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This thesis presents the results for experimental (e,2e) studies on both nitrogen (N2) and methane (CH4) molecules. The data from the experiments were compared to theoretical calculations using various models and approximation methods; the molecular three-body distorted wave (M3DW) approximation, the distorted wave Born approximation (DWBA), the Ward Macek (WM) approximation, the orientation-averaged molecular orbital (OAMO) approximation, the proper averaging (PA) approach, and the generalized Sturmian functions (GSF) approach. The Manchester (e,2e) spectrometer is described in detail along with new experimental hardware and software used for experimental control, optimization, data acquisition, extraction, visualization, and analysis. Two in-depth (e,2e) studies were carried out for the nitrogen (N2) molecule. The first was carried out in both coplanar and non-coplanar geometries, for incident electron energies ~10 and ~20eV above the ionization potential of the 3sigma_g, 1pi_u and 2sigma_u states of N2. The results used outgoing electron energies with E1 = E2 = 4.6 eV +/- 0.5 eV, E1 = E2 = 9.7 eV +/- 0.5 eV, E1 = 4.6 eV +/- 0.5 eV and E2 = 14.5 eV +/- 0.5 eV. The experimental results show that the cross-sections are very sensitive to the states from which the ionization occurs, as well as the incident energy and post collisional interactions. These measurements were compared to calculations based on three models, all of which confirmed the importance of post collision interactions at these energies. The second (e,2e) study was a continuation of the first. It was carried out with incident electron energies ~20 and ~40 eV above the ionization potential for the 3sigma_g and 1pi_u states of N2, using equal energies for the outgoing electrons. The data were obtained with the incident electron beam in the scattering plane. This experiment produced six sets of measurements of the ionization triple differential cross-sections, with fixed angles of 45 degrees, 90 degrees and 125 degrees with respect to the incident electron beam for one of the outgoing electrons. A disagreement was found between theory and experiment which is thought to be due to limitations of the OAMO technique used to average over all molecular orientations. The final (e,2e) study detailed in the thesis was carried out for ionization of the highest occupied molecular orbital (HOMO) 1t2 state and the next highest occupied molecular orbital (NHOMO) 2a1 state of CH4 at an incident electron beam energy of 250eV, for ejected electron energies of 50eV and 30eV. Five fixed scattering angles (20 degrees, 22.5 degrees, 25 degrees, 27.5 degrees, and 30 degrees) were used in these coplanar asymmetric experiments. The measured triple differential cross-sections were compared to experimental results of the Afyon group in Turkey. Both experimental results were also compared to theoretical calculations using the M3DW and GSF models. The results showed very good agreement between both experiment and theory. The structure and peak locations in the results for 50 eV ejected electrons are in good agreement with the theoretical calculations. However, the agreement at 30eV was not as satisfactory. The M3DW calculations were slightly better in their predictions of the location and magnitude of the experimental peaks than the GSF model. A significant portion of this thesis details the modernization of the Manchester (e,2e) spectrometer that was carried out by the author, and which was then used to perform the experiments that are detailed here. New computer-controlled variable voltage supplies were designed, built, and integrated with the (e,2e) spectrometer, alongside the new (e,2e) LabVIEW computer application used for experimental control and data acquisition. The inner-workings of the (e,2e) spectrometer, the vacuum system, and the experimental hardware and software are all detailed in the thesis.

F1-ATPase, the sector of ATP synthase where the synthesis of cellular ATP occurs, is a rotary molecular motor in its own right. Driven by ATP hydrolysis, direct observation of the rotation of the central axis within single molecules of F1 is possible. Operating at close to 100% efficiency, F1 from thermophilic Bacillus has been shown to produce ~40pN˙nm of torque during rotation. This thesis details the groundwork required for the direct measurement of the torque produced by F1 using a rotary angle clamp, an optical trapping system specifically designed for application to rotary molecular motors. Proof-of-concept experiments will be presented thereby demonstrating the ability to directly manipulate single F1 molecules from Escherichia coli and yeast mitochondria (Saccharomyces cerevisiae), along with activation of F1 out of its inhibited state by the application of external torque. Despite in-depth knowledge of the rotary mechanism of F1 from thermophilic Bacillus, the rotation of F1 from Escherichia coli is relatively poorly understood. A detailed mechanical characterization of E.coli F1 will be presented here, with particular attention to the ground states within the catalytic cycle, notably the ATP-binding state, the catalytic state and the inhibited state. The fundamental mechanism of E.coli F1 appears to depart little from that of F1 from thermophilic Bacillus, although, at room temperature, chemical processes occur faster within the E.coli enzyme, in line with considerations regarding the physiological conditions of the different species. Also presented here is the verification of the rotary nature of yeast mitochondrial F1. The torque produced by F1 from thermophilic Bacillus, E.coli and yeast mitochondria is the same, within experimental error, despite their diverse evolutionary and environmental origins.

