No description available.

Th. doct.-ing.--Génie chimique--Toulouse--I.N.P., 1983. N°: 288.

ABSTRACT SYNTHESIS AND CHARACTERIZATION OF SURFACE SULFONATED POLYPROPYLENE FILMS Ecevit, Safiye Tuba M.S., The Department of Polymer Science and Technology Supervisor: Leyla Aras, Prof. Dr. Co- Supervisor: Teoman Tin&ccedil / er, Prof. Dr. March 2004, 44 pages The basic reseach on the surface sulfonation of the polypropylene is very important due to the surface design for higher functionalization. For this purpose, liquid-phase sulfonation of the polypropylene surfaces at various temperatures for different time periods were performed by concentrated sulphuric acid. The physical and chemical changes formed by the effect of the sulfonation on the polypropylene surfaces were determined by contact angle measurement, mechanical analysis, UV-Vis spectrometer, differential scanning calorimeter (DSC) and scanning electron microscopy (SEM). The surface polarity and wetting properties of the samples were evaluated by contact angle measurement. It is seen that, sulfonation at low temperatures and short time periods improve these two properties of the polypropylene surfaces. Sulfonation at high temperatures and long time periods however, cause the partial breakdown of the polymer by degradation. Noticeable color change due to the degradation and carbonization of the polypropylene films sulfonated at high temperature and long time were supported by the UV-Vis spectra of the samples. Mechanical properties of sulfonated PP films were investigated. Consequently, after the sulfonation process the mechanical properties of the PP films showed a general trend of decrease with sulfonation time for a given temperature and a very fast decrease at high temperature of sulfonation. Thermal characteristics were found by differential scanning calorimeter (DSC). Thermal analysis revealed that sulfonated PP film samples displayed an additional endothermic peak. The physical effects of the sulfonation were examined by scanning electron microscopy (SEM) which showed a hexagonal hole formations due to the bursting of the air bubbles within the PP films by the effect sulfonation. The lamelae formations were also seen around these holes.

Recent years have seen a dramatic expansion in synthetic and structural molybdenum - sulfur chemistry. The amplest binary Mo-S moiety in MO$ ion. The thromolybdates derived by sulfur substitution from the 0x0 analogue have interesting chemical properties. Although they have been studied extensively by synthetic inorganic chemists and bio-inorganic chemists as models for enzymes like introgenases, their reactivity towards organic substrates remamed unexplored.

Nevirapine (NVP) can cause serious idiosyncratic drug reactions (IDRs); specifically, skin rash and hepatotoxicity. Treatment of rats or mice with NVP led to covalent binding to hepatic proteins. Studies of this covalent binding including the use of a deuterated analog of NVP leading to a decrease in oxidation of the methyl group indicated that the metabolite responsible for covalent binding in the liver is a quinone methide. Covalent binding in NVP-treated rats was also observed in the epidermis but by a different pathway. Incubation of 12-OH-NVP sulfate with homogenized human and rat skin led to extensive covalent binding. Inhibition of sulfation in the liver significantly decreased 12-OH-NVP sulfate in the blood, but it did not prevent covalent binding in the skin or the rash. In contrast, topical application of a sulfotransferase inhibitor prevented covalent binding in the skin as well as the rash, but only where it was applied. In contrast to rats, treatment of mice with NVP did not result in covalent binding in the skin or skin rash. These findings provide compelling evidence that 12-OH-NVP sulfate formed in the skin is responsible for the skin rash. IL-1β and IL-18 production in the skin of rats treated with NVP were increased. An anti-IL-1ß antibody significantly decreased rash severity. These cytokines were also produced by incubation of human keratinocytes with 12-OH-NVP sulfate. These data indicate that 12-OH-NVP sulfate activates the NLRP3 inflammasome, a pathway known to be responsible for contact hypersensitivity rashes. In summary, NVP was found to produce two different reactive metabolites, a quinone methide species in the liver, and a benzylic sulfate in the skin. Significant liver injury did not occur, presumably due to immune tolerance. Although it is usually assumed that reactive metabolites are responsible for most IDRs, this is the first example to actually demonstrate that a specific reactive metabolite is responsible for an IDR. This is also the first study to show that sulfotransferase in the skin is responsible for bioactivation of a drug leading to a skin rash. It is likely that there are other drugs that cause skin rashes by a similar mechanism.

