The purpose of this project is to reexamine established free-radical polymerization theories and build a mechanistic reactor model for multi-component (up to six monomers) bulk and solution polymerizations under batch/semi-batch reactor configurations. The six-monomer system of interest is: Styrene (Sty), n-Butyl acrylate (BA), Butyl methacrylate (BMA), Hydroxyethyl acrylate (HEA), Hydroxybutyl acrylate (HBA), and Acrylic acid (AA). In order to develop a flexible, comprehensive, and user-friendly model, not only a physical/kinetic database of individual monomers and ingredients such as solvents, initiators, and chain transfer agents, but also a co-polymer database of reactivity ratios, and glass transition temperatures were built and combined with the modeling steps. Through an extensive literature search for polymerization models and kinetics, the simulation model was developed in a general way to cover the range from homo- to hexa-polymerization at both regular and elevated temperature levels, and explain various polymerization kinetics and characteristics. Model testing was conducted with experimental data as much as possible to check the model’s reliability. Due to limited experimental data for higher multi-component polymerizations, the simulation model was tested with homo-polymerizations and other available cases of combinations of two to four monomers. Very reasonable agreement was found between model predictions and experimental data on rate of polymerization, molecular weight, polymer composition, sequence length, etc. through the entire conversion. This multi-component modeling study continuously requires experimental checkups and parameter fine-tuning for better predictions. Further literature search or experimental studies still remain necessary for the hydroxyalkyl acrylate kinetic database and model testing of the depropagation feature. Sensitivity analysis also could be performed to locate critical parameters. This model should find use in industry for analyzing and optimizing reactor conditions as well as in the academic field as a research and educational tool.

The purpose of this project is to reexamine established free-radical polymerization theories and build a mechanistic reactor model for multi-component (up to six monomers) bulk and solution polymerizations under batch/semi-batch reactor configurations. The six-monomer system of interest is: Styrene (Sty), n-Butyl acrylate (BA), Butyl methacrylate (BMA), Hydroxyethyl acrylate (HEA), Hydroxybutyl acrylate (HBA), and Acrylic acid (AA). In order to develop a flexible, comprehensive, and user-friendly model, not only a physical/kinetic database of individual monomers and ingredients such as solvents, initiators, and chain transfer agents, but also a co-polymer database of reactivity ratios, and glass transition temperatures were built and combined with the modeling steps. Through an extensive literature search for polymerization models and kinetics, the simulation model was developed in a general way to cover the range from homo- to hexa-polymerization at both regular and elevated temperature levels, and explain various polymerization kinetics and characteristics. Model testing was conducted with experimental data as much as possible to check the model’s reliability. Due to limited experimental data for higher multi-component polymerizations, the simulation model was tested with homo-polymerizations and other available cases of combinations of two to four monomers. Very reasonable agreement was found between model predictions and experimental data on rate of polymerization, molecular weight, polymer composition, sequence length, etc. through the entire conversion. This multi-component modeling study continuously requires experimental checkups and parameter fine-tuning for better predictions. Further literature search or experimental studies still remain necessary for the hydroxyalkyl acrylate kinetic database and model testing of the depropagation feature. Sensitivity analysis also could be performed to locate critical parameters. This model should find use in industry for analyzing and optimizing reactor conditions as well as in the academic field as a research and educational tool.

This thesis is directed towards expanding and refining a free radical multi-component polymerization model. The model considers up to six monomers (unique in the literature), both in bulk and solution polymerization, for either batch or semi-batch reactor modes. As the simulator database contains 13 monomers, 5 initiators, 4 solvents, 3 chain transfer agents and 2 inhibitors, all tested over a wide range of polymerization conditions, from data in both academic and industrial laboratories, several hundred combinations of ingredients can be modeled. The many outputs generated by the model include conversion, molecular weight, polymer composition, branching indicators, sequence length, as well as many others polymerization characteristics related to both production rate and polymer quality. Although the only literature data found to-date contains a maximum of four monomers, model predictions for homo-, co-, ter- and tetra-polymerizations show reasonable agreement against the data at both regular and elevated temperatures. Recently, with the basic polymerization kinetics modeled sufficiently, several expansions to the simulation software have been added. Specifically, depropagation, multiple initiators, back-biting, and composition control have been incorporated and/or improved, each adding to the advancement of the polymerization simulation tool. Depropagation is a vital mechanism that should be accounted for at elevated temperatures. Currently the software has the functionality to implement depropagation but requires further literature resources for improving the kinetic predictions for conversion and polymer composition. Consequently, depropagation research is ongoing. Back-biting and beta-scission of butyl acrylate (BA) is a recent development in free radical polymerization. The completed extension can model BA under the same diverse conditions as the base model, in homo-, co- and ter-polymerizations with depropagation, if applicable. The ability to generate a polymer with a constant (or controlled) composition throughout the reaction has several practical uses. Originally, three composition control scenarios were considered. At present, several methods as well as combinations of methods have been integrated into the model. With these new expansions and the ability to simulate several initiators at the same time, this model is directed towards becoming a complete free radical polymerization tool for training and educational uses both in industry and academia.

