Au, Ching Chi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 83-89). / Abstracts in English and Chinese. / Table of contents --- p.i / Acknowledgements --- p.iii / Abbreviations --- p.iv / Abstract --- p.v / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Importance of Transition Metal Amido Complexes --- p.1 / Chapter 1.1.1 --- Transition Metal Amido Complexes as Catalysts --- p.1 / Chapter 1.1.2 --- Transition Metal Amido Complexes as Reaction Intermediates --- p.2 / Chapter 1.2 --- Bonding Nature of Late Transition Metal Amido Complexes --- p.4 / Chapter 1.2.1 --- Theory of π Conflict --- p.5 / Chapter 1.2.2 --- E-C Approach --- p.7 / Chapter 1.3 --- Synthesis of Transition Metal Amido Complexes --- p.8 / Chapter 1.3.1 --- Transmetallation --- p.9 / Chapter 1.3.2 --- Deprotonation of Coordinated Amine --- p.10 / Chapter 1.3.3 --- Hydride Addition across Organic Azide --- p.11 / Chapter 1.4 --- Reactivity of Transition Metal Amido Complexes --- p.12 / Chapter 1.4.1 --- β-Elimination --- p.12 / Chapter 1.4.2 --- Insertion --- p.13 / Chapter 1.4.3 --- Reductive Elimination --- p.16 / Chapter 1.4.4 --- Bond Activation --- p.17 / Chapter 1.5 --- Structural Features of Rhodium Porphyrin Complexes --- p.18 / Chapter 1.6 --- Examples of Metalloporphyrin Complexes Containing Nitrogen Ligands --- p.19 / Chapter 1.7 --- Bond Activation by Rhodium Porphyrins --- p.21 / Chapter 1.8 --- Objectives of the Work --- p.23 / Chapter Chapter 2 --- Synthesis and Reactivity Studies of Rhodium Porphyrin Amido Complexes --- p.24 / Chapter 2.1 --- Synthesis of Porphyrin and Rhodium Porphyrin Chloride --- p.24 / Chapter 2.2 --- Synthesis of Rhodium Porphyrin Amido Complexes from Rhodium Porphyrin Chloride --- p.24 / Chapter 2.2.1 --- By Transmetallation with Lithium Amide --- p.25 / Chapter 2.2.2 --- By Base-promoted Ligand Substitution Using Rh(ttp)Cl --- p.27 / Chapter 2.2.2.1 --- Optimization of Reaction Conditions --- p.27 / Chapter 2.2.2.2 --- Substrate Scope --- p.31 / Chapter 2.3 --- X-ray Structure of Rh(ttp)NHS02Ph --- p.33 / Chapter 2.4 --- Bond Activation Chemistry of Rh(ttp)NHS02Ph --- p.36 / Chapter 2.5 --- Conclusion --- p.37 / Chapter Chapter 3 --- Reactivity Studies of Rh(ttp)NHS02Ph --- p.39 / Chapter 3.1 --- Thermal Reaction of Rh(ttp)NHS02Ph in Benzene-d6 --- p.39 / Chapter 3.2 --- Mechanistic Studies of the Conversion from Rh(ttp)NHS02Ph to [Rh(ttp)]2 --- p.41 / Chapter 3.2.1 --- Mechansim A (Hydrolysis of Rh(ttp)NHS02Ph) --- p.42 / Chapter 3.2.2 --- Mechanism B (Rh-N Bond Homolysis - (PhS02NH)2 Hydrolysis) --- p.44 / Chapter 3.2.3 --- Mechanism C (Rh-N Bond Homolysis - (PhS02NH)2 Nitrogen-Hydrogen Bond Activation) --- p.45 / Chapter 3.3 --- Discussions --- p.52 / Chapter 3.3.1 --- Estimation of Rhodium-Nitrogen Bond Dissociation Energy --- p.52 / Chapter 3.3.2 --- Effect of Excess PhS02NH2 in the Synthesis of Rh(ttp)NHS02Ph --- p.58 / Chapter 3.4 --- Conclusion --- p.58 / Chapter Chapter 4 --- Experimental Section --- p.60 / References --- p.83 / Appendix I X ray data --- p.90 / Appendix I List of Spectra --- p.96

