benzoxazaborole)s derived from alkyl-linked bis(aminophenol)s by both experimental and computational methods. Characterization of these materials was carried out using 1H NMR, 13C NMR, IR spectroscopy techniques. 1H NMR results indicate that the polymers exhibit dynamic covalent nature under mild conditions. Furthermore, IR spectroscopic analysis reveals that the degree of polymerization is quite high for the polymers due to the absence of signals related to the starting materials. The thermodynamic calculations predicted that the formation of benzoxazaboroles depends on the difference in the connectivity of the benzoxazaborole rings within the structure. Additionally, those calculations predicted that the linear benzoxazaboroles are more favorable than the ring structures. However, the energy difference is less than 53 kJ/mol.
Lipids of Decomposing Vertebrate Tissue Analyzed with GC-MS and ATR-IR
(2017-04-18) Bittner, Brianna F.; Haines, Donovan C.; Petrikovics, Ilona; Thompson, David E.
Lipids are unique molecules that are significant to the structure of cell membranes, metabolism, and cell signaling. Their abundance and stability make them great molecular targets for studying tissue decomposition. Chicken drumsticks and segments of a donated human femur were buried at Southeast Texas Applied Forensic Sciences (STAFS), and sampling of the decomposing bones and the surrounding soil were conducted over a three month period. The Haines lab has employed an extraction method to detect lipids in bone tissue and soil using Gas Chromatography Mass Spectrometry (GC-MS) and Attenuated Total Reflectance Infrared Spectroscopy (ATR-IR) at Texas Research Institute for Environmental Sciences (TRIES). Principal Component Analysis (PCA) of IR spectra in R demonstrated several principle components of variation, including one representing ester hydrolysis in formation of carboxylate groups in the 1400-1600 cm-1 region. PCA data for GC-MS also supports the ester hydrolysis in the degradation of monoacylglycerols. Additional correlations were identified between fatty acid decomposition products, but there is less confidence in the time dependence of the patterns of decomposition. Lipid detection in soil through GC-MS analysis confirmed leaching of tissue lipids into soil.
LONG-TERM STORAGE STABILITY AND OXIDATION PRODUCTS OF THE CYANIDE ANTIDOTE DIMETHYL TRISULFIDE
Warnakula, Indika Kasun; Petrikovics, Ilona
Exposure to cyanide (CN) leads to the malfunction of mitochondrial activity by inhibiting the terminal oxidase, cytochrome c oxidase. The brain and heart are the highest oxygen consumers and are the critical target organs harmed by CN. Dimethyl trisulfide (DMTS) is a well-studied CN antidote with the major mechanism of sulfur donation for CN conversion to SCN. However, recent investigations revealed a minor mechanism of methemoglobin formation from DMTS that is a CN scavenger type antidote. Formulation efforts of DMTS focus on optimizing pharmacokinetic and storage stability parameters. This study reports the storage stability of a formulation for DMTS (F3-formulation) developed by Southwest Research Institute, San Antonio, Texas. The F3-formulated DMTS was stored in glass ampules at 4, 22 and 37 ºC. At regular time intervals over the period of one year, nine ampules (three stored at each temperature) were opened and analyzed by HPLC-UV to determine their DMTS content. The results showed that there was no measurable loss of DMTS over the one-year period of the study for the samples stored at 4 and 22 ºC. The samples stored at 37 ºC showed good stability for five months. However, in the sixth month of storage, these samples showed a 10% (M/M) decrease in DMTS content. Discoloration and the appearance of a new peak in the HPLC chromatogram accompanied this loss of DMTS. Continued growth of these new peaks and deepening discoloration was observed over the final 5 months of the study. To identify the degradation products formed during storage at 37 ºC, separate oxidation studies were performed with DMTS using strong oxidizing agents, such as mCPBA or H2O2. The products of the oxidation studies were compared to those of the stability study samples. Dimethyl tetrasulfide and dimethyl pentasulfide were observed as products of both studies. Dimethyl disulfide was observed as a product of degradation and S-methyl methanethiosulfonate was revealed as a product of oxidation. The HPLC and GC-MS SPME analysis revealed a good agreement between the degradation products of the stability study and the direct oxidation reactions. Because the 22 and 4 ºC samples remained stable for a year, we can conclude that the F3-formulated DMTS fulfills the criteria for storage stability.
