The present investigation yielded an orange product upon refluxing 2-butyramido-3-chloro-1,4-naphthoquinone and 2-aminopyridine in ethanol. When this material was purified, by recrystallization from glacial acetic acid, the melting point was 306 [degrees]. This compound has been shown to be benzo(d)pyrido(a)-benzimidazole-5,12-quinone by the present investigation.

We use stepwise [3+3] annulation to prepare the asymmetric glutarimides, and then we can build substituent group in C6 position after choosing regioselective addition reaction. And we establish a new approach to benzo[h]quinoline skeleton starting from glutarimides via ring-closing reaction. Finally, we applied this method to the synthetic studies toward benzo[h]quinoline derivatives.

Despite extensive research, the mechanisms behind cardiovascular effects of subchronic environmental tobacco smoke (ETS) remain unclear, but may be related to ETS-induced inflammation and oxidative stress. Additionally, the protective role of resveratrol (RES), a natural antioxidant available in red grapes, is controversial. We hypothesized that the polycyclic aromatic hydrocarbon (PAH) component of ETS is responsible for causing adverse cardiovascular effects. We also hypothesized that the administration of RES is protective against the adverse cardiovascular effects of ETS. In order to address these hypotheses, male juvenile pigs (4-weeks old) were exposed to ETS or ambient air for 28 consecutive days (1 hr/day) and effects compared to 7 days of i.v. injection of the PAH, benzo-a-pyrene (BAP; 5 mg/kg daily). In another experiment, pigs were sham-exposed or ETS-exposed, with or without oral RES treatment (5mg/kg daily). In all experiments, endothelial and left ventricular function were assessed by flow mediated dilation (FMD), and echocardiography, respectively, while blood pressure was evaluated by oscillometry. At the termination of each experiment, serum nitrotyrosine, total nitrate/nitrite (NOx) and C-reactive protein (CRP) were measured as well as hepatic and pulmonary ethoxyresorufin-o-deethylase (EROD) activity to indicate cytochrome P450 1A1 (CYP1A1) expression. Finally, the correlation between pulmonary inflammation and adverse cardiovascular effects was investigated by measuring total and differential white blood cell (WBC) count as well as leukocyte elastase activity in bronchoalveolar lavage fluid at the termination of each experiment. ETS exposure, but not BAP treatment, resulted in a significant impairment of FMD (P<0.0001) and increased left ventricular end diastolic volume (P=0.0032). Cotreatment with RES failed to restore the ETS induced impairment of FMD (P>0.05). However, a trend pointing to an increase in ejection fraction (EF) was noted (P=0.072). ETS, BAP and RES treatments failed to have any effect on blood pressure (P>0.05). BAP injection caused a significant increase in serum nitrotyrosine (P=0.0146) and CRP (P=0.012), but not serum NOx levels (P>0.05). In contrast, ETS exposure resulted in a significant increase in CRP serum levels (P=0.0092), a trend pointing to increased serum nitrotyrosine (P=0.105), and no change in serum NOx levels (P>0.05). The increased nitrotyrosine and CRP with ETS exposure was not reversed by RES administration (P>0.05). ETS exposure increased EROD activity in the lung (P=0.0093), but not the liver (P=0.12). In contrast, BAP treatment had the opposite effect (lung EROD: P=0.621, liver EROD: P=0.01), while RES administration had no effect (P>0.05). ETS exposure (P=0.0139), but not BAP treatment (P=0.723), resulted in increased WBC count in BAL fluid which was not affected by RES administration (P>0.05). These results show that ETS exposure causes lung inflammation, systemic inflammation, oxidative stress-mediated inactivation of nitric oxide and impaired endothelial function. In contrast, BAP failed to alter endothelial function, downstream of the lung, despite systemic inflammation and increased oxidative stress. Furthermore, RES failed to restore endothelial function, or decrease systemic inflammation and oxidative stress. Taken together, these results suggest either that pulmonary inflammatory responses or pulmonary increases in CYP1A1 activity may be more important links to endothelial dysfunction than systemic inflammation and nitric oxide bioactivity. The beneficial effects of RES by itself are manifested only at the cardiac level by improving the ejection fraction, but the work in this thesis failed to detect any ability of RES to ameliorate ETS cardiovascular effects.