Nevirapine (NVP) can cause serious idiosyncratic drug reactions (IDRs); specifically, skin rash and hepatotoxicity. Treatment of rats or mice with NVP led to covalent binding to hepatic proteins. Studies of this covalent binding including the use of a deuterated analog of NVP leading to a decrease in oxidation of the methyl group indicated that the metabolite responsible for covalent binding in the liver is a quinone methide. Covalent binding in NVP-treated rats was also observed in the epidermis but by a different pathway. Incubation of 12-OH-NVP sulfate with homogenized human and rat skin led to extensive covalent binding. Inhibition of sulfation in the liver significantly decreased 12-OH-NVP sulfate in the blood, but it did not prevent covalent binding in the skin or the rash. In contrast, topical application of a sulfotransferase inhibitor prevented covalent binding in the skin as well as the rash, but only where it was applied. In contrast to rats, treatment of mice with NVP did not result in covalent binding in the skin or skin rash. These findings provide compelling evidence that 12-OH-NVP sulfate formed in the skin is responsible for the skin rash. IL-1β and IL-18 production in the skin of rats treated with NVP were increased. An anti-IL-1ß antibody significantly decreased rash severity. These cytokines were also produced by incubation of human keratinocytes with 12-OH-NVP sulfate. These data indicate that 12-OH-NVP sulfate activates the NLRP3 inflammasome, a pathway known to be responsible for contact hypersensitivity rashes. In summary, NVP was found to produce two different reactive metabolites, a quinone methide species in the liver, and a benzylic sulfate in the skin. Significant liver injury did not occur, presumably due to immune tolerance. Although it is usually assumed that reactive metabolites are responsible for most IDRs, this is the first example to actually demonstrate that a specific reactive metabolite is responsible for an IDR. This is also the first study to show that sulfotransferase in the skin is responsible for bioactivation of a drug leading to a skin rash. It is likely that there are other drugs that cause skin rashes by a similar mechanism.

The sulfonation of chlorobenzene, chlorobenzene-benzene, and toluene-benzene mixtures by sulfur trioxide in liquid sulfur dioxide at -12.5° C. was studied to obtain isomer distribution and relative rate data. The isomer distribution for the reaction on chlorobenzene was determined by an isotope dillution technique. Relative rate experiments were conducted by sulfonating C14 labeled benzene in competition with nonradioactive chlorobenzene and toluene and the count rate of the products was used to determine product composition. Ultraviolet spectrophotometry was also used to investigate variations in isomer distributions as a function of sulfur trioxide concentration. The apparent relative rates of sulfonation (kX/kB) as calculated by Ingold's equation, vary with both the initial ratio of arenes and the concentration of sulfur trioxide. The ortho/para ratio decreases with increasing sulfur trioxide concentration. These observations are explained in terms of secondary sulfonation reactions which produce significant amounts of product sulfonic acids by reaction of the arenes with reagents other than sulfur trioxide. The secondary sulfonating agents are presumed to be sulfonic acid anhydrides and/or pyrosulfonic acids. The secondary reactions contribute proportionately more to the total product of that species formed in the smaller amounts by the primary reaction. Criteria for the applicability of Ingold's equation are discussed in connection with the possibility of secondary reactions. Relative rate constants for competitive chlorobenzene:benzene and toluene:benzene sulfonation with sulfur trioxide, corrected for secondary reaction effects, are 0.087±0.002 and 27.0±1.0 respectively. The observed isomer distribution for the sulfonation of chlorobenzene is o = 0.95 ± 0.03%, m = 0.09 ± 0.02%, and p = 98.96 ± 0.12%. Partial rate factors calculated for the sulfonation of chlorobenzene and toluene are pf = 0.517, of = 0.0025, mf = 0.00024 and pf = 144.6, of = 81.2, and mf = 0.59 respectively. Neither sulfonation fits the selectivity relationship predicted for it, although correction for secondary reaction effects greatly improves the fit for the toluene data. The deviation of the toluene data from the selectivity relationship probably results from a low percentage of meta isomer in the reported isomer distribution for toluene.

Th.--Sci. phys.--Toulouse--I.N.P., 1978. N°: 29.

