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<p>The controlled synthesis of functional low molecular weight polyethylene and polyethylene mimics is important in tuning polymer properties and is of great industrial interests. Living polymerization is a method that allows for precise control in polymer structure. Although high molecular weight polymers with controlled structures can be efficiently produced via living polymerization, the production of low molecular weight polymers faces the challenges of the use of large amounts of expensive catalyst and the broadening of polydispersity.</p> <p>The synthesis of well-defined functional low molecular weight polyethylene and polyethylene mimics is studied. Promising polymerization systems, including living ring opening metathesis polymerization (ROMP), living coordination polymerization, coordinative chain transfer polymerization (CCTP), and living C1 polymerization, are identified and are analyzed based on product properties, efficiency, cost, and safety.</p> <p>Within the identified systems, living ROMP is selected for study due to the industrial relevance of ROMP polymers, the availability of raw materials, and the ease of reaction setup. The efficiency of ROMP is challenged by polydispersity broadening resulting from slow initiation and poor reactor volume efficiency due to its implementation as a solution polymerization process. The challenges are addressed by the use of excess phosphine and the realization of ROMP as a bulk polymerization process.</p> <p>Experimental results demonstrate that bulk ROMP with and without phosphines yield product with similar or enhanced molecular weight distribution control as solution ROMP. Kinetic studies confirm living polymerization behaviour of bulk ROMP. A mathematical model is developed for the first time using method of moments to describe the kinetics and development of molecular weight distribution of ROMP. The model is a useful tool in preliminary research and commercialization of ROMP. The success of bulk ROMP and the development of a representative model yield ROMP as a promising method for the production of low molecular weight polymers with controlled architecture.</p> / Master of Applied Science (MASc)

Part I: Single sized, pure arylene ether macrocycles ranging from 30 to 60 atom ring sizes were synthesized in good yields (up to 83%) by the two component method under high dilution conditions. These macrocycles have unsymmetric structures containing sulfone/ketone or sulfone/phosphine oxide functional groups and have relatively low melting points. The melt ROP of the single sized macrocycles to form poly(arylene ether)s exhibits two stage characteristics: the first stage is very fast, driven by the large entropy difference between cyclics and linears; the second stage is very slow and is diffusion controlled due to the high viscosity created in the first stage reaction. The latter stage leads to incomplete polymerization at the low initiator concentrations (1-3 mol%). At high initiator concentrations (5-7 mol%), 100% conversion is reached due to improved initiator distribution in macrocycles; however, this reduces molecular weights of the polymers. The molecular weight is found to build up very rapidly, independent of conversion, reaction time and type of initiator. The ROP is initiated by CsF and alkali phenoxides. The efficiency of the alkali counterion is generally in the order of Cs+>K+>Na+, while a phenoxide initiator is more efficient than a fluoride initiator. It is also found that the Cs counterion leads to highest degree of crosslinking. The ROP of cyclic oligomeric mixtures is also reported for comparison; the study shows that the molecular weight depends on time and conversion, and that the conversion is sensitive to the content of linear impurities and the average ring size of cyclic mixtures. Part II: Polyrotaxanes are novel polymeric materials comprised of linear polymer molecules and threaded macrocycles with no covalent bond between the two components. With potential movements of the cyclic component and judicious combinations of the two components of different properties, these materials have brought interesting changes of physical properties, such as morphology, crystallinity, solubility, viscosity, etc. In this part of the dissertation, a new family of polyrotaxanes with poly(arylene ether)s as backbones and crown ethers as cyclic components are described. These include linear poly(arylene ether) based polyrotaxanes and hyperbranched poly(ether ether ketone) based polyrotaxanes; both are synthesized via aromatic nucleophilic substitution reactions. Preliminary studies show that these polymers exhibit great enhancement of solubility. The polymers form emulsions in water and methanol which are normally non-solvents for the poly(arylene ether) backbones. In some cases, they are even soluble in water to form a clear solution. The attempted syntheses of polyrotaxanes using aromatic macrocycles described in Part I was not successful, with no indication of threading. / Ph. D.

