<p> Radical chemistry has attracted a large amount of research interest over the last few decades and radical reactions have recently been recognized as powerful tools for organic synthesis. The synthetic applications of radicals have been demonstrated in many fields, including in the synthesis of complex natural products. Radical reactions have a number of inherent synthetic advantages over their ionic counterparts. For example, they typically proceed at fast reaction rates under mild and neutral conditions in a broad spectrum of solvents and show significantly greater functional group tolerance. Furthermore, radical processes have the capability of performing in a cascade fashion, allowing for the rapid construction of complex molecular structures with multiple stereogenic centers. To further enhance the synthetic applications of radical reactions, current efforts are devoted toward the development of effective approaches for the regioselective control of their reactivity as well as stereoselectivity, especially enantioselectivity, a challenging issue that is intrinsically challenged by the "free" nature of radical chemistry. </p><p> This research has identified a fundamentally new approach to radical reactions based on the concept of metalloradical catalysis (MRC) for controlling the stereoselectivity of both C- and N-centered radical reactions. Cobalt(II) porphyrins [Co(Por)], are stable metalloradicals, and have been shown to enable the activation of diazo reagents and azides to cleanly generate C- and N-centered radicals, respectively, with N₂ as the only byproduct in a controlled and catalytic manner. In addition to the radical nature of [Co(Por)], the low bond dissociation energy of Co-C/Co-N bonds plays a key role in the successful turnover of the Co(II)-based catalytic carbene and nitrene transfers. Through the support of porphyrin ligands with tunable electronic, steric, and chiral environments, this general concept of Co(II)-based metalloradical catalysis (Co-MRC) has been successfully applied to the development of various radical processes that enable stereoselective carbene and nitrene transfers. </p>

Thesis (Ph.D.)--Indiana University, Dept. of Chemistry, 2009. / Title from PDF t.p. (viewed on Jul 20, 2010). Source: Dissertation Abstracts International, Volume: 70-12, Section: B, page: 7527. Adviser: Bogdan Dragnea.

Thesis (Ph. D.)--Indiana University, Dept. of Chemistry, 2006. / "Title from dissertation home page (viewed July 16, 2007)." Source: Dissertation Abstracts International, Volume: 67-10, Section: B, page: 5718. Adviser: David E. Clemmer.

Thesis (Ph. D.)--University of Illinois at Urbana-Champaign, 2006. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6424. Adviser: Ralph G. Nuzzo. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph. D.)--University of Illinois at Urbana-Champaign, 2006. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6426. Advisers: Paul J.A. Kenis; Andrzej Wieckowski. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

In order to develop safe and effective topical and transdermal formulations to treat either local skin disorders or for systemic drug delivery, it is first imperative to assess skin permeation using a reliable and comprehensive analysis method. The assessment of drug permeation into/across the skin is traditionally accomplished using Franz diffusion cells with subsequent analysis by conventional chromatographic methods such as HPLC and more recently using advanced imaging techniques. In this context, time of flight-secondary ion mass spectrometry (ToF-SIMS) offers distinctive advantages in mapping drugs within skin with high sensitivity and chemical specificity without the need for fluorescent tags or radiolabels. The work in this thesis uses the combination of conventional and advanced methods to evaluate drug permeation into the skin. This approach provides complementary and detailed information regarding the permeated mass, the permeation depth and the spatial distribution and localisation of drugs within skin. As ToF-SIMS does not produce quantitative results, due to the matrix effects, a novel high throughput method was successfully developed to quantify ToF-SIMS data. This method involved the homogenisation of skin tissue followed by microarray printing of this skin homogenate with known concentrations of active pharmaceutical ingredients, specifically imiquimod and chlorhexidine. The subsequent analysis by ToF-SIMS of the resulting array allowed the generation of a calibration curve that can be used in the quantification of the unknown drug concentration in the tape strips. This work has demonstrated the potential of a method to quantify ToF-SIMS data of drugs within skin. Imiquimod is an immune modulator drug approved by the FDA for the treatment of superficial basal cell carcinoma (BCC) but not the nodular lesions. An assessment of imiquimod permeation from commercially available Aldara™ cream into ex vivo porcine skin was carried out using the complementary approach of HPLC and ToF-SIMS analysis. This work represents the most detailed assessment to date of the true extent of permeation of imiquimod from Aldara™ cream as previous studies analysed the permeation of Aldara™ cream showed a limitation in the analytical methodology employed (i.e. analysis by HPLC only). The results showed that imiquimod does permeate into the stratum corneum but is very limited in the deeper skin cell layers. In addition, the ToF-SIMS ion images of Aldara™ cream tape strips illustrated a non-uniform distribution of imiquimod within skin which may result in a decreased efficacy of the cream to uniformly treat whole BCC lesions giving rise to the likelihood of tumour recurrence. This offers previously unobserved insights about the spatial distribution of imiquimod delivered from Aldara™ cream. As other studies have reported that Aldara™ cream has some limitations in the treatment of nodular BCC lesions due to the cream’s inability to deliver imiquimod into the deeper more invasive nodular lesions, an enhancement of imiquimod permeation is thought to be useful to overcome these limitations. Therefore, an attempt to improve delivery of imiquimod into the deeper skin layers using microemulsions and microneedles was investigated. Imiquimod microemulsions were formulated, characterised and then tested for skin permeation enhancement. However, the assessment of imiquimod permeation from the formulated microemulsions alone and with microneedle pre-treatment using HPLC and ToF-SIMS demonstrated a limited ability of the microemulsions to improve delivery of imiquimod over Aldara™ cream. In contrast, Aldara™ cream with microneedle pre-treatment using a derma stamp electric pen showed improved delivery of imiquimod into the skin. This work is believed to be the first attempt to enhance imiquimod delivery using microemulsions and microneedles. Utilising the high sensitivity offered by the ToF-SIMS instrument in the analysis of individual tape strips, an in vivo and ex vivo comparison of chlorhexidine permeation into the stratum corneum was performed using commercial products currently used in hospitals within the UK for skin antisepsis. A comparison was carried out using the tape stripping technique with subsequent analysis of an individual tape strip by ToF-SIMS. The results showed that HiBiSCRUB® 4% produces a higher concentration of chlorhexidine in the upper stratum corneum layers than other products. This work demonstrated the first known application of ToF-SIMS to compare the in vivo skin permeation of commercially available chlorhexidine products and provides the foundation for the potential application of ToF-SIMS in assessing bioequivalence of topical products.

