Chlorpheniramine, a reversible competitive inhibitor at the H1-receptor that has demonstrated potent, long-lasting antihistaminic activity with only mild side-effects, has been a popular choice for the treatment of allergic conditions and is a common component of cold/cough preparations. A number of groups have studied the pharmacokinetics of chlorpheniramine since its development, but results have been conflicting. Moreover, most of the pharmacokinetic studies had only involved analysis of the parent compound and excluded pharmacologically active metabolites. / As part of a new pharmacokinetic study of chlorpheniramine, an enantiomeric method to resolve chlorpheniramine from its N-demethylated metabolites and chlorpheniramine N-oxide was required. The use of high performance liquid chromatography (HPLC) with the amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase (AD-CSP) failed to resolve the enantiomers of chlorpheniramine and its metabolites. Capillary electrophoresis was used to screen a number of chiral selectors including hydroxypropyl beta-cyclodextrin, sulfated beta-cyclodextrin and carboxymethyl beta-cyclodextrin. The resolution of the enantiomers of chlorpheniramine and its metabolites was achieved using carboxymethyl beta-cyclodextrin obtained from Wacker Chemie, Munich, Germany. Detection limits of chlorpheniramine down to 200 ng/mL were achieved by concentrating samples and using sample stacking methods.

The changes which occur in water absorbance in the near-infrared (NIR) region, specifically at 960 nm, are correlated to tissue temperature. One of the temperature-varying constituents of tissue is the change which occurs in the hydrogen-bound states of water. As the temperature is raised, there is an exchange of water species from the hydrogen-bound to non-hydrogen bonding. The aim of this thesis is to determine tissue temperature from NIR spectral profiles of tissue as temperature is increased. A NIR probe was used to obtain spectral profiles for a series of tissue measurements. / Using the data sets obtained, in-vitro measurements conducted on bovine lung tissues show that temperature can be measured to 1.0°C. Likewise, in-vivo measurements conducted on the human finger also show that temperature can be measured to 2.1°C precision. These measurements suggest that tissue temperature can be measured in living systems using NIR temperature detection.

The overall objective of this study was to develop a fluorescent chemosensor for cAMP by creating recognition sites for cAMP, that contain a fluorescent molecule, in a polymer matrix by molecular imprinting. Such a fluorescent molecularly imprinted polymer may, therefore, serve as both the recognition element and the measuring element for the fluorescent detection of cAMP in aqueous media. / Two new fluorescent molecules, known as 4-(p-dimethylaminostyryl)pyridinium salts or dyes, were synthesized as possible fluorescent components of a chemosensor. Upon excitation at 469 run, dye 1, trans-4-( p-N,N-dimethylaminostyryl)-N-vinylbenzyl-pyridinium chloride, displays a dramatic quantum yield enhancement in an emission band centered at ∼600 nm, with concomitant slight red shift of the emission maximum, in the presence of the cyclic nucleotides, cAMP and cGMP, in aqueous solution. Other purine nucleotides (AMP, ADP and ATP) and adenosine induce fluorescence quantum yield enhancements of lesser magnitude than those observed for cyclic nucleotides. The pyrimidine nucleotides, CMP and UMP, have almost no effect on the fluorescence of 1, suggesting a specificity of 1 for purine over pyrimidine analytes. Equilibrium association constants for 1 with the purine analytes, in aqueous solution (pH 7.2) range from 13.9 M --1 for cAMP to 0.15 M--1 for adenine. We conclude that the interaction of 1 with these analytes requires the presence of a purine base, and is enhanced by the presence of ribose and phosphate moieties. Dye 1 and a structurally-similar dye 2, trans-4-(p-N,N-dimethylaminostryl)-N-phenethylpyridinium bromide, also display dramatic fluorescence enhancements in the presence of DNA and proteins, suggesting that they also interact with these biomolecules. The environmentally-sensitive fluorescence of dyes 1 and 2 suggests that such compounds may be useful for developing fluorescent chemosensors for purine nucleotides, especially cAMP, and for the fluorescence detection or staining of DNA and proteins. / To increase the recognition ability of 1 for cAMP, we prepared recognition sites for cAMP that contain fluorescent dye 1 in a polymer matrix by molecular imprinting. This is a novel design for such template-selective sites, since dye 1 forms an integral part of the recognition cavity, thereby serving as both the recognition element and the measuring element for the fluorescence detection of cAMP in aqueous media. The polymer displays a concentration-dependent decrease in fluorescence in the presence of aqueous cAMP, whereas almost no effect is observed in the presence of the structurally-similar molecule, cGMP. An association constant of ∼105 M--1 was calculated for cAMP binding. Such fluorescent molecularly imprinted polymers could serve as a starting point in the development of highly effective synthetic fluorescent sensors for cAMP as well as other important biological molecules.