In recent years, there has been significant progress in the field of quantum information processing and quantum sensing. Researchers have been actively exploring new quantum systems that possess high accuracy, scalability, and compatibility with other systems. The focus of this thesis is to examine various molecular systems that hold promise for quantum sensing and information processing applications.We report a ferrocene-supported ytterbium based complex ((thiolfan)YbCl(THF), thiolfan = 1,1'-bis(2,4-di-tert-butyl-6-thiomethylenephenoxy)ferrocene) that exhibits an isolated ultranarrow absorption linewidth in solution at room temperature with a full width at half maximum (FWHM) of (151 $\pm$ 1) GHz. A detailed absorption spectroscopy analysis from room temperature (RT) to 5 K and emission spectroscopy allow us to assign the narrow near infrared (NIR) transitions to atom-centered \textit{f-f} transitions. Zeeman spectroscopy and electron paramagnetic resonance measurement help us to determine the dominant quantum numbers and Land\'e g-factors of the ground and excited states. A combination of density functional theory and multireference methods match experimental transition energies and oscillator strengths, providing insights into the role of spin-orbit coupling and asymmetric ligand field in enhancing absorption and pointing toward molecular design principles that create well-protected yet observable electronic transitions in lanthanide (Ln) complexes.We demonstrate that the ultranarrow linewidth of this system allows for magnetic field imaging and magnetic field sensing down to Earth scale, which we term an "atom-like molecular sensor" (ALMS). Furthermore, by optically depleting some population, we are able to selectively address the burned spectral hole with a FHWM of 99 kHz, paving the way for optical state preparation and readout of ground state coherence in this liquid molecular system.In addition, we also describe our efforts in building surface-based molecular systems for quantum information and we find that the sensitivity is limited by scatters from the substrate.Overall, our results suggest that molecular systems like ALMS may have great potential for quantum sensing and information applications.

Staphylococcus aureus is one of the leading causes of fatal nosocomial infections. Often, S. aureus can grow as a biofilm which protects the population from the surrounding environment. Strains of S. aureus are resistant to virtually all known antibiotics on the market. Variovorax paradoxus is a soil microbe with many unusual metabolic activities. It has been previously observed that, V. paradoxus can inhibit the growth of S. aureus when in co-culture. In this work we report on inhibition of S. aureus biofilm formation by V. paradoxus due to a suspected inhibitory soluble factor.

The Standard Model of particle physics accurately describes with amazing precision all particle physics measurements made in the laboratory. However, it is unable to answer many central questions that arise from cosmological observations, such as the nature of dark matter and why matter dominates over antimatter throughout the Universe. Theories containing particles and interactions beyond the standard model, such as models incorporating supersymmetry, may explain these phenomena. Such particles can come into virtual existence in the vacuum and then interact with real particles to modify their properties. For example, the existence of very massive particles whose interactions violate time-reversal symmetry, as needed to explain the cosmological matter–antimatter asymmetry, gives rise to an electric dipole moment along the spin axis of the electron. To date no electric dipole moments (EDM), of the electron or other fundamental particles, have been observed. However, dipole moments only slightly smaller than current bounds can arise from new particles more massive than any known to exist. Here we present a new measurement of the electron's electric dipole moment (eEDM), $d_e$=\result, obtained by measuring the spin precession of electrons subjected to the huge intramolecular electric field accessible in the thorium monoxide molecule. The sensitivity of our measurement is one order of magnitude better than any previous work and probes for the existence of new particles with mass far beyond the direct reach of the Large Hadron Collider. Since our measurement is consistent with zero, we report an upper limit of $|d_e|$

To date, topical therapies guarantee a better delivery of high concentrations of pharmacologic agents to the mucosa of the upper airways (UA). Recently, topical administration of ectoine has just been recognized as adjuvant treatment in the Allergic Rhinitis (AR) and Rhinosinusitis (ARS). The aim of this work is to review the published literature regarding all the potential therapeutic effects of ectoine in the acute and chronic inflammatory diseases of UA. Pertinent studies published without temporal limitation were selected searching on MEDLINE the following terms: “ectoine” and “nasal spray,” “oral spray,” “upper respiratory tract infections,” “rhinosinusitis,” “rhinitis,” “rhinoconjunctivitis,” “pharyngitis,” and “laryngitis.” At the end of our selection process, six relevant publications were included: two studies about the effect of ectoine on AR, one study about ARS, one study about rhinitis sicca anterior, and two studies about acute pharyngitis and/or laryngitis. Due to its moisturizing and anti-inflammatory properties, topical administration of ectoine could play a potential additional role in treatment of acute and chronic inflammatory diseases of UA, in particular in the management of sinonasal conditions improving symptoms and endoscopic findings. However, these results should be viewed cautiously as they are based on a limited number of studies; some of them were probably underpowered because of their small patient samples.