<p> Measurement of the vapor-liquid equilibrium (VLE) of fluid mixtures with many components presents a challenge. Data describing such mixtures, like fuels, are important for the development of alternative energy sources and to support forensic science, but there is a lack of suitable instrumentation to provide data with reasonable uncertainty for mixtures with many components. In this thesis, three different techniques for fluid characterization are explored: the advanced distillation curve (ADC), the advanced distillation curve with reflux (ADCR), and PLOT-cryoadsorption. Two pyrolysis fuels similar to gasoline and diesel fuel made from polypropylene were studied with respect to volatility, composition, and energy content using the advanced distillation curve. The diesel fuel demonstrated volatility very similar to previously measured diesel fuels. The gasoline was less volatile than petroleum-derived counterparts and did not meet specifications.</p><p> Two pyrolysis crude oils made from ponderosa pine and dairy manure were assessed using the ADC coupled to an approach for characterizing fluids with multiple, immiscible liquid phases. Both oils contained high water levels and would require further refinement before use. The organic phases of each oil contained components indicative of the feedstock used.</p><p> A modification of the ADC method, the advanced distillation curve with reflux, was introduced as an approach to measuring the VLE of fluids with many components. The ADCR additionally approximates the weathering of an ignitable liquid that occurs during an arson fire and measures VLE across a range of weathered conditions. The method was demonstrated using two simple mixtures. The measurements agreed well with models, indicating that ADCR is a suitable VLE metrology.</p><p> Vapor-liquid equilibrium data are crucial for interpreting the results of headspace characterization used often in forensic science. One headspace method, portable PLOT-cryoadsorption, was tested in a series of experiments in the laboratory and then deployed for the first time in a field environment that simulated a cargo container. The technology was found to be rapid and sensitive to a variety of compounds of interest to forensic science. Each of the three techniques described in this thesis contribute valuable property data for multicomponent mixtures, towards the development of high-quality predictive models.</p><p>