Cyclopropane derivatives are frequently utilized as "probes" for radical cation intermediates in a number of important chemical and biochemical oxidation. The implicit assumption in such studies is that if a radical cation is produced, it will undergo ring opening. Through a detailed examination of follow-up chemistry of electrochemically and chemically generated cyclopropylarene radical cations, we have shown that the assumption made in the use of these substrates as SET probes is not necessarily valid. While cyclopropylbenzene radical cation undergoes rapid methanol-induced ring opening (e.g., k = 8.9⁷ s⁻¹M⁻¹), the radical cations generated from 9-cyclopropylanthracenes do not undergo cyclopropane ring opening at all. The radical cations generated from cyclopropylnaphthalenes disproportionate or dimerize before undergoing ring opening. Utilizing cyclic, derivative cyclic, and linear sweep voltammetry, it was discovered that decay of radical cations generated from cyclopropylnaphthalenes in CH₃CN/CH₃OH is second order in radical cation and zero order in methanol. Anodic and Ce(IV) oxidation of all these naphthyl substrates in CH₃CN/CH₃OH led to cyclopropane ring-opened products. However, the rate constant for methanol-induced ring opening (Ar-c-C₃H₅⁺. + CH₃OH -> ArCH(·)CH₂CH₂O(H⁺)CH₃) is extremely small (<20 s⁻¹M⁻¹ for 1-cyclopropylnaphthalenes) despite the fact that ring opening is exothermic by nearly 30 kcal/mol. These results are explained on the basis of a product-like transition state for ring opening wherein the positive charge is localized on the cyclopropyl group, and thus unable to benefit from potential stabilization offered by the aromatic ring. Reactions of radical cations generated from 9-cyclopropylanthracenes in CH₃CN/CH₃CN have also been investigated electrochemically. The major products arising from oxidation of these anthryl substrates are attributable to CH₃OH attack at the aromatic ring rather than CH₃OH-induced cyclopropane ring opening. Ce(IV) oxidation of 9-cyclopropyl-10-methylanthracene and 9,10-dimethylanthracene further showed that radical cations generated from these anthryl substrates undergo neither cyclopropane ring opening nor deprotonation but nucleophilic addition. Side-chain oxidation products from Ce(IV) oxidation of methylated anthracenes arose from further reaction of nuclear oxidation products under acidic and higher temperature conditions. An analogous (more product-like) transition state picture can be applied for cyclopropane ring opening and deprotonation of these anthryl radical cations. Because of much higher intrinsic barrier to either nucleophile-induced cyclopropane ring opening or deprotonation of these anthryl radical cations, nucleophilic addition predominates. Stereoelectronic effects may be another additional factor contributing to this intrinsic barrier because the cyclopropyl group in these anthryl systems adopts a perpendicular conformation which may not meet the stereoelectronic requirements for cyclopropyl ring opening at either the radical cation or dication stage. / Ph. D.

Additive manufacturing (AM) creates 3D objects out of polymers, ceramics, and metals to enable cost-efficient and rapid production of products from aerospace to biomedical applications. Personalized products manufactured using AM, such as personalized dosage pharmaceuticals, tissue scaffolds, and medical devices, require specific material properties such as biocompatibility and biodegradability, etc. Polymers possess many of these qualities and tuning molecular structure enables a functional material to successfully deliver the intended application. For example, water-soluble polymers such as poly(vinyl pyrrolidone) and poly(ethylene glycol) both function as drug delivery materials because of their inherit water-solubility and biocompatibility. Other polymers such as polylactide and polyglycolide possess hydrolytically cleavable functionalities, which enables degradation in the body. Non-covalent bonds, such as hydrogen bonding and electrostatic interactions, enable strong connections capable of holding materials together, but disconnect with heat or solvation. Taking into consideration some of these polymer functionalities, this dissertation investigates how to utilize them to create functional biomedical products using AM. The investigation of structure-property-processing relationships of polymer molecular structures, physical properties, and processing behaviors is transforming the field of new materials for AM. Even though novel, functional materials for AM continue to be developed, requirements that render a polymeric material printable remain unknown or vague for most AM processes. Materials and printers are usually developed separately, which creates a disconnect between the material printing requirements and fundamental physical properties that enable successful printing. Through the interface of chemistry, biology, chemical engineering, and mechanical engineering, this dissertation aims to relate printability of polymeric materials with three types of AM processes, namely vat photopolymerization, binder jetting, and powder bed fusion. Binder jetting, vat photopolymerization, and powder bed fusion require different viscosity and powder requirements depending on the printer capabilities, and if the material is neat or in solution. Developing scaling