This thesis thoroughly investigates spintronic and frictional behaviors of individual magnetic molecules adsorbed on a metal surface and graphene nanoribbons utilizing scanning tunneling microscopy, tunneling spectroscopy and non-contact atomic force microscopy combined with atomic and molecular manipulation schemes in an ultrahigh vacuum environment at low temperatures. The atomic scale studies are realized by using a porphyrin based magnetic molecule, TBrPP-Co, directly adsorbed on Au(111) surface as well as on semiconducting graphene nanoribbons grown on Au(111). On Au(111) surface, the TBrPP-Co molecules exhibit a Kondo resonance due to many-body interactions between the magnetic moment of the molecule and free host electrons from the substrate. The observed Kondo resonance is dependent on three adsorption sites of the molecules on Au(111) surface. The Kondo resonance disappears when the molecules are located on the elbows of the Au(111) surface herringbone reconstructions, and reappears when the molecules are relocated off the elbows.When TBrPP-Co molecules are isolated from the Au(111) surface by forming TBrPP-Co-armchair graphene nanoribbons (AGNRs) – Au(111) heterostructures, the molecules are electronically decoupled from the metal surface as expected. However, surprisingly, a robust Kondo resonance with almost 100% interaction strength as in the case of the molecules directly adsorbed on Au(111) has been discovered. Tunneling spectra of TBrPP-Co molecules between AGNRs and on edges of AGNRs indicate that AGNRs mediate spin interactions between the TBrPP-Co and the free electrons from the substrate.The friction forces of TBrPP-Co molecules on Au(111) and on AGNRs are also measured separately. The comparison between the lateral force required to move the molecule on Au(111) surface and that on graphene nanoribbons reveals a superlubricity effect where the friction force is about two orders less than the friction force measured on Au(111). The measured friction force of the molecule on Au(111) is further confirmed by non-contact atomic force microscopy experiments, which provide a good agreement with the scanning tunneling microscope results.

We have analyzed the vibrational dynamics of HOCl above dissociation using a 3D energy surface which governs the vibrational dynamics of HOCl above dissociation. The dynamics is dominated by an invariant manifold which is trasversally unstable for small spacing between Cl and HO complex, and stable for large spacing. Above dissociation, the InM separates two mirror image periodic orbits, embedded in a large chaotic sea, that can hold a large number of quantum states. The periodic orbits have the capability of forming significant quasibound states of the molecule above dissociation.

The characterization of the material properties of Single Molecule Magnets (SMMs) has grown in importance over the last few decades with the rise of novel applications such as high-density magnetic storage and quantum computation. Many of the applications require the probing of SMMs with spectroscopic methods that make use of electromagnetic radiation. The interaction with these time-dependent fields leads to energy shifts, which can be attributed to the geometric phase acquired by the system or the Bloch-Siegert shift. We model an SMM by a giant spin Hamiltonian, and use Floquet perturbation theory to find the geometric phase shifts. The locations where the phase shift between two levels is zero is useful for performing accurate spectroscopies, whereas the regions where relative phase differences exist are useful in applications like quantum computing. Using the same giant spin Hamiltonian, we can use Floquet theory and Salwen perturbation theory to determine the Bloch-Siegert shift and derive a modified version of the Rabi formula for transition probabilities between the energy states E(alpha) -> E(alpha)±1, E(alpha) -> E(alpha) ±3, and E(alpha) -> E(alpha) ±5, where alpha is the index of an arbitrary initial state. The shifted eigenvalues and modified transition probabilities can be useful in spectroscopies where accurate values for the energy-splitting between magnetic states needs to be determined.

