The objective of this research was to develop and validate new macromolecular imaging agents to detect and characterize malignant tumours. Using well-defined, highly branched macromolecules called dendrimers as the structural scaffold, efficient functionalization of the periphery was demonstrated using “click” chemistry in order to prepare multivalent imaging probes. Furthermore, a transmetalation was demonstrated to displace chelated copper with technetium, enabling “click” reactions to be performed in the presence of the dipicolylamine (DPA), a ligand known to chelate many metals. The dendritic scaffold was functionalized with either hydrophobic or hydrophilic targeting vectors. The hydrophobic ligand, an acyloxymethyl ketone targeting the overexpression of cathepsin B exhibited poor in vitro affinity when coupled to either G1 or G2 dendrimers, despite the use of various linkers. A glu-urea-lys dipeptide, representing a hydrophilic prostate specific membrane antigen targeting vector, demonstrated excellent affinity in vitro. The lead compound, a G2 dendrimer bearing four PSMA targeting vectors attached via an alkyl spacer was further investigated in vitro and in vivo. Unfortunately, poor tumor uptake was observed and the compound was hypothesized to hydrolyze readily (<15min), based on the in vitro plasma stability data. To rectify the aforementioned problem, non neo-pentyl esters were replaced with either carbamate or ether linkages. In vitro plasma stability analysis of the analogous compounds demonstrated increased stability. In particular, the ether analogue was found to be most stable, with minimal degradation observed after 4 hours. / Thesis / Doctor of Philosophy (PhD)

Silicone oils (polysiloxane) and elastomers are a class of hydrophobic polymers with an extensive range of uses. While the high hydrophobicity can be beneficial in a variety of applications, it is not universally the case. Modification strategies for both fluid and elastomeric polydimethylsiloxane (PDMS) must be employed to create silicones with the appropriate properties for a given application, including enhanced hydrophilicity. Derivatization of PDMS leads to functional silicones with unique properties and added value. Strategies have been developed to modify both fluid and elastomeric PDMS, however, they all have varying degrees of drawbacks: the use of sophisticated equipment or expensive catalysts, restrictions to certain types of solvents, cumbersome multi-step synthetic procedures and surface reversion are some of the challenges faced. There is an opportunity to develop a simple and generic method for the controlled functionalization of PDMS. The Sharpless concept of ‘Click’ chemistry was an ideal approach to solving some of these challenges. Following nature’s lead, these reactions that are modular, wide in scope, high yielding, have simple reaction conditions and generate inoffensive byproducts. Herein, a synthetic method to functionalize silicones using the thermal Huisgen 1,3-dipolar cycloaddition of azides to alkynes is described. Initial exploration focused on the creation of inherently reactive elastomers that could be modified with a model hydrophilic moiety, poly(ethylene glycol). This was extended to the creation of amphiphilic multi-functional polysiloxanes and amphiphilic networks. Furthermore, the ‘Click’ approach was used to solve challenges faced in applications where silicones find use. The method described overcomes silicone modification challenges. The cycloaddition reaction is tolerant to many reaction conditions, is orthoganol to a variety of chemical reactions, does not require the use of a catalyst, the starting functional groups and bonds formed are stable and the reaction is high yielding, positioning the Huisgen ‘click’ reaction is an exceptional synthetic tool for the silicone chemist. / Dissertation / Doctor of Philosophy (PhD) / Polydimethylsiloxane (PDMS or silicone) fluids and elastomers are materials that find use in many applications owing to the many desirable properties they possess; personal care products, electrical insulators, sealants and biomedical are examples of products containing silicone. Native PDMS is highly hydrophobic (water repellent) and certain applications require silicones that are more compatible in environments containing water. Methods have been developed to modify both fluid and elastomeric silicones; incorporation of different molecules or polymers can enhance the properties of silicone for various applications or create unique materials. However, many of these methods have certain drawbacks: the use of sophisticated equipment, expensive ingredients, or a lack of permanence. For this reason, a new method to modify fluid and elastomeric silicones has been developed. The new method is based on the concept of ‘Click’ chemistry and has overcome some of challenges associated with other modification methods.

