Thesis (Ph. D.)--University of California, San Francisco, 2005. / Source: Dissertation Abstracts International, Volume: 66-06, Section: B, page: 3145. Advisers: Irwin D. Kuntz; R. Kiplin Guy.

Thesis (Ph. D.)--University of Illinois at Urbana-Champaign, 2008. / Source: Dissertation Abstracts International, Volume: 69-11, Section: B, page: 6816. Adviser: John Katzenellenbogen. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

Proefschrift--Amsterdam. / Includes bibliographical references.

Over the past few decades, tremendous efforts have been made to develop nanomaterials for biotechnological applications such as therapeutics. Understanding and engineering interfaces between biomacromolecules and nanomaterials is a key to the creation of successful therapeutic systems. My research has been oriented toward developing therapeutic systems using gold nanoparticles (AuNPs) incorporating material science, organic synthesis, and biology. For this purpose, mixed monolayer protected AuNPs (∼2 nm core size) with various functional groups have been employed for triggering therapeutic effects. Several strategies have been accomplished using anticancer drugs that non-covalently and covalently incorporate onto AuNPs as a drug delivery carrier. Alternatively, AuNPs were developed by regulating host-guest complexation processes inside the cell, allowing control of the therapeutic effect of the AuNP. In addition, by using host-guest chemical events on the AuNPs, exocytosis of the AuNPs was controlled, enabling their prolonged retention inside of the cells, providing new strategies for improving conventional drug delivery systems. Therefore, engineering of the AuNP surface can afford new pathways for designing and improving therapeutics.

This dissertation describes the synthesis, structure and phase behavior of polyurethanes based on the mesogenic biphenol 4,4$\sp\prime$-bis(6-hydroxyhexoxy)biphenyl (BHHBP) and meta substituted tolylene/phenylene diisocyanates. The structure-property relationships were determined as a function of hydrogen-bonding, the position of the methyl group in the tolylene diisocyanate moiety (TDI) and the biphenol moiety. The liquid crystalline phase (mesophase) and crystalline phase were investigated primarily with differential scanning calorimetry (DSC), wide angle X-ray scattering (WAXS) and infrared spectroscopy. From this combination of characterization techniques, a more detailed description emerges about the thermodynamic stability and kinetic accessibility of each phase. Previous investigation of the (2,4-TDI/BHHBP) mesogenic polyurethane, 2,4-LCPU-6, has shown that this polymer is a monotropic liquid crystal. The influence of H-bonding on the structure and phase behavior of 2,4-LCPU-6 was determined by the synthesis of high molecular weight N-Methyl 2,4-LCPU-6, using a novel high temperature polymerization of a biscarbamoyl chloride with the BHHBP mesogenic diol. The comparison of the structure and physical properties of these two polymers revealed that H-bonding does not affect the mesophase morphology although its absence disrupts crystallinity and results in an enantiotropic liquid crystal. In addition, it was found that the effect of H-bonding on the mesophase-isotropic transition is enthalpic in nature. In contrast to the "regular" ($\alpha,\omega$-hexane diol) based polyurethanes (PUs), BHHBP derived polyurethanes (LCPUs) crystallize rapidly from their melts. This is due to the strong nucleating power of their thermodynamically unstable mesophases (monotropic L.C.) Hexafluoroisopropanol fast solvent-evaporation casting or rapid cooling from the melt resulted in thin films or bulk samples with a glassy mesophase morphology. During the subsequent heating scan, the mesophase to crystal transition takes place. Considerable amount of effort was expended to understand the nature of this transition. With the combination of vibrational spectroscopy which provides a measure of the localized structure, along with DSC and WAXS (which examine the long range order) we established the microstructural changes occurring in the different phases. Applying the results of previously mentioned analysis (kinetic control and phase perfection), highly oriented fibers were obtained for the mesogenic polyurethanes. Atomistic molecular simulations coupled with X-ray intensity refinement allowed us to determine the crystalline chain conformation and packing characteristics for the 2,6-LCPU-6 and 1,3-LCPU-6 (2,6-TDI and 1,3-Phenylene Diisocyanate (1,3-PDI) derived LCPUs). On the basis of structural similarity and well resolved WAXS powder patterns we extended the similar analysis to the "regular" polyurethanes as well (2,6-PU-6 and 1,3-PU-6). The good correlation between H-bonding distance and melting temperature for these four polymers suggests that melting is primarily controlled by the dissociation of H-bonds in the ordered domains.