Cholera toxin (CT), secreted from Vibrio cholerae, causes a massive fluid and electrolyte efflux in the small intestine that results in life-threatening diarrhea and dehydration which impacts 3-5 million people per year. CT is secreted into the intestinal lumen but acts within the cytosol of intestinal epithelial cells. CT is an AB5 toxin that has a catalytic A1 subunit and a cell binding B subunit. CT moves from the cell surface to the endoplasmic reticulum (ER) by retrograde transport. Much of the toxin is transported to the lysosomes for degradation, but a secondary pool of toxin is diverted to the Golgi apparatus and then to the ER. Here the A1 subunit detaches from the rest of the toxin and enters the cytosol. The disordered conformation of free CTA1 facilitates toxin export to the cytosol by activating a quality control mechanism known as ER-associated degradation. The return to a folded structure in the cytosol allows CTA1 to attain an active conformation for modification of its Gsα target through ADP-ribosylation. This modification locks the protein in an active state which stimulates adenylate cyclase and leads to elevated levels of cAMP. A chloride channel located in the apical enterocyte membrane opens in response to signaling events induced by these elevated cAMP levels. The osmotic movement of water into the intestinal lumen that results from the chloride efflux produces the characteristic profuse watery diarrhea that is seen in intoxicated individuals. The current model of intoxication proposes only one molecule of cytosolic toxin is required to affect host cells, making therapeutic treatment nearly impossible. However, based on emerging evidence, we hypothesize a threshold quantity of toxin must be present within the cytosol of the target cell in order to elicit a cytopathic effect. Using the method of surface plasmon resonance along with toxicity assays, I have, for the first time, directly measured the efficiency of toxin delivery to the cytosol and correlated the levels of cytosolic toxin to toxin iv activity. I have shown CTA1 delivery from the cell surface to the cytosol is an inefficient process with only 2.3 % of the surface bound CTA1 appearing in the cytosol after 2 hours of intoxication. I have also determined and a cytosolic quantity of more than approximately .05ng of cytosolic CTA1 must be reached in order to elicit a cytopathic effect. Furthermore, CTA1 must be continually delivered from the cell surface to the cytosol in order to overcome the constant proteasome-mediated clearance of cytosolic toxin. When toxin delivery to the cytosol was blocked, this allowed the host cell to de-activate Gs, lower cAMP levels, and recover from intoxication. Our work thus indicates it is possible to treat cholera even after the onset of disease. These findings challenge the idea of irreversible cellular toxicity and open the possibility of postintoxication treatment options.

The abundance and relevance of organic molecules similar to benzene makes their study important. Studying the interactions of such molecules with intense light fields has implications for the generation of short-wavelength radiation, attosecond science, high-harmonic generation, and many other fields. However, the computing power necessary to complete fully ab initio calculations describing molecules of this size does not exist; this leaves theoretical studies to rely on assumptions and approximations just to calculate the energies of the ground state. Including any sort of dynamics in these calculations is prohibitively complicated, and this makes experimental observations important. Since many organic molecules are similar, it is possible to construct systematic series out of groups of molecules which differ from each other by a single structural parameter. Any differences in the intense-field behaviors between two molecules in such a series must then be a result of the structural parameter that is different. This dissertation is dedicated to the study of systematic series of organic molecules similar to benzene (C6H6). Our experiments are sensitive to the dynamics of photoionization and photofragmentation processes which result from interacting molecules in the gas phase with ultrafast (50 fs, 800 nm) laser pulses. Adviser: Professor Cornelis Uiterwaal

ATP is the most critical molecule for the maintenance and survival of cells in general, especially for the brain and neuronal cells to support essential processes including ion homeostasis, synaptic functions, neurotransmitter production and release. A considerable body of clinical evidence has shown that energy deficit is a very early hallmark of the Alzheimer's disease (AD) brain occurring even prior to clinical symptoms and consistently in association with the progression of the disease. Viewed from this perspective, AMP-activated protein kinase (AMPK), a key enzyme maintaining energy balance in the whole-body level and single-cell level, was hypothesized as a potential target for AD therapeutics. Besides that, another angle of energy disturbance focusing on risk factors of AD - metal stressors was also investigated in the thesis. The project aimed to provide solid scientific evidence for the protective effects of AMPK activators and potential risks of metal stressors in the energetic aspect in current neuronal culture models. A large portion of the project related to optimization of an HPLC method which provided an effective tool to determine numerous nucleotides simultaneously. Among a couple of AMPK activators tested in the project, Resveratrol manifested exciting pro-energetic benefits in the neuronal culture cells rapidly and lastingly. The results show that Resveratrol induced a strongly significant increase in the levels of the most important energy carriers, ATP and GTP, in Neuro 2a cells in a dose-dependent manner, even from the early time-point of 1 hour and extended up to 48 hours. In the experiments on metal stressors, it was discovered that whilst zinc exhibited its cytotoxicity in an adenosine and guanosine nucleotideindependent mechanism, iron revealed the potential harm on the energy generation. Since iron accumulation in the brain has been shown to be a common feature of neurodegenerative diseases including AD and Parkinson's disease (PD) in the literature, excessive iron exposure in AD and PD brains might contribute to the disturbance of energy production to be more severe. Collectively, we promote that Resveratrol and strategies against iron overload in the brain should be considered as potential candidates for prevention and treatment of energy depletion in AD.

