High-valent iron(IV)-oxo porphyrins are the central oxidizing species in hemecontaining enzymes and synthetic oxidation catalysts. Many transition metal complexes have been extensively studied as models of the ubiquitous cytochrome P450 enzymes to probe the sophisticated oxygen atom transfer (OAT) mechanism as well as to invent enzyme-like oxidation catalysts. In this work, two metalloporphyrin complexes have been successfully synthesized, and spectroscopically characterized. A new photochemical entry to porphyrin-iron(IV)-oxo derivatives, commonly referred to as compound II models, was also investigated in two porphyrin ligands that differ in electronic and steric environments. As determined by their distinct UV-vis spectra and kinetic behaviors, iron(IV)-oxo porphyrins [FeIV(Por)O] were successfully produced by visible light irradiation of highly photo-liable porphyrin-iron(III) bromates. The iron(IV)-oxo porphyrins investigated in this study include 5,10,15,20- tetra(pentafluorophenyl)porphyrin-iron(IV)-oxo (4a), and 5,10,15,20-tetra(2,6- difluorophenyl)porphyrin-iron(IV)-oxo (4b).

Actinomycins are a class of compounds consisting of phenoxazinone-like core attached to two peptidolactone rings, denoted as α and β. A unique component of a few families—actinomycins G, Y, and Z—is a chlorinated β-ring threonine residue. Families G and Y also contained an actinomycin that possess a β-ring heterocycle (actinomycins G5 and Y5, respectively); prior to this work, no β-ring heterocycle-containing actinomycins were reported for the Z family. Unlike other actinomycin derivatives, Y5’s cytotoxicity was abolished while still maintaining some antibacterial potency. We constructed a model compound to probe the physical properties of the actinomycin core to test conditions under which heterocycle formation would occur. We also analyzed the gene clusters of these actinomycin producers for gene candidates to from this structural motif. We found the the actinomycin core aniline to have pKa values of 2.976 and 8.429 and a significant shift in UV absorption between 300-310nm when the group becomes charged. We also found cyclization conditions and no obvious gene candidates to form the β-ring heterocycle based on our gene cluster analysis. We hypothesize that the familial diversity of the actinomycin G, Y and Z familes is due to the reactivity of the phenoxazinone-like core.

A large body of evidence has accumulated which indicates that infants of postpartum depressed mothers are at risk for negative sequelae including later psychopathology. However, methodological difficulties including discordant definitions of postpartum depression and the use of paradigms which used the mother-infant relationship to assess infant emotional expression and regulation have decreased the ability to reach a consensus regarding the nature and transmission of that risk. This study sought to address those methodological difficulties by employing an established paradigm designed to elicit emotionality in infants, the Laboratory Temperament Assessment Battery (Lab-TAB; Goldsmith & Rothbart, 1999). Participants were 30 women who met DSM-IV criteria for Major Depressive Disorder (MDD), 50 women who did not meet MDD criteria, and their 8-13 month old infants. The women were recruited from five counties within Iowa which contain both rural and urban centers. Consistent with state demographics the sample was predominantly Caucasian (76%). Mother-infant dyads were assessed approximately five months after the mother had completed a diagnostic interview. At that time six episodes from the Lab-TAB designed to elicit fear, anger, and positive affect were conducted. Emotional reactivity was coded used the AFFEX (Goldsmith & Rothbart, 1988) and composite scores were generated for each emotion. Infants of depressed mothers exhibited less intense pleasure to stimuli designed to elicit that emotion. There was also a slight, non-significant, trend for infants of depressed mothers to display more intense fear and to remain fearful longer. There was not a difference between the groups in anger expression. Emotional regulation was examined using a set of procedures set-forth by Buss and Goldsmith (1998) to determine effective regulation. These procedures involve calculating the change in affect from the coding epoch in which a "putative regulatory behavior" is displayed to the epoch immediately after the behavior. Change scores which involved no change in affect or a decrease in negative affect were considered effective regulation. Playing with clothing or an object and interacting with the stimulus were effective at regulating both fear and anger. In addition, averting gaze (disengaging with the task) was effective in regulating anger. Follow-up analysis revealed that infants of depressed mothers used gaze aversion more frequently than infants of nondepressed mothers. In addition, they were less likely to engage in social referencing (looking toward the mother) during episodes designed to elicit fear. The findings of this study are consistent with a growing body of evidence which documents the significance of considering low positive affect in examination of diagnosis and risk for depression and suggests that fear expression may be central to anxiety. Furthermore, results from the emotional regulation paradigms underscore the need for continued examination of the construct of "effective regulation." In addition, these results highlight disruptions in the mother-infant relationship which have implications for developing efficient regulatory mechanisms.