Modeling and Molecular Dynamics Simulations on the in situ Murine Cytochrome P450 4F System
(2020-07-07) Butler III, Jerome W; Haines, Donovan
Cytochrome P450s are major participants in the maintenance and well-being of cellular function and have important roles in the health and disease of living creatures. The ω-hydroxylation, catalyzed by CYP4 family members, has been observed to be an important metabolic pathway for the homeostasis of mammalian cells as it regulates inflammatory processes with the eicosanoid cascade of metabolites of the ω-6 polyunsaturated fatty acid, arachidonic acid. Many human CYP4F and murine Cyp4f subfamily members have recently gained interest for their usage as potential cancer biomarkers as the expression of these proteins are modified in tumor cells. 20-HETE, the ω-hydroxylated product of arachidonic acid, has gained attention for being the chief metabolic product of interest in vascular function, tumor progression and propagation. Whether or not individual Cyp4f isoforms are responsible for the production of this metabolite is of great interest to medicine as such insight could provide researchers with new avenues of study in the fight against cancer. One particular Cyp4f isozyme, Cyp4f13, has received relatively little study until only very recently and is the focus of the work presented in this thesis, as it has not fully had its role in eicosanoid metabolism understood. Using a combination of computational chemistry approaches, this study focuses on exploring the murine cytochrome P450 4f13 system and its active site using all-atomistic Molecular Dynamics Simulation of a homology model. With the embedded protein solvated and in situ environment replicated, the resting state of the substrate-free Cyp4f13 system was generated. Solvation of the active site was performed to explore the inner active cavity of the P450 system, with subsequent molecular docking and mutation of active site residues performed in order to gain insight into the interactions present in the protein-substrate complex. Protonation state changes were observed to have significant effects on both protein structure and arachidonate binding through electrostatic interactions. Leu137, Arg237, and Gly327 were modified and displayed drastic effects on predicted regiospecificity on the P450 substrate. With the insights obtained, we hope to further the understanding of murine Cyp4f13-catalyzed ω-hydroxylation of arachidonic acid.
New Polymer-Supported Photo-Catalysts from Unimolecular, Photo-Catalyst Initiator Systems (UPCIS)
(2020-08-01T05:00:00.000Z) Peavy, Matthew A; Hobbs, Christopher E
In today’s environmentally conscious world, the development of greener catalysts is at the forefront of discovery. This is because many catalysts are, traditionally, based on environmentally toxic transition metals that are discarded as waste after only a single use. In this regard, the recovery and recycling of such catalysts is vital, in academia and industry. This is often achieved through the incorporation of a catalyst and/ or ligand into a polymer support to enable liquid/liquid or solid/liquid recovery. This incorporation is frequently accomplished through (i) polymerizing a monomer that has been pre-functionalized to contain a ligand/catalyst or (ii) using a post-polymerization modification strategy in which a ligand/catalyst is linked to a pre-made polymer. However, either method relies on the synthesis of a polymer that can require multiple species of its own (i.e. monomer, catalyst, ligand, and initiator). This problem can be averted with the rational design of a unimolecular, photo-catalyst initiator system (UPCIS) that can facilitate the synthesis of a polymer support that can subsequently be used, as a multi-functional catalyst, to carry out other reactions. These systems (in which the initiator, ligand, and/ or catalyst, are covalently linked to one another) can be used to facilitate atom transfer radical polymerizations (ATRP). Additionally, the implementation of a greener energy source can be achieved through the utilization of visible light to initiate these reactions. For the current research, reactions are initiated through irradiation with visible light sources, and the catalyst is easily recovered by solid/liquid separation and can be recycled up to five times without loss of activity.
Non-Hydrolytic and Solvent-Assisted Mechanochemical Synthesis of Surface Modified Spinel Ferrite Nanoparticles: Comparative Investigation of Arsenic Extraction From Water
(2021-08-01T05:00:00.000Z) Weththasingha, Chamari; Trad, Tarek M
Magnetic nanoparticles are a class of nanomaterials commonly containing a magnetic aspect (a magnetic element or a compound) and a functional aspect. Magnetic nanoparticles can be synthesized by a variety of methods such as co-precipitation, sol-gel method, microemulsion, thermal decomposition, solvothermal, chemical vapor deposition, carbon arc, and laser pyrolysis. In this work, magnetic nanoparticles of cobalt ferrite have been synthesized by novel non-hydrolytic open and closed (pressure-assisted) reaction methods and solvent-assisted mechanochemical synthesis using iron/cobalt precursors. Cholic acid and stearic acid were used as capping agents to modify the surface of cobalt ferrite nanoparticles. The major goal was to prepare carboxylate capped spinel ferrite magnetic nanoparticles using an environmentally friendly, cost-effective, and facile method. In addition, a general comparative study was conducted exploring different chemical and physical properties of the particles as well as their efficiency for the removal of arsenic from aqueous solutions. The extraction efficiency of arsenic (V) was evaluated by using inductively coupled plasma (ICP). The carboxylate-capped nanoparticles were characterized through different characterization methods. The presence of the capping agents was confirmed by Fourier Transform Infrared (FTIR) spectroscopy. Particle diameter was characterized using dynamic light scattering (DLS). The crystallite size of the particles was studied by X-ray powder diffraction (XRD).

Browse

Browsing Theses and Dissertations by Department "Chemistry"