Redox active molecules have been studied for several years due to their interesting charge storage properties for future application in molecular memory devices with multi-bit low-voltage operation and ultimate scalability. Hybrid Si-Molecular devices with liquid electrolyte as gate contact have been demonstrated for future DRAM and FLASH memories. The focus of this dissertation work has been on developing the completely solid state hybrid Si-Molecular devices embedded with redox active molecules to facilitate ease of integration. In addition, redox active molecules have also been explored in potential application in organic photovoltaic cells. This work exploits the charge storage properties of redox molecules in solid state devices and the absorption profile of the redox polymers. The charge transfer and charge screening process in conventional electrochemical cell with liquid electrolyte has been characterized using cyclic voltammetry measurements. The role of the liquid electrolyte and the electrical double layer in electrochemical cell for the redox process has been discussed. The solid state approach to hybrid Si-Molecular devices has been proposed. The solid state dielectric layer has been considered to replace electrical double layer. The requirements of dielectric layer and deposition methods in solid state molecular memory device are investigated for preservation and characterization of the redox molecules. AlN, Al2O3 and HfO2 are deposited and examined on top of redox active polymers or redox monolayer in metal-insulator-molecules-silicon (MIMS) or metal-insulator-molecules-metal (MIMM) capacitors. The CyV measurements indicate that the redox properties are preserved after dielectric layer deposition on molecules. The leakage of MIMM capacitors has been greatly improved after the optimization on HfO2 atomic layer deposition conditions and the W/WN gate stack. The low leakage current of MIMM structure provide a reliable test platform for redox molecules as well as the other molecule with more functionalities. The redox process in the ionic cell has been modeled with equivalent circuits. The capacitance at different frequencies for EMS capacitors is simulated to study the electrical properties of the solid state molecular device. The frequency dispersion of capacitance measurements for MIMM capacitance has been explored for understanding the redox charging or trapping in the molecular layer. Si nano-membranes are fabricated as an alternative contact to molecules. Solid state molecular transistors are demonstrated for the possible application in FLASH memory. Redox polymers are investigated for the application in renewable energy area. The organic nanoparticles-polymer solar cell has been compared with conventional bulk Si solar cell. The integration of redox polymers helps to improve the absorption profile of active layer in organic solar cells. Organic solar cells with P3HT and PCBM are fabricated and characterized for the future incorporation of redox molecules. In summary, this work provides the fundamental insights and realistic approaches for the applications of redox active molecules with unique charge storage properties into solid state electronic devices and organic photovoltaic cells, which may enable the solutions for the low cost multi-bit low-voltage scalable molecular memories as well as the high efficiency organic solar cell embedded with redox molecules.

In this dissertation, the degrees of adsorption and stretching of DNA onto surfaces achieved by various stretching methods that use fluid flows are compared and the processes by which proteins find target sequences along these DNA molecules and either carry out cleavage or transcription are directly observed by fluorescence microscopy. DNA molecules either combed or spin-stretched onto hydrophobic surfaces stretch to a greater degree, but fewer are deposited, at pH 8.0 than at lower pH. At pH 8.0, DNA adhesion occurs primarily only at the DNA extremities, and avoids trapped regions of incompletely stretched DNA. A new technique, protein-assisted DNA immobilization (PADI), is developed to immobilize and stretch, but not overstretch, DNA molecules inside a micro/nanochannel at physiological pH. The biological activity of the immobilized DNA molecules is confirmed by digesting the DNA with restriction enzymes in the microchannel. Single molecule transcription, which has stringent requirements on the immobilized DNA with respect to surface interactions and stretched lengths, is also successfully demonstrated on DNA molecules immobilized by PADI. The one dimensional Brownian motion and transcription elongation of T7 RNA polymerase along aligned DNA molecules bound to substrates by molecular combing are directly visualized. Fluorescent antibodies are used to label T7 RNA polymerase and a shear flow is applied to convect proteins orthogonally to the DNA alignment direction, permitting observation and estimation of the protein diffusivity along the DNA at the single-molecule level. The ID diffusion coefficient varies from molecule to molecule over a large range, suggesting that the individual proteins have distinct diffusivities. From the measured dependence of the rate of transcription on concentration of nucleotide triphosphate, the combed DNA molecules capable of interacting with proteins are inferred to be under an average tension of 25 pN.