Due to the universal nature of stress, and its impact on physical health, it is important to understand how it is related to other psychological variables. The current study was undertaken in order to investigate whether an individual's cardiovascular reactivity to stress is impacted by their level of experiential avoidance, as measured by the Acceptance and Action Questionnaire (AAQ-II). Individuals who are experientially avoidant are more likely to attempt to escape or prevent certain experiences and make effort to change them or avoid the contexts in which they occur. Previous research has indicated that experiential avoidance is related to some measures of physiological stress. One hundred twenty-eight college students (ages 18-29) were administered a questionnaire that included measures of general stress, experiential avoidance, and depression. After completing the questionnaire, a baseline reading of cardiovascular activity was taken. After that baseline reading, research assistants administered the Trier Social Stress Test (TSST), a series of tasks designed to induce physiological stress that consists of an anticipation period, a speech, and a math task. Measurements of cardiovascular activity were taken throughout administration. It was hypothesized that increased experiential avoidance would predict higher blood pressure and heart rate both before engaging in the stress task. It was also hypothesized that increased experiential avoidance would predict higher cardiovascular reactivity during administration of the TSST. As was expected, higher experiential avoidance predicted higher baseline heart rate. This finding adds to the body of research that supports the connection between psychological constructs and physiological reactivity. However, experiential avoidance did not significantly predict baseline blood pressure or any measures of physiological reactivity during the TSST.

Glyoxalase II is one of two metalloenzymes found in the glyoxalase pathway and is responsible for catalyzing the hydrolysis of a thioester substrate. Its bimetallic active site is found to contain a variety of metal combinations, including Fe(III)Zn(II). A recent report indicates that human glyoxalase II, while containing a Fe(II)Zn(II) center, is catalytically active as a mononuclear Zn(II) enzyme. Detailed mechanistic studies of glyoxalase II enzymes are limited due to uncertainty in the metal ion content of recombinantly prepared samples. The research presented in this thesis is focused on gaining mechanistic insight into thioester hydrolysis promoted by well-characterized metal complexes The initial research is focused on studies involving a Fe(III)Zn(II) complex supported by the 2-{[bis(2-pyridylmethyl)amino]methyl}-6-[{[2-hydroxyphenyl)methyl]-(2- pyridylmethyl)amino}methyl]-4-methylphenol) ligand. Thioester hydrolysis reactions were examined by following the loss of a deuterium-labeled thioester (hydroxyphenyl thioacetic acid S-methyl(d3) ester) over time using 2H NMR as the monitoring method. Based on kinetic data and spectroscopic investigations (UV-vis and EPR), a reaction pathway for thioester hydrolysis promoted by the aforementioned Fe(III)Zn(II) complex has been proposed. An important feature of this pathway is the formation of a precursor complex wherein the deprotonated α-hydroxy group of the thioester coordinates to the Zn(II) center prior to nucleophilic attack by an Fe(III)-OH moiety. Of relevance to human glyoxalase II, the thioester hydrolysis reactivity of a mononuclear zinc complex containing the N,N-bis(2-pyridylmethyl)-tert-butylamine ligand, (bpta)Zn](ClO4)2⋅0.5H2O, has been examined. Based on kinetic data, it is proposed that thioester hydrolysis promoted by this complex proceeds via a bimolecular pathway, with a Zn-OH moiety being the nucleophile for attack on the thioester carbonyl. Activation parameters are reported for the zinc complex-promoted thioester hydrolysis reaction and are compared to those of OH- promoted thioester hydrolysis reactions. In a separate area of investigation, the chromium chloride complex {(C6H11N2)[CrCl3]}n has been isolated and characterized by elemental analysis and X-ray crystallography. This complex has been proposed as the catalyst responsible for high yield conversion of glucose to 5- hydroxymethylfurfural (HMF), which is an important reaction toward using renewable resources as feedstock chemicals.

Benzoquinone (BQ) is an extremely potent electrophilic contact allergen that haptenates endogenous proteins through Michael addition (MA). It is also hypothesized that BQ may haptenate proteins via free radical formation. The objective of this study was to assess the inductive effects (activating and deactivating) of substituents on BQ reactivity and the mechanistic pathway of covalent binding to nucleophilic thiols. The BQ binding by Cys34 on human serum albumin was studied, and for reactivity studies, nitrobenzenethiol (NBT) was used as a surrogate for protein binding of the BQ and benzoquinone derivatives (BQD). Stopped flow techniques were used to determine pseudo-first order rate constants (k) of methyl-, t-butyl-, and chlorine-substituted BQD reactions with NBT, whereas electron pair resonance (EPR) studies were performed to investigate the possible free radical mediated binding mechanism of BQD. Characterization of adducts was performed using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR). The rate constant values demonstrated the chlorine substituted (activated) BQD to be more reactive toward NBT, than the methyl and t-butyl-substituted (deactivated) BQD, and this correlated with the respective EPR intensities. The EPR signal, however, was quenched in the presence of NBT suggesting MA as the dominant reaction pathway. MS and NMR results confirmed adduct formation to be a result of MA of NBT onto the BQ ring with vinylic substitution also occurring for chlorine-substituted derivatives. The binding positions on BQ and NBT/BQD stoichiometric ratios were affected by whether the inductive effects of the substituents on the ring were positive or negative. The reactivity of BQ and BQD is discussed in terms of the potential relationship to allergenic potency. Hammett and Taft (HT) constants were then used to estimate the influence of these substituents on chemical reactivity. HT values demonstrated chlorine substituted BQD to be more reactive than methyl substituted BQD. BQ and BQD dermal allergenicity, as evaluated in the murine local lymph node assay, (LLNA) was consistent with that predicted by reactivity and HT parameters. These results demonstrate the effect of substituents on BQ reactivity and dermal allergic sensitization, and suggest the potential utility of chemical reactivity data and HT values for electrophilic allergen identification and potency ranking.

