ETD Search Results: instcode:ohiou

Skip navigation

ETD Center Search

40 matches in the database. These are records: 1 - 30.
Did you mean instcode:ohio?

[1] [2]

1. Acquaah-Harrison, George. Antibacterial Agents: 1,4-Disubstituted 1,2,3-Triazole Analogs of the Oxazolidinone.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► The rational design, development and synthesis of structurally diverse small molecule that… (more)

▼ The rational design, development and synthesis of structurally diverse small molecule that target RNA is immensely important in antibacterial therapy. Utilizing rational design approach to drug discovery, two lead 4,5-disubstituted 2-oxazolidinone compounds that bind to the highly conserved region of bacterial RNA with high affinity and specificity had been previously identified. This biological target called the T box antiterminator system regulates the expression of many genes including aminoacyl synthethase genes and is found predominantly in Gram-positive pathogens. But, owing to the moderate solubilities of these leads, the focus was directed to improving the solubility challenges without compromising biological activity. To address the solubility challenges with the intent of enhancing or maintaining biological activity, a library of one hundred eight 1,4-disubstituted 1,2,3-triazole compounds that encompasses the diversity elements of the oxazolidinones were developed. This library, which entailed the bioisosteric replacement of the oxazolidinone scaffold was afforded in high yield and purity by employing the regioselective copper(I)-catalyzed azide/alkyne cycloaddition reaction. Three lead compounds, GHB-7, GHB-9 and GHB-16 with enhanced biological activity were identified that rendered them important candidates for structural activity relationship studies (SAR). Besides the SAR studies, few 1,5-regioisomers were prepared to investigate the effect of regioselectivity on biological activity. By embarking on empirical observations, thirty-two structurally relevant analogs were prepared for the SAR and other structural elaboration studies. While biological evaluation is currently ongoing, the preliminary data of the analogs, GHB-144, GHB-151, GHB-153, GHB-156 and GHB-157 coupled with the enhanced biological activity of GHB-7 relative to the lead oxazolidinone compounds re-inforce the plausibility of finding new 1,4-substituted 1,2,3-triazole compounds with improved antibacterial activity. Advisors/Committee Members: Bergmeier, Stephen.

Subjects: Chemistry

Keywords: Antibacterial agents; Bioisosteric replacement; Analogs of oxazolidinones; RNA binding ligands

2. Carlson, Michael Thomas. Collective Heating Effects in Nanoparticle Solutions and Photothermal Studies of Gold Nanostructures Using a Novel Optical Thermal Sensor.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2012, Ohio University

► As the fields of science and technology approach smaller and smaller size… (more)

▼ As the fields of science and technology approach smaller and smaller size scales, it becomes increasingly vital to fully understand heat transfer at the nanoscale. For the continued construction and success of nanodevices and nanostructures, thermal transport and heat dissipation must be fully characterized. Classical theory and laws associated with heating are expected to be unable to accurately model the temperature behavior of the nanostructures and the surrounding medium. The research conducted here is at a unique position to explore ways of overcoming some of the deficiencies of classical theory. Photothermal studies and nanocalorimetry measurements have already helped elucidate some exciting information. However, these studies have largely focused on aggregates of nanoparticles and nanostructures. Heat transfer studies were conducted on a single-particle level to better understand what is occurring on the nanoscale. The specific aim of this research was to create a novel nanoscale temperature sensor using erbium ions in a III-V semiconductor thin-film host matrix on a silicon substrate, and use it and single-particle photothermal methods to characterize the heating effects of gold nanostructures on the surface. Combining the properties of gold with the properties of a rare-earth metal, in conjunction with a laser and a semiconducting thin film, the methods at the heart of this research will increase our current understanding of single particle heating on the nanoscale. This research will facilitate the measurement of heating effects at a scale previously unachieved. Multiple objectives were met to realize the specific aim of this project. First, a repeatable protocol was developed for immobilizing the gold nanoparticles and nanostructures on the thin-film surface with reliable single particle dispersion and coverage density. Next, a procedure was devised for locating and differentiating single nanostructures on the surface of the thin film. A 532 nm continuous-wave laser was then be used to create a calibration curve to correlate the relative photoluminescence (PL) intensities of the erbium (Er3+) ions in the semiconductor thin film with local thermal effects. Next, an algorithm using the calibration curve was developed and employed to convert the Er3+ PL spectra to changes in temperature. These methods allowed the investigation of interfacial effects, nano-confined thermal effects (such as the superheating of water), and the remote determination of absorption cross section and temperature-dependent thermal conductivity. Advisors/Committee Members: Richardson, Hugh.

Subjects: Chemistry; Physical Chemistry

Keywords: photothermal; nanoparticles

3. Cook, Shannon L. Metastable Atom-Activated Dissociation (MAD): A Novel Dissociation Method Employed within a Quadrupole Ion Trap Mass Spectrometer.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2012, Ohio University

► Recent advances in mass spectrometry have provided unprecedented investigative power for biomedical… (more)

▼ Recent advances in mass spectrometry have provided unprecedented investigative power for biomedical and clinical researchers. The long-term goal of this project is to catalyze the process of biomedical research by developing new and superior mass spectrometric techniques, thereby aiding in disease diagnosis, prognosis, and biomarker discovery. The traditional dissociation method typically employed in mass spectrometers, collision induced dissociation (CID), produces mainly b-/y-type ions with abundant neutral losses of the post-translational modification and generating incomplete sequencing information. Newer techniques which rely on radical-induced chemistry, electron capture and transfer dissociations (ECD/ETD), have become the preferred way to analyze peptides and proteins. However they are inapplicable to singly-charged cations and anions as well as ineffective on peptides of lower-charge states. Metastable atom-activated dissociation (MAD) induces fragmentation through the interaction of isolated ions with a high kinetic energy beam of metastable atoms. Extensive back-bone fragmentation resulting in a-, b-, c-, x-, y-, and z-type ions is observed of singly- and multiply-charged peptide cations, multiply-charged anions, and lipids through their interaction with a high kinetic-energy beam of argon or helium metastable atoms in a modified quadrupole ion trap mass spectrometer. The ability to determine post-translational sites, especially highly labile nitrosylation modifications, is demonstrated as well as the ability to distinguish between leucine and isoleucine residues and to cleave two covalent bonds of the proline ring resulting in z- and w-type ions. The fragmentation spectra indicate that fragmentation occurs through non-ergodic radical ion chemistry akin to ECD and ETD mechanisms. However, MAD demonstrates three apparent benefits to ECD and ETD: 1) the ability to fragment singly-charged precursor ions, 2) the ability to fragment negatively charged ions, and 3) the ability to cleave the proline ring, which requires the cleavage of two covalent bonds. Reaction times less than 250 ms and efficiencies approaching 5% are compatible with on-line fragmentation, as would be desirable for bottom-up proteomics applications. Advisors/Committee Members: Jackson, Glen.