Physical activity is known to offer health benefits. Additionally, research has linked religious involvement with health. Psychophysiological reactivity has links to coronary heart disease. This study examines the relationship between physical activity and religiosity in light of psychophysiological reactivity. The sample included 75 subjects, with a mean age of 71. 7 (SD = 6.11 ), with no history of cardiac incident. Religiosity was measured with the Religious Orientation Scale (ROS). Physical activity was assessed utilizing the Typical Week Physical Activity Scale. Psychophysiological reactivity was measured by blood pressure, heart rate, and self-report anger ratings in response to interpersonal challenge. Regression predicting reactivity, including ROS, total metabolic equivalence (MET) minutes, and interaction of the two resulted in significant prediction of systolic blood pressure change, F (3, 74) = 3.33, p = .024. Analyses suggest relationships between reactivity and religiosity are not mediated by physical activity. Indicating ROS may operate more influentially over prohibited than proactive behaviors.

Asbestos related research began approximately 60 years ago, yet, the mechanism(s) by which asbestos exerts its biological effects is not well understood. The hypothesis upon which this dissertation is based is that mobilization of iron from asbestos enhances the iron-dependent biochemical reactivity of asbestos in vitro and contributes to asbestos-dependent cytotoxicity. The specific aims for this hypothesis were, 1) to determine whether iron was responsible for the biochemical reactivity of asbestos in vitro and asbestos-induced cytotoxicity in cultured cells, and 2) to determine whether mobilization of iron from asbestos enhanced the reactions catalyzed by asbestos in vitro and contributes to asbestos-induced cytotoxicity. It was shown that a chelator (e.g., citrate) had to be present to mobilize iron from asbestos in vitro at pH 7.5. Factors that affected iron mobilization from asbestos (e.g., chelator, pH, or surface area) were investigated. Iron on crocidolite reacted with reducing agents and o2, catalyzed the formation of hydroxyl radical, and induced the formation of DNA single-strand breaks in vitro. However, mobilization of iron from crocidolite by a chelator greatly enhanced crocidolite-dependent o2 consumption, hydroxyl radical formation, and DNA damage in vitro. Crocidolite was more cytotoxic, as measured by cloning efficiency, to cultured Syrian hamster embryo cells than crocidolite that had been pretreated to reduce the amount of iron associated with the fiber, suggesting that iron was responsible for the cytotoxicity. Crocidolite-dependent transformation of these cells was not detected. Crocidolite-dependent cytotoxicity to the human lung carcinoma cell line, A549, was directly dependent upon dose. Intracellular mobilization of iron (55 Fe) from crocidolite was determined using neutron-activated crocidolite and A549 cells. A time- and dose-dependent increase in the amount of 55 Fe mobilized intracellularly from crocidolite into a soluble, 10,000 x g supernatant fraction of lysed cells was observed for cultured cells treated up to 72 h. All of the results presented here support the hypothesis that iron and/or iron mobilization from asbestos may contribute to the some of the biological effects of asbestos in vivo.