A study of the adsorption of block copolymers with respect to such variables as adsorption rate, concentration, molecular weight, relative block sizes, architecture, adsorption solvent, and temperature was conducted for the adsorption block copolymers to silanol surfaces. Poly(styrene-b-isoprene) and poly(styrene-b-1,2-butadiene) with precise molecular weight and narrow polydispersity were synthesized by anionic polymerization techniques. These block copolymers were then specifically modified to incorporate an organic moiety (sticky foot) which would promote adsorption. Hydrosilylation to incorporate trimethoxysilanes into the diene block was unsuccessful due to low reaction yields and crosslinking. Hydroboration/oxidation to incorporate alcohols into the diene block was used to prepare polymers for adsorption studies due to the high reaction yields with no crosslinking. Adsorption studies examining the effects of molecular weight, number of adsorbing segments, time, concentration, polymer architecture, and adsorption solvent were conducted for the adsorption to aerosil 130. Adsorptions were analyzed by UV spectroscopy and thermal gravimetric analysis. Adsorption studies examining the effects of molecular weight, relative block sizes, and temperature were conducted for the adsorption to glass slides. Adsorptions were analyzed by water contact angle and X-ray photoelectron spectroscopy. The competitive polymer adsorptions between two different polymers adsorbing to aerosil 130 were studied. Simultaneous adsorptions for two polymers with respect to concentration were examined for three separate sets of polymers. The polymers were adsorbed to aerosil 130 and analyzed by gel permeation chromatography. Sequential competitive adsorptions for these same polymer sets were also conducted using the same substrate and analysis technique. The effect of surface affinity on polymer adsorption was examined by adsorbing one polymer sample to a series of different surfaces. Poly(chlorotrifluoroethylene) polymers with carboxylic acid, alcohol, amine, and ethyl ester surfaces as well as glass slide and aminated glass slide surfaces were prepared and used for adsorptions. These adsorptions were analyzed by X-ray photoelectron spectroscopy.

The structure-property relationships in a new class of segmented copolymers, the smectic forming main chain liquid crystal polymers (LCPs), were systematically investigated. Soft segment length effects on polymer thermal phase behavior were studied. A series of segmented copolymers with different soft segment average lengths were prepared and characterized. Increasing soft segment length was found to favor the formation of smectic mesophases, irrespective of soft segment polydispersity. For interpreting the observations, a semi-quantitative thermodynamic theory was formulated, and a universal thermal phase diagram was proposed for segmented copolymers. Crystalline state structure and mesophase aggregation of these polymers were investigated. A crystalline state structure, in which the hard and soft segments are microphase separated, some of the soft segments have nearly fully extended conformation, and the hard segment crystal structure is independent of soft segment length, was proposed for smectic forming LCPs. The soft segment length was found to have significant effects on hard segment aggregation in the smectic phase. The observed thermal properties were interpreted. Morphology in the smectic state and melting behavior of a smectic forming LCP were studied. In the stable smectic state, the polymer showed a macrophase separated morphology, comprising smectic domains and an isotropic 'sea'. These smectic domains are cylindrical in shape and tens of microns in size. On cooling from smectic state, both smectic and isotropic phases crystallized and formed two different crystal structures. Consequently, the polymer showed dual melting endotherms, with their appearance strongly depending on sample thermal history. Crystallization kinetics of three different phases were investigated in a smectic forming LCP. The purely isotropic phase showed similar crystallization behavior as ordinary polymers. The crystallization of the purely smectic mesophase was found to be a local reorganization process and occurs within hard segment layers. The crystallization of the smectic-isotropic biphase showed complicated behavior, due to the simultaneous crystallization of both phases. The smectic phase was believed to nucleate the crystallization of the isotropic phase. Rheological behavior in the smectic state was investigated. A strong shear thinning at low shear rates was observed. On frequency sweeps, the polymer showed a two zone behavior, a 'solid-like' zone and 'liquid-like' zone. Further morphological investigations indicated that by low-rate shearing, the smectic domains were aligned along the shear direction. The domain alignment by flow was believed to be responsible for the observed rheological properties. By elongational flow, the polymer chains can also be oriented.

