Department: Chemistry ![[clear]](close-x.png "Remove this limiter")
185 matches in the database.
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1.
Annangudi Palani, Suresh Babu.
Lipid-based Oxidative Protein Modifications in Glaucoma.
Degree: PhD, Chemistry, 2006, Case Western Reserve University
► We and others have postulated that oxidative protein modifications, including covalent crosslinks,…
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▼ We and others have postulated that oxidative protein modifications, including covalent crosslinks, may accumulate in trabecular meshwork (TM) and contribute to impaired aqueous outflow and primary open angle glaucoma (POAG). To test this hypothesis, human TM from normal and POAG donors was probed with antibodies for oxidative protein modifications. Studies using SDS PAGE and Western blotting showed elevated levels of covalent protein modifications derived from lipid oxidation products (iso[4]Levuglandin E2 (isoLGE2) and 4-hydroxy-nonenal (HNE)), an advanced glycation end product (methylglyoxal), and a tryptophan oxidation product (3-hydroxy-kynurenine), in POAG compared to age-and-gender matched controls. Immunoprecipitation (IP) using iso[4]LGE2 and HNE antibodies showed the presence of several apparently crosslinked proteins in POAG donor TM. 2D PAGE Western analyses, also showed proteins with altered molecular weights and pIs, implying modified and/or crosslinked proteins. Immunohistochemistry showed that iso[4]LGE2 and HNE modifications were localized to the TM. Thus, the study provides direct evidence for lipid-based oxidative modification of TM proteins in POAG. Additionally, increased levels of iso[4]LGE2 in the TM of the DBA/2J mouse model of glaucoma was also established and several putative crosslinked proteins were identified using IP and mass spectrometry. These results support a role for levuglandins (LGs) in POAG pathology. LGs are known to avidly bind with and crosslink proteins. The inability of macrophages to processes modified proteins contributes to “foam cell” formation and atherosclerosis (AS). To identify the modified proteins in inflamed macrophages, lipopolysaccharide (LPS) stimulated macrophages were studied. LPS stimulation increased the levels of LGE2 modified proteins in macrophages.The modified proteins were identified by 2D PAGE and mass spectrometry. Many of the modified proteins are involved in cholesterol trafficking, gene expression, and/or lipid efflux. This suggests a role for LGE2 in AS. These observations inspired a pilot study to explore the possible role of LGs in LPS-induced inflammation of cornea in vivo. We found that LPS promotes the generation of LGs in cornea. An efficient synthesis of the ã-keto-á,â-unsaturated alkenoic acid functional array present in some of the oxidatively truncated phospholipids, was achieved by oxidation of furyl precursors using NaClO2. Additionally, detection and structural characterization of multiple HNE adducts onto lysine and histidine side-chain residues were accomplished using deuterated HNE and mass spectrometry.
Advisors/Committee Members: Salomon, Robert Gerd.
Keywords: Glaucoma; DBA/2J; Levuglandins; ã-keto-á,â-unsaturated alkenoic acid; sodium chlorite; Macrophages; Lipopolysaccharides; primary open angle glaucoma; 4-hydroxynonenal; HNE; LGE; HNE adduction; Michael adduct; deuterium labeled HNE
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2.
Apetri, Constantin Adrian.
Folding of the Prion Protein.
Degree: PhD, Chemistry, 2004, Case Western Reserve University
► Propagation of transmissible spongiform encephalopathies is believed to involve the conversion of…
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▼ Propagation of transmissible spongiform encephalopathies is believed to involve the conversion of the cellular prion protein, PrPC, into a misfolded oligomeric form,PrPSc. An important step towards understanding the mechanism of this conversion is to study the folding pathway(s) and the stability of PrPC. In the first part of this work, we examined the kinetics of folding and unfolding reactions for the recombinant wild type human prion protein fragment 90–231. The stopped flow data provided clear evidence for the existence of an intermediate on the refolding pathway of the prion protein as indicated by a pronounced curvature in chevron plots and the presence of significant burst phase amplitudes in the refolding kinetics. The protein folding studies were then extended to prion protein variants carrying mutations associated with inherited prion diseases. Analysis of kinetic data clearly indicates the presence of partially structured intermediates on the refolding pathway of each PrP variant studied. For the majority of PrP variants tested, mutations linked to familial prion diseases resulted in a pronounced increase in the thermodynamic stability – and thus the population – of the folding intermediate. These data strongly suggest that partially folded intermediates of PrP may play a crucial role in prion protein conversion, serving as direct precursors of the pathogenic PrPSc isoform. Previous studies indicate that salts promote the conformational conversion of the recombinant prion protein into a PrPSc-like form. To gain insight into the mechanism of this effect, we studied the influence of a number of salts on the thermodynamic stability of the recombinant human prion protein. Chemical unfolding studies in urea showed that at low concentrations (< 50 mM), all salts tested significantly reduced the thermodynamic stability of the protein. At higher salt concentrations, the destabilizing effect was gradually reversed, and salts acted according to their ranking in the Hofmeister series. The observations indicate that electrostatic interactions play an unusually important role in the stability of the prion protein and that ions present in the cellular environment may control the PrPC to PrPSc conversion by modulating the thermodynamic stability of the native PrPC isoform.
Advisors/Committee Members: Surewicz, Witold K.
Subjects: Biophysics, Medical
Keywords: protein folding; prion diseases; prion protein; folding intermediate; salt effect; kinetics; stopped flow
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3.
APETRI, MARIA MIHAELA.
BIOPHYSICAL STUDIES OF THE ALPHA-SYNUCLEIN PROTEIN ASSOCIATED WITH PARKINSON’S DISEASE AND OTHER SYNUCLEINOPATHIES.
Degree: PhD, Chemistry, 2006, Case Western Reserve University
► Many neurological diseases are linked to the aberrant folding of proteins and…
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▼ Many neurological diseases are linked to the aberrant folding of proteins and the production of amyloid fibrils. The misfolding and aggregation of the protein alpha-synuclein into Lewy bodies is thought to play a key role in the pathogenesis of Parkinson’s disease. Despite extensive studies on this protein, very little is known about the structures and molecular mechanisms associated with the aggregation events. This work unravels detailed structural data about the aggregation pathways of alpha-synuclein, using an array of spectroscopic techniques, including circular dichroism, Raman spectroscopy, atomic force microscopy, nuclear magnetic resonance and thioflavin-T fluorescence. Previous studies established that alpha-synuclein is predominantly unfolded in aqueous solution at neutral pH. My work revealed that under these conditions, alpha-synuclein adopts an ensemble of secondary structures (extended, alpha-helical and beta-sheet). This interpretation was based on the analysis of the Raman amide I band of the monomeric alpha-synuclein. The morphology and the secondary structure of the soluble protein aggregates (spheroidal and chainlike oligomers) observed as probable intermediates that form during alpha-synuclein fibrillization, were characterized by Raman and atomic force microscopies. During the formation of alpha-synuclein oligomers under physiological conditions or in methanol-water solutions, a significant change in the ensemble of structures present took place; beta-sheet structure was enhanced and the extended structure was diminished. Importantly, these aggregates retained a significant amount of alpha-helical secondary structure. Moderate (15 - 20%) concentrations of methanol encouraged alpha-synuclein aggregation into chainlike oligomers that were indistinguishable from those formed in the absence of methanol. In many sporadic neurodegenerative disorders, co-occurrence of alpha-synuclein and tau proteins as amyloid-like fibrils occurs, and it is thought that either protein may nucleate fibril deposition at the early stages that ultimately lead to the disease pathology. Despite the importance of these processes, the precise molecular changes and interactions have yet to be determined. In the last part of this work, we reveal by NMR that the major attractive forces between alpha-synuclein and tau are electrostatic and the interaction is localized in the C-terminal region (residues 119 -140) of alpha-synuclein and the microtubule binding domain of tau protein.
Advisors/Committee Members: Zagorski, Michael G.
Subjects: Biophysics, Medical
Keywords: alpha-synuclein; tau protein; oligomers; secondary structure; Raman spectroscopy; atomic force microscopy; nuclear magnetic resonance
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4.
Awad, Mohamed Khaled Hassan.
Small molecule chemisorption on metals and carbon-hydrogen and hydroxy 1 bond activation by electron hold centers: Molecular orbital theory.