Sepsis, a great challenge to the physician, is characterized with massive oxidative stress of tissue, cytokine inflammation and increases in nitric oxide (NO) production. Meanwhile, free radical induced by oxidative stress also injures cell membrane or DNA. The way to terminate free radical chain reaction is to administer antioxidant. The commonly used anesthetic, propofol, was thought to be with antioxidant capacity. In the first part of this thesis, we investigated the different role of oxidative injury and NO via systemic injection of LPS in rats. We demonstrated oxidative injury is associated with both early and late stage whereas NO is engaged primarily in late stage cardiovascular depression. Propofol, a rapid onset and fast recovery anesthetic, is attributed to protect anainst cardiovascular depression via attenuating the late stage NO surge in aorta by inhibition of iNOS upregulation. We also examine the influence of propofol on temporal changes in power density of frequency components of systemic arterial pressure (SAP) variability in rat with sepsis and the role of inducible NO synthase (iNOS). We have the conclusions that iNOS-induced NO might be involved in the manifestation of high-frequency and low-frequency components of the SAP spectrum during endotoxemia when low-dose propofol is used and the effect of NO is blunted when high-dose propofol is administered. Due to further investigation was needed to the cellular protective mechanisms of propofol, we delineate the effect of propofol to free radical related enzymel involved in sepsis via both in vivo and vitro studies with rats subjected to LPS (15 mg/kg) and H9C2, L2, NR8383 (derived from rat cardiac myocyte, lung, macrophage, respectively), respectively. Our results demonstrated that propofol may play the major protective role on iNOS, superoxide dismutase and p47 phox oxidative enzymes on lung epithelial cells. Propofol also provided protective effects on cardiac myocyte and macrophage with suppression of iNOS only although free radical production were all significantly suppressed. Ischemia-reperfusion (IR) injury may also produce a lot of free radical and cytokines to cause tissue damage and is common in clinical. We investigated the effect of propofol on free radical and cytokine production via this different model and compared with another rapid recovery anesthesitc, sevoflurane. Aortic decalmping surgery in porcine and their monocyte, aortic and coronary smooth muscle cells were applied for in vivo and in vitro model, respectively. We also demonstrated that propofol but not sevoflurane suppressed the production of free radical and cytokine in monocyte and smooth muscle cells but not in vivo model. In sepsis and IR model that produced a lot free radical and cytokines, propofol eliminated the free redical and cytokines via suppressed different kinds of oxidative enzymes in different cells of different organs to express its protective role. However, as an anesthetic, propofol must be used carefully to perform its maximal benefit.

This study was designed to investigate the cytotoxic and antioxidative properties of Aesculus hippocastanum L. (A. hippocastanum) bark extracts. Dried and powdered barks were extracted in ethanol, methanol, water and ethylacetate at a ratio of 1:6 (w/v). Antioxidative capacity of each extract (ethanol, methanol, water and ethylacetate) were determined by their ability to scavenge 1, 1 -diphenyl-2-picryl-hydrazyl radical (DPPH). Effective concentration (EC50) values were calculated as 0.010 mg/mL 0.011 mg/mL, 0.009 and 0.019 mg/mL, respectively for ethanol, methanol, ethylacetate and aqueous extracts. The highest DPPH radical scavenging activity was demonstrated by ethyl acetate among the four bark extracts of A. hippocastanum. Nevertheless, methanol extract was preferred for the separation, identification and further quantification of its phenolic compounds using HPLC method. Analytical and semi&ndash / preparative HPLC methods were applied to qualify and quantify the isolates. Human Myeloid Leukemia (HL - 60) cell line was used as a model system for the proliferation studies. HL - 60 cells were cultured in the presence of various concentrations (0 to 100 &micro / g/mL) of methanol bark extract and, also, with the various concentrations of standard esculetin. HL-60 cell viability was examined by tryphan blue and the metabolism of tetrazolium salt XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) -carbonyl]-2H-tetrazolium hydroxide). XTT effective dose (ED50) values for the proliferation studies of methanol extract and standard esculetin were calculated as 56.18 &micro / g/mL and 21.23 &micro / g/mL, respectively. These results suggested that A. hippocastanum methanol bark extract and esculetin could be considered as a potent antioxidant and cytotoxic agent.