The principal objectives of this thesis are to introduce a new method, colloidal particle scattering (CPS), to measure colloidal and surface forces, and to demonstrate various applications of this method. CPS determines particle-particle interaction forces through creating particle collisions and extracting the interaction forces from the degree of asymmetry of the collision trajectories. Since the force to deflect a micron-sized particle is much smaller than that to deform a macroscopic spring or cantilever used in a commercial force apparatus, this new technique increases the resolution of force determination by four orders of magnitude. / Based on the CPS principles, we have built a force apparatus called "microcollider". It successfully determined the van der Waals forces and the electrostatic force between two 5 $ mu$m latex spheres at different salt concentrations. A "hairy" latex model was introduced to explain the measured van der Waals forces which are weaker than those predicted by theory assuming smooth latex surfaces. This is consistent with other experimental findings about the surfaces of latex particles. / A similar "hairy" model was applied to determine the adsorption layer thicknesses of two triblock copolymers adsorbed on latex particles. The results show that the configuration of the buoy block composed of polyethylene oxide (PEO) is more extended than a random PEO coil, which agrees with theoretical predictions. Moreover, excellent quantitative agreement between the adsorption layer thicknesses determined by CPS and other methods has been found. / Dynamic steric interactions between two high molecular weight PEO adlayers have also been studied. Both the elastic modulus and the adsorption layer thickness were determined. The results show that a thick layer has a lower elastic modulus than a thin one composed of the same polymer. This implies that an extended loop/tail structure in a thick layer is less stiff than a flat compact one in a thin layer, which is consistent with theory. / In addition, the microcollider can accurately determine particle-wall interactions as well. A rather weak electrokinetic lift force was measured. The results are in good agreement with the solutions rigorously derived from two new theories.

Residual dipolar couplings have been introduced recently as a new type of experimental constraints in biomolecular structure determination by nuclear magnetic resonance (NMR). These interactions are obtained by imparting weak orientational ordering to a biomolecule in a dilute liquid crystal. This results in a partial cancellation of anisotropic interactions such as the chemical shift anisotropy (CSA), the quadrupolar coupling and the dipolar coupling. Because the alignment is weak, only strong interactions manifest. These measurements can be used to refine structure or to define folds in structural genomics projects. Here, I demonstrate the use of a new alignment medium that consists of a nematic Pf1 bacteriophage suspension embedded in an aqueous polyacrylamide gel matrix. In the absence of the gel, the phage particles align spontaneously in the NMR field.

<p> Several heterogeneous catalysts were studied for synthesis gas production through dry reforming of methane (DRM). This process uses carbon dioxide in lieu of the steam that is traditionally used in conventional methane reforming to produce hydrogen that can then be repurposed in more chemical processes [2]. The monometallic catalysts explored were Ni/Al₂O₃ and Ni/CeZrO₂ followed by their bimetallic versions PtNi/Al₂O₃ and PtNi/CeZrO₂ at 800&deg;C. In addition to these catalysts, platinum supported Zeolitic Imidazolate Framework (ZIF)-8 was also investigated in comparison with PtNi/CeZrO₂ at 490&deg;C. The studies suggest that these catalysts are suitable for promoting the dry reforming of methane for hydrogen production.</p>

<p> Many recent efforts in the field of microfluidics have been focused on reducing the size and the complexity of devices and on simplifying the methods of analysis performed with them. Gradient elution moving boundary electrophoresis (GEMBE) is a recently described counterflow electrophoresis method that was developed to simplify the analysis of ions in complex matrices. In this thesis, the improvement of the limit of detection of GEMBE and reduction of the GEMBE channel length is investigated. </p><p> Integration of simple and robust device components required for the successful adaptation of many analytical methods to multiplexed and field-portable devices often has negative effects on detection sensitivity, such as in the optical detection components in a capillary electrophoresis (CE) system. One of the simplest methods to improve sensitivity in the CE field is known as sample stacking. This method involves preparing the sample in a buffer with a different concentration (and conductivity) than that of the run buffer, such that when an electric field is applied the analyte concentration is increased at the boundary between the two different buffer concentrations. A method in which the sample is prepared in a buffer at a lower concentration than the run buffer has been implemented. This method achieves a significantly greater signal enhancement than expected for sample stacking. The concentration enhancement ability of this method is demonstrated utilizing GEMBE with channel current detection. </p><p> Current GEMBE device construction methods impose limitations on the minimum length of the separation channel. One technique well suited for minimizing the size of the GEMBE separation channel is multiphoton absorption polymerization (MAP). Because MAP is a non-linear optical fabrication method, polymerization is limited to a small region near the focal point of a laser beam. As a result, three-dimensional structures with small feature sizes can be easily created. The 3D capabilities of MAP have been exploited to create channels with circular cross sections and &sim;300 &mgr;m lengths for GEMBE. The integration of device components fabricated with MAP and molded with PMDS allows visualization of the GEMBE separations, and provides insights into the effect of channel length on GEMBE step width.</p>

