acase@tulane.edu

<p>We have found that calixarenes are good receptors of choline (trimethylammonium group) and they have strong affinity to form host-guest complexes with a variety of molecules carrying this moiety. Furthermore, the ability of lower rim carboxylic acid calix[n]arenes and upper rim phosphonic acid functionalized calix[4]arene to transport choline-conjugated drugs through a liquid membrane was discovered. The results demonstrate that these systems are highly efficient toward transporting choline-conjugated targets, as well as neurotransmitters that possess ionizable amine termini. The breadth of compounds that are transported is significant, facing limitations only when the payloads become extremely lipophilic. These developments reveal new approaches towards attempting synthetic receptor mediated selective small molecule transport in vesicular and cellular systems.

Toxicological and forensic applications of analytical chemistry provide both interesting and unique opportunities for analytical chemists to hone their skills and push their abilities. Modern analytical chemistry has afforded researchers the ability to probe into the intricate pathways of biochemical processes by systematic identification and characterization of biologically relevant compounds. Unfortunately, often due to the restrictive specifications of the instrumentation used, it is necessary to remove those compounds from their natural environments such that their structure and at the very least the significance of those compounds may not be fully recognized. The work described herein identifies and characterizes two biologically relevant arsenic and selenium containing species. These species were synthesized and identified in environments that are very similar to those found in vivo. The use of chemical information contained within a small arms cartridge has seen extremely limited use by forensic laboratories despite the wealth of chemical information that may be useful in differentiating between cartridges of various manufacturers. The study herein uses the elemental composition of small arms rifle primers to develop a multivariate model against which unknown primers were compared and ultimately classified. The FBI's practice of elemental analysis of small arms projectiles has recently come under fire as the result of an ex-FBI metallurgist's research study which concluded that the trace elements analyzed were too rigidly controlled by Pb smelters and therefore not useful in distinguishing between batches of ammunition. The scientific community is now scrutinizing the practice with a National Academy of Science review of the FBI's practices. Unlike the trace elements utilized by the FBI for distinguishing between projectiles of various "origins" Pb isotopic signature is not controlled by smelters and should, even in the case of recycled Pb, vary when Pb from differing origins is utilized for the manufacture of small arms projectiles. The study described herein shows that Pb isotopic analysis of small arms projectiles from various regions of the world is useful for differentiating between small arms projectiles and in limited cases may even be useful in determining the geographic origin of projectile manufacture.

A high-performance thin-layer chromatographic (HPTLC) separation system coupled with a scientifically operated charge-couple device detector (CCD) has been developed to improve the identification and quantitative analysis of pharmaceutical products and natural toxins. The combination of the fast, easy and high throughput properties of TLC, high speed, sensitivity, wide dynamic range of the CCD detector, and the high reproducibility and accuracy of the micro-nebulization sampler can be used to facilitate pharmaceutical industrial quality control and food industrial safety control. The application of this system in these areas has shown significant improvement in sensitivity, precision, and accuracy.

The synthesis, structure, and properties of a number of new octasubstituted phthalocyanines, were investigated in this work. Substituent functionality and design has a profound influence on the film forming, and hence, chemical/physical properties of these model molecular electronic materials. Highly ordered thin films, of the benzyl terminated Pc, (2,3,9,10,16,17,23,24-octa(2-benzyloxyethoxy) phthalocyaninato) copper, CuPc(OC₂OBz)₈ and its di-hydrogen analogue were prepared and characterized. These materials form ordered Langmuir films composed of close packed columnar assemblies. Full compression of these materials produces thin films of stable bilayers that show remarkable mechanical stability, and can be transferred with high efficiency to substrates using a horizontal transfer protocol. The physical, spectroscopic, spectroelectrochemical, electrochemical, and electronic properties of these materials were characterized. These properties are strongly dependent on film morphology and structure. The conductivity of these materials relative to the Pc column axis, is highly anisotropic, and with electrochemical doping, the conductivity along the column axis is ca. 10⁻⁶ S/cm. 2,3,9,10,16,17,23,24-Octa(2-benzyloxytriethoxy) phthalocyaninato) copper, and di-hydrogen materials were prepared and characterized. These Pc derivatives did not exhibit the extraordinary properties of their shorter chained analogues. Film preparation efforts with these materials produced poorly ordered isotropic films. Chain length and benzyl termination are combined, in CuPc(OC₂OBz)₈, to produce a unique self assembling material with properties comparable to that reported previously for rigid-rod polymeric Pc materials.