Subjects: Analytical Chemistry; Chemistry

Keywords: metastable atom; peptide fragmentation; MAD; liquid chromatography mass spectrometry; radical induced dissociation

4. Emara, Mahmoud M. Reducing Threshold of Biexciton Formation in Semiconductor Nanocrystals through Their Self-Assembly into Nano-Antennae.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2008, Ohio University

► The reduction in the threshold of biexciton formation in CdTe semiconductor nanocrystals… (more)

▼ The reduction in the threshold of biexciton formation in CdTe semiconductor nanocrystals (NCs) was studied, as an approach towards reducing the optical-gain threshold and improving the lasing abilities of semiconductor nanocrystals.CdTe quantum dots (QDs) were assembled into an antenna-like architecture. In this nanocomposite, an energy-acceptor CdTe QD was at the center and surrounded by several energy-donor CdTe QDs. The electronic structures of the involved QDs were tailored so that the donor QDs have larger band gap than the band gap of the acceptor QD, which directs the energy irreversibly from the donors to the acceptor through electronic energy transfer. Focusing the excitation energy at the center of this nano-antenna simply reduces the pump intensity required to excite the acceptor QD. In order to realize the required band-gap gradient, small CdTe QDs (2.9 nm) were used as donors, and large CdTe QDs (3.9 nm) were used as acceptors. Deriving the self-assembly of CdTe QDs to form the desired nanocomposite was managed by electrostatic interaction between the ligands attached to the surface of the QDs. Donor QDs were synthesized with thioglycolic acid on their surface (TGA), and acceptor QDs were synthesized with 2-mercaptoethylamine (MA) on their surface. The electrostatic interaction between the positive charge of MA and negative charge of TGA in the neutral medium leads to the desired self-assembly of the donors and acceptors. Occurrence of electronic energy transfer from the donors to the acceptors was investigated by analyzing the steady state photoluminescence (PL) spectra and the PL decay dynamics of the free and assembled donors and acceptors. Analyzing the PL decay dynamics of the free acceptors and comparing them with the dynamics of the acceptors in the nano-antenna shows reduction in the threshold of the biexciton formation by factor 3.6±2 times. This result is promising in the future reduction of the optical-gain threshold and so improving the lasing capabilities of semiconductor NCs. Advisors/Committee Members: Van Patten, P. Gregory.

Subjects: Chemistry

Keywords: nanocrystals; semiconductor; quantum dots; energy transfer; optical gain; biexciton; multiexciton; Auger; CdTe; CdSe

5. Fernandes, Elroy C. Investigating the Role of Novel Fusion Proteins of Interferon in Melanoma.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► Melanoma is an aggressive form of skin cancer with high occurrence in… (more)

Subjects: Biochemistry

Keywords: JAK; STAT; p53; melanoma; interferon; AGP fusion proteins

6. Gao, Yunxiang. Controlling Laminar Flow in Microfluidic Channels and Covalent Chemistry of Single-Walled Carbon Nanotubes.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► Since their discovery in 1993, single-walled carbon nanotubes (SWNTs) have been one… (more)

▼ Since their discovery in 1993, single-walled carbon nanotubes (SWNTs) have been one of the most interesting nanomaterials in the past 20 years. Their outstanding electric, optical, thermal, chemical and mechanical properties have opened many new research areas, among which electronic-type based SWNT separation and surface chemical functionalization are of vital importance due to the major challenges for SWNT applications: lacking synthetic approaches for simple electronic-type products and poor dispersion in most solvents. This dissertation describes my work on quadrupole microchannel fabrication for potential dielectrophoresis-based SWNT separation and the covalent chemistry study of SWNTs. Lab-on-a-chip device with interdigitated electrodes has been reported for SWNT separation. However, quadrupole microchannel would theoretically be more effective than planar interdigitated electrodes with respect to dielectrophoresis-based separation. The first part of this dissertation demonstrates the fabrication of quadrupole microchannel on a lab-on-a-chip device by controlling multiphase laminar flow in microfluidic channels. The n-dodecyl-β-D-maltoside (DDM)-sheathing phases and bi-layer T-junctions are introduced for the first time to control the electroless plating of silver electrodes on the channel sidewalls three-dimensionally. The method is readily accessible, inexpensive and completely based on planar soft-lithography. The fabricated microchip has the potential applications for high-resolution dielectrophoretic SWNT separation. The second part of this dissertation focuses on the covalent chemistry of carbon nanotubes. In this study, we discovered a general defluorination mechanism for fluorinated single-walled carbon nanotubes (FSWNTs) in the presence of a wide range of electron donors at room temperature. Depending on the electron donating ability of the donor molecules, spontaneous or photo-induced charge transfer occurs from the electron donors to FSWNTs, which is then followed by the elimination of F- ions. The same mechanism is also applicable when FSWNT obtains electrons electrochemically. Both chemical reaction condition and irreversible electrochemical reduction potential data indicate that the defluorination reactivity of C-F bonds in FSWNT is stronger than those in unstrained compounds but weaker than those in highly strained fullerene derivatives. The reactivity of the electron transfer assisted defluorination originates from not only the strong electron affinity of FSWNTs, but also the strained bonding configuration caused by molecular curvature as it is predicted by related theoretical studies. Cylindrically shaped SWNTs provide a middle point between undistorted molecules and spherical fullerenes in tuning chemical reactivities using molecular curvature effects. Electron-transfer assisted defluorination of FSWNTs generates reactive carbon radicals on carbon nanotubes. Raman spectra, X-ray photoelectron spectroscopy, transmission electron microscopy and the strengthened mechanical property of defluorinated FSWNT foams indicate that the products are cross-linked SWNTs directly bonding through sp3 C-C bond between adjacent nanotubes. The cross-linked SWNT networks show sensitive Raman response to different laser powers. An intense laser decomposes the cross-linked SWNT networks, making the cross-linked SWNT networks possible to find applications as light, strong and degradable materials. Besides the chemistry of carbon nanotubes, the covalent chemistry of several other carbon nanostructures including the C60 fullerene, carbon nanobuds (C60- SWNT) and fullerene/nanotube mixtures (C60/SWNT) is also studied by UV-vis-NIR absorption and NIR fluorescence. Carbon nanobuds synthesized in an aerosol reactor by our collaborators lose the characteristic absorption and fluorescence emission that belongs to SWNTs, indicating that the electronic structure of the tubes in the carbon nanobuds is destroyed. In an attempt to synthesize nanobuds from C60/SWNT mixtures in solution phase through UV-irradiation, it is found that although C60 polymerizes though [2+2] cycloaddition, similar reaction does not occur between C60 and the outer surface of SWNTs, which can be attributed to the lower reactivity of SWNTs due to their reduced surface curvature. The presence of SWNTs in C60 solution slows down the photopolymerization of fullerenes. A quenching effect of SWNTs towards excited C60 probably exists. Advisors/Committee Members: Chen, Liwei.

Subjects: Chemistry; Materials science

Keywords: microfluidic; quadrupole electrodes; fluorinated; carbon nanotubes; defluorination; crosslinking

7. George, Kimberly Suzanne. The Roles of Membrane Rafts in Ultraviolet Light-Induced Association of Apoptotic Proteins.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2011, Ohio University

► Membrane rafts, or lipid rafts, are microdomains of the plasma membrane enriched… (more)

Subjects: Biochemistry

Keywords: membrane rafts; lipid rafts; cholesterol; ultraviolet light; apoptosis

8. He, Jing. Design and Study of Novel Antimicrobial Peptides with Proline Substitution.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2009, Ohio University

► Microorganism-related diseases and their resistance to conventional antibiotics are proliferating at an… (more)