The principle objectives of this thesis are to determine which gases are evolved during alkaline hydrogen peroxide bleaching, and to develop techniques to measure these gases. Also, the relationship of the composition of the evolved gases from alkaline hydrogen peroxide bleaching of mechanical pulp to the reaction kinetics was elucidated. We have shown that the only gas being evolved into the bleaching headspace is oxygen; whereas, carbon dioxide is produced and fixed in solution as carbonate. / A new non-invasive technique for measuring the amount of oxygen evolved throughout the bleaching reaction was developed. This technique is able to be used in laboratory bleaching experiments that simulated most industrial parameters except consistency, which is limited to hand mixing at medium (10--12%) consistencies. With this method, we have shown that pulp washing, caustic charge and addition of chelating agent play key roles in the rates of oxygen evolution due to the decomposition of hydrogen peroxide. Better washing and higher chelating agent additions result in significant lowering of the rates of oxygen evolution. The rate of decomposition has been related to the dissociation of hydrogen peroxide which is dependent on pH. / The effect of transition metal ions on the kinetics of hydrogen peroxide decomposition during alkaline hydrogen peroxide bleaching of mechanical pulps was investigated. Iron, whether added or native to the pulp, did not contribute to the decomposition of hydrogen peroxide in the presence of lignin. Manganese is the main catalyst for peroxide decomposition, whether added or native to the pulp. The initial rate of oxygen evolution, in the presence of manganese, varies linearly with manganese concentration. Although alkali itself does decompose hydrogen peroxide, increased caustic charge results in an increase in the manganese induced decomposition rate. Kinetic equations are presented, which account for manganese concentration and caustic charge. The effect of DTPA on reducing the rate of hydrogen peroxide decomposition has been attributed to the chelation of manganese. / The relationship between hydrogen peroxide decomposition and the oxidation state of iron and manganese was determined visually. The effect of other bleaching additives on the catalyzed decomposition of hydrogen peroxide were also evaluated. Manganese is unreactive in the +II state, yet very reactive in the +III and +IV forms. Iron is not reactive in the presence of lignin. The presence of cellulose acts to prevent the formation of large low surface area precipitates of manganese III and IV. Manganese IV is the most likely reactive species in alkaline hydrogen peroxide bleaching. DTPA will bind Mn(II) but not the other oxidation states. The DTPA-manganese complex once formed is stable even after the pH is increased. / A new technique for the determination of carbon dioxide produced during hydrogen peroxide bleaching is presented. Carbon dioxide is produced during alkaline hydrogen peroxide bleaching, from reactions of hydrogen peroxide and lignin. The rate of carbon dioxide evolution varies linearly with lignin concentration. Kinetic equations are presented and rate constants have been calculated. The source of carbon dioxide is most likely decarboxylation of carboxylic acid groups formed in lignin by alkaline hydrogen peroxide oxidation.

31P NMR spectroscopy was further developed for the structural elucidation of lignin by undertaking a series of systematic studies. More specifically, a detailed model compound investigation showed that 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane is an additional phosphitylation reagent which may provide further quantitative structural information about lignin. Correlation analysis using the Hammet principles revealed that the 31P chemical shifts of lignin- related phenolic hydroxyls with various substitution patterns strongly depend on the nature of the substitution. Such structure-chemical shift correlations led, for the first time, the development of a set of empirical parameters that permits the accurate prediction of 31P chemical shifts of lignin-related phenolic compounds. Furthermore, the 31P NMR technique was coupled with the Mannich reaction. This unique combination allowed the quantification of various types of phenolic hydroxyls in lignin such as para-hydroxyl phenols, catechols, guaiacols, and phenols bearing C 5 or C6 substituents in a novel and nondestructive manner. / The 31P NMR technique was thus applied in order to reveal the structural changes that occur within lignin during kraft pulping and oxygen delignification. The major structural changes occurring on lignin, during the course of conventional kraft pulping were shown to be: (a) the progressive formation of carboxylic acids and condensed phenolic hydroxyl groups and (b) the progressive and stereoselective degradation of the arylglycerol-beta-aryl ether units. It was also discovered that condensed phenolic hydroxyl units are relatively stable toward oxygen delignification. Significant evidence was also supplied accounting for the enhanced delignification efficiency of modern modified pulping processes and the mechanism of xylanase prebleaching of kraft pulps. / The 31P NMR technique was also applied to examine the effect of a lignin isolation process variable (batchwise versus continuous) on the structural details of dioxane acidolysis lignin isolated from kraft pulps. The structure of the dioxane acidolysis lignin, isolated from kraft pulps using batchwise and continuous processes, was shown to have similar functional group distributions and elemental compositions. These results confirmed that the structure of residual lignin in kraft pulps is not altered significantly during a dioxane acidolysis isolation process.

The effect of electrical double layers on the diffusion of spherical colloidal particles was studied using photon correlation spectroscopy (PCS). The diffusion constant was found to equal that of a neutral particle at low and high electrolyte concentration and was reduced by several percent when the electrical double layer is comparable to the particle radius, in agreement with the general theory for charged particles. / PCS studies of bimodal colloidal dispersions included the experimental verification of the bimodal homodyne autocorrelation function and the introduction of quasi-heterodyne detection. / The effect of electrical double layers on the diffusion of rod shaped colloidal particles was studied with PCS, using tobacco mosaic virus particles as probes. The results are qualitatively similar to those for spherical particles, with the minimum occurring when the double layer is comparable to the radius of an equivalent sphere. / The intensity of the light scattered from latex particles in an evanescent wave was measured as a function of the penetration depth of the evanescent wave. The results were found to be consistent with those predicted from DLVO theory.