relationships between solution viscosity and concentration determined critical overlap (C*) and entanglement (Ce) concentrations, which are related to the printability of the materials. For example, this dissertation discusses and investigates the maximum printable concentration in binder jetting of multiple polymer architectures in solution as a function of C* values of the polymer. For thermal-type printheads, C* appeared to be the highest jettable concentration, which asserted an additional method of material screening for binder jetting. Another investigation of the photokinetics as a function of concentration of photo-active polymers in solution revealed increased viscosity leads to decreased acrylate/acrylamide conversion. Lastly, investigating particle size and shape of poly(stearyl acrylate) particles synthesized through suspension polymerization revealed a combination of crosslinked and linear polymers produced high resolution parts for phase change materials. These analytical screening methods will help the progression of AM and provide future scientists and engineers a better guideline for material screenings. / Doctor of Philosophy / Additive manufacturing (AM), also known as 3D printing, enables the creation of 3D objects in a rapid and cost-efficient manner for applications from aerospace to biomedical sectors. AM particularly benefits the field of personalized biomedical products, such as personalized dosage pharmaceuticals, hearing aids, and prosthetic limbs. In the future, advanced detection and prevention medical screenings will provide doctors, pharmacists, and engineers very precise data to enable personalized healthcare. For example, a patient can take three different medications in one pill with the exact dosage to prevent side-effects and drug-drug interactions. AM enables the delivery and manufacturing of these personalized systems and will improve healthcare in every sector. Investigations of the most effective materials is needed for personalized medicine to become a reality. Polymers, or macromolecules, provide a highly tunable material to become printable with slight chemical modifications. Investigation of how chemical structure affects properties, such as strength, stretchability, or viscosity, will dictate how they perform in a manufacturing setting. This process of investigation is called "structure-property-processing" relationships, which connects scientists and engineers through all disciplines. This method is used to discover which polymers will not only 3D print, but also carry medication to a patient or deliver therapeutics within the body.

Ring-opening metathesis polymerization (ROMP) is a robust synthetic technique for synthesizing complex polymer architectures (topologies). To achieve complex architectures, specifically bottlebrush polymers, using ROMP, attaining the highest degree of living character is essential. As the molecular weight of the side chain or backbone increases, the "livingness" of the polymerization suffers due to premature catalyst degradation. Attaining large, well-defined, bottlebrush polymers requires precision so it was our goal to determine how seemingly simple reaction variables could affect the rates of propagation and achievable conversion, as well as why these variables have these effects. We tested several reaction parameters to understand how they affect the rate of polymerization, the rate of catalyst degradation, and the conversion that can be reached. We performed a systematic study using six organic solvents to determine the propagation rate of three macromonomers (MMs), one polystyrene and two poly(n-butyl acrylate) MMs, in ROMP with varying side chain chemistries and end groups, as well as rate of catalyst degradation in each of the solvents. We determined that solvent affected that rate of propagation primarily by interacting with the catalyst, while there was some evidence of polymer sidechain chemistry affecting the rate. We found that ethyl acetate (EtOAc) and CH2Cl2 had the highest rates of propagation compared to the other solvents, while DMF and THF were the slowest. UV-Vis testing on the catalyst in each solvent revealed that DMF and THF had fast rates of catalyst decomposition, while toluene was much slower to decompose. From these experiments we learned that toluene, despite its slower propagation rate, has the most living character, due to its slower rate of decomposition. We also learned that purification greatly affects the propagation rate, with THF requiring purification to have any conversion to bottlebrush polymer, while purification of EtOAc slows the rate of propagation almost 2-fold. From the decrease in rate after purification, and the conclusion that it was due to an acetic acid impurity in the impure EtOAc, we decided to systematically test small molecule additives and found that acids can increase the propagation rate and the conversion of the polynorbornene backbone achievable in ROMP reactions. Notably, in reactions performed in DMF with added CF3COOH we were able to polymerize a norbornene-functionalized unprotected peptide, which was insoluble in most organic solvents, to a higher conversion than in DMF without the added acid. We learned from our research that changing reaction variables can lead to substantial changes in the rate of propagation as well as the achievable conversion in bottlebrush