▼ Microorganism-related diseases and their resistance to conventional antibiotics are proliferating at an alarming rate and becoming a severe clinical problem. Therefore, it is urgent to develop novel approaches in antimicrobial therapy. Most living organisms produce and utilize at least some small peptides as part of their defensive system in combating infections by virulent pathogens. Research focusing on the structure and function of these antimicrobial peptides from diverse sources has gained a great number of interests in the past three decades. Generally, many naturally existing antimicrobial peptides are positively charged and have the potential to adopt either amphipathic α-helix or β-sheet conformation. In this project, based on preliminary studies of β-sheet-forming peptides developed in our lab, analogs were designed to investigate the effects of introducing a single leucine-to-proline substitution on the structure and function of the peptides. The leucine-to-proline substitution was selected as a structural perturbation that could influence the antimicrobial and the cytolytic activity toward mammalian cells of these peptides. A series of experiments were performed in this project to investigate these potential changes, beginning with the determination of the antimicrobial activity and hemolytic activity of these peptides. Peptide conformation was determined by circular dichroism spectroscopy. Membrane permeability changes in both synthetic lipid bilayers and bacterial membranes were assessed by measuring peptide-induced calcein leakage from large unilamellar vesicles (LUV) and by peptide-induced entry of o-nitrophenyl-β-D-galactopyranoside into E.coli ML-35 cells. The ability of peptides to bind to lipid bilayers of defined composition was measured by tryptophan fluorescence enhancement, acrylamide quenching and 10-doxylnonadecane quenching. The activity of these peptides was further studied by measuring the planktonic bacterial cell killing (the live vs. dead bacterial viability), bacterial biofilm formation inhibition and inhibition of bacterial cells growth within established bacterial biofilms. The results show that the position of proline has a significant influence on the antimicrobial and hemolytic activity of these peptides. Some of these proline-containing analogs show high antimicrobial activity and good selectivity between bacterial vs. mammalian cells. In addition, the peptide binding studies suggest that at least some of the proline-containing peptides may kill bacteria by mechanisms other than simply inducing membrane leakage. In summary, amphipathic β-sheet-forming antimicrobial peptides with proline substitutions appear to be promising models for novel antimicrobial agents. Advisors/Committee Members: Blazyk, John.

Subjects: Biochemistry

Keywords: antimicrobial peptides; amphipathic beta-sheet forming; proline substitution; bacterial biofilm

9. Hood, Derrell L. Development of a Novel Loeb-Eiber Mass Filter.

Degree: MS, Chemistry and Biochemistry (Arts and Sciences), 2009, Ohio University

► Ongoing environmental, forensic, and homeland security needs dictate the necessity for rapid,… (more)

Subjects: Analytical chemistry; Chemistry

Keywords: miniature mass spectrometer; mass filter; Loeb-Eiber; instrument development; portable mass spectrometer

10. Huang, Xiaoyan. Nitric Oxide/Peroxynitrite Balance in Kidney – Effect of Diabetes and Obesity.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2008, Ohio University

► Nitric oxide (NO) is a vasoprotective signaling molecule. Peroxynitrite (ONOO-), the reaction… (more)

▼ Nitric oxide (NO) is a vasoprotective signaling molecule. Peroxynitrite (ONOO-), the reaction product of the superoxide (O2-) with the nitric oxide, is the main cytotoxic component of nitroxidative stress. This work elucidated the [NO]/[ONOO-] imbalance in the kidney of rats with type I and type II diabetes. Obesity factor has also been studied by induced high fat diet to rats before or after type II diabetes was established. The releases of NO and ONOO- were monitored in situ by placing NO and ONOO- nanosensors near the surface (5 ± 2 µm) of medulla part of kidney slices. Intracellular L-arginine was measured by HPLC-fluorescence and eNOS protein levels were examined by immunological Western blotting analysis. These studies clearly indicate that the [NO]/[ONOO-] imbalance in the type I and type II diabetes is caused by uncoupled eNOS. The deficiency of intracellular L-argnine and tetrahydrobiopterin may be linked to eNOS uncoupling. At early stage of diabetes, the [NO]/[ONOO-] balance could be restored after treatments with L-arginine and sepiapterin. Obesity, itself, showed inhibitory effect on eNOS activity and NO release. However, obesity and type II diabetes increased hyperglycemia, hyperlipidaemia and eNOS uncoupling at the late stage. All of these factors lead to a severe [NO]/[ONOO-] imbalance and form high oxidative/nitroxidative stress in kidney. Different herbal drug treatments improved the [NO]/[ONOO-] balance by different mechanisms. Corn silk, a hypercholesterol inhibitor, improved the [NO]/[ONOO-] balance more significantly than ginseng at the early stage of type II diabetes. However, ginseng showed better effect than corn silk on the improvement of the [NO]/[ONOO-] balance at the late stage. Our overall results indicate that the function of endothelial nitric oxide synthase can be severely uncoupled in diabetic kidney. The uncoupled eNOS is the main generator of cytotoxic ONOO-. An overproduction of ONOO- and diminished generation of NO shifts unfavorably [NO]/[ONOO-] balance in diabetes. This process can be significantly reversed or inhibited by treatment with L-arginine, sepiapterin, corn silk or ginseng. Therefore, these treatments can be potentially used for mollification of kidney capillary vascular injury induced by diabetes. Advisors/Committee Members: Malinski, Tadeusz.

Subjects: Analytical chemistry; Biochemistry; Biomedical research

Keywords: Nitric oxide; Peroxynitrite; diabetes; obesity; uncoupled eNOS

11. Jacoby, Adam M. The Role of Nitric Oxide and Nitroxidative Stress in Amyotrophic Lateral Sclerosis.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► Amyotrophic lateral sclerosis (ALS) has been studied for many years, yet there… (more)

▼ Amyotrophic lateral sclerosis (ALS) has been studied for many years, yet there have been few innovations in its therapy. This debilitating and fatal disease has proven elusive to all but a few treatments. These treatments have only extended life for short periods of time in ALS patients and have not succeeded in arresting the progression of ALS. Our approach to understanding the oxidative stress behind the disease was studied using nanosensors that directly measure nitric oxide and peroxynitrite concentrations in vivo. Nitric oxide (NO) was thought of as a nuisance in ALS patients, but new studies show that nitric oxide removal proves ineffective at preventing ALS progression. We determined that NO performs a much more vital role in ALS than previously understood. Our conclusions show that after ALS onset, the enzyme responsible for NO production, nitric oxide synthase (NOS), remains in a dysfunctional state. This proved that NO in ALS neurons was already depleted and that peroxynitrite was prevalent, in terms of global concentration, within the neurons. Dysfunctional NOS accounted for increased production of superoxide, which is a common pathological symptom in most ALS cases. We determined that one main malignant affector in ALS is the peroxynitrite produced from dysfunctional NOS. As a corollary, the restoration of coupled NOS and NO production would prove beneficial. The NOS cofactor and co-substrate levels were proven to be in a diminished state, failing to provide sufficient production of nitric oxide with respect to superoxide. The concentrations of the co-substrate L-arginine and the cofactor tetrahydrobiopterin were main targets for treatment in this study. The subsequent restoration of coupled NOS demonstrated that cofactor and co-substrate concentrations play an important role in ALS. Continued production of NO at a normal concentration was important to maintain the neuron function. The treatments with L-arginine and sepiapterin were beneficial and impeded some ALS progression, but did not curtail all the effects of the ALS progression. When added to the current ALS treatment riluzole, Larginine was more beneficial than treatment with riluzole alone. This was a major indicator that dysfunctional NOS only account for part of ALS pathology and that the cofactor and co-substrate treatments work through a different pathway than riluzole. Advisors/Committee Members: Malinski, Tadeusz.

