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Nitric oxide (NO) has been extensively studied due to its importance as a signaling agent. More recently, the pharmacological benefits of nitroxyl (HNO) in the treatment of cardiovascular disease, cancer, and alcoholism have been discovered.That HNO readily dimerizes complicates analysis and necessitates the use of donors. Diazeniumdiolates (NONOates), which can release either NO or HNO, are particularly attractive in this regard. NONOates from primary amines release HNO at physiological pH, and since the few existing examples have relatively short half-lives, a major research goal was to extend the lifetime range. The effect of amine structure on the lifetimes of ionic primary amine NONOates having the general structure Na(RN(H)[N(O)NO]) was unexpectedly small. This prompted the use of O2-protecting group methodology as an alternate method to stabilize donors toward decomposition. A detailed analysis of the decomposition mechanisms of a representative ionic primary amine NONOate and its O2-protected derivative is presented.NONOates were used as analytical tools to compare several commonly-used methods for detection of HNO. While these methods are used routinely for qualitative analysis of HNO, optimization for quantitative measurements was difficult. To improve method sensitivity, an HPLC assay using the fluorogenic reagent o-phthalaldehyde was developed, which may ultimately allow detection of endogenously-produced HNO.HNO donors such as cyanamide have been utilized in the treatment of alcoholism through the inhibition of aldehyde dehydrogenase (AlDH), which is critical for ethanol metabolism. Cyanamide also releases cyanide, and alternate HNO donors are thus desired for this clinical use. The efficacy of NONOates in the inhibition of AlDH was assayed in purified yeast AlDH and in mouse liver homogenate. However, efficacy was limited in a mouse model, perhaps due to a lack of selective delivery. This drug discovery project provided useful information for the future development of potentially liver-selective HNO-releasing NONOates.Together, these studies demonstrate the utility of NONOates as biomedical research tools, with synthetic modifications allowing for the modulation of decomposition profiles. As analytical tools for the development of HNO detection methods and potential pharmaceuticals in the treatment of alcoholism, NONOates provide convenience and control as donors of NO and HNO.

The research described in this Dissertation is concerned generally with the exploration of the potential use of lanthanide elements in nanostructured materials for the purpose of modification of the magnetic and optical properties. This is explored through a focus on the development of lanthanide-containing iron oxide nanosystems. Our objectives of producing lanthanide containing nanostructured materials with potentially useful optical and magnetic applications has been achieved through the development of lanthanide-doped Fe3O4 and -Fe2O3 nanoparticles, as well as a unique core-shell magnetic-upconverting nanoparticle system.Necessary background information on nanomaterials, rationale for the study of lanthanide-containing iron oxide nanosystems and context for discussion of the results obtained in each project is provided in the Introduction Chapter. The syntheses of Fe3O4 nanoparticles doped with Eu(III) and Sm(III) are discussed, along with structural characterization and magnetic property investigation of products In Chapter 2. The following Chapter expands the study of lanthanide doping to -Fe2O3, a closely related yet distinct magnetic nanoparticle system. A completely different synthesis is attempted, and comparisons between the two systems are made.The development of novel synthetic methodologies used to create such products has yielded high-quality lanthanide-containing materials and are evidenced by TEM images displaying nearly monodisperse particles in each of our efforts. The modifications to the magnetic properties resulting from lanthanide doping include theobservation of ferromagnetism in the Fe3O4 system and increased magnetic saturation of -Fe2O3 nanoparticles, and are characterized by VSM and the visual observation of magnetic alignment of products. Our efforts towards developing a novel methodology capable of producing high quality Fe3O4 nanoparticles, and subsequent characterization of products, were published in the Journal of the American Chemical Society.Optically active, magnetic, core-shell nanoparticles are investigated in Chapter 4 for the potential uses in diagnosis and treatment of cancer. This multifunctional system uses Fe3O4 as a magnetic core, shelled by upconverting lanthanide-containing nanomaterials, and is rendered biocompatible through encapsulation of the core-shell structure by a silica shell. Added functionality is achieved through amine functionalization of the silica surface, with the goal of coupling the inorganic nanoparticle with drug targeting groups. TEM results indicate successful formation of the core-shell nanoparticles, and expected magnetic and optical properties are shown by visual observation and luminescence spectroscopy, respectively.

This dissertation reports on the development of a nonlinear surface spectroscopy and the observation of nonlinear optical phenomena using sputtered zinc oxide waveguides. The first is known as Surface Coherent Raman Spectroscopy, or SCRS, and is capable of monolayer sensitivity. The second, discovered during the development of SCRS, is optical limiting and a previously unobserved form of optical switching based on an absorptive nonlinear coupling mechanism. Overviews of the theories of waveguiding, linear coupling, and SCRS are given. Experiments showing that the spectrum of a monolayer coverage of molecules on the surface of a metal oxide waveguide can be obtained using SCRS are reported. For this purpose ZnO waveguides were fabricated using rf magnetron sputtering; the details of which are presented. The results of the characterization of these films, using an optical loss technique, Rutherford backscattering, and X-ray diffraction, are also presented. Experiments are described and data are presented to show the existence of optical limiting and optical switching phenomena in ZnO waveguides. The experimental dependence of these phenomena on input pulse energy, wavelength, temporal pulse width, and type of distributed coupling mechanism is described. Existing nonlinear distributed coupler theory is extended to include the effect of an absorptive nonlinearity and the results of this theory are used to explain some of the characteristic features of the experimental results. A value of n₂ ≅ 2 x 10⁻¹⁶ m²/W for the nonlinear coefficient of sputtered ZnO films is obtained.