Despite extensive research, the mechanisms behind cardiovascular effects of subchronic environmental tobacco smoke (ETS) remain unclear, but may be related to ETS-induced inflammation and oxidative stress. Additionally, the protective role of resveratrol (RES), a natural antioxidant available in red grapes, is controversial. We hypothesized that the polycyclic aromatic hydrocarbon (PAH) component of ETS is responsible for causing adverse cardiovascular effects. We also hypothesized that the administration of RES is protective against the adverse cardiovascular effects of ETS. In order to address these hypotheses, male juvenile pigs (4-weeks old) were exposed to ETS or ambient air for 28 consecutive days (1 hr/day) and effects compared to 7 days of i.v. injection of the PAH, benzo-a-pyrene (BAP; 5 mg/kg daily). In another experiment, pigs were sham-exposed or ETS-exposed, with or without oral RES treatment (5mg/kg daily). In all experiments, endothelial and left ventricular function were assessed by flow mediated dilation (FMD), and echocardiography, respectively, while blood pressure was evaluated by oscillometry. At the termination of each experiment, serum nitrotyrosine, total nitrate/nitrite (NOx) and C-reactive protein (CRP) were measured as well as hepatic and pulmonary ethoxyresorufin-o-deethylase (EROD) activity to indicate cytochrome P450 1A1 (CYP1A1) expression. Finally, the correlation between pulmonary inflammation and adverse cardiovascular effects was investigated by measuring total and differential white blood cell (WBC) count as well as leukocyte elastase activity in bronchoalveolar lavage fluid at the termination of each experiment. ETS exposure, but not BAP treatment, resulted in a significant impairment of FMD (P<0.0001) and increased left ventricular end diastolic volume (P=0.0032). Cotreatment with RES failed to restore the ETS induced impairment of FMD (P>0.05). However, a trend pointing to an increase in ejection fraction (EF) was noted (P=0.072). ETS, BAP and RES treatments failed to have any effect on blood pressure (P>0.05). BAP injection caused a significant increase in serum nitrotyrosine (P=0.0146) and CRP (P=0.012), but not serum NOx levels (P>0.05). In contrast, ETS exposure resulted in a significant increase in CRP serum levels (P=0.0092), a trend pointing to increased serum nitrotyrosine (P=0.105), and no change in serum NOx levels (P>0.05). The increased nitrotyrosine and CRP with ETS exposure was not reversed by RES administration (P>0.05). ETS exposure increased EROD activity in the lung (P=0.0093), but not the liver (P=0.12). In contrast, BAP treatment had the opposite effect (lung EROD: P=0.621, liver EROD: P=0.01), while RES administration had no effect (P>0.05). ETS exposure (P=0.0139), but not BAP treatment (P=0.723), resulted in increased WBC count in BAL fluid which was not affected by RES administration (P>0.05). These results show that ETS exposure causes lung inflammation, systemic inflammation, oxidative stress-mediated inactivation of nitric oxide and impaired endothelial function. In contrast, BAP failed to alter endothelial function, downstream of the lung, despite systemic inflammation and increased oxidative stress. Furthermore, RES failed to restore endothelial function, or decrease systemic inflammation and oxidative stress. Taken together, these results suggest either that pulmonary inflammatory responses or pulmonary increases in CYP1A1 activity may be more important links to endothelial dysfunction than systemic inflammation and nitric oxide bioactivity. The beneficial effects of RES by itself are manifested only at the cardiac level by improving the ejection fraction, but the work in this thesis failed to detect any ability of RES to ameliorate ETS cardiovascular effects.

Non-point source pollution is not generated from any single source, rather can arise from a mixture of agricultural, residential, and industrial activities. As a result of these activities millions of tons of chemicals enter into aquatic environments annually with the potential to disrupt the fragile ecosystems existing within. Common anthropogenic compounds most frequently seen in estuarine environments include pesticides, antifoulants, polycyclic aromatic hydrocarbons (PAH), and industrial solvents. This dissertation examines the acute toxicity and sub-lethal effects of diuron, CuPT, B(a)P, and styrene in the mud snail, Ilyanassa obsoleta, the American oyster, Crassostrea virginica, the sea urchin, Lytechinus variegatus, and/or the barnacle, Amphibalanus (= Balanus) amphitrite. In addition, the general effects of non-point source pollution within the Rachel Carson Estuarine Research Reserve (RCERR) were examined at six sites in order to gain a better understanding of the current health of this unique habitat. Of the four compounds tested, only the industrial solvent, styrene, resulted in an LC50 (1341 µg L-1, I. obsoleta) that was within the range of currently reported environmental levels. Diuron and CuPT did not elicit mortality at environmentally relevant concentrations, but did significantly reduce fecundity in I. obsoleta and C. virginica and fertilization success and larval development in L. variegatus. The only notable sub-lethal effect elicited by the PAH, benzo(a)pyrene, was a significant decrease in egg capsule production by I. obsoleta following exposure to concentrations as low as 50 µg L-1. Within the RCERR, animals from Sites 4, 5, and 6 were observed to have significant differences with respect to fecundity, condition index, and/or ECOD activity when compared to conspecific organisms from control Site 1. This is most likely a consequence of their proximity to anthropogenic sources. Large variation in mortality (15-98.9%) was observed when families of A. amphitrite from a single population where exposed to CuPT. It is often difficult to extrapolate data from laboratory findings into natural populations. Frequently the organisms used under laboratory conditions are genetically very similar, while field population can vary with anthropogenic exposure. Caution must be taken when developing protocols for risk assessment to ensure that actual environmental conditions are being represented. / Dissertation