Degree: PhD, Chemistry, 1990, Case Western Reserve University
► CO is calculated to favor adsorption at 3-fold sites on Pd (111)…
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▼ CO is calculated to favor adsorption at 3-fold sites on Pd (111) and at 2-fold sites on Pd (100) surfaces in agreement with experimental literature. It is shown that the different binding site preferences of CO on Pd and Pt are caused by the different metal valence band positions. The adsorption of Ru and O atoms and RuO n (n = 1-4) on the Ru (001) surface has been studied. It is found that the Ru and RuO n have about the same barrier to surface diffusion, all equal to about half of the oxygen barrier. The binding energy of RuO n decreases as n increases. These findings show how oxide molecules may provide a transport mechanism for oxide nucleation on the Ru (001) surface, which supports suggestions in the experimental literature. Calculations show that π*gets n excited p-benzoquinone abstracts an H atom from coordinated H2O to form semiquinone. In acidic solution, hydroquinone is most likely to form by a second hydrogenation of semiquinone leaving stable di-μ-oxo Mn IV dimers. It is proposed that dimers disproportionate, going through a 4 Mn intermediate, to give O2 and a stable O-bridged Mn III dimer. According to the calculations, this last step is rate limiting. It is shown that dimerization of the Mn complexes is the key to O2 evolution in the active systems, and this is controlled by the ligand structure. CH4 activation by N2- hole centers in AlN is calculated to be very similar to activation by O- hole centers in oxides such as MgO. Surface HN2- and gas phase methyl radical are formed by H abstraction. Recent experimental literature has demonstrated the photodimerization of cyclohexene by excited W10O324- to yield 3,3′-dicyclohexene. Our calculations show that the hole in the top of O 2p band of photoexicted polyoxyanion is reduced by an electron from the CH bond early in the course of H abstraction, and this is why the activation energly is low. The adsorption of ethylidyne on cluster models of Rh(100) and (111) surfaces has been studied. Higher coordination sites are favored, with the C-C bond of ethylidyne perpendicular to the surface. (Abstract shortened with permission of author.
Advisors/Committee Members: Anderson, Alfred B.
Subjects: Chemistry, Physical
Keywords: Small molecule chemisorption metals carbon-hydrogen and hydroxy 1 bond activation electron hold centers: Molecular orbital theory.
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5.
Bae, In Tae.
In situ infrared spectroscopic studies of electrocatalytic systems.
Degree: PhD, Chemistry, 1990, Case Western Reserve University
► Electrochemical interfaces were examined with Drude-Fresnel equations for the 3-phase system in…
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▼ Electrochemical interfaces were examined with Drude-Fresnel equations for the 3-phase system in order to obtain the dependence of infrared external reflectance spectra on the angle of incidence, the electrolyte layer thickness and the optical polarization state. Electrochemical effects such as ionic transports and pH changes in the spectroelectrochemical thin layer designed for external reflection were observed in in situ spectra. The IR peak intensity corresponding to the concentration change due to the net anions transported into the thin layer was proportional to the charge observed in the voltammetric measurements for Au or Pt anodic film formation in 0.1 M HClO4, 0.1 M HNO3, or mixed electrolyte solutions. The pH changes within the thin layer due to the charge passed between the working and counter electrode were also observed in the spectra for 0.1 M Na2CO3 and 0.1 M CH3CO2Na. Electrooxidation of glucose on Pt electrodes was studied by infrared spectroscopy in acid and alkaline electrolyte solutions to elucidate the reaction steps and to identify species strongly adsorbed on the electrode surface during the reaction. The strongly adsorbed species was the linearly adsorbed CO on Pt which is believed to poison the further oxidation of glucose on Pt in both 0.1 M H ClO4 and 0.1 M NaOH. Gluconic acid and CO2 were detected as the intermediate and the final product, respectively in the Pt oxide region. Transition metal macrocycles adsorbed on smooth surfaces and high area carbon were also investigated. The surface orientation of metalloporphyrin is believed to be strongly dependent on the method employed for the adsorption. This was evident from IR reflection-adsorption spectra for the adsorbed porphyrins on the basal plane of HOPG obtained from different adsorption methods. Voltammograms for metallomacrocycles adsorbed on such an electrode showed that some molecular restructuring occurs during the potential cycling. EXAFS studies of cobalt porphyrin adsorbed on high area carbon and its heat treatment product under inert atmosphere provided evidence for physisorption of this material on carbon and the pyrolysis product is containing reduced cobalt metal clusters. (Abstract shortened with permission of author.
Advisors/Committee Members: Yeager, Ernest B.
Keywords: In situ infrared spectroscopic electrocatalytic systems
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6.
Balachander, Natarajan.
Chemical transformations of siloxane-anchored monolayers.
Degree: PhD, Chemistry, 1990, Case Western Reserve University
► Long chain trichlorosilyl terminated surfactants containing ω-functional groups have been used to…
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▼ Long chain trichlorosilyl terminated surfactants containing ω-functional groups have been used to form siloxy-anchored self-assembled monolayers on various substrates including glass, Si, Ti, Ge and ZnSe. The functional groups used are Br, SCN, CN, SCOCH3 and CnF2n + 1CO (n = 1-3). The conditions for the formation of these monolayers have been determined and they have been characterized by contact angle measurements, attenuated total reflection IR spectroscopy and X-ray photoelectron spectroscopy. The stability of these monolayers under different environments has been assessed. In situ chemical transformations of these monolayers have led to the generation of a new set of monolayers with different functional groups at the surface. Among these new monolayers are many that are not accessible by direct surfactant deposition. A variety of successful SN2 displacement reactions have been achieved at the surface of a well packed monolayer. Different starting surfaces and different reaction pathways have been used to arrive at the same surfaces as a crosscheck of the composition and integrity of these functionalized monolayers. Amine containing surfaces have been generated by in situ chemical transformations. This was achieved by transforming the Br terminated surface to the azide followed by its reduction or by the reduction of a directly deposited nitrile surface. A series of sulfur containing surfaces have been generated either by direct deposition or by in situ chemical transformations. The sulfur containing surfaces are -SH, -SCN, -SCOCH3, -S-S-, -S- -(SO2)- and -SO3H. This work has demonstrated the feasibility of carrying out surface transformations using bidentate nucleophiles (S-2 and S2-2) to generate functional groups bridging neighboring alkyl chains of the monolayer. In a different study, using monolayers formed from fluoroketone surfactants, two issues have been addressed. The influence of polar groups 2 to 4 carbon atoms deep from the surface, on the wetting behavior has been studied. The reduction of the carbonyl groups in these monolayers with LiAlH4 and DIBAL-H has been investigated to understand the packing and reactivity of buried functional groups. Self-assembled monolayers have been used in the study of the adhesion of cells and bacteria to various surfaces. These studies attempt to understand the adhesion process and to develop new functionalized surfaces that show potential as future biomaterials for implants.
Advisors/Committee Members: Sukenik, Chaim N.
Subjects: Chemistry, Organic
Keywords: Siloxane-anchored monolayers
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7.
Basu, Shubhamita.
STUDIES TOWARDS THE TOTAL SYNTHESIS OF VANCOMYCIN AGLYCON.
Degree: PhD, Chemistry, 2007, Case Western Reserve University
► Vancomycin is a glycopeptide antibiotic, clinically the last resort for physicians to…
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▼ Vancomycin is a glycopeptide antibiotic, clinically the last resort for physicians to combat deadly bacterial infection. The complex structural motif along with the numerous stereocenters has made it a challenging target for synthetic chemists. Emerging bacterial resistance against vancomycin has inspired scientists to look at its synthesis from the standpoint of developing new antibiotics. In this work, application of the ruthenium-mediated SNAr reaction was explored to synthesize the aryl ether linkage, that is a key structural feature of vancomycin. Two different pathways were investigated for this purpose (Chapter 2 and Chapter 3), and while the pathways were not greatly successful, they helped us understand the different facets of reactivity of the ruthenium complexes. In Chapter 3, the ruthenium-promoted SNAr reaction was tested on molecules with two different halides that can be displaced, and the chemoselectivity of such displacement was examined. While fluoride is displaced selectively over chloride in the case of amine nucleophiles, the opposite happened when the reaction was done with phenoxides. This prompted us to revisit the standard mechanistic dogma of metal-promoted SNAr reactions and rationalize the experimental results in light of both electronegativity and leaving group ability.
Advisors/Committee Members: Pearson, Anthony J.
Subjects: Chemistry, Organic
Keywords: vancomycin, glycopeptide antibiotics, ruthenium-mediated SNAr
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8.
Batzel, Daniel Austin.
Synthesis of amphiphilic phthalocyanines and Langmuir-Blodgett film balance studies of these compounds.