Subjects: Biochemistry

Keywords: nitric oxide; peroxynitrite; nitroxidative stress; ALS

12. Jasinski, Krystian. Impact of Gaseous Nitric Oxide and Carbon Monoxide on Normal Excisional, Diabetic Excisional and Burn Wound Healing.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2009, Ohio University

► Nitric oxide (NO) and carbon monoxide (CO) are two transmitters that play… (more)

▼ Nitric oxide (NO) and carbon monoxide (CO) are two transmitters that play significant roles in many physiological processes. In pathological conditions such as diabetes or burn the nitrooxidative stress evoked by peroxynitrite formed in reaction between nitric oxide and superoxide contributes to endothelial dysfunction and further leads to an impairment in wound repair. We tested the effect of topical application of nitric oxide and carbon monoxide on excisional wound healing and also diabetic excisional wound and burn wound healing. We investigated the hypothesis of exogenous NO and CO ability to affect [NO]/[ONOO-] imbalance during progression of wound repair. The release of NO and ONOO- was monitored in situ by placing NO and ONOO- nanosensors near the surface (5 ± 2 µm) of wounded tissue. Measurements made with nanosensors indicated the correlation between decreased bioavailability of NO and excessive formation of peroxynitrite (ONOO-) by uncoupled eNOS and impaired wound healing. The reduced bioaviability of NO could be restored by exogenous NO delivered directly to the wound. However, in wounds treated with CO, in order to increase the production of bioavailable NO, we found that only treatment with low concentrated CO has positive effect on healing process. On the contrary, treatment with a high concentration CO led to a high ONOO- production and as a result heavy oxidative/nitroxidative stress. Treatment with NO improved the [NO]/[ONOO-] balance and accelerated the collagen synthesis and maturation of collagen fibers and enhanced the reepithelialization process as well. However, therapy with gNO showed better effect than gCO on the improvement of the wound healing parameters such as collagen formation, reepithelialization and wound contraction rate. The ability of CO to induce NO production may contribute over the time to increased peroxynitrite formation. In wounds exposed to exogenous NO there was a significant decline in endogenous NO and parallel decrease in ONOO- formation. Inhibition of endogenous NO contributed to reduction in nitroxidative stress that further led to improved healing process supported by delivered exogenous NO. As a result a new potential treatment for acceleration of wound healing including diabetic excisional and burn wounds was established. Advisors/Committee Members: Malinski, Tadeusz.

Subjects: Biochemistry

Keywords: Nitric oxide; carbon monoxide; wound healing; NOS; diabetic wound; burn wound

13. Laskay, Ünige A. Dynamic Collision Induced Dissociation - A Novel Fragmentation Method in the Quadrupole Ion Trap.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2009, Ohio University

► The development of dynamic collision induced dissociation (DCID), a novel collisional activation… (more)

▼ The development of dynamic collision induced dissociation (DCID), a novel collisional activation method for quadrupole ion traps (QITs) is described. The effect of experimental parameters such as the excitation frequency, excitation amplitude and mass scanning rate were investigated, as well as the effect of frequency spacing and relative phase angle when a two-frequency excitation waveform is used. With careful selection of the excitation conditions the internal energy deposition was significantly increased when compared to conventional collision induced dissociation (CID). While the maximum ratio of 91/92 reported in the literature for n-butylbenzene, a test molecule, using CID in a QIT is 4.2 (corresponding to ~5 eV internal energy), DCID can achieve ratios of 91/92 as large as 15. DCID fragmentation efficiencies in excess of 60% were achieved for n-butylbenzene and simultaneously efficient and energetic fragmentation may be attained with judicious selection of the DCID waveform. Upon investigation of excitation at the Ω - ω higher order resonance of the fundamental secular frequency of motion of the precursor ion, large internal energy depositions were possible with a greater flexibility in the selection of experimental parameters. Application of a high amplitude, two-frequency excitation waveform where the two frequencies were spaced at more than 5 kHz resulted in 91/92 fragment ion ratios of n-butylbenzene greater than 3 with concomitant fragmentation efficiencies in excess of 20%. This implies that the internal energy deposited to n-butylbenzene was in excess of 5 eV, which is considerably larger than is generally achievable with conventional CID. The application of DCID in a pulsed fashion (PqDCID) followed by a fast lowering of the rf amplitude on the ring electrode allowed for mass analysis of low mass product ions. PqDCID was applied to the on-line investigation of tryptic peptides eluting from an HPLC column. PqDCID was successful in accomplishing tandem mass analysis and provided an increased number of peaks in the mass spectrum compared to CID. The ability to analyze low mass product ions such as iTRAQ reporter ions was shown to be applicable for quantitative analysis of iTRAQ-labeled peptides. Advisors/Committee Members: Jackson, Glen P.

Subjects: Analytical chemistry

Keywords: quadrupole ion trap; dynamic collision induced dissociation; N-butylbenzene; iTRAQ

14. Liang, Shengwen. Nitrene Transfer Reactions Mediated by Transition Metal Scorpionate Complexes.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2012, Ohio University

► Transition metal catalyzed C=C bond aziridination and C-H bond amination reactions are… (more)

Subjects: Chemistry

Keywords: nitrene transfer; scorpionate ligand; transition metal catalyst; aromatic C-H bond amination; [3+2] cycloaddition of aziridine

15. Li, Huamin. Synthesis of Curcumin-based Ligands for Molecular Knots.

Degree: MS, Chemistry and Biochemistry (Arts and Sciences), 2008, Ohio University

► The aesthetics of molecular knots have been a strong interest for organic… (more)

Subjects: Chemistry

Keywords: curcumin; molecular knots

16. Liu, Wei. The Roles of Nitric Oxide Synthases in Epithelial Cell Apoptosis and Melanoma Cell Adhesion after UVB Irradiation.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2011, Ohio University

► Ultraviolet B light (UVB) activated nitric oxide synthase(s) (NOSs) and nitric oxide… (more)

▼ Ultraviolet B light (UVB) activated nitric oxide synthase(s) (NOSs) and nitric oxide (NO•) production, which played a role in regulation of apoptosis. However, the role of NO• in UVB-induced apoptosis was controversial. In this study, we showed that the expression of neuronal NOS (nNOS) increased, but endothelial NOS (eNOS) uncoupled in the early phase post-UVB. The data indicated that constitutive nitric oxide synthases (cNOSs) regulated the ratio of NO•/ONOO– after UVB-irradiation. Our data suggested that the activation of cNOSs in the early phase led to decrease of NO•/ONOO– ratio and promoted apoptosis via a caspase 3-independent pathway. The elevation of NO• in the late phase of UVB-irradiation was mainly produced by inducible nitric oxide synthase (iNOS). However, cNOSs may also contribute to the NO· production and to maintain a higher NO•/ONOO– ratio, which reduced caspase 3 activity and protected cells from UVB-induced apoptosis. UVB irradiation also induced the release of zinc from cells. Removal of Zn2+ with a lower concentration of TPEN, a Zn2+ specific chelator, did not induce cell death or prevent cells from UVB-induced apoptosis. However, a higher [TPEN] induced cNOS uncoupling, and it was also cytotoxic to cells, but prevented cells from further UVB induced apoptosis. UVB irradiation also affected the avidity of melanoma cancer cells. UVB-reduced avidity between M624 melanoma and HUVEC cells was dependent on the interaction between very late antigen-4 (VLA-4) and its endothelial ligand vascular cell adhesion molecule 1 (VCAM-1). Our previous studies suggested that a spatial organization of α4 integrin, one of the two subunits of VLA-4, was a major contributor to the changes in avidity for VCAM-1 upon UVB-irradiation. In this study, we demonstrated that Akt played an important role in regulation of the expression and surface level of α4 integrin on melanoma cells after UVB-irradiation. Inhibition of Akt also reversed the reduction of avidity of cells after the irradiation. Our data also suggested that UVB irradiation reduced the level of Akt. The inhibition of Akt activity correlated with a reduced amount of coupled cNOS and reduced amount of iNOS after UVB-irradiation. However the effect of NOSs on melanoma cell adhesion appeared because of their roles in regulation of apoptosis after UVB-irradiation. Base on these results, we proposed that the UVB-induced reduction of avidity of melanoma cells was regulated by NOSs and Akt through two differential mechanisms. Advisors/Committee Members: Wu, Shiyong.