An experimental study of pure iron foil exposed to a hot, dense hydrogen and argon gas mixture in a ballistic compressor yielded evidence of structural and compositional changes of the metal due to the presence of the hydrogen gas. Three iron foils have been compared, one of unexposed pure iron, another of pure iron exposed to a mixture of hydrogen and argon gas, and the third of pure iron exposed to argon alone. Exposure to these high temperature, high pressure gases took place in a ballistic compressor. Line formations were found on the surface of the iron foil exposed to both hydrogen and argon. These appeared as 'V'- or 'W'-shaped configurations, giving the appearance of a serrated edge. Such lines were not found for the other two iron foils. Characteristic peaks of energy dispersive x-ray spectra yield different surface concentrations of oxygen when each iron foil sample is compared. This concentration is much less for iron foil exposed to both hydrogen and argon gases than for the other two samples. Also a larger carbon peak was found for the former sample, when compared to the latter two. A shift in the 200 x-ray diffraction peak by one degree 29 was observed for the sample exposed to hydrogen and argon, and a 'triple' peak was observed for the 310 plane for the same iron sample.

Disordered sleep is strongly linked to depression, but reasons for this are not well understood. One possibility is that this link is partially explained by deficits in the emotional processing system. This model is substantiated based on the strong link between sleep and emotions, as well as ties between affect and depression. Therefore, this study tested whether various emotional and non-emotional deficits mediated the link between poor sleep quality and depression. Two hundred undergraduate students were recruited via an online university system. Participants completed self-report scales of depression, sleep quality, emotion recognition, and affective response to pre-tested pleasant or unpleasant stimuli. Mediation models were tested for viable emotion and non-emotion mediators, as well as using other mediators as covariates. The indirect effect for all models was tested using bootstrapping. Only affective response to unpleasant stimuli emerged as a significant mediator of the relationship between sleep quality and depression and accounted for 5% of the variance in that relationship; it remained a mediator after controlling for non-emotion related mediators. Recently, sleep problems have gained attention due to serious consequences for public health, including a strong association with psychological disorders. This study was a first step in testing pathways by which disordered sleep leads to increases in depression symptoms. In our sample, blunted emotional responding to unpleasant images partially accounted for the link seen between sleep and depression. Future research may aim to extend the study of process and pathway-related models, particularly in the realm of emotional responding in the relationship between sleep and depression.

A three part study involving aspects of radical properties of various aromatic species was accomplished. Experiments to ascertain the importance of geometric and electronic effects on the intramolecular transfer of a pi-complexed radical to a terminal double bond was performed. Several 4-aryl-1-butenes were reacted in competition with 1-undecene with a variety of radical precursors at 70��C. The reactions were studied in both complexing and noncomplexing solvents. Most of the relative rates varied little from unity and no dependence on solvent was observed. A series of 21 phenacylarenes was subjected to mass spectrometry. The fragmentation process leading to arylmethyl radicals and benzoyl cations was measured by calculating the ratios of parent ion to benzoyl cation signal strength. In the case of the eleven homoaromatic compounds little overall correlation of these values to traditionally accepted arylmethyl radical stabilities was found. The degree of fragmentation for isomers of the same compound were found to be explicable in term of arylmethyl radical stabilities. Degrees of fragmentation of some compounds could be rationalized in terms of the bond order of the bond being broken, as calculated by AM1 methods. The ten heteroaromatic compounds showed little correlation of fragmentation with bond order. The degree of fragmentation was found to be dependent on many different variables of the individual molecules. No correlation with any one factor could be found. The relative rates of benzylic hydrogen atom abstraction from a series of substituted toluenes and cumenes under conditions of bromination by diethyl bromomalonate were determined at 70��C. A range of reactivity of 21.7 and 10.5 was found for the toluenes and cumenes respectively. The relative rates were found to correlate best with Hammett sigma plus constants. Hammett values of -0.89 and -0.73 were calculated for the substituted toluenes and cumenes. Reactivities for several alkyl benzenes having different steric requirements at the reaction site were also studied. The relative rates for these compounds indicate a relatively large radical to be the atom abstracting agent. The results of the Hammett correlations combined with the studies involving the steric properties of the abstracting radical suggest that diethyl malonyl radical is the hydrogen atom abstracting species. / Graduation date: 1997