Degree: PhD, Chemistry, 1990, Case Western Reserve University
► This thesis describes the synthesis and spectroscopic characterization of the Langmuir-Blodgett film-forming…
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▼ This thesis describes the synthesis and spectroscopic characterization of the Langmuir-Blodgett film-forming phthalocyanines (n-C6H13)3SiO(SiPcO)1-2H, C18H37(C4H9)2SiO(SiPcO)1-2H, (n-C6H13)3SiO-(SiPcO)3C(O)CCl3, C18H37(C4H9)2SiO(SiPcO)3C(O)CCl3, (n-C6H13)3SiO-SiPcOGePcOH, C18H37(C4H9)2SiOSiPcOGePcOH, and C18H37(C4H9)2SiO-SiPcOAlPc (where Pc is the phthalocyaninato dianion). It also describes the synthesis and characterization of some of the precursors of these compounds including (n-C6H13)3SiO(SiPcO)1-4Si(n-C6H13)3, C18H37(C4H9)2SiO(SiPcO)1-4Si(C4H9)2C18H37, CH3GePcCl, CH3GePcOH, and C18H37(C4H9)2SiOAlPc. In addition, the thesis describes the formation and properties of monolayers of (n-C6H13)3SiOSiPcOGePcOH, C18H37(C4H9)2SiOSiPcOGePcOH, C18H37(C4H9)2SiOSiPcOAlPc, (n-C6H13)3SiO(SiPcO)1-2H, and C18H37(C4H9)2SiO(SiPcO) 1-2H from solutions of these compounds and monolayers of (n-C6H13)3SiO(SiPcO)3H and C18H37(C4H9)2SiO(SiPcO)3H from solutions of (n-C6H13)3SiO(SiPcO)3C(O)CCl3 and C18H37(C4H9)2SiO(SiPcO)3C(O)CCl3. It is shown from co-area data that the phthalocyanine rings of the (n-C6H13)3SiO(SiPcO)1-3H, C18H37(C4H9)2SiO(SiPcO)1-3H, (n-C6H13)3SiOSiPcOGePcOH, and C18H37(C4H9)2SiOSiPcOGePcOH monolayers are oriented parallel to the plane of the monolayer, while the phthalocyanine rings of the C18H37(C4H9)2SiOSiPcOAlPc monolayers are not. This is attributed to the presence of OH head groups and R3SiO tail groups on the central metal. From phase-transition pressure data and compressive creep curves it is concluded that the stability of the (n-C6H13)3SiO(SiPcO)2-3H and (n-C6H13)3SiOSiPcOGePcOH monolayers is greater than the stability of the (n-C6H13)3SiOSiPcOH monolayers. This is attributed to the thicker ring profile of the two- and three-ring compounds. Finally, a summary of the results of collaborative work on the preparation, characterization, and properties of Langmuir-Blodgett multilayers of the n-C6H13)3SiOSiPcOGePcOH is given. It is shown by X-ray and electron diffraction experiments that the multilayer films are highly anisotropic and the phthalocyanine rings are parallel to the plane of the substrate. Furthermore, metal-insulator-metal and gas-sensing device studies incorporating these multilayer films indicate that they have high thermal, electrical, chemical, and photochemical stability
Advisors/Committee Members: Kenney, Malcolm E.
Keywords: amphiphilic phthalocyanines Langmuir-Blodgett
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9.
Braz, Valerie Ann.
Binding of the Nonnucleoside Reverse Transcriptase Inhibitor Efavirenz to HIV-1 Reverse Transcriptase Monomers and Dimers.
Degree: PhD, Chemistry, 2010, Case Western Reserve University
► Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) was the first…
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▼ Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) was the first target of antiretroviral therapy in the treatment of AIDS. RT converts single-stranded viral RNA into double-stranded proviral DNA. The enzyme has two activities, DNA polymerase and RNase H. The biologically relevant form is a heterodimer composed of two subunits, p66 and p51. The subunits are products of the same gene and have identical N-terminal amino acid sequences; p51 lacks the C-terminal RNase H domain. In solution RT exists as a complex equilibrium mixture of p66/p51 heterodimer, p66/p66 and p51/p51 homodimers, and p66 and p51 monomers. Two classes of inhibitors have been developed and approved for clinical use, NRTIs and NNRTIs. NNRTIs are highly effective and relatively noncytotoxic small, amphiphilic, noncompetitive inhibitors that nestle into a hydrophobic pocket near the polymerase active site in the p66 subunit of RT. NNRTIs also have diverse effects on RT subunit dimerization; some enhance dimerization and others weaken dimerization. Efavirenz is an NNRTI capable of affecting several steps in HIV-1 reverse transcription and replication. This work reports two novel functions of the inhibitor: (1) efavirenz, and presumably also other NNRTIs, binds to monomeric forms of RT and (2) efavirenz is a slow binding inhibitor of heterodimer and monomers. In addition, the binding site on p66 and p51 monomers was identified. Five techniques were used to characterize the interaction of efavirenz to all species of RT; equilibrium dialysis, tryptophan fluorescence, native gel electrophoresis, and hydrogen-deuterium exchange and Fourier transform ion cyclotron resonance mass spectrometry. Although the biological significance of efavirenz binding to monomeric forms of RT is not known, this work suggests that monomeric forms of RT may be potential targets for HIV-1 therapeutics.
Advisors/Committee Members: Barkley, Mary.
Subjects: Biochemistry; Biophysics; Chemistry
Keywords: Nonnucleoside Reverse Transcriptase Inhibitor; Efavirenz; Reverse Transcriptase; HIV-1
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10.
Braz, Valerie Ann.
Binding of the Nonnucleoside Reverse Transcriptase Inhibitor Efavirenz to HIV-1 Reverse Transcriptase Monomers and Dimers.
Degree: PhD, Chemistry, 2009, Case Western Reserve University
► Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) was the first…
(more)
▼ Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) was the first target of antiretroviral therapy in the treatment of AIDS. RT converts single-stranded viral RNA into double-stranded proviral DNA. The enzyme has two activities, DNA polymerase and RNase H. The biologically relevant form is a heterodimer composed of two subunits, p66 and p51. The subunits are products of the same gene and have identical N-terminal amino acid sequences; p51 lacks the C-terminal RNase H domain. In solution RT exists as a complex equilibrium mixture of p66/p51 heterodimer, p66/p66 and p51/p51 homodimers, and p66 and p51 monomers. Two classes of inhibitors have been developed and approved for clinical use, NRTIs and NNRTIs. NNRTIs are highly effective and relatively noncytotoxic small, amphiphilic, noncompetitive inhibitors that nestle into a hydrophobic pocket near the polymerase active site in the p66 subunit of RT. NNRTIs also have diverse effects on RT subunit dimerization; some enhance dimerization and others weaken dimerization. Efavirenz is an NNRTI capable of affecting several steps in HIV-1 reverse transcription and replication. This work reports two novel functions of the inhibitor: (1) efavirenz, and presumably also other NNRTIs, binds to monomeric forms of RT and (2) efavirenz is a slow binding inhibitor of heterodimer and monomers. In addition, the binding site on p66 and p51 monomers was identified. Five techniques were used to characterize the interaction of efavirenz to all species of RT; equilibrium dialysis, tryptophan fluorescence, native gel electrophoresis, and hydrogen-deuterium exchange and Fourier transform ion cyclotron resonance mass spectrometry. Although the biological significance of efavirenz binding to monomeric forms of RT is not known, this work suggests that monomeric forms of RT may be potential targets for HIV-1 therapeutics.
Advisors/Committee Members: Barkley, Mary.
Subjects: Biochemistry; Biophysics; Chemistry
Keywords: Nonnucleoside Reverse Transcriptase Inhibitor; Efavirenz; Reverse Transcriptase
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11.
Bruhn, Paul Robert.
Organomanganese complexes in organic synthesis.
Degree: PhD, Chemistry, 1990, Case Western Reserve University
► Tricarbonylcycloheptatrienemanganese underwent stereospecific nucleophilic addition of stabilized enolates to give exo-substituted adducts…
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▼ Tricarbonylcycloheptatrienemanganese underwent stereospecific nucleophilic addition of stabilized enolates to give exo-substituted adducts in good yield. Decomplexation with ceric ammonium nitrate in buffered wet acetone gave a mixture of 3-hydroxycyclohepta-4,6-diene and lactonecyclohepta-3,5-diene products from the stereospecific addition of external water at the remote terminus or the adjacent terminus of the dienyl system respectively. A pendent hydroxyl group added intramolecularly and stereospecifically to the adjacent terminus of the dienyl system in the absence of external nucleophiles during iodine-mediated decomplexation. Tricarbonylchlorobenzenemanganese(1+) underwent aromatic nucleophilic substitution when treated with phenoxides from protected tyrosine and 4-hydroxyphenylglycine amino acid derivatives. In situ decomplexation occurred in the presence of acetonitrile. No racemization of the amino acid moiety was observed in these reactions. This diaryl ether synthesis was envisioned as an entry to the synthesis of models of glycopeptide antibiotics of the ristocetin and vancomycin families. A survey of these families led to a generic model as a synthetic goal. One necessity of this synthesis, the ability to form diaryl ethers and triaryl diethers selectively, was demonstrated. All attempts to synthesize manganese complexes of chlorophenylalanine derivatives, also crucial to the original synthetic plan, failed. However, several novel arenetricarbonylmanganese complexes with functionalized side chains were prepared via Mn(CO)5BF4. Differences in the mode of complexation between the standard Mn(CO)5Br-AlCl3 method and hits new method may explain the inability to synthesize any chloroaromatic complexes via Mn(CO)5BF4. An alternative synthesis of fragments of the target antibiotic molecules through aromatic nucleophilic substitution followed by stereoselective nucleophilic addition was developed. Diaryl ether manganese salts of 1-6-η-benzene and protected derivatives of L-tyrosine, D-tyrosine, and L-leucine-L-tyrosine were prepared. These reacted with the lithium anion of 3R(2,5-dimethoxy-3-isopropyl)3,6-dihydropyrazine to give phenyl glycine equivalents in 70% d.e. Hydrolysis of the dihydropyrazinemoiety gave the respective N-acetyl-4-O-(3-D-phenylglycine methyl ester) -D- and -L-tyrosine methyl esters thereby demonstrating the potential of success for the synthesis of antibiotic fragments by this methodology.