Advances in medical treatment are leading away from generalized care towards intelligent systems or devices which can sense and respond to their environment. With these devices, the burden of monitoring and dosing for treatment can be removed from the doctor (or the patient) and be placed on the device itself. Implicit closed-loop control systems will allow the device to respond to its environment and release therapeutic agent in response to a specific stimulus. Environmentally responsive hydrogels show great promise in being incorporated in such an intelligent device, such as pH-responsive hydrogels which can swell and deswell in response to changes in the pH of the media. Thus, pH changes can be exploited for controlled and intelligent drug delivery when used in combination with these pH-responsive hydrogels. In this work, heterogeneous, thermal-redox initiated free-radical polymerizations were developed to synthesize novel pH-responsive hydrogels, microparticles, and nanogels. The specific disease of interest was type I diabetes, which requires daily doses of insulin both at a basal amount and either a postprandial or preprandial bolus in order to maintain blood glucose levels within safe limits. To allow pH-responsive hydrogels to be sensitive to glucose, glucose oxidase was incorporated which oxidizes glucose to gluconic acid. A novel inverse-emulsion polymerization method was developed for the synthesis of poly[2-(diethylaminoethyl methacrylate)-grafted-polyethylene glycol monoethyl ether monomethacrylate] (P(DEAEM-g-PEGMMA)) nanogels (100-400 nm) for intelligent insulin delivery. The new polymerization method allowed the incorporation of hydrophilic components, such as glucose oxidase and catalase, as well as PEG surface tethers of lengths 400 Da up to 2000 Da. Surface tethers successfully decreased the surface charge of the nanogels. Insulin loading and release was determined for microparticles which were able to imbibe substantial amounts of insulin from solution when swollen, entrap the insulin when collapsed, and then release the insulin in response to either a pH or glucose stimulus. / text

This thesis is directed towards expanding and refining a free radical multi-component polymerization model. The model considers up to six monomers (unique in the literature), both in bulk and solution polymerization, for either batch or semi-batch reactor modes. As the simulator database contains 13 monomers, 5 initiators, 4 solvents, 3 chain transfer agents and 2 inhibitors, all tested over a wide range of polymerization conditions, from data in both academic and industrial laboratories, several hundred combinations of ingredients can be modeled. The many outputs generated by the model include conversion, molecular weight, polymer composition, branching indicators, sequence length, as well as many others polymerization characteristics related to both production rate and polymer quality. Although the only literature data found to-date contains a maximum of four monomers, model predictions for homo-, co-, ter- and tetra-polymerizations show reasonable agreement against the data at both regular and elevated temperatures. Recently, with the basic polymerization kinetics modeled sufficiently, several expansions to the simulation software have been added. Specifically, depropagation, multiple initiators, back-biting, and composition control have been incorporated and/or improved, each adding to the advancement of the polymerization simulation tool. Depropagation is a vital mechanism that should be accounted for at elevated temperatures. Currently the software has the functionality to implement depropagation but requires further literature resources for improving the kinetic predictions for conversion and polymer composition. Consequently, depropagation research is ongoing. Back-biting and beta-scission of butyl acrylate (BA) is a recent development in free radical polymerization. The completed extension can model BA under the same diverse conditions as the base model, in homo-, co- and ter-polymerizations with depropagation, if applicable. The ability to generate a polymer with a constant (or controlled) composition throughout the reaction has several practical uses. Originally, three composition control scenarios were considered. At present, several methods as well as combinations of methods have been integrated into the model. With these new expansions and the ability to simulate several initiators at the same time, this model is directed towards becoming a complete free radical polymerization tool for training and educational uses both in industry and academia.

