Pairing of a consensus sequence of the precursor (pre)-mRNA intron with a short region of the U2 small nuclear (sn)RNA during assembly of the eukaryotic spliceosome results in formation of a complementary helix of seven base pairs with a single unpaired adenosine, whose 2' OH initiates the nucleophilic attack at the pre-mRNA 5' splice site during the first step of splicing. The structure of the spliceosomal branch site solved by Newby and Greenbaum showed that a highly conserved pseudouridine residue in U2 snRNA induces a dramatically altered structure compared with that of its unmodified counterpart. In this study, both modified and unmodified U2 snRNA-intron duplexes were analyzed using computer simulations including preliminary molecular dynamics (MD) simulations, electrostatic potential, surface area, and solvation free energy calculations. The preliminary MD simulations produce stable trajectories of the RNA duplexes in solution. The surface electrostatic potentials were calculated using finite difference Poisson-Boltzmann algorithm and a hybrid boundary element and finite difference Poisson-Boltzmann approach. Results show a region of exceptionally negative potential near the 2' OH of the branch site adenosine. The two RNA duplexes have similar solvent accessible surface areas, whereas the surface accessible area of the 2' OH of the branch site adenosine of the modified RNA duplex is considerably smaller than that of the unmodified RNA duplex. The solvation free energy calculation indicates that the unmodified RNA duplex is favored over the modified RNA duplex. / A Thesis submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Master of Science. / Degree Awarded: Fall Semester, 2003. / Date of Defense: November 21, 2003. / U2 snRNA, Splicing, Solvation Free Energy, Electrostatics / Includes bibliographical references. / Nancy L. Greenbaum, Professor Directing Thesis; Hong Li, Committee Member; Igor Alabugin, Committee Member.

Polyelectrolyte complexes (PECs) have received a growing interest since the early sixties. PECs have been used for large-scale industrial applications and have demonstrated enormous potentials in various fields such as coatings, binders and flocculants. Using the Layer-by-layer deposition technique, an ultrathin polyelectrolyte multilayer coating was first built in 1990 and soon both theoretical and practical interest in these coatings were growing exponentially. In the first part of this dissertation, studies were focused on the fundamental properties of polyelectrolyte multilayer and complex systems, such as the effect of molecular weight of polyelectrolytes and the effect of ionic strength on the multilayer buildup and the thermodynamics of the polyelectrolyte complexation. In the second part, a series of pH-tunable polyelectrolyte complexes and pH-responsive multilayers were designed and studied. Random copolymers composed of pH-independent "strongly" charged parts and pH-dependent "weakly" charged parts were introduced for making pH-tunable polyelectrolyte complex and pH-responsive multilayers. A systematic study of the pH induced change of multilayer configuration, including film decomposition, phase separation and surface charge rearrangement, was conducted. It was found, by varying the mole percent of the weakly charged segments in the multilayers, the outcome of external pH changes on the multilayers varied from total film decomposition, to forming microporous surface, and finally to yielding a surface-charge-tunable multilayer, which meant the ability of controlling the surface charge polarity and density via pH. The outcome was essentially due to the combination of two types of charge interaction, charge extrusion and charge expulsion. It was also demonstrated that, with the use of the pH-responsive polyelectrolyte multilayer coatings to modify the substrate surface, the adsorption and release of biomaterials, such as proteins, could be controlled by varying the surface charge property via simple pH switch. Potential applications of this finding were proposed in the dissertation. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Degree Awarded: Summer Semester, 2004. / Date of Defense: May 5, 2004. / Polyelectrolyte, PH-Responsive, Multilayers, Complex / Includes bibliographical references. / Joseph B. Schlenoff, Professor Directing Dissertation; Rufina G Alamo, Outside Committee Member; John G. Dorsey, Committee Member; Randy L. Rill, Committee Member.