Subjects: Biochemistry

Keywords: nitric oxide, UVB irradiation, apoptosis, cell adhesion

17. Liu, Yan. The Roles of Two Different Pathways in Hypoxia: p53/HDM2 and PERK/GCN2/eIF2α.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2009, Ohio University

► Hypoxia always occurs in solid tumors. These hypoxic tumor cells are not… (more)

▼ Hypoxia always occurs in solid tumors. These hypoxic tumor cells are not sensitive to chemotherapic agents because of poor drug delivery and slow proliferation. Hypoxia activates two adaptive signaling pathways. On one hand, adaptation to hypoxia can be regulated by hypoxia-inducible factor 1 (HIF-1) and its downstream genes. On the other hand, hypoxia reduces protein synthesis and inhibits cell growth to adapt this stress. HIF-1α plays a crucial role in tumor hypoxia and therapeutic resistance and its protein level is under tight control. Previous studies show that p53 suppresses HIF-1α protein through HDM2-mediated ubiquitination and proteasomal degradation. However, the forced expression of HDM2 or growth factor-induced HDM2 can increase HIF-1α protein level, making it difficult to decipher how p53 and HDM2 regulate HIF-1α in hypoxia. In the first part of this study, we found that the increased p53 in hypoxia contributed to the downregulation of HIF-1α mRNA to suppress HIF-1α protein level. In addition, HIF-1α protein level was also inhibited by decreasing HDM2 protein level in hypoxia. Furthermore, p53 and HDM2 knockout MEF cells were employed to determine the biological functions of p53 and HDM2 in hypoxia through modulating HIF-1α protein level. We showed that the presence of p53 inhibited hypoxia-induced cell growth arrest and cell cycle arrest through the suppression of HIF-1α and its downstream target, p21; loss of HDM2 exhibited similar effects through the same mechanism; p53 strengthens chemotherapeutic-induced apoptosis in hypoxia via downregulating HIF-1α, loss of HDM2 displayed similar effects via the same mechanism. Recent studies suggest that activation of PERK and phosphorylation of alpha subunit of eIF2 (eIF2α) confer cell adaptation to hypoxic stress. However, eIF2α is still phosphorylated at a lowered level in PERK knockout cells under hypoxic conditions. The mechanism for eIF2α kinase(s)-increased cell survival is not clear. In the second part of this study, we investigated the roles of GCN2-mediated eIF2α phosphorylation in hypoxia. Here we provided evidence that another eIF2α kinase, GCN2, was also involved in hypoxia-induced eIF2α phosphorylation. We demonstrated that both GCN2 and PERK mediated the adaptation to hypoxic stress. High levels of eIF2α phosphorylation led to G1 arrest and protected cells from hypoxia-induced apoptosis. Reduced phosphorylation of eIF2α by knocking out either PERK or GCN2 suppressed hypoxia-induced G1 arrest and promoted apoptosis via activation of p53 signal cascade. However, totally abolishing phosphorylation of eIF2α inhibited G1 arrest without promoting apoptosis. In addition, reduced, but not abolished, phosphorylation of eIF2α sensitized cells to chemotherapeutics, but not to gamma-radiation in hypoxia. Based on our results, we propose that the levels of eIF2α phosphorylation serve as a “switch” in regulation of G1 arrest or apoptosis under hypoxic conditions. Advisors/Committee Members: Evans, Susan C.

Subjects: Biochemistry

Keywords: Hypoxia; HIF-1; p53; HDM2; PERK; GCN2; eIF2

18. László, Csaba F. Translation Regulation of UV-induced Transcription Factor NF-κB and Oncogene COX-2.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2009, Ohio University

► NF-κB plays an important role in ultraviolet light-induced skin tumorigenesis. Activation of… (more)

▼ NF-κB plays an important role in ultraviolet light-induced skin tumorigenesis. Activation of NF-κB by UV-irradiation is composed of two phases. The early-phase culminates with maximal levels of DNA binding ability at 4 hours post-irradiation and is dependent on translational inhibition. The late-phase activation of NF-κB occurs between 16 and 48 hours post-irradiation and the mechanism is not clear due to the fact that NF-κB was activated even in the presence of high level of its inhibitor protein, IκBα. Here, we provide evidence that in the late-phase of UV-induced NF-κB activation, IκBα depletion is the combined result of regulation at both transcriptional and translational levels. Neither ubiquitination nor proteasomal degradation have detectable attributions to IκBα breakdown. We also demonstrate that UV only induces phosphorylation of p65 at Ser 276, while TNFα induced phosphorylation at both Ser 276 and 536 sites of p65. Based upon our results, we propose a novel mechanism for translation-regulated IκBα depletion and MSK-mediated NF-κB activation at 24 hours post UV-irradiation. Besides NF-κB activation, ultraviolet light also induces a prolonged expression of COX-2. While transcriptional regulation of COX-2 expression is intensively studied, the role of translational regulation of COX-2 synthesis upon UV-irradiation is not yet clear. Here, we show that phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF2α) plays an important role in the regulation of COX-2 expression after UV-irradiation. Our data shows that UV light induces COX-2 expression in wild-type mouse embryo fibroblasts (MEFS/S) and that the inducibility is reduced in MEFA/A cells in which the phosphorylation site, Ser-51 in the eIF2α, is replaced with a nonphosphorylatable Ala (S51A). UV light-induced transcription of COX-2 is delayed in MEFA/A cells, which correlates with NF-κB activation, as previously reported. Our data also shows that translational efficiency of COX-2 is higher in MEFA/A cells than in MEFS/S cells, but not at the late stage of UV-irradiation. This may be due to the translational regulation of COX-2 binding protein TIAR expression, which is reduced in MEFS/S cells but not in MEFA/A cells at 24 hours post-UV. In addition, our data indicates that newly synthesized COX-2 protein is more stable in MEFA/A cells than in MEFS/S cells. These results suggest that translation initiation plays a role in the complex and dynamic regulation of COX-2 expression. Based on our results, and the use of Ingenuity Pathway Analysis™, we propose a novel eIF2α phosphorylation-centered network for the regulation of COX-2 expression after UV-irradiation. Advisors/Committee Members: Wu, Shiyong.