The development of single molecule spectroscopy over the last two decades has made it possible to probe the conformational structure and dynamics of biomolecules with an unprecedented level of detail. Room-temperature Single-Molecule Fluorescence Resonance Energy Transfer (SM-FRET), in particular, provides the ability to probe intra- and inter-molecular distances as a function of time in a direct manner. These experiments also give rise to many new theoretical questions regarding the behavior of single molecules as apposed to averages over large ensembles. Previous theoretical work on SM-FRET has been based on relatively simple phenomenological stochastic models. In this thesis, we take the next step by attempting to provide a more molecular view of the conformational structure and dynamics underlying SM-FRET experiments. To this end, we use combination of Langevin Dynamics simulations of the biopolymer together with kinetic Monte Carlo simulations of the photon statistics. The analysis focuses on quantities which are particularly relevant to SM-FRET experiments, such as the distribution of donor-acceptor distance and its displacement. Emphasis is put on the unique ability of those experiments to provide information on the correlations between conformational structure and dynamics. We also explore the effect of immobilizing the biopolyiner on surface or trapping it in a pore. Our investigation focuses on two off-lattice models, one of a freely-joined homopolymer and another of a polyypeptide. In the homopolymer case, we consider the conformational structure and dynamics in good and poor solvents, as well as the effect of immobilization on attractive or repulsive surfaces. The polypeptide model is designed to mimic the two-stranded coiled-coil from the yeast transcription factor GCN4 that was studied in the pioneering SM-FILET experiment by Hochstrasser and co-workers[46, 47]. In this case, we consider itninobilizations on repulsive and attractive surfaces as well as encapsulation inside of a pore with varying sizes and shapes. We also consider two types of denaturated states that differ with respect to the amount of residual secondary structure. Finally, we propose a new way for extracting the dine scales of conformational dynamics from single-molecule single-photon fluorescence statistics. To this end, we derive a general relation between the autocorrelation function of the time-delay, between excitation and single photon emission and the autocorrelation function of the fluorescence life-time. We also examine the conditions under which there is a direct relation between the decay of the delay-time autocorrelation function and the time scale of conformational dynamics. We demonstrate how the time scales of conformational dynamics can be extracted from the time-delay autocorrelation function via applications to the above-mentioned homopolyner and polypeptide models.

A phosphonate coupling molecule containing a vinyl double bond was synthesized and anchored onto the surface of TiO2 nanoparticles. Diffuse reflectance infra-red (DRIFT) spectroscopy confirmed the presence of the coupling molecule on the particulate surface while thermogravimetric analysis revealed the coupling molecule covered 28% of the surface. Methyl methacrylate was free radically polymerized through the immobilized vinyl bond on the surface in the presence of the reversible additionfragmentation chain-transfer (RAFT) agent 4-cyanopentanoic acid dithiobenzoate using 2,2'-azobisisobutylnitrile (AIBN) as an initiator. DRIFT measurements confirmed the presence of methacrylate groups on the surface. Differential scanning calorimetry detected a weak glass transition for poly(methylmethacrylate) at ~65oC. Thermogravimetric analysis found that grafted PMMA accounted for 1.2% of the particle's mass. In addition, a synthetic route was developed for a novel phosphonatedithioester coupling molecule, with progress made towards its synthesis.

The bacterial enzyme para-hydroxybenzoate hydroxylase (PHBH) catalyzes a multiple step reaction that requires precise control of solvent access to the catalytic site during the reaction cycle and strict differentiation between structurally similar substrates. Previous studies on PHBH have indicated conformational changes in the active site are essential for some steps in the reaction. However, detection of the hypothesized conformational changes in the substrate binding phase of the reaction has remained elusive because of the need to synchronize the reaction to distinguish the conformational species existing at equilibrium. Single molecule spectroscopy allows one to follow each individual molecule in time, thus eliminating the need to synchronize and offering a way of detecting these conformational changes at equilibrium. In this thesis we report single-molecule fluorescence studies of PHBH in the absence of substrate that support the hypothesis that a critical step in substrate binding is the movement of the isoalloxazine between an in conformation and a more exposed open conformation. The conformational switches are followed directly by changes in fluorescence intensity, confirmed by studies with the Y222A mutant form of PHBH which suggest that the exposed conformation is fluorescent while the in-conformation is quenched. We note that many of the single-molecule fluorescence trajectories reveal a conformational heterogeneity, with populations of the enzyme characterized by either fast or slow switching between the in- and open-conformations. Our data also allow us to construct a model in which one flavin in the dimer inhibits the motion of the other. This model is supported by single-molecule studies of PHBH in sucrose, an osmolyte that favors dimer formation by minimizing exposed protein surface area. Sucrose also minimizes flavin dissociation from the enzyme, which has possible applications for the extension of the available observation time in future single-molecule experiments. Finally, the conformational changes in the subsequent stage of the catalytic cycle were followed by observing the interaction of PHBH with three substrate analogues, each of which stabilizes a different conformational state of PHBH upon binding. Single-molecule fluorescence allows direct observation of the conformational switching upon substrate binding, which previously had been inferred through kinetic studies and crystallographic structures.