Malaria is a global epidemic, resulting in the deaths of nearly one million people every year. Part 1 of this dissertation will focus on the history of Malaria and ways to combat this devastating disease. Artemisinin has emerged as the drug of choice for treatment of malaria due to its effectiveness against all strains of the malaria parasite. Access to artemisinin through isolation, bio-engineering, and chemical synthesis will be described. Our attempts to access the artemisinin family of anti-malarials through the total synthesis of dihydro-epi-deoxyarteannuin B and dihydroartemisinic acid will be discussed fully. Key features of the syntheses will include alkylation of menthone derivatives using Noyori's zincate enolate method and nucleophilic addition to a hindered ketone using either organocerium or acetylide nucleophiles. In addition, two alternative olefin metathesis approaches are described for the final cyclization. Problems associated with the olefination of a key intermediate in our efforts toward dihydroartemisinic acid led us to develop a two-step olefination of ketones and aldehydes. Part II will discuss this olefination strategy which consists of acetylide addition to generate a propargyl alcohol followed by a Meyer-Schuster rearrangement to the corresponding α,β-enone. A complete history of the Meyer-Schuster rearrangement will be presented, highlighting the short comings of the method prior to our work. A complete overview of our research pertaining to the Meyer-Schuster reaction will be given. Key topics will include development of a Au(III)-catalyzed rearrangement of propargyl ethynyl ethers into α,β-unsaturated esters and its use in the olefination of hindered ketones, efforts to control the (E/Z)-selectivity of the Meyer-Schuster rearrangement, and the search for more affordable catalysts. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Degree Awarded: Summer Semester, 2009. / Date of Defense: June 30, 2009. / Scandium, Meyer-Schuster, Gold-Catalysted, Artemisinin / Includes bibliographical references. / Gregory B. Dudley, Professor Directing Dissertation; Thomas Keller, Outside Committee Member; Marie Krafft, Committee Member; Lei Zhu, Committee Member; Geoffery Strouse, Committee Member.

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has ultrahigh mass resolving power (m/Dm50% >300,000) and high mass accuracy (300,000) and high mass accuracy (ppm), which enables separation and identification of elemental compositions of complicated mixture. Electrospray ionization (ESI) provides selective ionization of polar heteroatomic compounds without chromatographic isolation. In addition, Kendrick mass plot is introduced in petrochemical analysis for an easy and fast data reduction. We first applied ESI FT-ICR mass spectrometry to the analysis of petrochemical samples like coal extracts and crude oils then extended this work into other complex mixtures, such as vegetable oils, hydrotreated fuels and military explosives. Detailed elemental compositions can be used as "fingerprint" to characterize each mixture sample. Three-dimensional van Krevelen diagram can be applied to characterize different fossil fuels. We demonstrate the great potential of ESI-FT-ICR MS in analysis of complex organic mixtures. / A Dissertation submitted to the Department of Chemistry and Biochemistry in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy. / Degree Awarded: Spring Semester, 2004. / Date of Defense: April 7, 2004. / Kendrick Mass, Oil, Explosives, Adulteration, Van Krevelen Diagram, ESI, FT-ICR / Includes bibliographical references. / Alan G. Marshall, Professor Directing Dissertation; William M. Landing, Outside Committee Member; William T. Cooper, Committee Member; Timothy A. Cross, Committee Member; Ryan P. Rodgers, Committee Member.

The role of charge density in polyelectrolyte multilayer coatings used in 2-D cell culture was investigated in this dissertation. First it is important to comprehend that cells do not attach directly to surfaces, they attach to proteins adhered to surfaces. Surface charge density in polyelectrolyte films affects not only protein coverage, but also interferes with protein exchange (Vroman effect), highly charge surfaces favor irreversible absorption of non-adhesive proteins like albumin, which directly affects cell behavior on these ultrathin films. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the Doctor of Philosophy. / Spring Semester 2016. / April 4, 2016. / Includes bibliographical references. / Joseph B. Schlenoff, Professor Directing Dissertation; Thomas C. S. Keller, University Representative; Alan Marshall, Committee Member; Hedi Mattoussi, Committee Member.