polymer synthesis. By understanding this we can further test other reaction variables and do systematic studies on atmosphere and temperature. We hope this research and future fundamental research can guide scientists toward synthesizing large, well-defined, complex polymer architectures using ROMP. / Doctor of Philosophy / Nature has shown that complex molecular architectures lead to unique material properties. This has inspired scientists to synthetically mimic nature to create these polymer architectures in an effort to obtain novel material properties. Ring-opening metathesis polymerization (ROMP) has become a powerful synthetic method for synthesizing complex polymer architectures. Specifically, ROMP has been used to synthesize bottlebrush polymers, so named due to the polymer backbone with long, densely grafted, polymer side chains attached. These materials exhibit very interesting properties compared to their linear polymer counterparts. Using ROMP to synthesize bottlebrush polymers is not uncommon; however, difficulties can arise if trying to use sidechains that are very long or bulky. We have worked to understand how manipulating some of the reaction parameters can allow us, and other researchers, to synthesize bottlebrush polymers that contain long and/or bulky polymer side chains. We tested the purity and type of solvent that the reaction was performed in on one polystyrene macromonomer and two poly(n-butyl acrylate) macromonomers, as well as adding small molecules, including acids, bases, and salts, to determine if these variables could improve the synthesis of bottlebrush polymers. What we found was that all of the tested variables, solvent, purity, additives, and combinations of all of these variables, did have an effect on the synthesis of these materials. This fundamental information will assist our lab, and many others, in efficiently synthesizing complex architectures, thus achieving unique material properties.

Ring-opening metathesis polymerization (ROMP) is a great tool for synthesizing polyolefin materials with different topologies, including hyperbranched polymers—polymers with high degrees of branching and many end groups. However, hyperbranched polymer synthesis via ROMP is challenging due to multifunctional-monomer or multi-polymerization requirements. To simplify the synthesis of hyperbranched ROMP polymers, we developed a new synthetic approach: Self-condensing ROMP. The self-condensing ROMP approach involves a ROMP initiator modification to attach a ROMP-polymerizable group (a ROMP monomer), producing a ROMP "inimer" (initiator + monomer). The ROMP inimer initiates the polymerization and becomes a branching unit in the polymer structure, resulting in single-step hyperbranched polymer synthesis. The key challenge is controlling of this approach the ROMP initiator reactivity to avoid initiating polymerization during the ROMP inimer synthesis. Well-defined ruthenium-based olefin metathesis catalysts are common ROMP initiators due to their high stability, reactivity, and functional group tolerance. Thus, we studied the olefin metathesis catalyst activation temperature to enable ROMP initiator-monomer coupling. Based on the catalyst activity, we designed and synthesized a series of ROMP inimers. Then, we synthesized hyperbranched polymers via self-condensing ROMP. The characterization of hyperbranched polymers indicated the effect of branching density on the physical properties of the polymer. This approach introduced a new class of olefin metathesis complexes, ROMP inimers, containing both the initiator and propagating center. This approach provides a way to synthesize hyperbranched polymers from any known ROMP monomers in a single step. This dissertation also includes the synthesis and characterization of a bimetallic Ru complex that could directly synthesize cyclic polyolefin. We also include the synthesis and characterization of copper-ruthenium bimetallic olefin metathesis catalysts. / Doctor of Philosophy / Hyperbranched polymers are a class of polymers having highly branching structures and functional end-groups, and presenting distinct physical and chemical properties compared with linear polymers. Hyperbranched polymers have been used for many applications including processing additives, cross-linkers, compatibilizers, and catalyst supports. Well-defined ruthenium-based olefin metathesis catalysts enable the synthesis of materials with different topologies, functionalities, and chemical and physical properties via ring-opining metathesis polymerization (ROMP). Ligand modifications on ruthenium catalysts have been applied to improve the catalyst stability and reactivity. However, this dissertation modifies olefin metathesis catalysts to synthesize hyperbranched polymers in a single step. This dissertation illustrates catalyst functionalization with a ROMP monomer moiety to synthesize a ROMP inimer (inimer= initiator + monomer). The ROMP initiator—olefin metathesis catalyst—and ROMP monomer coupling produces an "inimer". The inimer can undergo self-condensing ROMP with a ROMP monomer addition to synthesize hyperbranched polymers. This approach introduced a new class of olefin metathesis complexes containing both the initiator and propagating center. This approach also provides a way to synthesize hyperbranched polymers from any known ROMP monomers in a single step.