The properties of superconducting YBa₂Cu₃O₇₋(δ) thin films have been studied. Films have been prepared by multilayer deposition followed by ex situ furnace annealing. Deposition consists of a combination of dc triode sputtering from metallic targets of Y and Cu and thermal evaporation from a BaF₂ source. Superconducting and structural properties of the films strongly depend on the annealing conditions. Several heat treatment cycles were investigated, as well as different compositions. Best results were obtained for films deposited on (100) SrTiO₃ substrates, exhibiting T(c)(onset) as high as 92 K and zero resistance by 85 K. The second part of this dissertation examines the properties of ceramic Nd₂₋ₓCeₓCuO₄₋(δ) and Nd₁ͺ₈₅Ce₀ͺ₁₅(Cu₁₋(y)Zn(y))O₄₋(δ) bulk samples. Superconducting properties are examined as a function of x and y. Accurate (± 0.001 Å) lattice parameter calculations are performed from experimental x-ray diffraction data. Comparisons with previous zinc-doping studies in the hole superconducting material La₁ͺ₈₅Sr₀ͺ₁₅CuO₄₋(δ) are made. Theoretical implications and the question of electron-hole symmetry in the copper oxide superconductors are also discussed.

This dissertation is a study in how heme facilitates biology using two heme proteins as examples. I write about my mechanistic studies on Cimex nitrophorin and preliminary studies on Ecdysone inducible protein 75, respectively. Nitrophorins are salivary heme proteins used by bloodfeeding insects to deliver NO to the victim, leading to vasodilation and antihemostasis. The bedbug nitrophorin cNP, a thiolate heme protein accomplishes this via an unusual heme-assisted S-nitrosation reaction, requiring proximal ligand cleavage. This dissertation explores this mechanism through mutational, crystallographic and transient kinetic approaches. I present the detailed investigation of the two NO binding events, one at the heme and the other at the proximal cysteine. The heme nitrosyl shows marked pH dependence arising out of the apparent protonation of the proximal cysteine ligand, a feature crucial to cNP function. The structures and spectroscopy of cNP mutant proteins reveal the SNO modification to be regulatory in nature. Laser flash photolysis measurements and the structures of mutant proteins reveal the negative influence of steric hindrance on SNO stability.Studies of insect embryogenesis and metamorphosis reveal the regulatory role of the hormone ecdysone via its target, the ecdysone receptor. Ecdysone triggers expression of several nuclear receptors in a time and tissue dependant fashion, which in turn carry out gene regulation. Ecdysone inducible protein 75 (E75), a nuclear receptor and an early ecdysone responsive gene product, regulates a subset of the developmental activities attributed to ecdysone. We are investigating E75 from Aedes aegypti to uncover its role in ecdysone signaling in mosquitoes. I have expressed and partially purified the full length protein using the baculovirus driven expression in SF9 cells, and purified to homogeneity the heme binding domain resolubilized from inclusion bodies obtained by expression in E. coli. Preliminary characterization of the proteins using UV-visible spectroscopy indicates that E75 has a b type heme with a low spin six-coordinate ferric iron. In the E75 heme binding domain, the heme exhibits an unstable ferrous state and only binds NO and CO at high non-physiological levels. These data place into doubt the suggested roles for E75 as a gas regulated transcription regulator.

Nitric oxide (NO) has been shown to both suppress and promote tumor growth, depending in part on concentration. Exogenous delivery of NO may lead to tumor suppression. Recent studies have proposed ruthenium nitrosyl complexes as catalytic donors of NO in reductive environments. Catalytic donation can provide a long-term, elevated NO flux compared to single use donors. Site-specific delivery is desirable to reduce systemic side effects, such as lowering of blood pressure. Three new ruthenium nitrosyl complexes were synthesized to impart site-specificity through amide coupling to polymers, silica nanoparticles, iron oxide nanoparticles and antibodies. The catalytic activity of new and existing compounds was then assessed. However, upon one-electron reduction of ruthenium nitrosyl complexes, insignificant amounts of NO were detected, suggesting an alternative mechanism than that proposed in prior reports. The mechanism of [Ru(EDTA)NO]²⁻ decay was more thoroughly analyzed. Spectrophotometric decay of [Ru(EDTA)NO]²⁻ indicates that one or multiple nitrogen oxide species are released. Previous studies have suggested a disproportionation mechanism leading to the generation of more highly reduced species such as N₂ and NH₄⁺. Experiments were designed to analyze possible decomposition products such as [Ru(EDTA)NO]⁻ and [Ru(EDTA)H₂O]²⁻. A disproportionation mechanism was determined likely. Decomposition of [Ru(EDTA)NO]²⁻ was also observable following reductive nitrosylation of [Ru(EDTA)H₂O]⁻ in the presence of HNO. The decomposition product, [Ru(EDTA)H₂O]²⁻, was observed through the binding of pyrazine (pz) or dipyridine (bipy) and formation of [Ru(EDTA)pz]²⁻ or [Ru(EDTA)bipy]³⁻. Formation of [Ru(EDTA)bipy]³⁻ or [Ru(EDTA)pz]²⁻ via reductive nitrosylation of [Ru(EDTA)H₂O]⁻ also provides an indirect method of HNO detection that is selective from NO.

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