Abstract Gas-Solid reactivity was extensively studied throughout the early 20th century and the kinetics of these systems have become well established and well understood. Recently, microwave active materials (conductive or magnetic materials that absorb microwave irradiation) have been shown to produce increased reactivity in a significantly different way when compared to conventional heating. Any of these materials can be used to improve reactivity in industrially relevant gas-solid systems. Many of these rate enhancements can be measured by using reaction kinetics, and these kinetic rates can be compared to the previously studied, well established, thermal measurements. By understanding the difference between microwaves and conventional heating we may better predict which systems would be ideal candidates for increased reactivity. Specifically the reaction between steam and carbon has been measured extensively in the past and could be ideal to benefit from microwave irradiation. C + H2O → H2 + CO. At 131 kJ/mol this endothermic reaction uses carbon as its microwave active material. This solid can be any form of carbon (activated carbon, graphite, coal etc.) and it selectively heats in a microwave reactor. This reaction was shown to have a large difference in apparent activation energies and kinetic rates when compared to the thermal rates and energies. By using an Arrhenius plot, the apparent microwave equilibrium constants were calculated at various wattages and shown to be lower when matched against comparable temperature ranges of the conventional thermal reactions. The enthalpy and entropy of the systems were then calculated to give an effective thermodynamic value to describe the energy differences. Not only was the reaction more efficient in the microwave, but the microwave composition of the product gases included less CO2, which would be produced from a water gas shift side reaction. These findings, of a system that produces less side products at lower temperatures, are evidence that microwave gas-solid reactions could provide unique chemistry that should be applied to more industrially relevant systems. Probing the mechanisms of these results was done by using a nitrous oxide and carbon system to observe the compositional difference in reactivity. 2C + 2NO2 → N2 + 2CO2. The interfacial polarization of the carbon is understood to be the method of heating in a microwave reactor. Electron hole pairs are created as the charges separate and become trapped at grain boundaries across the surface of the material. These electron hole pairs create an active site on the surface that helps facilitate reactivity and sometimes leads to different compositional makeup of product gases. Probing this mechanism was important to help describe which systems would be good candidates to study in further research endeavors. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the Doctor of Philosophy. / Fall Semester 2015. / November 12, 2015. / Carbon, Enhancement, Gas-Solid, Kinetics, Microwave, Nitrous / Includes bibliographical references. / Albert Stiegman, Professor Directing Dissertation; Vincent Salters, University Representative; Greg Dudley, Committee Member; Susan Latturner, Committee Member; John Dorsey, Committee Member.

The focus of this dissertation is the study of the magnetic properties of several novel lanthanide and actinide metal complexes, of particular concentration is the use of SQUID magnetochemistry coupled with electron paramagnetic resonance (EPR). Through these techniques, a deeper understanding of the magnetic behavior of the f elements and their structure-property relationships are realized. The novel neptunium selenite compounds presented in Chapter 3 are simple systems in which to probe the magnetic susceptibilities of transuranic compounds and a soft ferromagnetic material with strong temperature independent paramagnetic effects was synthesized. Chapter 4 also concerns neptunium but in this case a comparison between neptunium iodates, which are expected to be nonmagnetic, assuming a formal oxidation state of +5 which yields a singlet ground (S = 1) assuming spin only contributions. The compounds actually display ferromagnetic ordering at approximately 12 K. Of even further interest is the frequency dependence of the magnetic susceptibility which should not be evident in a magnetically ordered system thus signifying the material have spin glass properties or exhibit magnetic frustrations. The focus of Chapter 5 is the correlations between structure and magnetic properties that are correlated in a large family of heterobimetallic compounds containing lanthanides and copper. The tuning of the magnetic properties can be controlled by careful substitution of lanthanide ions. Of particular interest is the magnetic information revealed via electron paramagnetic resonance which may go unnoticed by bulk magnetization techniques. These measurements clarified the magnetic description of the compounds. Chapter 6 highlights several other compounds that were found to be magnetically interesting. Particularly interesting is a uranium ion in the +4 oxidation state that exhibits spin frustration. Furthermore, a large family of lanthanide-transition metal ions with tellurium and sulfate anions, where both the lanthanides and transition metal ions are able to be substituted yielded a large diversity of magnetic properties. Finally, a compound was synthesized that exhibited two crystallographically unique copper atoms which are distinguishable via high field electron paramagnetic resonance and order antiferromagnetically. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the Doctor of Philosophy. / Fall Semester 2015. / October 13, 2015. / Actinide, EPR, Inorganic, Lanthanide, Magnetism, SQUID / Includes bibliographical references. / Thomas E. Albrecht-Schmitt, Professor Directing Dissertation; Irinel Chiorescu, University Representative; Naresh S. Dalal, Committee Member; Joeseph B. Schlenoff, Committee Member; Oliver Steinbock, Committee Member.