Positional proteomics is emerging as an attractive technique to characterize protein termini, which play important biological roles in cells. Even with the advances in past decades, there still are areas for improvement. This thesis focuses on improving data quality and assignment confidence in positional proteomics. A novel workflow was designed for the large-scale identification of protein N-terminal sequences. 4-sulfophenyl isothiocyanate (SPITC) is used for N-termini sulfonation; Upon higher energy collisional dissociation (HCD), SPITC peptides in electrospray ionization ESI generate predominately y-type ion series; such simplification of spectra enables the identification of N-termini with high fidelity. The presence of b1 + SPITC product ions upon HCD furthers the confidence for N-terminal identifications. Secondly, sulfonated N-terminal peptides possess one negative charge site at low pH, which was exploited to enrich the SPITC modified N-terminal peptides by electrostatic repulsion hydrophilic interaction (ERLIC) chromatography. Such enrichment process allows both N-termini enriched and N-termini deficient fractions to be collected and analyzed by LC-MS/MS. This method was applied to an E. coli cell lysate, identifying approximately 350 N-terminal peptides (85% represented neo-N-termini from protein degradation and 15% from leading methionine excision). These N-terminal peptides represented 274 distinct E.coli proteins, 224 of which were also identified in the analysis of flow-through fractions from internal peptides. Another approach we took to boost the identification confidence is by exploiting iTRAQ (isobaric tag for relative and absolute quantitation) in the positional proteomics workflow. This approach allows for multiplexed comparison between different samples, and thus is well-suited for degradadomics analyses where degraded samples are compared to control samples. Both control and protease treated sample are labeled by different tags which allows direct comparison of protein N-termini with neo-N-termini. In addition, samples are analyzed duplicate by labeling with two tags, aiming for quick validation of peptides by internal replicates. In this study, Asp-N digested E.coli cell lysate is taken as a model system. A total of 500 N-terminal peptides, corresponding to 370 proteins, were identified with high confidence in one experiment, with 87% of those proteolytic products matching the expected protease digestion specificity, validating the assignment accuracy of this approach.

A proposta deste trabalho consistiu em realizar o estudo experimental e matemático do processo de sulfonação de resinas estirênicas reticuladas com etileno-glicol dimetacrilato (PS-EGDMA) e trietileno-glicol dimetacrilato (PS-TEGDMA). O processo de sulfonação de resinas estirênicas é uma das modificações químicas mais utilizadas na indústria e permite conferir características como seletividade às resinas, favorecendo seu uso em diversos processos. Foi utilizado um planejamento de Taguchi L9 com os fatores: fração monomérica, fração de agentes reticulantes e fração de solventes inertes (tolueno e heptano), referentes ao processo de polimerização. As resinas produzidas foram utilizadas na sulfonação, na qual a temperatura foi variada para determinar o ponto ótimo em termos de capacidade de troca iônica e variação de massa. Por meio de balanços de massa e fazendo o uso do modelo do núcleo não reagido foi feita a modelagem matemática do processo. Os resultados obtidos mostram que as resinas reticuladas com etileno-glicol dimetacrilato (EGDMA) e trietileno-glicol dimetcrilato (TGDMA) apresentam boa capacidade de troca iônica (CTI) quando comparadas às resinas comerciais de estireno-divinilbenzeno (S-DVB), como, por exemplo, a Amberlyst®. As partículas sulfonadas de PS-EGDMA apresentaram CTI de 3,988 meq/g com ganho de massa de 30% enquanto as de PS-TEGDMA apresentaram capacidade de 3,477meq/g com ganho de massa de 47% no ponto ótimo tendo sido produzidas com temperaturas de sulfonação de 57,5ºC e 65ºC respectivamente. O modelo desenvolvido apresentou bom ajuste no intervalo entre o início da reação e o ponto máximo de capacidade de troca iônica, sendo capaz de prever as constantes cinéticas e de difusão da reação. Além disso, as partículas produzidas foram testadas na catálise heterogênea e conversões acima de 78% foram obtidas mostrando-se um eficiente catalisador. / The purpose of this work was to carry out the experimental and mathematical study of the sulfonation process of styrenic resins cross-linked with ethylene glycol dimethacrylate (EGDMA) and triethylene glycol dimethacrylate (TEGDMA). The sulfonation process of styrenic resins is very used in industry and allows particles to achieve characteristics like selectivity, favoring its use in several processes. It was used Taguchi L9 experimental design with the following factors: monomer molar fraction, fraction of crosslinking agents and fraction of inert solvents (toluene and heptane), referring to the polymerization process. The resins produced were used in the sulfonation process, in which the temperature was varied to determine the optimum point in terms of ion exchange capacity and mass variation. Mass balances and the unreacted core model were in order to develop the mathematical model. The results showed that PS-EGDMA and PS-TGDMA crosslinked resins exhibit good ion exchange capacity when compared to styrene-divinylbenzene (S-DVB) commercial resins, such as Amberlyst®. The sulfonated PS-EGDMA particles showed ion exchange capacity of 3,988 meq/g with a mass gain of 30% while those of PS-TEGDMA presented a capacity of 3,477meq/g with mass gain of 47% at the optimum point and were produced with sulfonation temperatures of 55.7ºC and 65ºC respectively. The developed mathematical model showed a good fit in the interval between the beginning of the reaction and the maximum point of ion exchange capacity, being able to predict the kinetic and diffusion constants of the reaction. In addition, the produced particles were tested in the heterogeneous catalysis and conversions above 78% were obtained proving an efficient catalyst.