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has proven its ability to characterise (in)organic surfaces, and is increasingly used for the characterisation of biological samples such as single cells. By combining ion imaging and molecular depth profiling it is possible to render 3D chemical images, which provides a novel, label-free way to investigate biological systems. Major challenges lie, however, in the development of data analysis tools and protocols that preserve the cell morphology. Here, we develop and employ such tools and protocols for the investigation of neuronal networks. One of the reasons 3D ToF-SIMS imaging of cells is underused is the lack of powerful data analysis tools as 3D ToF-SIMS measurements generate very large data sets. To address this issue, we developed a method that allows the application of principal component analysis (PCA) to be expanded to large 3D images making 3D ToF-SIMS image processing of whole, intact cells and cellular networks with multivariate analysis now accessible on a routine basis. Using this method, we are able to separate cellular material from the substrate and can then correct z-offsets due to the cells' topography resulting in a more accurate surface heightmap. The method also facilitates differentiation between cellular components such as lipids and amino acids allowing the cell membrane, the cytoplasm and the extracellular matrix (ECM) to be easily distinguished from one another. These developments permit us to investigate the intracellular localisation of specific native and non-native compounds label-free, not just in single cells but also in larger cellular networks. The visualisation of the cellular uptake of non-native compounds, namely fluorescent dyes, in primary rat cortical neurons and the chemical differentiation between cell types, namely primary rat cortical neurons and retinal pigment epithelium (RPE) cells, are presented as applications. Even though the dyes have distinct fragment ions in the high mass range, it was not possible to detect the fluorophores by 3D ToF-SIMS imaging of freeze-dried cells. However, it was possible to detect distinct differences in the kind of ions detected for freeze-dried primary rat cortical neurons and RPE cells albeit in the low mass range. To obtain meaningful results, however, it is paramount that sample preparation does not induce significant physical or chemical changes. We present the first comprehensive comparison between large 3D ToF-SIMS images of freeze-dried and frozen-hydrated cells using PCA to facilitate the data analysis of these large data sets. A higher degree of colocalisation of the K+ signal with cell regions is observed for frozen-hydrated cells, which indicates a lower degree of membrane damage and migration of diffusible chemical species. Frozen-hydrated cell samples are therefore considered to best reflect the native cell state, but freeze-dried cell samples allow far easier sample handling. The mass spectrum of frozen-hydrated cellular material also has increased ion intensities for higher-mass fragments, which is an additional advantage, because the poor signal-to-noise ratio of molecular species with m/z > 200 is a major bottleneck in the advancement of ToF-SIMS imaging as a diagnostic tool.

Made available in DSpace on 2014-06-11T19:35:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-09-19Bitstream added on 2014-06-13T19:44:57Z : No. of bitstreams: 1 paschoal_fmm_dr_araiq.pdf: 1129326 bytes, checksum: ba6f1cd9d72e5bcf9c9195583366e128 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O presente trabalho ilustra diversas aplicações da técnica de fotoeletrocatálise, tais como: degradação de corantes têxteis, corantes de curtumes, surfatantes, redução de Cr(VI) a Cr(III) e redução de bromato a brometo, usando eletrodos de filmes finos de Ti/TiO2 e luz ultravioleta. A oxidação fotoeletrocatalítica de soluções simuladas de efluentes de curtumes contendo dicromato de potássio, o corante ácido vermelho e o surfatante Tamol® foi investigada em Na2SO4 0,1 mol L-1 usando anodos de filme fino de TiO2 sob potencial de + 1,0 V e irradiação UV-Vis. Foi obtido 100% de remoção do corante ácido vermelho 151 e 98,5% de redução de Cr(VI) a Cr(III) e 94,6% de remoção de carbono orgânico total (COT), após 60 min de fotoeletrocatálise em pH = 2,0. A técnica de fotoeletrocatálise foi ainda aplicada na degradação de dois efluente industriais contendo corantes dispersos em Na2SO4 0,1 mol L-1. Os resultados obtidos mostraram descoloração de 95%, 97%, e 100% de remoção dos corantes dispersos: laranja, rubi e vermelho dispersil, sendo que a porcentagem de mineralização foi de 62,7%; 43,3% e 61,3%, respectivamente. Remoção de 80-89% da coloração dos efluentes foram conseguidas após 360 min de fotoeletrocatálise, concomitante à redução de 49,8% e 46,8% de COT e 50% de redução da demanda química de oxigênio (DQO). O método mostrou-se ainda adequado para a redução de 0,25 mg L-1 de bromato a brometo com máxima performance sob potencial de -0,2 V e luz UV, usando o Ti/TiO2 como fotocátodo. O método promoveu 65% de redução de bromato após 75 min de tratamento. / In the present work has been studied the application of photoelectrocatalytic process to degradation of acid dyes, disperse dyes, surfactant, Cr (VI)/Cr (III) reduction and BrO3 -/Brreduction, using Ti/TiO2 electrodes and UV- Vis irradiation. The photoeletrocatalytic oxidation of simulated leather industry wastewater containing Cr(VI), acid red 151 dye, Tamol® surfactant was investigated in Na2SO4 0,1 mol L-1 solution using Ti/TiO2, potencial of + 1.0V and UV irradiation. 100% of color removal, 98.5% of Cr(VI)/Cr (III) reduction and 94.6% of TOC removal were obtained after 60 min of treatment at pH = 2.0. The photoelectrocatalytic process was successfully applied in the wastewater degradation of textile industry too. The results have shown 95%, 97% and 100% of color removal for orange, ruby e red disperse dyes concomitant to reduction of 62,7%; 43,3% e 61,3% TOC values, respectively. Two wastewater was analyzed and the results present 80-89% of color removal, 49,8% and 46,8% of TOC removal and 50% of COD after 360 min of photoeletrocatalytic treatment. The reduction of bromate to bromide was also followed by photoeletrocatalytic treatment testing 0.25 mg L-1 of bromate in NaCl using Ti/TiO2 electrode, UV irradiation and potential of - 0.2V. The method has shown 65% of bromate concentration reduction after 75 min of treatment.