Hydrogen sulfide (H₂S) was recognized as a critical signaling molecule in mammals nearly two decades ago. Since this discovery biologists and chemists have worked in concert to demonstrate the physiological roles of H₂S as well as the therapeutic benefit of exogenous H₂S delivery. As the understanding of H₂S physiology has increased, the role(s) of other sulfur-containing molecules as potential players in cellular signaling and redox homeostasis has begun to emerge. This creates new and exciting challenges for chemists to synthesize compounds that release a signaling compound in response to specific, biologically relevant stimuli. Preparation of these signaling compound donor molecules will facilitate further elucidation of the complex chemical interplay within mammalian cells. To this end we report on two systems for the sustained release of H₂S, as well as other sulfur signaling molecules. The first system discussed is based on the N-thiocarboxyanhydride (NTA) motif. NTAs were demonstrated to release carbonyl sulfide (COS), a potential sulfur signaling molecule, in response to biologically available nucleophiles. The released COS is shown to be rapidly converted to H₂S in the presence of the ubiquitous enzyme carbonic anhydrase (CA). A synthetic route that affords NTAs with reactive functionalities was devised and the functional "parent" NTAs were successfully conjugated to a variety of substrates, ranging from small molecules to polymers. These functional NTAs provide a platform from which a library of NTA-based COS/H₂S may be readily prepared convergently in an effort to move towards H₂S-releasing drug and polymer conjugates. Additionally, preliminary in vitro cytotoxicity studies indicate that NTAs are noncytotoxic at concentrations above 100 µM. The second system discussed in this dissertation leverages the 1,6-benzyl elimination reaction (or self-immolative reaction) to facilitate the release of a persulfide (R–SSH) from a small molecule prodrug platform as well as a separate system that releases COS/H₂S from a polymer. The self-immolative persulfide prodrug was designed to be responsive to reactive oxygen species (ROS) and demonstrates efficacy as an antioxidant in vitro. Furthermore, the polymeric COS/H₂S self-immolative system was designed to respond to reducing agents, including H₂S itself, and shows promise as a H₂S signal amplification platform. / Doctor of Philosophy / Hydrogen sulfide (H₂S) has long been recognized as a malodorous and toxic byproduct of industrial chemical processes. However, the discovery of H₂S as a key signaling molecule in mammals has drastically shifted the paradigm of H₂S research over the last two decades. Research into the production and roles of H₂S in the body is ongoing, but has pointed to the implication of changes in H₂S production to the onset of a variety of disease states, including cardiovascular disease and Alzheimer’s. As alterations in the body’s production of H₂S have been correlated to certain disease states, collaborative research efforts among biologists and chemists have demonstrated the utility of H₂S-based therapeutics in helping to alleviate these disease states. Our understanding of the roles of H₂S in the body, and potential benefits derived from H₂S-releasing drugs, can only continue to advance with the development and improvement of H₂S releasing compounds. The first portion of this dissertation focuses on the synthesis of a new class of H₂S-releasing compounds, termed N-thiocarboxyanhydrides (NTAs). NTAs release H₂S through an intermediate sulfur-containing molecule, carbonyl sulfide (COS), which may have signaling properties independent of H₂S. The COS that is released from the NTAs is rapidly converted to H₂S by the action of the ubiquitous enzyme carbonic anhydrase. A variety of functional NTAs were synthesized, which in turn were used to prepare a small library of NTA-based COS/H₂S releasing compounds. This work informs the preparation of H₂S-drug or H₂S-polymer conjugates. The second portion of this dissertation examines a class of compounds broadly termed self-immolative prodrugs. The self-immolative prodrug platform was leveraged to release H₂S, or persulfides (R–SSH), another class of sulfur-containing molecules of biological interest. The self-immolative persulfide prodrug system was designed to be responsive to reactive oxygen species (ROS), a harmful cellular byproduct. The persulfide donor was successful in mitigating the harmful effects of ROS in heart cells. Independently, a polymeric self-immolative H₂S releasing system was designed to depolymerize in the presence of H₂S, resulting in the generation of 6-8-fold excess of H₂S upon depolymerization. We envision the self-immolative H₂S-releasing polymer will show promise in biological applications where a vast excess of H₂S is needed rapidly.