Advisors/Committee Members: Pearson, Anthony J.
Subjects: Chemistry, General
Keywords: organomanganese complexes organic synthesis
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12.
Burello, Marco Paolo.
Synthesis and reactions of some carbomethoxy-substituted cycloheptadiene-tricarbonyl iron complexes.
Degree: PhD, Chemistry, 1991, Case Western Reserve University
► 1-carbomethoxy(cyclohepta-1,3-diene)tricarbonyliron 1 and 2-carbomethoxy-(cyclohepta-1,3-diene)tricarbonyliron 2 were prepared in good yield from 2-carbomethoxy-cyclohept-1,3-diene…
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▼ 1-carbomethoxy(cyclohepta-1,3-diene)tricarbonyliron 1 and 2-carbomethoxy-(cyclohepta-1,3-diene)tricarbonyliron 2 were prepared in good yield from 2-carbomethoxy-cyclohept-1,3-diene by complexation with pentacarbonyliron or diiron nonacarbonyl. The corresponding dienyl salts 3 and 4 respectively were prepared by hydride abstaction with triphenylmethyl hexafluorophosphate. A range of nucleophiles including dimethyl malonate, nitrile, hydride and thiophenoxide were added to these dienyl salts and some interesting regiochemical results were observed. Addition of dimethyl malonate to both of the dienyl complexes gave a σ-π-allyl complex such as 5 as product. In all previous cases, addition of dimethyl malonate went at the terminus of the dienyl system to give a diene complex. In order to explain this unusual observation 13C NMR studies and extended Huckel calculations were done on some model dienyl complexes to determine charge densities and LUMO coefficients for the carbons of the dienyl system. Also, a classical resolution of the complexes was accomplished via the corresponding caboxylic acid-substituted complex.
Advisors/Committee Members: Pearson, Anthony J.
Keywords: Synthesis reactions carbomethoxy-substituted cycloheptadiene-tricarbonyl iron complexes
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13.
Cai, Yu.
Theory for Fundamental Reactions in Fuel Cells.
Degree: PhD, Chemistry, 2005, Case Western Reserve University
► Quantum mechanical theory and a local reaction center model were applied to…
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▼ Quantum mechanical theory and a local reaction center model were applied to study electron transfer reactions in different systems. It was revealed that potential-dependent activation energies can be related to experimentally measured Tafel plot by an Arrhenius-like equation. This approach should be very helpful in future determinations of reaction pathways in the electrochemical environment. The local reaction center model for the Heyrovsky reaction during hydrogen evolution on platinum is: Pt−H⋯H+(OH2)(OH2)2 + e−(U) → Pt⋯H−H⋯OH2(OH2)2 The calculated reversible potential with the adjustment of Pt−H bond strength, was 0.04 V, in good agreement with experiment. At the reversible potential the activation energy was calculated to be 0.076 eV, compared to the experimental value 0.12 eV. The calculated potential-dependent activation energies were substituted into an Arrhenius-like equation: ik = |ioxk − iredk | = A(U)|exp(−Eoxa(U)/RT) − exp(−Ereda(U)/RT)| The predicted Tafel plot using this equation fitted the experimental one for Pt(100) electrodes, giving a strong support for Volmer-Heyrovsky mechanism with Heyrovsky step being rate limiting. Two redox reactions were studied on platinum electrode in basic solutions: the formation of underpotential deposited hydrogen by forming a Pt−H bond, Pt⋯H2O + e−(U) → Pt−H + OH−(aq) and the electro-oxidation of water, forming a Pt−OH bond. Pt−OH2 + OH−(aq) → Pt−OH + H2O + e−(U) Both the linear correlation model and the double layer model yield satisfactory onset potentials for forming Pt−H and Pt−OH bonds in base. For the first electron transfer step in the oxygen reduction reaction, Pt2O2 + H+(aq) + e−(U) → Pt2OOH we found that it is necessary to calculate both reduction and oxidation activation energies. When the transition states for reduction and oxidation were in significant disagreement, the structure averaging technique was found to work, making it possible to iteratively find better converged transition states. In the absence of defects, conducting diamond is a poor electrocatalyst for hydrogen evolution relative to platinum. This is expected since it is more difficult to break a surface C−H bond than a surface Pt−H bond. Consequently, the activation energies for the Heyrovsky reaction, C* −H⋯H+(OH2)(OH2)2 + e−(U) → C*⋯H−H⋯OH2(OH2)2 are higher for all potentials. The observed catalytic reactivity for hydrogen evolution on boron-doped diamond electrodes was attributed to the formation of weakly adsorbed hydrogen atoms that was made possible by the subsurface substitutional boron atoms.
Advisors/Committee Members: Dunbar, Robert C.
Subjects: Chemistry, Physical
Keywords: Reversible Potentials; Pt; Hydrogen; eV; aq; Activation Energies
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14.
Chaka, Anne Marie.
Predicting the crystal structure of organic molecular materials.
Degree: PhD, Chemistry, 1993, Case Western Reserve University
► Considerable interest has developed in organic molecular materials since the discovery of…
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▼ Considerable interest has developed in organic molecular materials since the discovery of a wide range of properties previously thought to be the exclusive domain of inorganic materials and metals. Many of these properties of organic materials, such as conductivity, nonlinear optical susceptibility, and ferromagnetism, are dependent upon the relative orientation of the constituent molecules within the material. Hence, to be able to predict crystal packing has long been recognized as being of great importance, but was believed to be too complicated or to involve too many long calculations to be feasible. We have developed a novel method which employs a series of successive approximations to focus on structures of high probability without resorting to a brute force search and energy minimization of all possible structures. The problem of multiple local minima was overcome by assuming that the crystal structure is closest packed, thereby eliminating 217 of the 230 possible space groups. Structures within the 13 remaining space groups were searched in rotational increments of 15°. Initial energy minimization was performed using Lennard-Jones pair potentials to produce a set of closest-packed structures. These structures were then refined with the introduction of a Coulombic potential calculated using molecular multipole moments. This method has successfully predicted the crystal structure of several saturated and unsaturated hydrocarbons with no a priori information provided. For large polycyclic aromatic hydrocarbons, additional refinements of the energy calculations are required to distinguish the experimental structure from a small number of closest-packed structures. All calculations were performed on the Ohio Supercomputer Center's Cray Y-MP.
Advisors/Committee Members: Klopman, Gilles.
Keywords: Predicting crystal structure organic molecular materials
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15.
Challa, Jagannadha Reddy.
Electronic and Vibrational Dynamics of Heme Model Compounds-An Ultrafast Spectroscopic Study.
Degree: PhD, Chemistry, 2007, Case Western Reserve University
► The ultrafast electronic and vibrational dynamics of a model five-coordinate, high-spin heme…
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▼ The ultrafast electronic and vibrational dynamics of a model five-coordinate, high-spin heme FeIIOEP-2MeIm, following excitation in the Soret band, have been studied in a coordinated fashion using ultrafast transient absorption, time-resolved Stokes and anti-Stokes resonance Raman spectroscopies. Electronic excitation on the blue side of the Soret band region led to sub-100 fs S2→S1, followed by 800 fs nonradiative decay to a vibrationally hot, nonthermal ground state species S0*. S0* then evolved to the thermally equilibrated ground state species S0 on ~10 ps timescale. The initial accepting modes during the S1→S0 internal conversion underwent rapid vibrational relaxation evidenced by 1-3 ps decay of transient anti-Stokes signals. Comparison to other studies in heme proteins where the initial excited electronic state was prepared by ligand photolysis led to insight into the state dependence of vibrational dynamics in hemes. The ultrafast dynamics of a six-coordinate low-spin heme FeIIOEP-(Im)2 were studied following photolysis of one of the imidazole ligands upon electronic excitation. No detectable vibrationally hot six-coordinate ground state heme is observed, indicating the intrinsic quantum yield of the photolysis to be close to unity. The intramolecular vibrational relaxation is the major contribution to the photoproduct cooling on the order of 0.6 to 4.5 ps time scale. The intermolecular vibrational cooling has a lifetime of approximately 10 ps. On average 75% of the photolysed ligand geminately recombines on the time scale of 10-20 ps strongly overlapping with the vibrational cooling dynamics. In addition to the two heme compounds, the effect of methyl groups on the vibrational relaxation processes of para-nitroaniline (PNA) was studied. Minimal impact upon electronic dynamics, significant impact upon vibrational dynamics was observed in 2-methyl, 2, 6-dimethyl and N, N-dimethyl PNA compounds. NO2 group wagging overtone (~1495 cm-1) acts as the coupling and primary accepting mode during internal conversion in all four compounds. N-methyl substitution increases vibrational cooling lifetimes, phenyl ring substitution populates two new low frequency ring vibrations not present in PNA or N, N-dimethyl PNA. Anti-Stokes intensity decay and peak-shift evolution yield different lifetimes. Off-diagonal anharmonic coupling to populated low frequency motions of the phenyl are likely to be important.