Subjects: Molecular biology

Keywords: NF-kappa-B; eIF2α; UV; COX-2; translation regulation

19. Lu, Wei. The Reciprocal Regulation of Nitric Oxide Synthase and Alpha-subunit of Eukaryotic Initiation Factor 2 Post Ultraviolet B Irradiation.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► Ultraviolet light (UV) induces phosphorylation of the alpha subunit of the eukaryotic… (more)

▼ Ultraviolet light (UV) induces phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF2a) and inhibits global protein synthesis. Both eIF2 kinases PERK and GCN2 have been shown to phosphorylate eIF2a in response to UV-irradiation. However, the roles of PERK and GCN2 in UV-induced translation inhibition are controversial. The upstream signaling pathway(s) that leads to the activation of PERK or GCN2 remains unknown. In this research, evidences are provided to demonstrate that both PERK and GCN2 contribute to UVB-induced eIF2a phosphorylation in human keratinocyte (HaCaT) and mouse embryonic fibroblast (MEF) cells. Reducing expression of PERK or GCN2 by small interfering RNA (siRNA) decreases phosphorylation of eIF2a after UVB irradiation. The data also show that nitric oxide synthase (NOS)- mediated oxidative stress plays a role in regulation of eIF2a phosphorylation upon UVB irradiation. Treating the cells with the broad NOS inhibitor NG-Methyl-L-Arginine, the free radical scavenger N-Acetyl-L-Cysteine or the NOS substrate L-Arginine partially inhibits the UVB-induced eIF2a phosphorylation. The same treatments also partially rescue the translation inhibition induced by UVB irradiation. The results presented above led us to propose that NOS mediates UVB-induced eIF2a phosphorylation by activation of both PERK and GCN2 via oxidative-stress and L-Arginine starvation signaling pathways. While NOS activation regulates translation initiation, it is not known if the NOS-mediated translation regulation affects NOS expression. In this study the impact of eIF2a phosphorylation on three NOS isoforms (nNOS, iNOS and eNOS) are investigated in both human keratinocyte (HaCaT) and mouse embryonic fibroblast (MEF) cells. Our results indicate that no apparent changes of nNOS and eNOS are observed. While iNOS is dynamically regulated in different time points post UVB irradiation. By comparing the results obtained from MEFS/S (wild type) and MEFA/A (contain a mutated site, 51 SàA, on eIF2a thus cannot be phosphorylated), it suggests that UVB-induced eIF2a phosphorylation negatively regulates the expressions of iNOS, on the translational level in a feedback manner. Advisors/Committee Members: Wu, Shiyong.

Subjects: Biochemistry; Molecular biology

Keywords: Nitric oxide synthase; Eukaryotic initiation factor 2; Ultraviolet; Translational regulation; Kinase; Phosphorylation

20. Lu, Weiying. Development of Radial Basis Function Cascade Correlation Networks and Applications of Chemometric Techniques for Hyphenated Chromatography-Mass Spectrometry Analysis.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2011, Ohio University

► A cascade correlation learning architecture has been devised for radial basis function… (more)

▼ A cascade correlation learning architecture has been devised for radial basis function neural networks. Cascade correlation furnishes incremental learning networks. The proposed algorithm was applied to three different datasets: a synthetic dataset and two chemical datasets. The synthetic dataset was used to test the novelty detection ability of the proposed network. In the chemical datasets, the growth regions of Italian olive oils were identified by their fatty acid profiles; mass spectra of polychlorobiphenyl compounds were classified by chlorine number. The prediction results by bootstrap Latin partition indicate the proposed neural network is useful for pattern recognition. A discriminant based charge deconvolution analysis pipeline is proposed. The molecular weight determination (MoWeD) charge deconvolution method was applied directly to the discrimination rules obtained by the fuzzy rule-building expert system (FuRES) pattern classifier. This approach was demonstrated with synthetic electrospray ionization mass spectra. Identification of the tentative protein biomarkers by bacterial cell extracts of Salmonella enterica serovar typhimurium strains A1 and A19 by liquid chromatography-electrospray ionization-mass spectrometry (LC-SI-MS) was also demonstrated. The data analysis time was reduced by applying this approach. Furthermore, this method was less affected by noise and baseline drift. The gasoline and kerosene collected from different locations in the United States were identified by gas chromatography/mass spectrometry (GC/MS) followed by chemometric analysis. Classifications based on two-way profile and target component ratio were compared. The projected difference resolution (PDR) mapping was applied to measure the differences among the ignitable liquid (IL) samples by their GC/MS profiles quantitatively. FuRESs were applied to classify individual ILs. The FuRES models yielded correct classification rates greater than 90% for discriminating between samples. PDR mapping, a new method for characterizing complex data sets, was consistent with the FuRES classification result. Advisors/Committee Members: de B. Harrington, Peter.

Subjects: Analytical Chemistry; Chemistry

Keywords: Chemometrics; Radial Basis Function Cascade Correlation Networks; FuRESï¿½“MoWeD; Projected Difference Resolution Mapping; Fuzzy Rule-Building Expert System

21. Lu, Yao. Forensic Applications of Gas Chromatography-Differential Mobility Spectrometry, Gas Chromatography/Mass Spectrometry, and Ion Mobility Spectrometry with Chemometric Analysis.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► Rapid, practical, and low-cost analytical methods are always desirable in forensic analysis.… (more)

▼ Rapid, practical, and low-cost analytical methods are always desirable in forensic analysis. Using proper sample preparation techniques with the application of gas chromatography/mass spectrometry (GC/MS), gas chromatography-differential mobility spectrometry (GC-DMS) and ion mobility spectrometry (IMS) with chemometric analysis, analytical methods were developed for fast and practical identification and classification of analytes in complicated matrices.GC-DMS was investigated as a tool for analysis of ignitable liquids from fire debris. The combined information afforded by gas chromatography and differential mobility spectrometry provided unique two-way patterns for each sample of ignitable liquid. Fuzzy rule-building expert system (FuRES) models constructed with the neat ignitable liquids identified the spiked samples from simulated fire debris with 99.07±0.04% accuracy. The performances of DMS as gas chromatographic detector was also compared with mass spectrometry (MS) using a chemometric tool, projected difference resolutions (PDRs). The PDR results show that one-way mass spectra data exhibit higher resolution than DMS data, while total ion chromatograms from GC-DMS show higher resolution than that from GC/MS for differentiating seven kinds of ignitable liquids. Direct methylation and solid phase microextraction (SPME) were used as a sample preparation technique for classification of bacteria based on fatty acid methyl esters (FAMEs) profiles. Compared with traditional chemical derivatization and liquid-liquid extraction (LLE), the method presented in this work avoids using inorganic and organic solvents and greatly decrease sample preparation time as well. The difference between Gram-positive and Gram-negative bacteria was clearly observed with the application of principal component analysis (PCA) of GC/MS data of bacterial FAMEs. The cross-validation study using ten bootstrap Latin partition (BLP) and fuzzy rule building expert system (FuRES) presented an 87±3% correct classification rate. A comparatively rapid and reliable screening method for detection of cocaine and its metabolites, benzoylecgonine and cocaethylene in urine was demonstrated using solid phase extraction (SPE) coupled with IMS. Data analysis with alternating least squares (ALS) was used to model the IMS spectral datasets and separate the reactant ion peak from the product ion peaks. This method provides forensic chemists a viable approach for fast and simple drug screening. Advisors/Committee Members: Harrington, Peter.