This doctoral dissertation is concerned with modeling electron transport through nanoscopic structures, such as quantum dots, metal particles, or molecules. In Chapter 2, we consider statistical correlations between the heights of conductance peaks corresponding to two different levels in a Coulomb-blockaded quantum dot. Correlations exist for two peaks at the same magnetic field if the field does not fully break time-reversal symmetry as well as for peaks at different values of a magnetic field that fully breaks time-reversal symmetry. In Chapter 3, we present a density-matrix rate-equation approach to sequential tunneling through a metal particle weakly coupled to ferromagnetic leads. Our formalism is valid for an arbitrary number of electrons on the dot, for an arbitrary angle between the polarization directions of the leads, and with or without spin-orbit scattering on the metal particle. Interestingly, we find that the density-matrix description may be necessary even for metal particles with unpolarized leads if three or more single-electron levels contribute to the transport current and electron-electron interactions in the metal particle are described by the `universal interaction Hamiltonian'. In Chapters 4 and 5, we consider transport through molecular devices with strong coupling to a single vibrational mode for the case that the vibration is damped by coupling to the environment. We focus on the weak tunneling limit, for which a rate-equation approach is valid. The role of the environment can be characterized by a frequency-dependent frictional damping term and corresponding resonance frequency shift. We calculate current-voltage curves in Chapter 4 and find qualitative agreement between our theory and recent experiments on C_{60} single-molecule devices. In Chapter 5, we see that, depending on how the characteristic length scales of the van der Waals and electrostatic interaction of the molecule with the environment compare to each other, orthogonality catastrophe may appear or disappear, resulting in a smooth or discontinuous current-voltage curve, respectively. Finally, in Chapter 6, we investigate the influence of electron-phonon coupling on the current through a metallic single-walled carbon nanotube. In particular, we consider the high-energy optical and zone-boundary phonons and calculate an effective high-bias electron scattering rate, which is close to the experimentally observed value.

Since its onset in 1941, matrix isolation has become a popular and common technique for studying species using spectroscopy by isolating them in an inert host solid [1]. Due to the large, spherical shape of the molecules, solid C60 has large interstitial voids making it a good host for matrix isolation. These voids come in two varieties. The larger of the two, the octahedral sites, have an ideal size for studying the dynamics of H2 molecules because the sites are large enough that a hydrogen molecule can be trapped, resulting in quantized translational motion, and can rotate nearly freely within the site. On the other hand, the sites are also small enough that each will contain only one hydrogen molecule thus eliminating H2-H2 interactions. The dynamics of a single hydrogen molecule isolated within the potential well of an octahedral site are very interesting because it represents a real-life example of the famous quantum mechanical situation of a “particle-in-a-box”. While the quantum dynamics of hydrogen within a C60 host lattice is worthy of investigation purely on the basis of the interesting physics involved in the system, there is also a practical importance for gaining a better understanding of the C60-H2, host-guest interaction because of the continuing interest in the possible use of carbon nanostructures as devices for hydrogen storage 3]. Using infrared spectroscopy to study H2 intercalated within a C60 lattice gives insight into the nature of the C60-H2 interaction because H2 is not infrared-active under normal conditions and so the H2 absorption peaks in our spectra are purely due to interaction with the C60 host. Initial results the H2 absorbance spectrum were published in 2002 by Professor Stephen FitzGerald, Scott Forth, and Marie Rinkoski [4]. This paper presents a continuation and a further understanding of using Fourier transform infrared spectroscopy to study the quantum behavior of H2 molecules within the octahedral lattice sites of C60.