Treatment of 1-(methylsulfinyl)-2-(phenylethynyl)benzene with 10 mol % of mercury dichloride and 1 equivalent of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in refluxing benzene gave benzo[b]thiophene in good yields. This method tolerated various functional groups in phenylethynyl moiety, including electron donating groups and electron withdrawing groups. Useing 1-(benzylsulfinyl)-2-(phenylethynyl)benzene as reaction substrate increased the yields of benzo[b]thiophene derivatives. Isotope effect showed that this cyclization reaction belong to Pummerer type cyclization reaction.

In this study, we measured the binding constant, KCOC, between several humic acids and benzo(h)quinoline, a nitrogen contained PAHs via using fluorescence quenching method. KCOC of humic acids and phenanthrene, a parent PAHs, is also studied in comparison. Moreover, pH and ionic strength effect on the KCOC were investigated. According to our results, the phenanthrene¡¦s KCOC decreases as the pH increases due to the lower hydrophobicity of humic acid in higher pH values. The variation of benzo(h)quinoline¡¦s KCOC with pH exhibits a more complicated trend, with a maximum value at pH close to the pKb of benzo(h)quinoline. For pH lower than pKb, benzo(h)quinoline is protonated to be benzo(h)quinolinium, a cation, so that the ionic exchange is the dominant prosess in sorption mechanism. Therefore, the binding sites of humic acid increase with pH such that the KCOC increases with pH. In contrast, different mechanism involved in the binding for pH higher than pKb, neutral benzo(h)qunoline becomes dominant and hydrophobic interaction controls the binding prosess in sorption mechanism. At last, the composition of different functional groups of humic acid is also found significant in the binding affinity of benzo(h)qunoline or phenanthrene. Moreover, the benzo(h)qunoline¡¦s KCOC exhibits decreasing trend with increasing magnesium ionic strength because of the reduction of molecular size as well as the benzo(h)qunoline binding sites of humic acid. Findings from this study could provide valuable information for numerical simulation of transport and fates of HOPs in aquatic environment.

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in the environment and are generated by many sources. Though the potential of PAH-rich mixtures to cause health effects has been known for almost a century, there are still unanswered questions about the levels of PAHs in the environment, the potential for human exposure to PAHs, the health effects associated with exposure, and how genetic susceptibility influences the extent of health effects in individuals. The first objective of this research was to quantify concentrations of PAHs in samples of settled house dust collected from homes in Azerbaijan, China, and Texas. The trends of PAH surface loadings and percentage of carcinogenic PAHs were China > Azerbaijan > Texas, indicating that the risk of health effects from exposure to PAHs in house dust is highest in the Chinese population and lowest in the Texas population. PAHs in China and Azerbaijan were derived mainly from combustion sources; Texas PAHs were derived from unburned fossil fuels such as petroleum. The second objective of this research was to investigate the effect of pregnane X receptor (PXR) on the genotoxicity of benzo[a]pyrene (BaP). BaP treatment resulted in significantly lower DNA adduct levels in PXR-transfected HepG2 cells than in parental HepG2 cells. Total GST enzymatic activity and mRNA levels of several metabolizing enyzmes were significantly higher in cells overexpressing PXR. These results suggest that PXR protects cells against DNA damage by PAHs such as BaP, possibly through a coordinated regulation of genes involved in xenobiotic metabolism. The third objective of this research was to investigate biomarkers of exposure in house mice (Mus musculus) exposed to PAH mixtures in situ. Mice and soil were collected near homes in Sumgayit and Khizi, Azerbaijan. Mean liver adduct levels were significantly higher in Khizi than in Sumgayit. Mean lung and kidney adduct levels were similar in the two regions. The DNA lesions detected may be a combination of environmentally-induced DNA adducts and naturally-occurring I-compounds. PAHs were present at background levels in soils from both Khizi and Sumgayit. It appears that health risks posed to rodents by soil-borne PAHs are low in these two areas.

