Browsing by Subject "Benzene"

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    Analyses Of Detoxification And Dna Damage From The Human Carcinogens Benzene And N′-Nitrosonornicotine
    (2016-05) Zarth, Adam
    The process of chemical carcinogenesis is initiated by DNA damage. This dissertation will describe quantitative approaches to assess the detoxification and DNA damage pathways of two human carcinogens: benzene and N′-nitrosonornicotine (NNN). The aspects of carcinogenesis relevant for this work include exposure to the carcinogen, biological activation to a reactive electrophile, metabolic detoxification processes, and DNA addition product (adduct) formation upon reaction of the electrophile with DNA. This dissertation will begin by presenting a collaborative study on exposure to benzene when smoking tobacco via a hookah; a urinary biomarker of benzene exposure significantly increases after a single smoking event. Next, it will describe studies of enzyme kinetics which determined for the first time that a human enzyme, GSTP1, is a good catalyst for the detoxification of benzene oxide, the activated form of benzene. This study also provided direct biochemical confirmation that GSTT1 is an important enzyme in this detoxification process. The next chapter will present collaborative data demonstrating that sulforaphane, an active phytochemical in broccoli sprouts, can upregulate these enzymatic detoxification processes in humans exposed to benzene and other air pollutants, likely by upregulating GSTP1. The last chapter on benzene will describe data showing that the major DNA adduct arising from the reaction between benzene oxide and DNA, 7-phenylguanine, is not detectable in humans or animals exposed to benzene. Thus, 7-phenylguanine is not likely to be the etiological agent responsible for the mechanism of benzene carcinogenicity, but instead some other mechanism of carcinogenesis is more important. The final chapter of this dissertation will shift focus to the analysis of a DNA adduct arising from NNN metabolic activation. NNN can be activated via two pathways: 2′-hydroxylation and 5′-hydroxylation. 2′-Hydroxylation has been more extensively studied, as it is the major pathway in rat esophagus, a target tissue of NNN carcinogenicity. However, the work presented here demonstrates that 5′-hydroxylation of NNN by human enzymes leads to higher levels of DNA adducts than does the 2′-hydroxylation pathway, and thus, 5′-hydroxylation may be the more relevant pathway for future DNA adduct studies in humans who use tobacco products.
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    Kinetics and mechanism of deoxygenation reactions over proton-form and molybdenum-modified zeolite catalysts
    (2014-07) Bedard, Jeremy William
    The depletion of fossil fuel resources and the environmental consequences of their use have dictated the development of new sources of energy that are both sustainable and economical. Biomass has emerged as a renewable carbon feedstock that can be used to produce chemicals and fuels traditionally obtained from petroleum. The oxygen content of biomass prohibits its use without modification because oxygenated hydrocarbons are non-volatile and have lower energy content. Chemical processes that eliminate oxygen and keep the carbon backbone intact are required for the development of biomass as a viable chemical feedstock. This dissertation reports on the kinetic and mechanistic studies conducted on high and low temperature catalytic processes for deoxygenation of biomass precursors to produce high-value chemicals and fuels. Low temperature, steady state reaction studies of acetic acid and ethanol were used to identify co-adsorbed acetic acid/ethanol dimers as surface intermediates within specific elementary steps involved in the esterification of acetic acid with ethanol on zeolites. A reaction mechanism involving two dominating surface species, an inactive ethanol dimeric species adsorbed on Brønsted sites inhibiting ester formation and a co-adsorbed complex of acetic acid and ethanol on the active site reacting to produce ethyl acetate, is shown to describe the reaction rate as a function of temperature (323 - 383 K), acetic acid (0.5 - 6.0 kPa), and ethanol (5.0 - 13.0 kPa) partial pressure on proton-form BEA, FER, MFI, and MOR zeolites. Measured differences in rates as a function of zeolite structure and the rigorous interpretation of these differences in terms of esterification rate and equilibrium constants is presented to show that the intrinsic rate constant for the activation of the co-adsorbed complex increases in the order FER < MOR < MFI < BEA. High temperature co-processing of acetic acid, formic acid, or carbon dioxide with methane (CH3COOH/CH4 = 0.04-0.10, HCOOH/CH4 = 0.01-0.03, CO2/CH4 = 0.01-0.03) on Mo/H-ZSM-5 formulations at 950 K and atmospheric pressure in an effort to couple deoxygenation and dehydrogenation reaction sequences results instead in a two-zone, stratified bed reactor configuration consisting of upstream oxygenate/CH4 reforming and downstream CH4 dehydroaromatization. X-ray absorption spectroscopy and chemical transient experiments show that molybdenum carbide is formed inside zeolite micropores during CH4 reactions. The addition of an oxygenate co-feed causes oxidation of the active molybdenum carbide catalyst while producing CO and H2 until completely converted. Forward rates of C6H6 synthesis are unperturbed by the introduction of an oxygenate co-feed after rigorously accounting for the thermodynamic reversibility caused by the H2 produced in oxygenate reforming reactions and the fraction of the active catalyst deemed unavailable for CH4 dehydroaromatization. All effects of co-processing C1-2 oxygenates and molecular H2 with CH4 can be interpreted in terms of an approach to equilibrium. Co-processing H2O, CO2, or light (C1-2, C/Heff < 0.25) oxygenates with CH4 at 950 K over Mo/H-ZSM-5 catalysts results in complete fragmentation of the oxygenate and CO as the sole oxygen-containing product. The C/Heff accounts for removal of O as CO and describes the net C6H6 and total hydrocarbon synthesis rates at varying (0.0-0.10) C1-2 oxygenate and H2 to CH4 co-feed ratios. Co-processing larger (C3-5, C/Heff ≥ 0.25) oxygenates with CH4 results in incomplete fragmentation of the co-fed oxygenate and preferential pathways of C6H6 synthesis that exclude CH4 incorporation. This results in greater net C6H6 synthesis rates than would be predicted from observations made when co-processing C1-2 oxygenates. Catalytic technologies have served a crucial role in processing petroleum feedstocks and are faced with new challenges as the feedstock shifts to chemically diverse but renewable biomass sources. This research addresses these challenges at fundamental and applied levels as it offers the potential to convert readily available biomass to commodity chemicals and fuels while simultaneously examining the elementary concepts of deoxygenation reactions on catalytic surfaces.