Cognitive theories of depression have long posited automatic interpretation biases (AIB) as a central contributor to depressed mood. The current study was first to examine AIB in a clinically defined depressed sample. While assessing AIB using a semantic association paradigm, pupillary reactivity was simultaneously recorded to build insight into the AIB process. A total of 53 individuals (25 depressed and 28 healthy control) completed the Word Sentence Association Paradigm for Depression (WSAP-D) while pupillary reactivity was recorded. Results revealed the depressed group was significantly more likely to endorse negative AIB and less likely to endorse benign AIB compared to healthy controls. The depressed group demonstrated a modest effect size difference indicating they were faster to endorse negative AIB compared to the healthy controls, but did not differ in endorsing benign AIB or in rejecting either valence. Pupillary reactivity was found to differentiate behaviorally defined AIB type from a natural processing condition when counter to theorized, group relevant AIB. The depressed group demonstrated greater initial pupillary constriction during initial presentation of ambiguous information and comparatively less pupillary dilation during and after endorsing a benign AIB. Taken together, the results suggest that theorized negative AIB and lack of benign AIB are characteristic of depression, that greater cognitive effort is required to reject interpretations consistent with theorized biases consistent with reinterpretation processes, and that depressed individuals are less engaged with benign AIB compared to healthy controls, possibly associated with hedonic deficits. Theoretical implications and future directions are discussed.

Becoming more physically active is associated with increased confidence to maintain smoking abstinence as well as success at stopping smoking. The purpose of the current study was to assess the effects of two different types of exercise (cardiovascular and Hatha yoga) on general and cue-elicited craving for a cigarette. Participants were 76 smokers ages 18-45 (mean=29) who smoked at least 10 cigarettes per day (mean=20) for at least one year. Participants were randomly assigned to engage in 30 minutes of cardiovascular activity (walking on a treadmill), yoga, or to view a video about exercise (control). Participants completed a self-report measure of craving (Questionnaire of Smoking Urges-Brief [QSU-brief]; Cox, Tiffany, & Christen, 2001) and a brief mood form, as well as a picture-based cue reactivity assessment before and approximately five minutes after the activity. Results demonstrated that participants in both exercise groups reported a significant decrease in anticipation of pleasure from smoking following exercise as compared to the control group, as measured by Factor 1 of the QSU-brief (p < .05) up to 20 minutes following exercise. Participants in both exercise groups also reported significant decrease in smoking to relieve negative affect or withdrawal only 20 minutes after exercising, as measured by Factor 2 of the QSU-brief (p < .05). There was also a trend toward a significant group x time interaction effect for the QSU-brief Global scale (p = .053) immediately following exercise and a significant decrease in craving 20 minutes after exercise (p = .040). These effects were fully mediated by both an increase in positive mood and a decrease in negative mood following exercise (ps < .05) and a decrease in negative mood 20 minutes after exercise. Following activity, the cardiovascular group had a significant decrease in craving towards smoking pictures and an increase in craving towards neutral pictures, the yoga group demonstrated a significant decrease towards both smoking and neutral cues, and the control group had an increase in craving over time for both types of cues (ps < .05). Overall, these findings suggest that both cardiovascular activity and yoga may reduce urges to smoke following exercise, but that cardio exercise may be specifically associated with reduced cue-elicited craving. Future studies should examine the relationship between acute and long-term effects of exercise on cravings and smoking behavior. This can inform the potential application of exercise regimens within smoking cessation programs.