Atmospherically-relevant surface reactions were studied. These reactions were investigated to provide insight into the products formed on sea salt atmospheric particle surfaces, the quantitative distribution of species on the surface of model sea salt particles, and the molecular environment of the interfacial region of HNO₃/H₂O ices. The reactions of model sea salt particles (NaCl) exposed to mineral acids (HNO₃ and H₂SO₄) were studied using Raman spectroscopy and atomic force microscopy (AFM). The reaction of powdered NaCl with HNO₃ was studied using Raman spectroscopy. NaNO₃ growth was monitored as a function of HNO₃ exposure in a flow cell. Mode-specific changes in the NO₃- vibrational mode intensities with HNO₃ exposure suggest a rearrangement of the NaNO₃ film with coverage. In the absence of H₂O, intensities of NaNO₃ bands increase with HNO₃ exposure until a capping layer of NaNO₃ forms. The capping layer prevents subsequent HNO₃ from reacting with the underlying. The reaction of NaCl with H₂SO₄ is investigated using Raman spectroscopy and atomic force microscopy (AFM). Raman spectra are consistent with the formation of NaHSO4 with no evidence for Na₂SO₄. The spectra indicate that the phase of NaHSO₄ varies with the amount of H₂O in the H₂SO₄. The reaction produces anhydrous β-NaHSO₄ which undergoes a phase change to anhydrous α-NaHSO₄. AFM measurements on NaCl (100) show the formation of two distinct types of NaHSO4 structures consistent in shape with α-NaHSO₄ and β-NaHSO₄ . Model sea salt particles were gown from solution to determine the surface Br/Cl of crystals grown from solution. These studies show surface Br concentration is 35 times that of the bulk concentration. This data is useful in the understanding of enhanced volatile Br compounds in the Arctic troposphere. Thin films of model polar stratospheric cloud (PSC) surfaces were studied in ultrahigh vacuum. Low temperature data show the preferential orientation of HNO₃ on crystalline H₂O ice. Thermodynamically-stable HNO₃ · 3H₂O is formed at ∼170 K, and subsequently desorbs from the surface. These studies show the chemical specificity of Raman spectroscopy in this chemical system. Studies of ClONO₂ adsorption onto crystalline H₂O ice suggest that ClONO₂ is weakly adsorbed.

Xenobiotics and their metabolites are capable of covalent modification of proteins that may lead to cellular injury. Determining the identity of modified proteins, however, has to date been hindered by available analytical instrumentation. Advances in mass spectrometry now allow for routine analysis of large biomolecules. This has given rise to the field of proteomics , which uses mass spectrometry in conjunction with various separation techniques to gain information about large numbers of proteins. This dissertation describes the development of a new proteomic methodology to identify unknown protein targets and its application to identifying protein targets and metabolites of 1,1-dichloroethylene (1,1-DCE). 1,1-DCE undergoes P450 bioactivation in hepatocytes to produce 1,1-DCE oxide and 2-chloroacetyl chloride. These either modify proteins directly, or form the glutathione conjugate S-(2-chloroacetyl)glutathione, which in turn is capable of protein cysteinyl sulfhydryl alkylation. In animals, exposure to 1,1-DCE results in selective injury to the biliary canalicular membrane. Biochemical and physiological evidence suggests damage to the canalicular membrane transport proteins. Putative 1,1-DCE metabolite adducts, including S-carboxymethylated and 2-chloroacetylated peptides and GSCOCH₂-S-cys-peptide adducts, were synthesized using model peptides containing one or two cysteines. The adducts were analyzed by ESI-MS-MS and resulted in fragmentation patterns characteristic of the adduct moiety, including fragment ions, losses from the parent ion and pairs of ions separated by the mass of the modified cysteine residue. The data reduction algorithm SALSA was developed to search for user-specified fragmentation characteristics in MS-MS data dependent scans. Bile samples obtained from animals exposed to 1,1-DCE were analyzed by ESI-MS-MS. SALSA was then used to search the data for spectra containing adduct-specific fragmentation. Five hepatic S-carboxymethylated proteins were identified, as were the 1,1-DCE metabolites S-carboxymethylglutathione, S-(cysteinylacetyl)glutathione and the cyclic product of the intermolecular rearrangement of S-(2-chloroacetyl)glutathione. This work demonstrates the use of mass spectrometry to characterize unknown, modified proteins in complex mixtures without the use of radio- or immunochemical labeling.