Orientador: Meuris Gurgel Carlos da Silva / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química / Made available in DSpace on 2018-08-22T16:47:28Z (GMT). No. of bitstreams: 1 Souza_RenatadosSantos_D.pdf: 2889400 bytes, checksum: 692c0c9b405b4f550e07f530c56c124c (MD5) Previous issue date: 2013 / Resumo: Muitos compostos orgânicos derivados do petróleo são encontrados na água subterrânea, oriundos de processos industriais ou, principalmente, dos vazamentos de combustível em postos de distribuição. Dentre esses compostos encontram-se benzeno, tolueno e xileno (BTX), substâncias tóxicas e carcinogênicas e que se constituem nos componentes mais poluidores da gasolina. Processos de remoção dos BTX devem atender aos limites da legislação e, nesse sentido, a adsorção é um dos métodos mais eficientes. Neste trabalho foi proposto avaliar a lama vermelha, resíduo da indústria de beneficiamento do alumínio, nas formas bruta, calcinada e quimicamente tratada, como material adsorvente alternativo para remoção dos BTX em soluções sintéticas com um e dois adsorbatos. A caracterização da lama vermelha indicou que o material é macroporoso, muito heterogêneo e constituído de uma mistura de óxidos principalmente sodalita, hematita, goetita, gibbsita e quartzo. A calcinação provocou alterações na estrutura do adsorvente, aumentando a área superficial e a quantidade e tamanho de macroporos. O estudo do pHzpc mostrou que o pH natural da lama vermelha tornou a superfície carregada negativamente, atraindo assim o anel benzênico e melhorando a adsorção. Os ensaios de cinética de adsorção mostraram um processo rápido com no máximo 2h para atingir o equilíbrio e o percentual de remoção foi acima de 85% para todos os compostos. Nos ensaios de equilíbrio com monocomposto a ordem decrescente de adsorção foi benzeno, tolueno e xileno. As maiores capacidades de adsorção de benzeno foram qe = 0,332 mmol/g com lama bruta, e com lama calcinada qe = 0,335 mmol/g, esses valores são elevados quando comparados com adsorventes do tipo argilominerais. Os modelos Langmuir com dois sítios e múltiplos espaços de adsorção foram os que melhor se ajustaram aos resultados experimentais de adsorção com monocomposto, porém não conseguiram prever as multicamadas existentes nas isotermas. Foi verificada uma diminuição na remoção de todos os BTX na condição de mistura binária. A ordem de remoção de BTX foi inversa e com maiores remoções de xileno (qe = 0,3406 mmol/g). O modelo de Langmuir se ajustou adequadamente aos resultados experimentais, nessa condição / Abstract: Many organic compounds derived from oil are found in groundwater from industrial processes or specially from leaks at fuel tanks in gas stations. Among these compounds are benzene, toluene and xylene (BTX), toxic and carcinogenic substances that are the most polluters compounds from gasoline. BTX removal processes must attend to legislation limits and thus the adsorption process is one of the most efficient methods. In this work it was used red mud, an aluminum industry waste, in the raw, calcined forms and chemically treated forms, as an alternative adsorbent, to remove the BTX from single and two-component aqueous solutions. The characterization of the red mud indicated that this material is macroporous, very heterogeneous and compound from an oxides mixture, mainly sodalite, hematite, goethite, gibbsite and quartz. The calcination caused changes in the adsorbent structure, increasing the superficial area and the macroporous quantities and size. The pHpzc study showed that the natural red mud pH lets the surface negatively charged, attracting then the benzene rings and improving the adsorption. The kinetic adsorption showed a fast process that needs 2 h to achieve the equilibrium and a removal percentage of 85% for all compounds. In the single component equilibrium studies the adsorption order was benzene, toluene e xylene. The maximum adsorption capacities were qe = 0,332 mmol/g on raw red mud (RM), and on calcined red mud (CRM), qe = 0,335 mmol/g. DSL and MSAM models were the best fit to the experimental data in the single component adsorption, although they could not to predict the multiple layers existing in the isotherms. It was verified a decrease in the removal of all BTX in the two-component adsorption. There was a change in the BTX removal order and more removal of xylene (qe = 0,3406 mmol/g). The Langmuir model showed good fit to the experimental data in this condition / Doutorado / Engenharia de Processos / Doutora em Engenharia Quimica

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