Diverse experimental techniques were used for the determination of acetaminophen (N-(p-Hydroxyphenyl)acetamide, N-acetyl-p-aminophenol) in aqueous and non-aqueous media. A study was performed on the electrochemical characterization of acetaminophen at a noble-metal electrode. A pretreatment procedure on the gold electrode was developed under basic conditions. The anodic peak current was the analytical parameter used. Spectrometric techniques were used as detection means, and their analytical potential was evaluated. Infrared techniques such as transmission and attenuated total internal reflection (ATR) were used for the quantitative determination of acetaminophen. The molar absorptivity of acetaminophen was calculated at the carbonyl infrared band from the calibration data obtained from the experiments performed in non-aqueous solvents using the transmission technique. The attenuated total internal reflection technique was used to overcome limitations on the use of the infrared transmission technique for aqueous based systems. A quantitative study was undertaken of the possibilities for the determination of acetaminophen in aqueous solutions by coupling flow injection analysis (FIA) with Fourier transform-infrared (FT-IR) spectrometry. Optimization of the basic flow injection FT-IR system was performed. The cylindrical internal reflection cell for liquid evaluation (CIRCLE$\sp\circler$) was used as the detector cell compatible with aqueous solutions. Applications to systems involving on-line chemical reactions by coupling the flow injection analysis technique with infrared spectrometric detection were described. Flow injection spectrophotometric and infrared detection methods were developed for the determination of acetaminophen based on its hydrolysis reaction with sodium hydroxide to form p-aminophenol and its oxidation with potassium ferricyanide to produce an orange-red species, p-benzoquinonemonoimine. The developed methods were evaluated by analysis of tablets of a commercial formulation. The ability of flow injection techniques for generating transient product profiles combined with the infrared mode for monitoring reaction species was investigated to help in the study of reaction mechanisms. Ab initio calculations were performed on acetaminophen at the 3-21G level of the theory. Structural parameters were optimized for the two conformations of acetaminophen. The calculated and experimental spectra were compared in terms of the infrared vibrational frequencies.

<p> In this work the redox properties of cytochrome c nitrite reductase (CcNiR), a decaheme homodimer that was isolated from <i>S. oneidensis,</i> were determined in the presence and absence of the strong-field ligands cyanide and nitrite. Four hemes per CcNiR protomer are hexa-coordinate with tightly bound axial histidines, while the fifth (active site) has one tightly bound lysine and a distal site that can be open, or contain exogenous ligands such as the substrate nitrite. Controlled potential electrolysis in combination with UV/visible absorption (UV-vis) and electron paramagnetic resonance (EPR) spectroscopies allowed for assignment of all heme midpoint potentials under each set of conditions. The studies show that the active-site heme is the first to be reduced under all conditions. The midpoint redox potential of that heme shifts approximately 70mV to the positive upon binding a strong field ligand such as nitrite or cyanide. When controlled potential electrolysis was carried out in the presence of nitrite, a concerted two electron reduction was observed by UV-vis, and a {Fe(NO)}⁷ reduced product was revealed in EPR. In addition, an asymmetry in ligand binding between active sites was revealed. This information is relevant for the interpretation of planned and ongoing mechanistic studies of CcNiR. </p><p> Over-expression, partial purification and characterization of another <i> S. oneidensis</i> multiheme enzyme, known as octaheme tetrathionate reductase (OTR), is also described herein. Though of unknown cellular function, OTR was previously reported to have tetrathionate reductase activity, in addition to nitrite and hydroxylamine reductase activities. The new results indicate that the expression of OTR has no effect on tetrathionate or nitrite reductase activities in the whole cell lysate, and only hydroxylamine reductase activity was substantially elevated in the overexpressing bacteria. OTR was stable in buffered solutions, but substantial activity loss during all attempts at column chromatography was a major obstacle to the complete purification. OTR also proved quite hydrophobic, so possible membrane association should be considered in future attempts to purify this protein. </p><p> Finally, this dissertation also reports attempts to improve <i> S. oneidensis'</i> ability to express foreign proteins. Though ideally suited to expressing c-hemes, it proved difficult to express carboxy his-tagged proteins in <i>S. oneidensis</i> because of persistent tag degradation. Attempts to knock out lon protease, a cytoplasmic carboxypeptidase, as well as the result of redirecting ccNiR from the SecA to the possibly more protected signal particle recognition (SRP) secretion pathway, are described. </p><p> Iron heme cofactors are single-electron transport moieties that play a crucial role in respiration. While oxygen is the electron acceptor of choice in aerobic atmospheres, microorganisms that live in anaerobic environments utilize other molecules with similarly high reduction potentials. <i> S. oneidensis</i> can utilize numerous terminal electron acceptors, including nitrite, dimethylsulfoxide and even uranium, thanks to a particularly rich array of multi c-heme respiratory proteins. Understanding of how the midpoint potentials and heme arrangements within the proteins influence these exotic respiratory processes is of interest in the fields of bioremediation and fuel development.</p>

Thesis (Ph. D.)--University of Pennsylvania, 1927. / 'Literature": p. 29.