Factors affecting the deposition of cocaine into hair and the relationships between those concentrations, survey questionnaire results and natural killer cell activities were investigated. First, two and 18 month old mice were infected with LP-BM5, injected with cocaine, and hair cocaine content measured. There was no difference in cocaine concentration between the age groups. Retrovirally infection mice had greater amounts of cocaine in their hair. Next, a group of mice were fed an ethanol diet and injected with cocaine. There was a decrease in cocaine recovered in the hair of the ethanol-fed mice. In a group of human drug users no correlation was found between survey questionnaire answers and hair cocaine concentrations. There was a correlation between natural killer cell activity and hair cocaine concentrations. It was concluded that hair analysis for cocaine may have a place in clinical settings, but a predictive correlation between drug intake and hair concentration may not be possible.

This thesis investigates the nature of the potential variations in an electrochemical cell. The cell consists of palladium electrodes immersed in a phosphate buffer electrolyte with a Ag/AgCl double junction reference electrode. The relaxation response of the electrodes to an applied potential is examined and current-potential curves ("voltammograms") are generated by plotting the current flowing through an external circuit versus the measured electrode potential. These graphs show regions of hydrogen adsorption/desorption and areas of oxygen adsorption/desorption. The response of the cell to both nitrogen and oxygen "sparging," a technique that alters the gas concentration of the electrolyte, is also studied. Under these conditions, the potential fluctuates in a predictable manner. In addition, the voltage variations of palladium electrodes inserted into stems of tomato plants is investigated to compare results. The goal of this project is to provide evidence supporting the "Oxygen Hypothesis."

<p> This study examines dust in the San Francisco Peaks located on the Colorado Plateau of northern Arizona, USA. Sample dusts were collected from potholes on Humphreys Peak (35^o20'22"N, 111^o41'42"W) in order to detect exogenous material and constrain dust sources. Bulk dust and local rock were characterized by Sr and Nd isotope fingerprints as well as elemental composition. Sr and Nd isotope ratios were analyzed by MC-ICP-MS; trace element concentrations were analyzed by Q-ICP-MS. Mineralogical analyses were also performed in an effort to characterize individual particles. Mineral grains were separated from bulk samples by conventional heavy mineral separations. The heavy fraction was imaged and characterized by SEM/EDX. </p><p> Both the isotopic and elemental bulk analyses indicated that the dust composition reflected not only a weathered local rock material but also exogenous material of continental crust origin. The dust was characterized by an average ⁸⁷Sr/⁸⁶Sr ratio of 0.7095 &plusmn; 0.0010 and an average &epsi;_Nd of -7.13 &plusmn; 0.97. These signatures systematically and significantly deviate from the isotope fingerprints of the local rock, which exhibited an average ⁸⁷Sr/⁸⁶Sr ratio of 0.7037 &plusmn; 0.0002 and an average &epsi;_Nd of -2.43 &plusmn; 0.43. The negative correlation between &epsi;_Nd and ⁸⁷Sr/⁸⁶Sr is consistent with two component mixing of rock evolved from a mantle source and continental crust derived material. </p><p> Several geologically relevant trace elements were found to have significantly different average concentrations in the dust than in the local rock samples. Furthermore, the elemental abundances of most elements in the dust samples suggested a mixture of local rock and continental crust end members with the exception of Pb, which indicated an anthropogenic influence exhibiting enrichment factors between 1.65 and 7.44. </p><p> The mineral analysis provided further evidence of exogenous material and offered the opportunity for further constraint of the sources. Zircons were identified only in the dust and will be analyzed for U-Pb signatures in order to characterize the isotopic fingerprint of individual mineral grains, which will better distinguish external sources. Diatom skeletons were also found exclusively in the dust samples and offer a unique opportunity to more specifically implicate sources through a diatom assemblage.</p>