Advisors/Committee Members: Simpson, Miriam Cather.
Subjects: Chemistry, Physical
Keywords: Heme; Push-pull chromophore; Vibrational relaxation; Vibrational cooling; Time-resolved spectroscopy; Pump-probe method; Transient absorption; Time-resolved Resonance Raman spectroscopy
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16.
Chang, Kieyoung.
Stereocontrolled functionalization of dienes using organoiron chemistry.
Degree: PhD, Chemistry, 1994, Case Western Reserve University
► Conversion of η4-cycloheptatriene-Fe(CO)2P(OPh)3 (2.23) to cycloheptadienone-Fe(CO)2P(Ph)3 (2.25) was accomplished by hydroboration/oxidation followed…
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▼ Conversion of η4-cycloheptatriene-Fe(CO)2P(OPh)3 (2.23) to cycloheptadienone-Fe(CO)2P(Ph)3 (2.25) was accomplished by hydroboration/oxidation followed by Swern oxidation. Methylation and hydroxylation of the enolate from 2.25 proceeds with complete stereoselectivity, anti to the metal moiety, and introduction of two methyl or hydroxyl groups at the α and α′ positions was accomplished in high overall yield. Reduction of dialkylated ketone 2.30 occurs with high stereoselectivity and is controlled by the boat conformation adopted by this coplex. The stereochemistry of the corresponding protected alcohol complex 2.34 was confirmed by single crystal X-ray structure determination. Demetallation of this complex, followed by stereocontrolled oxygenation and Mitsunobu reaction, then ring cleavage provides methodology for the construction of a C(9)-C(14) subunit of calyculin A. Stereoselective cuprate addition to the enone 2.85, syn to the methoxymethyl ether group, gives the cycloheptanone derivative 2.86 Hydroxylation of an enolsilane obtained from the cuprate adduct on 2.85, followed by reduction and ring cleavage, provides methodology for the construction of a C(19)-C(25) subunit of swinholide A. Asymmetric complexation of dienoic acid amides, derived from chiral amines, were st udied. Syntheses of dienoic acid amides proceed by the reaction of dienoic acid with chiral secondary amines such as Evans' oxazolidinone, (-)-(2R,5R)-dimethylpyrrolidine, or (S)-(-)-α , α-diphenyl-2-pyrrolidinemethanol. Complexation of the dienoic acid amide 4.34 occurs with complete stereoselectivity, anti to the substituent, to give the complex 4.41 in optically pure form. The stereochemistry of the complex 4.41 was determined by single crystal X-ray structure determination. ftn*Please refer to dissertation for diagrams
Advisors/Committee Members: Pearson, Anthony J.
Subjects: Chemistry, Organic
Keywords: Dienes; Organoiron chemistry; Stereocontrolled
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17.
Chen, Chien-Chih.
Controlled Flow Cavitation Technology For Use In Pharmaceutical Processing Applications And Its Commercialization Plan.
Degree: MS, Chemistry, 2012, Case Western Reserve University
► Many new drugs fail to pass clinical trials every year because of…
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▼ Many new drugs fail to pass clinical trials every year because of poor bioavailability. More than 40% of those New Chemical Entities fail to reach commercialization due to poor solubility. Nanotechnology, which can increase the active surface area, often is employed to improve the solubility of drugs. However, existing technologies using top-down approaches such as grinding, milling, and homogenization have issues of inconsistent particle size distribution, batch contamination, scalability, and high maintenance costs. There is a need to develop a bottom-up nanotechnology approach. This thesis focuses on the development and commercialization of GenSyn’s particle engineering capabilities using in-house Controlled Flow Cavitation (CFCâ„¢) Technology for its use in pharmaceutical processing. Based on the initial results, the commercialization of GenSyn’s particle engineering capabilities is considered feasible.
Advisors/Committee Members: Lee, Irene.
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18.
Cheng, Shih-Song.
Surface modification with siloxane anchored self-assembled monolayers.
Degree: PhD, Chemistry, 1994, Case Western Reserve University
► Long chain trichlorosilyl terminated surfactants have been used to modify surfaces of…
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▼ Long chain trichlorosilyl terminated surfactants have been used to modify surfaces of different substrates such as Si, Ge, and ZnSe by forming self-assembled monolayers on these surfaces. Four different kinds of studies of these systems are described in this thesis: (i) The kinetics for the formation of an alkylsiloxane monolayer film is monitored by FTIR-ATR and a Langmuirian model has been used to fit the FTIR-ATR results. The Langmuirian model indicates that the rate of film formation is proportional to the unoccupied sites available for the surfactant molecules. (ii) Surfaces coated with monolayers containing ω-carboxylic acid groups have been developed. The ionization of carboxylic acid groups bound to the surface is studied by in situ FTIR-ATR. The results indicate that the extent of ionization of the surface and near-surface carboxylic acid groups at a given pH differs from that in bulk-phase liquid and the carboxylic acid groups become less acidic when packed on the surface. A model based on the neutral oligomer of the acid groups is used to fit the in situ FTIR-ATR results. (iii) A series of fluoroketone and fluoroalcohol modified surfaces have been created. The wetting properties of these monolayer coated surfaces are characterized by contact angle measurements and ex situ FTIR-ATR. The relative reduction rates of the carbonyl groups in ho mogeneous solution are compared to those of the self-assembled monolayers. (iv) Self-assembled monolayers have shown potential as coatings for biomaterials for implants. Previous studies suggested that surfaces with different compositions modulate the conformation of fibronectin and thus affect the differentiation response of fibroblasts and neuronal cells in a cell type-specific pattern.32-34 Using aqueous FTIR-ATR we have directly evaluated that the conformation of adsorbed fibronectin depends on the composition of the self-assembled monolayer coating. Our results clearly demonstrate a surface dependent conformational change for fibronectin which correlates with the independent biological measurements of cell behavior on these surfaces
Advisors/Committee Members: Sukenik, Chaim N.
Subjects: Chemistry, Organic
Keywords: Surface modification; Siloxane; Monolayers, self-assembled
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19.
Cheng, Yu.
Gold Nanoparticles as Drug Delivery Vectors for Photodynamic Therapy of Cancers.
Degree: PhD, Chemistry, 2011, Case Western Reserve University
► Gold nanoparticle-drug conjugates have attracted increasing attention in drug delivery for photodynamic…
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▼ Gold nanoparticle-drug conjugates have attracted increasing attention in drug delivery for photodynamic cancer therapy. The nanoparticle acts as a water-soluble and bio-compatible platform that allows the delivery of hydrophobic drugs to the site of therapy. Due to the favorable surface area, hundreds of molecules can be attached to a 5 nm gold nanoparticle. More importantly, the versatile nanoparticle surface plays a vital role in targeted drug delivery. In this dissertation, we focus on efficient drug vectors for cancer therapy by synthesizing PEGylated gold nanoparticle-phthalocyanine conjugates. Both covalent and non-covalent drug binding can be achieved by designing the functionality of the nanoparticle surface. Due to the design of the gold nanoparticle carrier, using amphiphilic polymers, the drug delivery can be facilitated based on its size and the enhanced permeability and retention in the tumor tissue. Compared to the covalent approach, the non-covalent delivery approach of the hydrophobic photodynamic therapy drug Pc 4 through gold nanoparticles has provided rapid release and enhanced photocytotoxicity in cancer cells. In vivo studies in cancer bearing mice have shown an efficient deep penetration of the drug into the target tumors by the nanoparticle carriers within hours. In addition, controlled drug delivery system using visible-NIR light is achieved by a masked Pc 4-gold nanoparticle conjugate system. Targeted drug delivery can be achieved by modification of the carrier surface with active targeting ligands. After modification of the gold nanoparticle-Pc 4 conjugates with an EGF peptide, drug uptake into the tumor cells is dramatically improved due to the combination of active and passive targeting compared to untargeted conjugates. A 10-fold increase of the drug accumulation in a brain tumor was observed for the targeted drug delivery system. This shows that the designed gold nanoparticle-based drug delivery vector is able to cross the blood brain tumor barrier to address the brain tumor owning to the EGF targeted effect. The biodistribution of the drug and gold nanoparticles in vivo was investigated over a time frame of seven days. The biodistribution of the drug was studied by monitoring its intrinsic fluorescence in the organs and the gold nanoparticle concentrations in the corresponding organs have been quantified as well. Both gold nanoparticles and the drug can be removed from the body through renal clearance and the hepatobiliary system within days after drug administration.
Advisors/Committee Members: Burda, Clemens.
Subjects: Chemistry
Keywords: gold nanoparticles; drug delivery; cancer; photodynamic therapy; targeted drug delivery
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20.
Chen, Rongrong.
Applications of scanning probe microscopies in electrocatalytic systems.