Subjects: Analytical chemistry

Keywords: Forensic analysis; DMS; GC/MS; IMS; chemometrics

22. Ma, Huaibo. Modeling the Structure and Mechanism of Nickel Superoxide Dismutase.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2011, Ohio University

► Superoxide dismutases are metalloenzymes that catalyze the disproportionation of superoxide radical to… (more)

Subjects: Chemistry

Keywords: NiSOD; superoxide dismutase; spin crossover; biomimetic chemistry

23. Marin Cordoba, Roberto. Chromium Carcinogenesis: Characterization of DNA damaging Intermediates by EPR 31P NMR, HPLC, ESI-MS and Magnetic Susceptibility.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► The hydrolytic cleavage and oxidative degradation mechanisms of dGDP by the oxochromate-(V)… (more)

▼ The hydrolytic cleavage and oxidative degradation mechanisms of dGDP by the oxochromate-(V) complexes bis(2-ethyl-2-hydroxybutanoato)oxochromate(V) (I) and bis(hydroxyethyl)-amino-tris((hydroxymethyl)methane)oxochromate(V) (II) in the presence of H2O2 were investigated at neutral pH. The products of the reactions were separated and characterized by chromatographic and spectroscopic methods. The oxidative degradation is supported by the detection of free G, furfural, phosphoglycolate, pyrophosphate, guaninepropenal, 8OHdG and guanidinohydantoin. These products are formed through two parallel mechanisms that start with a common Cr-dGDP intermediate in which the oxochromate binds the α phosphate moiety followed by abstraction of H from C4' and C5' from the ribose. The detection of inorganic phosphate and dGMP suggests that when the oxometal binds the β phosphate it mainly promotes hydrolytic cleavage of the phosphate diester bond. By estimating the amount of each catabolite it was concluded that the oxo metal ion does not show selectivity during the hydrogen abstraction and that oxidation of the substrate is preferred over its hydrolysis. The reaction between diperoxoaquaethylendiamine chromium(IV) (III) and glutathione (GSH) at neutral pH was studied by EPR and ESI-MS. The ions of m/z ratios of 450 and 757 were identified as intermediates while the ions of m/z ratios of 484 and 775 were identified as products. Three EPR signals detected at g = 1.996, 1,986 and 1.983 were attributed to Cr(V) intermediates while a signal at g = 1.975 (peak to peak line width = 259.72 G) that appeared after the Cr(V) signals had disappeared was attributed to Cr(IV). Spin trapping experiments with DMPO and DEPMPO revealed that the G radical but not H radical was formed during this reaction. The G and the Cr(V) intermediates detected by EPR confirmed that the reaction occurs in a series of one electron transactions. Overall this reaction proceeds in two cycles. The reaction produces Cr(V) intermediates followed by accumulation of a chromium(IV) second intermediate that decays slowly. The DNA damage assay suggests that during its reaction with glutathione, III becomes a DNA damaging agent. The mixture of intermediates of the reaction between chromate and glutathione in glycine buffer (pH 2.8) was investigated with a SQUID susceptomer. The saturation magnetic moment was calculated to be 1.39 μB while the effective magnetic moment was 2.55 μB. Based on the saturation magnetic moment, the intermediates were characterized as 30 % Cr(IV) and 69 % Cr(V). Using the effective magnetic moment the mixture was characterized as 58 % Cr(IV) and 42 % Cr(V). The spin only formula gave a total spin angular momentum of 0.88 which supports Cr(IV) as the predominant intermediate. As previous studies did not detect Cr(V) EPR signals, it was assumed that only a Cr(IV) intermediate was formed. In light of the present work and stoichiometric data from previous work, the silent part of the mixture of intermediates was interpreted as a Cr(V) dimer in which the Cr centers are diamagnetically coupled. With this data in consideration, the proportion of Cr(IV) in the mixture of intermediates should be at least 65%. Advisors/Committee Members: Bose, Rathindra.

Subjects: Biochemistry; Biomedical research; Chemistry; Epidemiology; Experiments; Toxicology

Keywords: dna damage; chromium carcinogens; chromate; EPR; chromium (IV); chromium (V); chromium intermediates; phosphate hydrolysis; sugar ring oxidation

24. McClure, Beth Anne. Spectroscopic and Kinetic Characterization of Photochromic Ruthenium Chelating Sulfoxide Complexes.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► Complexes of the type [Ru(bpy)2(OSOR)]+, where OSOR is a sulfinyl benzoate chelate… (more)

▼ Complexes of the type [Ru(bpy)2(OSOR)]+, where OSOR is a sulfinyl benzoate chelate with various substituents, R, attached to the sulfur, and [Ru(bpy)2(pySO)]2+, (pySO = 2-(isopropylsulfinylmethyl)pyridine) were synthesized and characterized by a number of spectroscopic techniques. Structural characterization was done by 1H NMR and IR spectroscopy as well as X-ray crystallography for some complexes. Analysis of the structural features such as S-O bond lengths and ν(S=O) vibrational stretches are suggestive of a π-back bonding interaction between the ruthenium metal center and the sulfoxide group in the S-bonded isomer. Electrochemical measurements also support such an interaction by large positive Ru2+/3+ reduction potentials for the S-bonded isomer. Cyclic voltammetry reveals irreversible oxidation behavior that agrees with previous studies finding an S-to-O isomerization to occur after oxidation to the Ru3+ state. However, compared to similar non-chelate ruthenium sulfoxides, the rate of isomerization is significantly slower indicating that the chelate hinders the degrees of freedom utilized in this reaction. Electronic absorption spectra are also consistent with a stabilization of the dπ orbitals as a result of π-back bonding, especially as compared to similar non-chelate sulfoxide complexes. Irradiation of the complexes was found to promote an S-to-O isomerization. The complex [Ru(bpy)2(pySO)]2+ was found to undergo reversible O-to-S phototriggered isomerization as well which is very rare for transition metal based photochromes. Analysis of the UV-Vis absorption and low temperature emission spectra of these complexes reveal significant distortion of nuclear coordinates between the ground state potential energy surface and the Franck-Condon state and lowest energy excited state potential energy surfaces. Emission spectral fitting indicates strong vibronic coupling between a vibrational mode similar in energy to the ν(S=O) mode with relaxation to the ground state. Transient absorption measurements indicate rapid non-adiabatic isomerization from a MLCT state of S-bonded or η2-SO character to the O-bonded ground state, with time constants of isomerization as fast as 84 ps. The complex O-[Ru(bpy)2(pySO)]2+ shows a similar reverse isomerization with relaxation to the S-bonded ground state as well. The non-adiabatic mechanism is consistent with the large distortion indicated by spectral analysis, further supporting an η2-SO geometry for the excited state minimum geometry. Advisors/Committee Members: Rack, Jeffrey.

Subjects: Chemistry

Keywords: photochromic; ruthenium; sulfoxide; spectral characterization; isomerization; kinetics

25. Muccio, Zeland. Isotope Ratio Mass Spectrometry - A Rapidly Developing Tool for Forensic Samples.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► The development of a dual detection system that provides simultaneous structural elucidation… (more)