Abstract Metal eutectic fluxes are useful for exploratory synthesis of rare earth intermetallics. In this work, the use of rare earth/transition metal eutectics such as: Nd/Co, Pr/Co, Ce/Co, Nd/Ni and Sm/Ni have yielded many structually and magnetically complex phases, which also help us to to gain better understanding of reactivity trends of various elements in the flux. The intermetallic compounds R₂Co₂SiC (R = Pr, Nd) were prepared from the reaction of silicon and carbon in either Pr/Co or Nd/Co eutectic flux. These phases crystallize with a new structure type in orthorhombic space group Immm, with unit cell parameters a = 3.978(4) Å, b = 6.094(5) Å, c = 8.903(8) Å (Z = 2; R₁ = 0.0302) for Nd₂Co₂SiC. Silicon, cobalt, and carbon atoms are connected with each other to build up two-dimensional flat sheets which are separated by puckered layers of rare-earth cations. Magnetic susceptibility measurements indicate that the rare earth cations in both analogs order ferromagnetically at low temperature (TC = 10 K for both). Single crystal neutron diffraction data for Nd₂Co₂SiC indicates this ordering occurs in two steps. Crystals of two new germanide intermetallic compounds were grown from Nd/Co or Pr/Co eutectic flux. The crystal structure of Nd₈Co[subscript 4-x]Al[subscript x]Ge₂C₃ (Pbcm, a=8.00Å, b=11.71Å,c=15.07Å; Z=4, R₁=0.0261) features germanium centered neodymium clusters Ge@Nd₉ capped with Co and C atoms which form infinite zigzag chains. Magnetic susceptibility measurements indicate the Nd ions order at 50K. Magnetic anisotropy studies show the Nd[superscript 3+] magnetic moments tend to align ferrimagnetically along the c axis. The phase RE₆Co₅Ge[subscript 1+x]Al[subscript 3-x] (RE=Pr, Nd) crystallizes with the Nd₆Co₅Ge[subscript 2.2] structure type in hexagonal space group P-6m2 (a = 9.203(2)Å, c = 4.202(1) Å, R1 = 0.0109 for Pr₆Co₅Ge[subscript 1.80]Al[subscript 2.20]; and a = 9.170(3) Å, c = 4.195(1) Å, R1 = 0.0129 for Nd₆Co₅Ge[subscript 1.74]Al[subscript 2.26]), featuring chains of face-sharing Ge@RE₉ clusters intersecting hexagonal cobalt nets linked by aluminum atoms. Magnetic susceptibility measurements indicate that both phases exhibit ferromagnetic ordering of the cobalt layers with TC in the range of 130-140K, and the rare earth ions order at low temperature (30-40K). The magnetic measurements on oriented crystals of Nd₆Co₅Ge[subscript 1.74]Al[subscript 2.26] show a strong preference of the Co moments to order along the c-axis. A cerium cobalt borocarbide compound, Ce₁₀Co[subscript 2.75]B[subscript 11.5]C₁₀(triclinic, P-1, a = 8.5131(5)Å, b = 8.5144(5)Å, c = 13.5709(7)Å, ɑ = 100.870(1)°, β = 93.677(1)°, ɣ = 90.041(1)°, Z = 2, R₁ = 0.0293) was grown as large crystals from reactions of boron and carbon in cerium/cobalt eutectic melts. The structure of the cerium-rich product features Co₄ squares capped by borocarbide chains. Magnetic studies show a ferromagnetic transition at 10 K and also indicate fluctuating cerium valence. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester 2015. / November 4, 2015. / Includes bibliographical references. / Susan Latturner, Professor Directing Dissertation; Bruce Locke, University Representative; Michael Shatruk, Committee Member; Albert Stiegman, Committee Member.