Degree: PhD, Chemistry, 1993, Case Western Reserve University
► The objective of this thesis research is to understand the structures of…
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▼ The objective of this thesis research is to understand the structures of electrocatalysts adsorbed on an electrode surface for an oxygen reduction electrocatalytic system using scanning tunneling microscopy (STM), atomic force microscopy (AFM), and electrochemical techniques. The work includes: (1) applications of ex-situ and in-situ STM and AFM techniques to characterize the surface structure of a highly ordered pyrolytic graphite (HOPG) electrode, which is the substrate used for the adsorption of electrocatalysts; (2) characterization of the molecular orientation of electrocatalysts adsorbed on an HOPG electrode surface; (3) determination of the molecular structures of polymeric transition-metal phthalocyanines and comparison of the electrocatalytic activities with corresponding monomers to gain insight into the critical factors controlling oxygen reduction. The Co- and Fe-tetrasulfonated phthalocyanines (TsPc) adsorbed on an HOPG graphite surface were studied by cyclic voltammetry, AFM and in-situ STM. Based on a set of AFM topographies obtained in air for macrocyclic molecules preadsorbed on an HOPG surface at monolayer coverage, it is concluded that both Co- and Fe-TsPc molecules are oriented with their molecular planes forming an angle to the HOPG substrate surface. The tilted angles can be estimated according to the molecular size and corrugation heights of the molecular features obtained. With macrocyclic species in an H2SO4 electrolyte solution saturated with air, in-situ STM and AFM images showed that the macrocyclic molecules are oriented parallel to the HOPG substrate surface. Clear individual CoTsPc molecular structures were revealed, which agreed well with the structure simulated with a molecular modeling program. Different orientations observed for the ex-situ AFM and in-situ STM and AFM measurements are explained due to the various specimen preparation procedures. Voltammetry of the polymeric phthalocyanines and the corresponding monomers preadsorbed on an ordinary pyrolytic graphite (OPG) surface showed comparable redox properties. The studies of oxygen reduction catalyzed with the macrocyclic molecules preadsorbed on an OPG surface also showed similar electrocatalytic activities between the polymers and corresponding monomers. It is concluded that the interactions of oxygen molecules with the macrocycle molecules preadsorbed on an graphite electrode surface are essentially the same for the polymers and monomers. (Abstract shortened by UMI.
Advisors/Committee Members: Yeager, Ernest B.
Subjects: Chemistry, Physical
Keywords: scanning probe microscopies; electrocatalytic systems
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21.
Chen, Xi.
Oxidatively Truncated Ether Phospholipid: Synthesis, Detection in LDL and Biological Activities.
Degree: PhD, Chemistry, 2008, Case Western Reserve University
► Heart disease and stroke are the most common causes of death in…
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▼ Heart disease and stroke are the most common causes of death in Westernized societies. Mounting evidence over the past decade suggests that oxidation of low density lipoprotein (LDL) plays an important role in the initiation and promotion of atherosclerosis. Platelet-activating factor (PAF) is a phospholipid with potent, diverse physiological actions, particularly as a mediator of inflammation. Some PAF-like phospholipids, formed during the oxidative modification of LDL, i.e., oxPAF, may act via the PAF receptor. In this work, a diverse family of oxidatively truncated ether phospholipids was prepared to facilitate the identification and biological testing of these compounds that are generated through oxidative cleavage of polyunsaturated phospholipids. Using HPLC with on-line tandem mass spectrometry, the formation of these phospholipids in oxidation reactions of docosahexaenoate, arachidonate and linoleate esters of 1-alkyl-2-hydroxy-sn-glycero-3-phosphocholine(lyso-PAF) was demonstrated. The oxidation of LDL by myeloperoxidase (MPO) also produced oxidized alkyl acyl phosphocholines (oxPAFs). We discovered a profound influence of membrane environment on the stability of γ-hydroxyalkenal oxPAFs. Under autoxidative conditionsthe aldehyde group of γ-hydroxyalkenal oxPAFs is stable in small unilamellar vesicles (SUVs) composed of saturated diacyl-PCs, but is rapidly oxidized in SUVs that contain 1 equivalent of the linoleic acid ester of 2-lysophosphatidylcholine (LA-PC). Various oxPAFs are potent platelet-activating factor receptor (PAFR) agonists, such as OB-PAF, S-PAF, KHdiA-PAF, KOdiA-PAF and HOHA-PAF. Several of these oxPAFs, at micromolar concentrations, can initiate calcium accumulation and these responses were increased in a concentration-dependent way. The oxidatively truncated alkyl acyl phosphocholines tested were all biologically active as mitochondrial depolarizing agents. Apoptosis was initiated upon exposure of HL 60 cells to these oxPAFs. The potencies of these oxPAFs apparently show structural dependences. With the recent development of soft ionization methods, electrospray ionization (ESI)has become an informative method for detecting oxidized phospholipids. In the present study, the fragmentation pattern of a series of oxidatively truncated PAF analogs, formed during oxidation of alkyl phosphocholines, was systematically investigated using negative mode ESI-MS/MS. In comparison with the positive ion mode, the negative mode provides more structural information, obviating the need for derivatization. Negative ion MS fragmentation readily distinguishes structurally similar acyl phosphocholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS) oxidative products without the need for phospholipase A1 treatment, that is commonly used to distinguish alkyl from acyl phosphatidylcholines.
Advisors/Committee Members: Salomon, Robert G.
Keywords: PAF; oxPAF; PHOSPHOLIPID; HOHA-PAF; 2H; OB-PAF; LPAF
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22.
Chen, Xiaobo.
Synthesis and Investigation of Novel Nanomaterials for Improved Photocatalysis.
Degree: PhD, Chemistry, 2005, Case Western Reserve University
► Since the discovery of the photocatalytic splitting of water on TiO2 electrode…
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▼ Since the discovery of the photocatalytic splitting of water on TiO2 electrode by Fujishima and Honda in 1972, enormous effort has been spent on the study of TiO2 under light illumination, due to its various potential applications, such as photovoltaics and photocatalysis. The optical properties, in particular the absorption, of TiO2 are essential to its photon-driven applications. Typically, TiO2 absorbs in the UV regime, which is only a small fraction of the sun’s energy (< 10%). The performance of TiO2 can be enhanced by shifting the onset of its absorption from the UV to the visible region. Metals have been employed to tune the electronic structure of TiO2-based material. The photocatalytic reactivity of metal-doped TiO2 depends on many factors, and metal doping can result in thermal instability and increased carrier trapping. The desired visible-light absorption of TiO2 can be also achieved by using main group dopants. In this dissertation, different non-metal elements, C, N and S, are incorporated to the lattice of TiO2 to induce the absorption in the visible-light regime. Both bottom-up and top-down methods are used to synthesize these doped TiO2 nanoparticles. The optical, physical, electronic and photocatalytic properties of these doped TiO2 nanoparticles are explored with different techniques. The relationship between the optical, electronic and photocatalytic properties are elucidated. The photocatalytic performance of the doped TiO2 nanoparticles is applied not only to the model photodegradation of methylene blue, but also on other industrial dyes under natural sun-light illumination. The non-metal-doped TiO2 nanoparticles demonstrated improved photocatalytic performance over the non-doped TiO2 nanoparticles, i.e. in the visible-light regime. On the other hand, as the size of nanoparticles decreases, the surface-to-volume ratio increases dramatically (~ 1/r), so does the surface area (1/r2). The high surface area brought by the small size of nanoparticles becomes more important for the optical and electronic properties of nanomaterials, compared to the bulk materials. Besides the well-know quantum-confinement effect, the surface effect should be taken into account for small nanoparticles. Thus in this dissertation, the synthesis and properties of II-VI (CdSe, CdSe/CdS) semiconductor nanoparticles are investigated to elucidate the surface effect on the properties of nanoparticles, which helps to understand the photocatalytic property of TiO2 nanomaterials, since the main catalytic reactions occur on the surface. The gradual crystallization of small nanoparticles, as well as its effect on the optical properties is elucidated. The interface strain/stress in the CdSe/CdS core/shell system is explored on their optical properties, as well as the hot carrier relaxation dynamics in CdSe nanoparticles.
Advisors/Committee Members: Burda, Clemens.
Keywords: TiO2; CdSe; Nanoparticles; doped TiO2; eV; Nanocrystals
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23.
Chen, Xufang.
Synthesis and Characterization of Molecules and π-Conjugated Materials Containing Low-Coordinate Phosphorus.
Degree: PhD, Chemistry, 2005, Case Western Reserve University
► There are many similarities between phosphaalkenes and phosphaalkynes, low-coordinate phosphorus compounds containing…
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▼ There are many similarities between phosphaalkenes and phosphaalkynes, low-coordinate phosphorus compounds containing RP=CR2 and RC≡P functional groups, and olefins (R2C=CR2), their unsaturated carbon analogues. Phosphanylidene-σ4-phosphoranes have proven to be phospha-Wittig reagents that react with aldehydes to generate phosphaalkenes. Using the phospha-Wittig reaction, phosphaalkene oligomers and polymers were synthesized and characterized and shown to exhibit bathochromic shifts in comparison with related olefins. meta-Terphenyl phosphaalkynes have also been prepared. These materials were prepared for possible synthesis of transition metal complexes of phosphaalkynes. In addition, phosphanylidene-σ4-phosphoranes react with ortho-quinones to form 1,3,2-dioxaphospholanes or β-phosphaenones depending on the nature of the quinone. Furthermore, meta-terphenyls containing methoxy groups were investigated which have different properties from those having alkyl substitutents. 2,6-Dimesitylphenyl difluorophosphine was synthesized and characterized and found to be relatively inert to reduction by active magnesium.