Single-walled carbon nanotubes (SWNTs) have excellent electronic, mechanical, and optical properties that make them promising materials for various applications. However, SWNT production methods produce a mixture of semiconducting and metallic species and non-SWNT impurities limiting their incorporation into devices. Among the different purification methods, conjugated polymer sorting has proven to be a scalable and cost-effective method. Conjugated polymers can easily be tuned to disperse SWNT species and obtain solubility in target solvents. They are multifunctional structures that enable the purification and extraction of specific SWNTs while simultaneously enhancing their processability. Therefore, they are suitable as purification methods for the fabrication of SWNT-based devices, particularly for printed electronics. However, the polymer backbone and the non-conductive side-chains negatively impacts the performance of SWNT devices by preventing good contact between the nanotubes. We first functionalized our polymer with thermally cleavable side-chains and demonstrated that the removal of the side-chains leads to a higher conductivity. We obtained stable dispersions in two green solvents compatible with inkjet printing. We also functionalized our polymer with photocleavable side-chains and showed efficient cleavage in solution. These investigations represent a proof-of-concept that could be used for the development of SWNT-based devices where the removal of the side-chains will improve the device performance. Lastly, we synthesized a fluorene-based polymer that contains a photocleavable ortho-nitrobenzylether unit and is functionalized with hydrophilic side-chains. We demonstrated the degradation of the polymer in organic and aqueous solvents. These investigations highlight the challenges of dispersing SWNTs in aqueous solvents using conjugated polymer. / Thesis / Doctor of Philosophy (PhD) / The objective of this thesis is to develop cleavable complexes between conjugated polymers and single-walled carbon nanotubes (SWNTs) to maximize the potential performance of printed devices post-processing. We functionalized a conjugated polymer with cleavable side-chains and investigated the impact on the conductivity after their removal. In addition, this work also focuses on dispersing SWNTs in green solvents that are compatible with printing processes such as inkjet printing. Lastly, we synthesized a degradable and water-soluble conjugated polymers to produce dispersant free-SWNTs.

The thesis work described herein explores two avenues of post-functionalization of conjugated polymers using ‘click’ chemistry. The first avenue utilizes the Strain-Promoted Alkyne-Azide Cycloaddition (SPAAC) and the second an Inverse Electron-Demand Diels-Alder (IEDDA). In the first part of this thesis, various azide moieties were SPAAC ‘clicked’ onto a dibenzocyclooctyne-containing polymer, such as small molecules like para-phenyl-nitroazide, as well as larger azide-terminated chains like polystyrene and polyethylene glycol. Host-guest chemistry and self-healing organogels were also explored. The synthesis of each component, including the cyclooctyne diamine monomer, dialdehyde comonomer, resulting polymer, various azide moieties, as well as the SPAAC click reactions, are all described in detail along with extensive characterization. Similarly, the second part of this thesis involved the synthesis and characterization of several components, including the tetrazine monomer, fluorene comonomer, resulting polymer, and various TCO derivatives for the post-polymerization IEDDA ‘click’ reactions onto the backbone. Some of the click reactions described include small molecule TCO derivatives, polymeric PEG TCO, and a difunctional linker to generate a crosslinked foam. / Conjugated polymers attract significant attention due to their interesting optoelectronic and physical properties. Over the past few decades, tremendous effort has been devoted to expanding the structural diversity and applications of this class of macromolecules. The pursuit of structural variability of conjugated polymers has resulted in a broad range of research to understand their structure-property relationships via functionalization. This functionalization is crucial for tailoring performance in any given application. Thus, the ability to synthesize a library of homologous polymers would prove very useful. Efficiency is of utmost importance when creating a library of homologous conjugated polymers, as the faster a library can by synthesized, the sooner said polymers can be screened for any desirable properties. Such an approach requires a post-polymerization functionalization strategy, whereby a progenitor polymer undergoes efficient reactions at each repeat unit of the backbone. The work presented in this thesis involves synthesizing a reactive conjugated polymer scaffold, followed by efficiently post-polymerization functionalization via “click” chemistry. Two elegant click reactions are described in this work; the Strain-Promoted Alkyne-Azide Cycloaddition (SPAAC) and Inverse Electron-Demand Diels-Alder (IEDDA). The SPAAC reaction allowed for rapid functionalization of triazole moieties on a dibenzocyclooctyne-containing polymer backbone, creating a small polymer library with a consistent degree of polymerization (DP). Grafting with polystyrene and polyethylene glycol azide-terminated polymers allowed the efficient syntheses of a series of graft-co-polymers with Mn values up to 800 kDa and varying solubilities. Secondly, The IEDDA reaction was applied to a poly(tetrazine-co-fluorene) conjugated polymer, which resulted in the rapid and quantitative functionalization of the polymer backbone with trans-cyclooctene derivatives. These reactive conjugated polymers were explored in a variety of applications, including supramolecular chemistry and gel formation. / Thesis / Doctor of Philosophy (PhD) / Conjugated polymers are a class of macromolecular materials that attract significant attention due to their interesting behaviors and properties. Under certain conditions, these polymers even display conductivities like that of metals. As such, they show promise in applications such as organic solar cells, chemical sensors, organic light-emitting diodes, and supercapacitors. Over the past few decades, tremendous effort has been devoted to expanding on the types of conjugated polymers as well as their structural diversity. This, of course, has resulted in polymers that exhibit vastly different behaviours depending on what they are made of. As certain applications (e.g.: solar cells) require polymers with very specific properties, being able to ‘tune’ a conjugated polymer to ‘match’ a required property would be extremely useful. This tuning of polymer properties can be successfully accomplished by attaching different structures onto the polymer chain by utilizing a reaction known as ‘post-polymerization functionalization’. In doing so, a starting reactive polymer can be transformed into an entirely different polymer with specific chemical properties and behaviors. The work presented in this thesis involves synthesizing two types of conjugated polymers and attaching various structures onto their backbones to yield different properties. The synthesis, characterization, and potential applications of said polymers are described herein.

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