The work in this dissertation presents a method for multiplexing fluorescence measurements in both polymerase chain reaction (PCR) and anisotropy. For PCR, two dual color infrared mediation assays were demonstrated on a microfluidic device. Infrared mediated PCR on a microchip allowed a 40 cycle assay, which would require 1 hour on a traditional instrument to be reduced to 35 min due to the decrease volume and increased heating and cooling efficiency. A plasmid, PU19, was amplified in the presence of a DNA intercalating dye, EvaGreen™, and a passive reference dye, ROX, with an efficiency of 96%. The ROX signal was used to correct for inter-run and inter-chip variations in excitation volume. A melt curve was taken simultaneously with amplification and showed a single peak at 82 °C corresponding to the known melt temperature of the plasmid. Frequency modulation was used to isolate the fluorescence signals for the EvaGreen™ and the ROX from the large background present due to the tungsten lamp providing infrared light for the heating of the microfluidic device as well as demonstrate the first multi-color infrared quantitative PCR on a microfluidic device. Frequency modulation was used to demonstrate a multi-analyte anisotropy method inflow on a microfluidic device. An anisotropy immunoassay was developed for the simultaneous detection of insulin and glucagon at physiologically relevant levels. Frequency modulation was used to reduce the number of optics required for multi-fluorophore anisotropy measurements as well as increase the signal to noise in the measurement by 20 fold. The increased signal to noise ratio resulting in an improvement in the limit of detection from 10 nM to 50 pM. The anisotropy immunoassay assay was expanded to an online format used to measure the secretion of insulin by islets of Langerhans which were housed on the microfluidic device. The microfluidic system was able to stimulate islet with 3mM and 20 mM glucose and measure the resulting secretions. The temporal resolution of the system was less than 5 minutes and the highly automated fashion in which the online assay function should make it amenable to further islet studies as well as other biological systems. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the Doctor of Philosophy. / Fall Semester 2015. / November 10, 2015. / anisotropy, fluorescence, frequency modulation, microfluidic, PCR / Includes bibliographical references. / Michael G. Roper, Professor Directing Dissertation; Bruce R. Locke, University Representative; John G. Dorsey, Committee Member; Scott M. Stagg, Committee Member.

Controlling particularly reactive substances to achieve desired outcomes is a constant challenge in materials chemistry. Reactants and products consisting of main group and transition metal elements often exhibit extreme sensitivity to their environments. Therefore, it is desirable to develop new methods of synthesis and handling of the starting materials and resulting products in order to extend the chemical space available within this domain of science. Reactivity must be defined within the context of this dissertation. Herein, 'reactive' is exceptional sensitivity to air and moisture leading to degredation of reactants or desired products. Reactivity may also correspond to the explosive or pyrophoric nature of reactants and products inevitably preventing their isolation and handling under ambient conditions. Several observations which are pertinent to the fundamental understanding of the reactivity of various metalorganic, orgnaometallic, and main group complexes are chronicled within this dissertation. A comparison is provided for two methods (batch and flow) that are typically used to perform and control reactions. Due to the prevalence flow chemistry within my work, emphasis will be placed upon flow-based methods. In chapter 1, a short primer on fluid dynamics relevant to materials chemistry will be provided to compare and contrast batch versus flow chemistry. Examples of flow chemistry applied to organic reactions are given, followed by examples of inorganic chemistry in flow which is much less developed. Finally, the overarching goals of this work are as follows: 1) Present the basics of fluid dynamics to provide a basis for the flow chemical approaches within this work. 2) Provide a discussion of current flow-based methods applied to organic and inorganic synthesis. 3) To detail and study the application of flow chemistry techniques to the synthesis of new and existing metal organic, organometallic, and main group compounds and materials. In chapter 2, a simplified droplet generator is introduced and utilized to yield hollow silica capsules from a liquid–liquid interfacial polymerization reaction. Further use of this simple droplet generator is examined for preparation of SiO2-TiO2 hybrid capsules along with a cartridge-based method to modify the capsule surface with additional TiO2. In chapter 3, our growing interest in reactive materals led to the discovery that alkali metal oxides can be trapped and crystallized using diethlyzinc. From this observation, a family of complexes were isolated and characterized. Chapter 3 will also incoporate flow-based synthesis of organozinc complexes. First, the continuous preparation of organozinc halides is established and then coupled directly to Negishi reactions for the production of desirable building blocks for active pharmaceutical ingredients. Second, a catridge-based method for the utilzation of pyrophoric solid reagent Na2(HZnEt2)2 is presented leading to a series of novel organozincates. In chapter 4, the traditional methods used to synthesize alkali metal polyphosphides are discussed. Our discovery of solution-phase methods which allow facile access to homoatomic polyanions of phosphorus which do not involve harsh reducing alkali metals or the white allotrope of the element is detailed. We then demonstrate a high-throughput continuous-flow approach for rapid generation of gram quantities of these soluble polyphosphide anions. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the Doctor of Philosophy. / Fall Semester 2015. / November 9, 2015. / Flow chemistry, Inorganic chemistry, Materials chemistry / Includes bibliographical references. / Michael Shatruk, Professor Co-Directing Dissertation; D. Tyler McQuade, Professor Co-Directing Dissertation; Rufina G. Alamo, University Representative; Albert E. Stiegman, Committee Member; Geoffrey F. Strouse, Committee Member; Michael Roper, Committee Member.