Verdazyl radicals are a family of multicoloured stable free radicals. Aside from the defining backbone of four nitrogen atoms, these radicals contain multiple highly modifiable sites that grant them a high degree of derivatization. Despite having been discovered more than half a century ago, limited applications have been found for the verdazyl radicals and little is known about their chemistry. This thesis begins with an investigation to determine whether verdazyl radicals have a future as mediating agents in living radical polymerizations and progresses to their application as substrates for organic synthesis, an application that to date has not been pursued either with verdazyl or nitroxide stable radicals. The first part of this thesis describes the successful use of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical as a mediating agent for styrene and n-butyl acrylate stable free radical polymerizations. The study of other verdazyl derivatives demonstrated the impact of steric and electronic properties of the verdazyl radicals on their ability to mediate polymerizations. The second part of this thesis outlines the initial discovery and the mechanistic elucidation of the transformation of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical into an azomethine imine, which in the presence of dipolarophiles, undergoes a [3+2] 1,3-dipolar cycloaddition reaction to yield unique pyrazolotetrazinone structures. The reactivity of the azomethine imine and the scope of the reaction were also examined. The third part of this thesis describes the discovery and mechanistic determination of a base-induced rearrangement reaction that transforms the verdazyl-derived pyrazolotetrazinone cycloadducts into corresponding pyrazolotriazinones or triazole structures. The nucleophilicity, or the lack thereof, of the base employed leading to various rearrangement products was examined in detail. The final part of this thesis demonstrates the compatibility of the verdazyl-initiated cycloaddition and rearrangement reactions with the philosophy of diversity-oriented synthesis in generating libraries of heterocycles. A library of verdazyl-derived heterocycles was generated in a short amount of time and was tested non-specifically for biological activity against acute myeloid leukemia and multiple myeloma cell lines. One particular compound showed cell-killing activity at the 250 mM range, indicating future potential for this chemistry in the field of drug discovery.

Acrylic resins, synthesized from a mixture of monomers selected from the methacrylate, acrylate and styrene families, are the base polymer components for many automotive coatings due to their excellent chemical and mechanical properties. The low molecular weight polymers with reactive functionalities are made via high-temperature starved-feed free-radical solution semibatch terpolymerization, operating conditions that greatly promote the importance of secondary reactions, such as methacrylate depropagation, and acrylate backbiting, chain scission and macromonomer propagation. In this work, a generalized model for styrene/methacrylate/acrylate terpolymerization has been developed and formulated in the PREDICI software package and poorly understood high temperature mechanisms have been studied. Unknown rate coefficients for methacrylate depropagation, reactivity of acrylate macromonomer and penultimate copolymerization kinetics were determined via separate kinetic experiments. The generality of the terpolymerization mechanistic model was verified against data obtained under a range of polymerization conditions, and provides an exclusive insight into the kinetic complexity of methacrylate/styrene/acrylate terpolymerization at high temperatures. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2010-04-28 19:56:36.906

Functional water-soluble polymers find applications in a variety of fields including waste-water treatment, pharmaceuticals, cosmetics, drug delivery, and hygiene. Despite the increased demand for these products, understanding of their synthesis by free-radical aqueous-phase polymerization has lagged behind that of polymers produced in organic solvents. In this doctoral work, the free-radical batch and semibatch aqueous-phase polymerization of N-vinylpyrrolidone (NVP), N-vinylformamide (NVF), N-vinylimidazole (NVI) and quaternized vinylimidazole (QVI), as well as NVP polymerized in n-butanol, has been studied. Kinetic models are developed to describe monomer conversion and polymer molecular weight (MW) behaviour of these systems. The expressions developed from independent pulsed-laser studies for propagation (kp) and termination (kt) rate coefficients, including their variation with monomer concentration and conversion, are shown to provide an excellent description of aqueous-phase NVP polymerization. Polymerization of NVP in butanol and of NVF in water are well-represented by the base NVP model, with differences in polymerization rate and polymer MWs simply accounted for by the differences in kp for the systems, indicating that the kt behaviour must be quite similar. The NVI/QVI study demonstrates the importance of a pH-dependent degradative addition reaction to monomer for NVI, with polymerization behaviour identical to that of QVI for pH 1, an effect captured in the model developed to describe the system. The aqueous-phase copolymerization of NVP and NVF was also studied, and reactivity ratios were determined to be very close to unity. This information was combined with the kp and kt expressions used to describe NVP and NVF homopolymerizations, with no other additional parameters required to model the copolymerization rate, copolymer composition and copolymer MW. This result demonstrates that the improved homopolymerization knowledge of these water-soluble monomers can be easily extended to understand their behaviour in copolymerization. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2011-12-21 16:05:14.904