The sense of smell is a primal sense for humans as well as animals.In everyday life the smells encountered are composed of dozens, even hundreds of odors; few arise from a single odorant. Enormous numbers of odors occur due to the vast variation in the concentration, size and structure of odorant molecules that makes olfaction differ from simpler visual or auditory dimensions. Accordingly, little is known about the ways in which changes in molecular structure and concentration of individual odorants change odor quality. Also, currently not much is understood about synergism/antagonism, how one odorant masks or suppresses another in mixtures and there is no method for predicting which odor will be suppressed. The two main objectives of this thesis were to determine whether a part of a molecular structure rather than the whole structure plays a key role in odor quality and whether a key part of a molecule can be used to choose antagonists for that odorant. For this study three classes of musks and two potential antagonists were used. The results of the study are discussed in some detail. It is concluded that future studies of the importance of molecular structure in mixture interactions require substantially more information on the relation between structure and odor quality to allow systematic studies to be developed. In summary the two hypotheses investigated were not supported by the results. Importantly, however, they do support the view that it is likely that odor quality is dependent on the whole structure of an odorant not a single feature.

Understanding reactions in nanoporous materials from a purely experimental perspective is a difficult task. Measuring the chemical composition of a reacting system within a catalytic material is usually only accomplished through indirect methods, and it is usually impossible to distinguish between true chemical equilibrium and metastable states. In addition, measuring molecular orientation or distribution profiles within porous systems is not easily accomplished. However, molecular simulation techniques are well-suited to these challenges. With appropriate simulation techniques and realistic molecular models, it is possible to validate the dominant physical and chemical forces controlling nanoscale reactivity. Novel nanostructured catalysts and supports can be designed, optimized, and tested using high-performance computing and advanced modeling techniques in order to guide the search for next-generation catalysts - setting new targets for the materials synthesis community. We have simulated the conversion of several different equilibrium-limited reactions within microporous carbons and we find that the pore size, pore geometry, and surface chemistry are important factors for determining the reaction yield. The equilibrium-limited reactions that we have modeled include nitric oxide dimerization, ammonia synthesis, and the esterification of acetic acid, all of which show yield enhancements within microporous carbons. In conjunction with a yield enhancement of the esterification reaction, selective adsorption of ethyl acetate within carbon micropores demonstrates an efficient method for product recovery. Additionally, a new method has been developed for simulating reaction kinetics within porous materials and other heterogeneous environments. The validity of this technique is first demonstrated by reproducing the kinetics of hydrogen iodide decomposition in the gas phase, and then predictions are made within slit-shaped carbon pores and carbon nanotubes. The rate constant is found to increase by a factor of 47 in carbon nanotubes, as compared to the same reaction in the bulk gas phase. Overall, the results of these simulation studies demonstrate improvements in chemical reaction yield and chemical kinetics that are possible by understanding the nature of confined reactions, and applying this knowledge to catalyst design.

Polypeptide hormones and growth factors regulate a variety of vital activities via binding and activating their cognate cell surface receptors which in turn recruit intracellular signaling molecules and transmit signals inside cells. In this dissertation, SH2-B is identified as an important intracellular signaling protein for growth hormone (GH), platelet-derived growth factor (PDGF) and nerve growth factor(NGF). SH2-B was found to be phosphorylated in response to GH, PDGF and NGF. However, the mechanisms by which SH2-B was phosphorylated are different among these polypeptide hormones and growth factors. GH stimulates activation of JAK2, and promotes association of SH2-B with JAK2 and tyrosyl phosphorylation of SH2-B by JAK2 in 3T3-F442A fibroblasts. PDGF stimulates the binding of SH2-B directly to tyrosyl phosphorylated PDGF receptor, and promotes the phosphorylation of SH2-B on both tyrosines and serines and/or threonines in 3T3-F442A and NIH3T3 cells. NGF stimulates phosphorylation of SH2-B predominantly on serines and/or threonines via a MEK-dependent pathway in PC12 cells. SH2-B was found to play an essential role in PDGF-induced actin rearrangement including membrane ruffling, and is required for NGF-induced neurite outgrowth in which actin cytoskeletal rearrangement is thought to be a driving force. The SH2 domain of SH2-B was found to be vital for SH2-B binding to JAK2 and PDGF receptor as well as for its phosphorylation by JAK2 and NGF stimulation. The SH2 domain is also required for the action of SH2-B in GH- and PDGF-stimulated membrane ruffling and NGF-induced neurite outgrowth. These data indicate that SH2-B is a crucial, previously unknown signaling molecule involved in the regulation of the actin cytoskeleton and cell morphology by polypeptide hormones and growth factors including GH, PDGF and NGF.