Made available in DSpace on 2014-06-11T19:35:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-06-05Bitstream added on 2014-06-13T19:44:58Z : No. of bitstreams: 1 fenga_pg_dr_araiq.pdf: 2825323 bytes, checksum: eb7999dc4367e967d0bf7e64d6ce6966 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Anilinas substituídas de interesse farmacológico, empregando-se cristais piezelétricos de quartzo modificados com hexacianoferrato de zinco (ZnHCF) e de prata (AgHCF). Além da utilização dos cristais piezelétricos, empregaram-se eletrodos compósito grafite-epóxi e nanotubos de carbono modificados com estes hexacianometalatos de metais de transição, também, para a determinação das anilinas substituídas em formulações farmacêuticas. Todos estes eletrodos testados foram empregados com êxito no desenvolvimento de um método eletroanalítico para a determinação das anilinas substituídas, baseado na voltametria cíclica associada ou não à técnica da microbalança de cristal de quartzo. Sendo assim, o primeiro capítulo apresentado nessa tese explora o comportamento eletroquímico da procaína perante o ZnHCF e AgHCF. Para o ZnHCF, após varreduras sucessivas de potencial nos quais, apenas o hexacianoferrato é eletroativo, picos voltamétricos controlados por difusão bem definidos do cristal piezelétrico de quartzo, recoberto com este filme foram obtidos em +0,95/+0,75 V e com excesso superficial de (1,82±0,76)x10-4 mol cm-2 enquanto que para o AgHCF, este par de picos redox localiza-se em +0,74/+0,65 V, no intervalo de potencial de 0,3 V a 1,0 V, e com excesso superficial em torno de (1,33±0,04)×10-5 mol cm-2. Após a otimização de todos os parâmetros voltamétricos e inerentes da técnica, construiu-se a curva analítica para a procaína, em presença do ZnHCF, a qual apresentou um intervalo linear de 1,0x10-4 a 1,0x10-3 mol L-1, com limite de detecção (LOD) = 1,08x10-4 mol L-1. O método desenvolvido foi aplicado para a determinação desse analito em amostras comerciais de procaína, sendo os resultados obtidos, neste trabalho, comparados aos obtidos pelo método oficial extração-espectrofotometria apresentado na Farmacopéia Americana... / In this work, electroanalytical methods for the determination of substitued anilines of interest medical were developed, employing piezoelectric quartz crystal modified with zinc (ZnHCF) and silver hexacyanoferrate (AgHCF) In addition to the use of the piezoelectric, graphite-epoxy composites and carbon nanotubes modified with these metal transition hexacyanoferrates, also, were used for the determination of substitued anilines in pharmaceutical formulations. All these electrodes were tested successfully in developing an electroanalytical method for determining these analytes based on cyclic voltammetry associated or not at the crystal quartz microbalance technique. So, in the first chapter presented in this thesis explores the electrochemical behaviour of the procaine before the zinc and silver hexacyanoferrates For the ZnHCF, after the scans successive potential where only the hexacyanoferrate is electroative, voltammetric peaks controlled by well-defined diffusion of the quartz piezoelectric crystal covered with this film were obtained at +0.90 V/+1.02 V and superficial excess of (1.82 ± 0.76)x10-4 mol cm-2 while for the AgHCF, this pair of redox peaks are located at +0.74 V/+0.65 V, in the potential range of 0.3 V a 1.0 V, and superficial excess around (1.33 ± 0.04)×10-5 mol cm-2. After optimizing all voltammetric parameters and inherent of the technique, the analytic curve was built for procaine in presence of ZnHCF which presented a linear range of 1.0 x 10-4 a 1.0 x 10-3 mol L-1, with detection limit (LOD) = 1.08 x 10-4 mol L-1. The developed method was applied for the determination of this analyte in commercial samples, and the results obtained in this work were compared with those obtained with the official method extraction - spectrophotometry showed by the United States Pharmacopoeia. The voltammetric method associated with the quartz crystal microbalance... (Complete abstract click electronic access below)