Advisors/Committee Members: Protasiewicz, John D.
Keywords: phosphaalkenes; phosphaalkynes; Phosphanylidene-σ4-phosphoranes; phospha-Wittig reaction; phosphaalkene oligomers and polymers; meta-Terphenyl phosphaalkynes; 1,3,2-dioxaphospholanes; β-phosphaenones
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24.
Chen, Yanwen.
Structural Basis of Substrate and Inhibitory Activity of Bovine Plasma Amine Oxidase.
Degree: PhD, Chemistry, 2008, Case Western Reserve University
► The copper-containing amine oxidases, like bovine plasma amine oxidase (BPAO), carry out…
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▼ The copper-containing amine oxidases, like bovine plasma amine oxidase (BPAO), carry out a transaminative oxidation of primary amines to aldehydes via use of an active site Tyr-derived 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor. Propargylamine is a potent inactivator of BPAO (IC50 = 3 µM), possibly through active-site modification by the α,β-unsaturated aldehyde turnover product, but the simple structure is expected to confer low selectivity. On the basis of the finding by previous students that certain extended conjugation analogs such as 1,6-diamino-2,4-hexadiyne and 3-cyanopropargylamine preserve strong inactivation potency, other extended conjugation analogs of propargylamine were evaluated. In particular, 1-amino-2,4-hexadiynes with a 6-OH rather than 6-NH2 group were found to be potent inhibitors. Structure-substrate relationships for a broad family of monoamines, diamines, and polyamines were investigated to reveal information on the binding modes to BPAO. The results indicated that (i) monoamines only bind to the hydrophobic wall at the entrance to the active site, (ii) the alkyl chain of long-chain diamines (≥ 8 carbons) would also bind to the hydrophobic region near the active site, while their terminal amino groups can interact electrostatically with D445', (iii) the medium-chain diamines (6-7 carbons) were moderate substrates because their alkyl tether can barely extend beyond the hydrophobic region and can only interact weakly with D445', (iv) short chain diamines (≤ 5 carbons) are weak substrates because the terminal amino groups in these cases would reside in a hydrophobic region that prefers neutral groups, (v) triamines like spermidine will bind to the enzyme with the middle amino group being neutral, and where the terminal amino groups should have favorable electrostatic interactions with the D445' if the total chain length is sufficiently long, and (vi) one of the internal amino groups (AM2) of spermine should be neutral for optimal binding to the enzyme, where the AM3 and AM4 should have interaction with D445' and D179, respectively, in their protonated form. The bis-quaternary diamines are found to be a new class of potent competitive inhibitors of BPAO. The bis-quaternary diamines are proposed to bind to two ancillary cation binding sites: D445' and D179, in contrast to only one binding site for monoquaternary amines. The longer chain bis-quaternary diamines have higher inhibitory potency, suggesting that their alkyl tethers can have some hydrophobic interactions with the hydrophobic region between D445' and D179, and this region is different from the hydrophobic "wall" to which monoamines bind. The C3-alkyl-extended analogs of propargylamine were evaluated and their inhibitory potencies were found to be much lower than propargylamine itself, though the methyl- and ethyl- extended analogs exhibited higher substrate activity than propargylamine. This result prompted an evaluation of possible high substrate activity for other analogs of potent mechanism-based inhibitors that displayed anomalously low inhibitory potency. The results showed that there is no obviously predictable correlation between substrate activity and inhibitory potency. A series of 3-(trialkylsilyl)propargylamines were investigated as possible pro-drugs for delivery of propargylamine as an inhibitor of copper amine oxidases. The mechanism involves hydrolysis of the acetylenic C-Si bond. The hydrolysis speed and the aqueous/lipid disribution can be adjusted by variation of the alkyl substituents on silicon.
Advisors/Committee Members: Sayre, Lawrence.
Subjects: Chemistry
Keywords: BPAO; diamines; propargylamine; NMR; enzyme
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25.
Chen, Youjiang.
Fundamental Aspects of Electrocatalysis at Metal and Metal Oxide Electrodes.
Degree: PhD, Chemistry, 2011, Case Western Reserve University
► This work explores certain aspects of the behavior of interfacial systems of…
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▼ This work explores certain aspects of the behavior of interfacial systems of relevance to areas fundamental and technical interest from a strictly physical electrochemistry viewpoint. Attention was focused on four distinct topics: i. The dynamics of charge injection into/from iridium oxide (IrOx) films using a combination of simultaneous chronocoulometry and in situ time-resolved normalized reflectance spectroscopy. This tactic enables charge storage contributions derived from capacitive (due to the finite conductivity of the film) and pseudocapacitive processes (due to changes in oxidation state of Ir sites in the film) to be independently determined. The rates of charge-discharge dynamics were found to be faster in alkaline compared to acidic aqueous electrolytes. These films displayed no detectable activity for oxygen reduction in neutral phosphate buffer (pH = 7) over a potential range of about 0.9 V, allowing 90% of the total charge stored in the film to become available for functional neural stimulation without producing harmful oxygen-derived species. ii. The development and implementation of solution phase ohmic microscopy as a spatially resolved probe of ideal polarizable electrode|electrolyte interfaces by two microreference electrodes to monitor the potential drop in the solution associated with the passage of current through the interface using. iii. The rational design and assembly of electrocatalytic interfaces capable of performing sequential transfers of multiple electrons using the reduction of nitrate in a weakly buffered acetate solution as a model system. The specific electrode architecture involved Au nanoparticles supported on a hemin modified glassy carbon surface. Polarization of the electrode in solutions containing a Cd salt at negative potentials promoted reduction of nitrate to nitrite which was then reduced on the Hm modified GC surface to yield further reduced products including hydroxylamine. iv. Fundamental studies of the oxidation of hydroxylamine on Au surfaces in pH 4 buffered solutions employing rotating disk and ring disk electrodes and normal incidence differential reflectance spectroscopy. The results obtained provided evidence that the oxidation of hydroxylamine proceeds via two sequential steps in the potential range negative to the onset of Au oxide formation to yield first nitrite and then nitrate products.
Advisors/Committee Members: Scherson, Daniel A.
Subjects: Chemistry
Keywords: Electrocatalysis; Iridium Oxide; Charge Injection Dynamics; Oxygen Reduction; Ohmic Microscopy; Nitrate; Nitrite; Hydroxylamine; Hemin Modification; Cadmium Underpotential Deposition
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26.
Chiang, Ray-Kuang.
Calcium-based sorbents for flue gas desulfurization.
Degree: PhD, Chemistry, 1995, Case Western Reserve University
► A literature survey of the known calcium silicates was carried out. Eight…
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▼ A literature survey of the known calcium silicates was carried out. Eight of these silicates were made or purchased and their ability to take up SO 2 was examined. The calcium silicate hydrate C-S-H, when in a porous form, was shown to take up SO 2 well. A sorbent composed largely of such C-S-H was prepared by vigorously agitating high water-to-solids slurries of Ca(OH) 2 and diatomite, perlite or pumice at moderate temperatures. A related sorbent composed of porous C-S-H and Ca(OH) 2 in which the Ca(OH) 2 was embedded in the C-S-H was also prepared. This sorbent was made by agitating at a moderate temperature a high water-to-solids slurry of Ca(OH) 2 and an amount of fumed silica sufficient to react with only part of the Ca(OH) 2 . Another related sorbent composed largely of porous C-S-H, Ca(OH) 2 and the aluminate phase AFm was made by vigorously agitating a high water-to-solids slurry of type I portland cement at a moderate temperature. Still another related sorbent composed largely of porous C-S-H and a hydrotalcite-like phase was made by vigorously agitating a high water-to-solids slurry of ground granulated blast furnace slag at a moderate temperature. In the latter three sorbents, the Ca(OH) 2 , the Ca(O H) 2 and AFm, and the hydrotalcite-like phase respectively all contribute to the activity of the sorbents. All four sorbents show excellent SO 2 uptake and Ca utilization values compared to those of the fly ash-Ca(OH) 2 sorbent and those of a reference Ca(OH) 2 . Limits are placed on the temperature ranges and vigor of agitation ranges that can be used in the preparation of these four sorbents by competing reactions. The reactions leading to these sorbents are heterogeneous and complex. Some suggestions as to the nature of these reactions based in part on studies of model compounds are offered
Advisors/Committee Members: Kenney, Malcolm E.
Subjects: Chemistry, Inorganic
Keywords: Sorbents, calcium based; Desulfurization
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27.
Chin, Yuan-Tung.
Studies of passivation of iron and its breakdown by chloride ions using in situ spectroscopic ellipsometric technique.