Under certain conditions, reactive chemicals may proceed into uncontrolled chemical reaction pathways with rapid and significant increases in temperature, pressure, and/or gas evolution. Reactive chemicals have been involved in many industrial incidents, and have harmed people, property, and the environment. Evaluation of reactive chemical hazards is critical to design and operate safer chemical plant processes. Much effort is needed for experimental techniques, mainly calorimetric analysis, to measure thermal reactivity of chemical systems. Studying all the various reaction pathways experimentally however is very expensive and time consuming. Therefore, it is essential to employ simplified screening tools and other methods to reduce the number of experiments and to identify the most energetic pathways. A systematic approach is presented for the evaluation of reactive chemical hazards. This approach is based on a combination of computational methods, correlations, and experimental thermal analysis techniques. The presented approach will help to focus the experimental work to the most hazardous reaction scenarios with a better understanding of the reactive system chemistry. Computational methods are used to predict reaction stoichiometries, thermodynamics, and kinetics, which then are used to exclude thermodynamically infeasible and non-hazardous reaction pathways. Computational methods included: (1) molecular group contribution methods, (2) computational quantum chemistry methods, and (3) correlations based on thermodynamic-energy relationships. The experimental techniques are used to evaluate the most energetic systems for more accurate thermodynamic and kinetics parameters, or to replace inadequate numerical methods. The Reactive System Screening Tool (RSST) and the Automatic Pressure Tracking Adiabatic Calorimeter (APTAC) were employed to evaluate the reactive systems experimentally. The RSST detected exothermic behavior and measured the overall liberated energy. The APTAC simulated near-adiabatic runaway scenarios for more accurate thermodynamic and kinetic parameters. The validity of this approach was investigated through the evaluation of potentially hazardous reactive systems, including decomposition of di-tert-butyl peroxide, copolymerization of styrene-acrylonitrile, and polymerization of 1,3-butadiene.

BACKGROUND: Alcohol and tobacco misuse and dependence are highly comorbid disorders. Varenicline alleviates symptoms of cigarette craving while preventing nicotine from binding to nicotinic acetylcholine receptors, thereby reducing nicotine’s reinforcing effects. Recent studies have shown that varenicline decreased alcohol self-administration in animal models and in one human study of heavy-drinking smokers. AIMS: To assess the effect of two-week varenicline (0.5-2mg) vs. placebo administration on cue-induced craving for tobacco and alcohol in smokers with heavy alcohol use (n = 24). METHODS: Subjects participated in two study visits where nicotine and alcohol craving and withdrawal were assessed with self-report questionnaires under four conditions (abstinence/one cigarette/neutral cues/tobacco-alcohol cues). RESULTS: Two-week administration of varenicline reduced tobacco-alcohol cue-induced cigarette cravings and reduced emotionality aspects of alcohol craving after smoking a cigarette compared to abstinence in heavy-drinking smokers. CONCLUSION: It is possible that varenicline may have particular advantages as a smoking cessation aid in heavy drinkers.

BACKGROUND: Alcohol and tobacco misuse and dependence are highly comorbid disorders. Varenicline alleviates symptoms of cigarette craving while preventing nicotine from binding to nicotinic acetylcholine receptors, thereby reducing nicotine’s reinforcing effects. Recent studies have shown that varenicline decreased alcohol self-administration in animal models and in one human study of heavy-drinking smokers. AIMS: To assess the effect of two-week varenicline (0.5-2mg) vs. placebo administration on cue-induced craving for tobacco and alcohol in smokers with heavy alcohol use (n = 24). METHODS: Subjects participated in two study visits where nicotine and alcohol craving and withdrawal were assessed with self-report questionnaires under four conditions (abstinence/one cigarette/neutral cues/tobacco-alcohol cues). RESULTS: Two-week administration of varenicline reduced tobacco-alcohol cue-induced cigarette cravings and reduced emotionality aspects of alcohol craving after smoking a cigarette compared to abstinence in heavy-drinking smokers. CONCLUSION: It is possible that varenicline may have particular advantages as a smoking cessation aid in heavy drinkers.