Persistent organic pollutants are a well-known threat to the environment. Substances such as polycyclic aromatic hydrocarbons and chlorinated organic compounds in contaminated soil and groundwater can have severe and long-lasting effects on health in animals and humans. There is an urgent need for the development of safe technologies for their effective removal. Originally developed for mineral processing, mechanical treatment by ball milling is an extremely versatile technique for the degradation of toxic compounds. Reactive milling can rapidly destroy organic compounds without producing hazardous wastes. Complete breakdown of the organic molecules is achieved after relatively short milling times. Successful tests were conducted on polychlorobiphenyls (PCBs), DDT, DDD, DDE, Dieldrin and hexachlorobenzene with a conversion yield in the of greater than 99% (Hall et al., 1996; Monagheddu et al., 2000; Zhang et al., 2001; Zhang et al., 2002; Tanaka and Zhang, 2003; Pizzigallo et al., 2004; Nomura et al., 2005; Bellingham, 2006).In this study reactive ball milling was used to investigate the destruction of two classes of persistent organic pollutants environmental contaminants. The compounds studied are either known environmental pollutants or simple analogues. These were chosen as being representative of pollutants to investigate the pathway using ball milling destruction and in most cases were relatively small molecules so that the intermediates could be more easily identified. The first class of compounds was polycyclic aromatic compounds. Some smaller members of this class such as naphthalene, anthracene were investigated. The second class of compounds were some analogues of environmentally hazardous hydroxylated and halogenated compounds such as chloronaphthalene, bromonaphthalene, 1- naphthol, 2-naphthol and pentachlorophenol under reactive milling using GCMS analysis of the degradation pathway. Destruction efficiencies greater than 99% have been achieved for a number of organic compounds. Several different intermediates have been identified during the milling degradation. There was also some evidence from this study that halogens could be transferred between compounds during milling. The final products of the milling destruction of these compounds are an amorphous carbon residue and inorganic chloride or bromides. It was proposed that large amounts of halogens could be found however the results showed that small amounts detected. At early stages of milling a number of intermediate breakdown products were detected which were destroyed on extended milling. The core objective of this research was to clarify the reaction mechanisms pathways used of more complex polycyclic aromatic hydrocarbons and aromatic organ halogen compounds. This study is a part of a long-term research project on the destruction of toxic organic compounds by reactive milling.

<p>The conventional viscose manufacturing process is a mature process that needs to be improved with respect to its environmental impact and its production cost structure. Therefore a research study has been done with the aim to improve the reactivity of the dissolving pulp used, in order to reduce the chemical demand in the viscose process and thus reduce the cost and indirectly the environmental impact.</p><p>The work described in this thesis has shown that it is possible to enhance the pulp reactivity and to use less carbon disulphide in the production of viscose, while maintaining a good quality viscose dope, by two entirely different pretreatment methods, one chemical and one enzymatic.</p><p>The chemical method used pressurized oxygen after the mercerisation step, which increased the reactivity of the alkali cellulose. The viscose dopes produced from the pressurized oxygen treated alkali cellulose had lower filter clogging values, Kw, compared to conventionally produced viscoses. The temperature and the oxygen treatment time of the alkali cellulose were however crucial for the viscose quality.</p><p>The best performing enzyme of several tested was a cellulase of the mono component endoglucanase preparation Carezyme®. This enzymatic treatment was optimized with respect to viscose dope preparation. The study showed that the enzyme treatment could be carried out under industrially interesting conditions with respect to temperature, enzyme dose and reaction time. A re-circulation study of the enzyme showed that it was possible to re-use the spent press water from the enzymatic treatment step several times, and thus lower the production cost. Some of the viscose process stages were modified to properly fit the enzymatically treated dissolving pulp and a comparison between viscose made from enzyme-treated pulp and viscose made from conventional pulp, showed that the enzyme-treated samples had a lower filter clogging value, Kw. This indirectly indicates that the enzyme pretreatment could reduce the carbon disulphide charge in the viscose manufacturing process. An initial study of how the Carezyme® influenced different cellulosic sources was also performed.</p>

The Lattrell-Dax method of nitrite-mediated substitution of carbohydrate triflates is an efficient method to generate structures of inverse configuration. In this study, the effects of the neighboring group on the Lattrell-Dax inversion were explored. A new carbohydrate/anion host-guest system was discovered and the ambident reactivity of the nitrite anion was found to cause a complicated behavior of the reaction. It has been demonstrated that a neighboring equatorial ester group plays a highly important role in this carbohydrate epimerization reaction, restricting the nitrite N-attack, thus resulting in O-attack only and inducing the formation of inversion compounds in good yields. Based on this effect, efficient synthetic routes to a range of carbohydrate structures, notably β-D-mannosides and β-D-talosides, were designed by use of double parallel and double serial inversion. A supramolecularly activated, triggered cascade reaction was also developed. This cascade reaction is triggered by a deprotonation process that is activated by anions. It was found that the anions can activate this reaction following their hydrogen bonding tendencies to the hydroxyl group in aprotic solvents. / QC 20100709