Degree: PhD, Chemistry, 1990, Case Western Reserve University
► The passive film on iron and its breakdown by chloride ions in…
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▼ The passive film on iron and its breakdown by chloride ions in borate buffer (pH 8.4) has been studied using in situ UV/VIS spectroscopic ellipsometry and fast step potentiostatic method. A new highly stabilized light source and an improved computer algorithm have been developed. Interpretation of the ellipsometric measurements are based on the three parameter (3-P) method, which was used to obtain unambiguous solutions for the film. Errors in the resultant 3-P solutions were found to be caused mainly by the fluctuation and random noise in the reflectivity measurement. A combined 3-P/2-P method was used to minimize this problem. Some insights into the use of the three parameter method are presented. It is concluded that the accuracy of the ellipsometric measurements depend primarily on the accuracy of the film thickness measurement, which in turn depends on the accuracy of the relative reflectivity measurement. Optical spectra of passive films on iron formed at various potentials are presented. Several distinct features of the spectra were observed: (1) a broad absorption band ranging from 2.5 to 5 eV (photon energy); (2) an absorption peak at 3.5 eV which exists at all potentials but becomes smaller at lower potentials, which is attributed to a Fe2p→O3d transition; (3) some unresolvable background absorption; and (4) an evident structure above 5 eV. No fine structures were found. During the potentiostatic reduction in a potential region between 0.4 to 0.2, significant changes were observed in the optical constants. No spectral changes were observed on the passive film due to Cl-
Advisors/Committee Members: Cahan, Boris D.
Subjects: Chemistry, Physical
Keywords: passivation iron chloride ions situ spectroscopic ellipsometric technique
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28.
Choi, Jaewoo.
Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids.
Degree: PhD, Chemistry, 2010, Case Western Reserve University
► Identification of an interaction between the scavenger receptor CD36 and oxidized phosphatidylserines…
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▼ Identification of an interaction between the scavenger receptor CD36 and oxidized phosphatidylserines (oxPSs) can offer insight into the mechanism of the externalization of PSs which is essential for triggering anti-inflammatory responses in macrophages. To determine relative affinities for CD36, a diverse family of oxidatively-truncated PSs possessing various oxidatively truncated sn-2 acyl groups, i.e.,ω-carboxylalkanoyl, ω-oxoalkanoyl, and γ-keto-α,β-unsaturated carbonyl, were efficiently synthesized (Chapter 2). Elevated levels of sn-2-lysophosphatidylcholine (lysoPC) have been linked to cardiovascular complications, and some oxidized phosphatidylcholines undergo facile spontaneous non-enzymatic deacylation. This leads to the expectation that lipase-inhibiting drugs cannot completely prevent the release of lysoPC from oxidatively damaged phospholipids (Chapter 4). The decomposition of 4-hydroxy-7-oxohept-5-enoic acid ester of 2-lyso-phosphatidylcholine (HOHA-PC, t1/2 = 30 min) was more rapid than that of 5-hydroxy-8-oxo-6-octenoic acid ester of 2-lyso-phosphatidylcholine (HOOA-PC, t1/2 = 2 h) under neutral conditions (pH 7.4). In contrast, after 24 h, the decomposition of 9-hydroxy-12-oxododec-10-enoic acid ester of 2-lyso-phosphatidylcholine (HODA-PC), for which intramolecular transesterification is disfavorable since it requires formation of a 10-membered lactone, was only 50% complete. The decomposition of HOHA-PC to generate, inter alia, lysoPC occurs more readily (t1/2 = 30 min) under near-neutral conditions (pH 7.4) as compared to weakly acidic (t1/2 = 3 h at pH 6) or moderately acidic conditions (t1/2 = 6 h at pH 4). To investigate non-enzymatic spontaneous deacylation of oxidized PCs, efficient new syntheses of HOHA, HOOA and HODA-PCs were devised (Chapter 3). We postulated that 4-hydroxydocosahexaenoyl-phosphatidylcholine (4-HDHE-PC) was not detected previously in the singlet oxygen reaction product mixture (after reduction) because it is unstable owing to the proximity of the hydroxyl group to the ester carbonyl (Chapter 5). To support hypothesis, we demonstrated that 4-HDHE-PC undergoes spontaneous deacylation to form 4-hydroxydocosahexaenoic acid lactone and lysoPC. The formation of lysoPC and lactonized by-product was confirmed by LC/MS/MS. The rate of 4-HDHE-PC decomposition is affected by the reaction environment: deacylation was faster in homogeneous solution (t1/2 = 8 h at pH 7.4), a relatively more aqueous environment, than in heterogeneous solution (liposome, t1/2 = 15 h), where the oxidized acyl chain is buried in a relatively more hydrophobic environment.
Advisors/Committee Members: Salomon, Robert G.
Subjects: Chemistry
Keywords: Phosphatidylserines; lysophosphatidylcholine; nonenzymatic spontaneous deacylation
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29.
Ciurea, Diana Victoria.
Studies Towards the Total Synthesis of Ristocetin A and Orienticin C Aglycones.
Degree: PhD, Chemistry, 2008, Case Western Reserve University
► Vancomycin-related glycopeptides constitute a large family of clinically important antibiotics, used as…
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▼ Vancomycin-related glycopeptides constitute a large family of clinically important antibiotics, used as drugs of last resort in treating infections caused by methicillin-resistant Staphylococcus aureus. However, the frequency of vancomycin resistant pathogens has increased significantly over the past decade, prompting an interest in the development of synthetic and semi-synthetic glycopeptides. The research work presented in this thesis has been focused on the application of ruthenium-mediated SNAr methodology for the synthesis of diaryl ether linkages both inter- and intramolecularly. As described in chapter two, our efforts first targeted the synthesis of the F-O-G subunit 2.8 of ristocetin A via an intermolecular SNAr reaction between the phenolic OH of the Teoc protected F amino alcohol 2.9 and the chloro substituent of the amino alcohol corresponding to G ring 2.10. Considerable competing demetalation of the starting material G-ruthenium complex 2.10 occurred during the attempted coupling, which was overcome by stepwise addition of the solid G-ruthenium complex 2.10 to the reaction mixture increasing the yield of this transformation to 66% yield. Chapter three provides details for the construction of the intermediate 3.3, a tripeptido-arene-ruthenium complex, required for a projected synthesis of orienticin C aglycone 3.1. Also, a model study on ruthenium-mediated macrocyclization for the formation of the 16-membered diaryl ether ring 3.32 was investigated, assuring the applicability of this approach to the synthesis of orienticin C aglycone.
Advisors/Committee Members: Pearson, Anthony J.
Subjects: Chemistry, Organic
Keywords: Vancomycin; equiv; 1H; RISTOCETIN; Diaryl; OMe
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30.
Clark, Terri Roxanne Dular.
Oligomeric germanium phthalocyanine Langmuir-Blodgett films for microelectronics and molecular electronics.
Degree: PhD, Chemistry, 1993, Case Western Reserve University
► The synthesis and characterization of GePc (OSi(n- C6H13)3]2, ( n- C6H13)3SiOGePcOC(O)CCl3, (n-…
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▼ The synthesis and characterization of GePc (OSi(n- C6H13)3]2, ( n- C6H13)3SiOGePcOC(O)CCl3, (n- C6H13)3SiOGePcOH, ( n- C6H13)3SiO[ GePcO]2Si( n- C6H13)3, ( n- C6H13)3SiO[ GePcO]2C(O)CHCl2, and (n- C6H13)3SiO[ GePcO]2H are reported. On an HCl-acidified subphase of pH 4.2, (n- C6H13)3SiO[ GePcO]2C(O)CHCl2 gives a Langmuir monolayer of (n- C6H13)3SiO[ GePcO]2H having a molecular co-area of 1.55 nm2/molecule. The co-area of this monolayer varies with pH on unbuffered subphases. On hydrophilic substrates, (n- C6H13)3SiO[ GePcO]2H gives a Langmuir-Blodgett multilayer. This multilayer has been characterized by transfer ratio, X-ray photoelectron spectroscopy, Auger spectroscopy, polarized and unpolarized attenuated total reflectance Fourier transform infrared spectroscopy, polarized variable angle visible spectroscopy, ellipsometry, X-ray diffraction, and contact angle, resistance and current-voltage measurements. The results of this characterization work show that the multilayer is comprised of HOGePcOGePcOH molecules oriented with their rings parallel to the substrate surfaces. The monolayers of the HOGePcOGePcOH multilayer are ∼6.9 A thick. They probably are slightly wavy and not in full registry with their neighboring monolayers. The multilayer is free of a significant number of defects. It absorbs both strongly and anisotropically in the infrared and visible regions. The multilayer is a semiconductor and is probably a photoconductor. It is apparently lightly doped with O2. It is hydrophilic, stable in air and mechanically robust. The film may be useful for the fabrication of optical, microelectronic and molecular electronic devices
Advisors/Committee Members: Kenney, Malcolm E.
Subjects: Chemistry, Inorganic
Keywords: Langmuir-Blodgett films; Microelectronics and molecular electronics
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