▼ The development of a dual detection system that provides simultaneous structural elucidation and isotopic analyses of forensic samples is described. A gas chromatograph (GC) was coupled to an isotope ratio mass spectrometer (IRMS) in parallel with a single quadrupole mass spectrometer (MS). The modification was achieved by using a low, dead volume x-connector to split the effluent coming from the column so that approximately 10% entered the EI MS and the remaining 90% entered the combustion interface for IRMS. The transfer line that connected the GC to the MS was fabricated to extend the line into the GC oven. Heat tape was tightly wrapped around the extension to maintain a predetermined, constant temperature by use of a manual heat controller. The modified instrumentation was then applied to forensic samples to simultaneously determine the structural elucidation and the isotopic ratios of individual compounds and impurities within the sample. Illicit drugs are one of the most analyzed forensic samples in federal, state, and private forensic laboratories. Cocaine was analyzed and identification was confirmed using a NIST library. The probability scores from the NIST library for all of the cocaine samples ranged between 52.9% and 77.1%. Several cocaine samples were used to determine if the cocaine could have come from the same source using carbon isotopic analysis. Marijuana was another illicit drug that was analyzed using this instrumentation method. We report the first application of GC-IRMS to individual components of Cannabis sativa L. to discriminate between different sources. Different manufacturers, or lot numbers, of common household accelerants such as Goof Off, turpentine, charcoal lighter fluid and WD-40 were also analyzed. The analysis of accelerants demonstrated that this modification of instrumentation could be used for not only pure compounds but, also for very complex compounds. IRMS could distinguish between different sources of accelerants by analyzing trace residues remaining after combustion. To further examine the versatility of this tool, individual amino acids in hair were analyzed. We have shown that it is possible to determine minimally nine individual amino acids within hair samples using a single step derivatization method. In the future, we would like to study single strands of hair and the possibilities of segmenting the hair into sections of monthly growth. The analysis of forensic samples using this modification is virtually unlimited. Advisors/Committee Members: Jackson, Glen.

Subjects: Analytical chemistry; Chemistry

Keywords: Gas chromatography - isotope ratio mass spectrometry; forensic chemistry; cocaine; marijuana; cannabinoids; accelerents; arson; hair; amino acids; carbon isotopes

26. Muchenditsi, Abigael M. Effects of Metal Ions and Loop Stability on the Structure and Function of the T Box Antiterminator RNA and its complex with Model tRNA.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2009, Ohio University

► The T box antitermination mechanism is a novel transcription regulatory system found… (more)

▼ The T box antitermination mechanism is a novel transcription regulatory system found in many Gram-positive bacteria. The mechanism serves to regulate aminoacyl tRNA synthetases, amino acid transport genes and amino acid biosynthesis genes. The genes regulated by this system are characterized by highly conserved primary and secondary structural elements in the 5' untranslated region. Two mutually exclusive secondary structures can form in the 5' untranslated region; the antiterminator, stabilized by uncharged tRNA binding, leads to transcription read through and full synthesis of the gene. The formation of the terminator element, in the absence of uncharged tRNA leads to transcription termination. The antiterminator consists of two helices, A1 and A2 separated by a seven-nucleotide bulge and a closing loop in the A2 helix. This study investigated the effects of the loop region and Mg2+ on the structure and functions of the antiterminator and microhelix tRNA model. The use of computational, spectroscopic and molecular biology techniques demonstrated that the loop region had an effect on the structure and stability of the antiterminator and microhelix RNA but did not change the overall functions of the antiterminator model. A series of antiterminator models and microhelix RNA models were constructed with a substitution of well-characterized stable GNRA and UNCG tetraloops. A part from these mutations, the wild type antiterminators AM2 with a loop sequence AAUCA and the GlyQS (Glycine synthetase) with a loop sequence (GAAC) that is not a classified stable loop were also investigated. Using Mfold thermodynamic stability and UV monitored thermal denaturation, it was demonstrated that the loop region contributes significantly to the stability of the antiterminator. There was no clear correlation in the Circular Dichroism (CD) study of the different antiterminators. Enzymatic probing study showed that the loop region affected the A2 helix of the antiterminators but not the nature of the bulge. Binding studies using fluorescence-based binding assays demonstrated that divalent metal requirement for tRNA binding to the antiterminator RNA is dependent on antiterminator sequence and structure. Monovalent metal ions alone did not sufficiently facilitate tRNA binding to the antiterminator. Interaction of small molecules with different antiterminators showed that the small molecules bind antiterminators differently due to RNA structural differences. Finally this study provided further evidence that binding of tRNA to antiterminator model occurs by means of an induced fit. Advisors/Committee Members: Hines, Jennifer.

Subjects: Chemistry

Keywords: T box; Antitermination; microhelix; Tetraloop

27. Orac, Crina M. Stereochemical Synthesis of Ring E Analogs of Methyllycaconitine and 4,5-Disubstituted Oxazolidinones.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2009, Ohio University

► The pharmacological activity of enantiomers of a chiral compound can be influenced… (more)

▼ The pharmacological activity of enantiomers of a chiral compound can be influenced to a great extent by molecular chiral recognition, the ability of a chiral biological system to discriminate between enantiomers. Typically one enantiomer will have better activity than its enantiomer. This difference in biological response generated by enantiomers upon binding to a biological target is a consequence of their differential interaction with the binding site. When designing new ligands for biological targets it is important to examine their constituent enantiomers. This dissertation is concerned with the synthesis of enantiomerically pure ring E analogs of methyllycaconitine and trans 4,5-disubstituted oxazolidinones in an effort to understand their interaction with their biological targets in a three-dimensional sense. Due to their involvement in many physiological functions, nicotinic acetylcholine receptors (nAChRs) are important potential therapeutic targets for a large variety of neurodegenerative and psychiatric disorders. Ring E analogs of methyllycaconitine have been previously reported to act as noncompetitive antagonists of a subtype of nAChRs. In this dissertation, a new set of 20 compounds was prepared, consisting of enantiomers and various diastereomeric mixtures of three lead compounds from previously studied ring E analogs. The examination of the 3-D interaction of this set of compounds with the nAChRs leads to a better understanding of the formation of ligand-receptor complex and the structural demands required for a good binding. A new class of antibacterial agents, the 4,5-disubstituted oxazolidinones, has been developed that exhibit inhibitory activity at the T box transcription antitermination system that controls the gene expression in many bacteria. In this dissertation, the enantiomers and the cis isomers of two lead compounds were prepared and used to study the effect of their chirality on the binding to the T box antiterminator. The biological results indicated that there is chiral recognition associated with the binding of 4,5-disubstituted oxazolidinones to the T box antiterminator. Advisors/Committee Members: Bergmeier, Stephen.

Subjects: Organic chemistry

Keywords: nicotinic; acetylcholine; methyllycaconitine; enantiomers; antibiotics; antiterminator; oxazolidinones

28. Pavlyuk, Oksana M. Synthesis of Nitrogen-Containing Heterocycles via Carbenoid Insertion/Ring-Closing Metathesis Sequence.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2011, Ohio University

► A series of five- to nine-membered nitrogen-containing heterocycles were prepared via a… (more)

Subjects: Chemistry

Keywords: Diazocarbonyl; N-H Insertion; C-H Insertion; Cyclopropanation; RCM

29. Soans, Eroica. Investigating the Molecular Mechanism of Novel Quinuclidinone Derivatives in Lung Cancer Cells with Different p53 Status.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► Most chemotherapeutics affect normal cells as much as cancer cells leading to… (more)

Subjects: Biochemistry

Keywords: chemotherapeutics; sphingomyelinase; apoptosis; p53; ceramide; bax

30. Stengel, Jason H. The Application of Tandem O-H Insertion/Ring-Closing Metathesis to the Synthesis of Unsaturated Cyclic Ethers: Approaches to Rogioloxepane and Isolaurepinnacin.

Degree: PhD, Chemistry and Biochemistry (Arts and Sciences), 2010, Ohio University

► The utilization of rhodium-mediated insertion reactions and ring-closing metathesis (RCM) in a… (more)

Subjects: Chemistry

Keywords: Tandem reactions; diazoester; O-H insertion; Ring-closing metathesis; metallocarbenoid

[1] [2]