<p> Aryl radical ring closures onto the azo functional group were investigated. A series of ortho-substituted aryl radicals (83a-f) have been generated by bromine abstraction from the corresponding 1-(orthobromophenyl)-1-methoxy-azoethanes (82a-f) by tributyltin radicals. The radicals generated underwent cyclization in the 5-endo sense, to ultimately afford the substituted indazoles (86a-f). There was also some evidence for cyclization to the other azo nitrogen (closure in the 4-exo sense) to form a 4-membered ring. The aryl radical also underwent hydrogen atom abstraction from tributyltin hydride in competition with cyclization. Since the rate constant for hydrogen atom abstraction from tributyltin hydride by aryl radicals is known, this makes it possible to estimate the rate constants for cyclization throughout the series.</p> / Thesis / Master of Science (MSc)

Abstract Not Provided / Thesis / Master of Science (MSc)

<p> The free radical polymerization of styrene in benzene using azo-bisisobutyronitrile as a catalyst has been studied both theoretically and experimentally. The molecular-weight distribution and conversion are predicted on the basis of a simplified kinetic mechanism, neglecting a number of minor side reactions. The steady-state assumption is investigated and is shown to be applicable in the case of styrene polymerization, a pseudo-steady-state being reached in less than one second. Using the steady-state approach a relatively simple kinetic model is obtained, suitable for computer simulation. The prime variables consist of the ordinary reaction conditions such as monomer concentration, solvent concentration, catalyst concentration, reaction temperature and reaction time.</p> <p> The polymerization was carried out isothermally in a stirred batch reactor from which samples were abstracted at various time intervals. Conversion was determined by precipitating the polymer with methanol, filtering, and weighing, and the molecular-weight distribution has been obtained by gel-permeation chromatography. A computer program was written to interpret the variation of refractive index with respect to the elution volume trace from the chromatograph, giving a readout of molecular chain length in monomer units versus weight fraction.</p> <p> The experimentally obtained conversion and distribution curves are compared with those obtained from the mathematical model. Except for bulk polymerization agreement between the two is good. Good agreement for conversion is obtained for all cases if the catalyst initiation efficiency is adjusted according to the monomer or solvent concentration. However, the same considerations do not give good agreement for molecular-weight distribution. Rather it appears that the rate constants instead of the catalyst efficiency are monomer or solvent concentration dependent, which would explain the discrepancies.</p> / Thesis / Master of Engineering (MEngr)

<p> Polymerization of styrene was carried out in continuous and batch reactors using azobisis obutyronitrile as initiator and benzene as solvent. Monomer conversion, molecular weight distribution (MWD) and viscosity were measured.</p> <p> Corrections to the conventional kinetic mechanism using results from the continuous reactor were determined. These corrections were applied to the batch reactor kinetic model and the conversion and MWD thus predicted were compared to experimental results. It was found that the corrections applied to the batch system were not adequate to give accurate predictions of conversion and MWD.</p> <p> A short computer study of the effect of oscillating monomer flow and temperature, as opposed to steady flow, on a transient continuous reactor was also carried out. It was found from this study that at low conversions oscillations in monomer flow will not affect the time average conversion and molecular weight. Oscillations in temperature caused an increase in time average conversion and a decrease in time average molecular weight as compared to results obtained when the reactor was operated at a steady temperature which was the average of the oscillating temperatures.</p> / Thesis / Master of Engineering (MEngr)

Ferroptosis is a recently characterized iron-dependent form of regulated cell death associated with the accumulation of (phospho)lipid hydroperoxides. Since its characterization, there has been a spirited debate in the literature over the origin of the lipid hydroperoxides in ferroptotic cells. Many investigators have implicated lipoxygenases (LOXs), enzymes known to catalyze the oxidation of polyunsaturated fatty acids (especially linoleate and arachidonate) to yield lipid hydroperoxides. Previous work by our group, investigated the induction and suppression of ferroptosis in human embryonic kidney (HEK-293) cells transfected to overexpress the three most widespread isoforms of LOX (5-LOX, 15-LOX-1 and p12-LOX). The results suggested that LOX catalysis is not required for ferroptosis. Our previous work did not include investigations into cells transfected to overexpress 15-LOX-2. However, a series of recent publications has since implicated the 15-LOX-2/PEPB1 complex as a key player in ferroptotic cell death. Therefore, in this work, HEK-293 cells were transfected to overexpress the 15-LOX-2 isoform, as confirmed by immunodetection, and were subject to induction and suppression of ferroptosis pharmacologically. A library of small molecules was assembled consisting of LOX inhibitors, radical-traping antioxidants (RTAs) and LOX inhibitors that display off-target RTA activity. Consistent with our previous investigations, only LOX inhibitors with radical trapping activity or iron chelators were effective at suppressing ferroptosis. Furthermore, the poor performance of 15-LOX-2 inhibitors at rescuing cells transfected to overexpress 15-LOX-2 from ferroptosis does not support the role of the 15-LOX-2/PEBP1 complex as a central mediator of ferroptotic lipid peroxidation. We also report the details of corresponding investigations in cell lines that are reported to express high levels of LOXs and that have been used to establish characteristics of ferroptosis, including HT-22 mouse hippocampal cells (15-LOX-1 and/or 15-LOX-2) and HT-1080 human fibrosarcoma cells (all LOXs). The two cellular models were also subject to cell-rescue studies with our small molecule library. Again, only LOX inhibitors that possess radical-trapping antioxidant activity or which are good iron chelators could rescue cells from ferroptosis. These results underscore our previous conclusion that although lipoxygenase activity may contribute to the pool of cellular lipid hydroperoxides, autoxidation drives ferroptotic cell death.

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