Polyolefins are the number one commercially produced polymeric material by volume, and find ubiquitous uses as plastics, elastomers, and fibers. They are produced from gaseous olefins such as ethylene and propylene by the action of a transition metal catalyst. Despite tremendous academic and industrial efforts and successes in catalyst development over the past decades, the copolymerization of polar functionalized olefins with sufficiently high activities still remains a largely unsolved issue. Late transition metal catalysts were shown to be more suitable for this kind of polymerization reaction due to their generally lower oxophilic character. The main goal of this thesis was the development of novel late transition olefin polymerization catalysts based on ruthenium and palladium. Prior to this work, only few active olefin polymerization Ru-catalysts

were reported.

Several series of complexes based on ruthenium were synthesized, characterized and

investigated for olefin polymerization. Ru(II)-complexes of the type RuCl2(N,N,N)L with facially coordinating nitrogen donor ligands (N,N,N = trispyridyl-, trispyrazoyl-, trisimidazoyl-methane derivatives) were found to be inactive towards ethylene polymerization. Employing bisanionic disulfonate phosphines as ligands gave Ru-complexes that produced linear, high-molecular weight polyethylene in the presence of an aluminum-alkyl based cocatalyst. Increasing the electrophilicity of the complex, by decreasing the donor strength of the ligand and using higher oxidation state Ru(IV)-complexes, the polymerization activity could be increased, and one of the highest activities for any Ru-based catalyst was observed. Polar additives such as acetone fully inhibited even the most electron-rich catalysts and copolymerization reactions yielded no polymer.

In a different approach to solve the same problem, Pd-diimine complexes were modified

with pendant olefin and boronate groups. Pd-diimine complexes can facilitate the copolymerization of ethylene with acrylates, and interactions of the pendant Lewis acid group with the functional, Lewis basic comonomer was anticipated to increase catalyst activity. However, no effect of a pendant pinacol boronate was observed on the incorporation ratio of methyl acrylate in room temperature copolymerizations. The ability of the pendant olefin to coordinate to cationic Pd-species resulted in hemilabile effects. Increased catalyst stability at the cost of decreased activities was found in comparison with unfunctionalized ligands.

Engineering transient interactions is a powerful method that can be used to encode structure and function in chemical systems. This is the common theme in all three chapters of this dissertation, despite the slight differences in initial motivations. I begin my dissertation by describing my efforts to direct peptide folding in organic environments using supramolecular amino acids (SAAs). The incorporated supramolecular motif has a strong driving force to dimerize in a sequence- and orientation-specific manner. By introducing SAAs into the primary sequence of peptides, we envisioned to perturb the native hydrogen bond patterns and facilitate the folding of the peptides through specific and directional dimerization of the supramolecular units.

In Chapter 2, I describe the synthesis and characterization of a new self-healing multiphase polymer, in which, a pervasive network of dynamic metal-ligand (zinc-imidazole) interactions are programmed in the soft matrix of a hard/soft two-phase brush copolymer system. Following mechanical damage, these thermoplastic elastomers show excellent self-healing ability under ambient conditions without any intervention. The mechanical and dynamic properties of the materials can be tuned by varying a number of molecular parameters (e.g., backbone/brush degree of polymerization and brush density) as well as the ligand/metal ratio. This chapter concludes by noting an attempt to correlate the observed mechanical properties to the small molecule parameters of metal-ligand complexes.

Synthesis of multiphasic self-healing polymers prepared from simple commercially-available monomers in a facile and scalable manner was the motivation behind the work described in the Chapter 3. The mechanical properties of these new polymers are easily tunable across a broad range (from soft rubber to hard plastic) by changing several molecular parameters. Self-healing ability was investigated at mild conditions, and most notably, most samples demonstrate excellent self-healing abilities with minimal intervention.

RNA based therapeutics have transformed biomedical research and attracted enormous attention due to the potential to treat uncurable genetic diseases. RNA based therapeutics involves the delivery of foreign RNA into cells to control gene expression, and ultimately alter protein expression. Through RNA therapeutics, a protein of interest can be produced through the introduction of specific messenger RNA (mRNA), transiently suppressed via RNA interference (RNAi), or permanently edited or deleted through the delivery of CRISPR-Cas9 gene editing machinery. However, the application of these groundbreaking technologies is hampered due to the lack of safe and effective delivery vehicles.

Chapter 1 provides a brief introduction to the background of gene therapy, along with challenges and considerations for developing effective gene delivery vehicles. Chapter 2 discusses a novel dipeptide functionalization strategy for developing new dendritic bolaamphiphile vectors for efficient siRNA transfection. Chapter 3 discusses the translation of the bolaamphiphile system into clinically relevant applications and in vitro delivery of siRNA to primary adipocyte and hepatocyte cells without the disruption of the underlying cellular function of the cells. Chapter 4 reports the delivery of CRISPR/Cas9 gene editing machinery via the codelivery of Cas9 mRNA and sgRNA in single polymeric nanoparticle.

In nature, living systems operate far from equilibrium by consuming and dissipating energy to perform vital processes. Chapter 1 will introduce the background, history, and field of nonequilibrium systems. Biological systems use chemically derived energy to power out-of-equilibrium processes to generate complex macroscopic motion by dissipating energy at the molecular scale. In contrast, it remains a major challenge to create synthetic out-of-equilibrium systems that operate on the macroscopic scale.

In Chapter 2 we report a chemically fueled out-of-equilibrium system that can perform macroscopic actuation and do work by lifting objects. We achieve this by driving a lower critical solution temperature (LCST) transition of poly(N-isopropylacrylamide) (pNIPAAm) hydrogels with heat generated by a copper-catalyzed azide-alkyne cycloaddition (CuAAc) reaction. Upon completion of reaction, heat dissipates to the environment, and the system returns to equilibrium completing one cycle of out-of-equilibrium behavior, which can be repeated multiple cycles by adding new chemical fuels.

In Chapter 3 the groundwork from Chapter 2 is employed in efforts to achieve a self-regulating device. We set out to attach a copper catalyst in and LCST hydrogel in order to modulate reaction rate using the change in diffusion of the chemical fuels to the active catalytic sites. Efforts to achieve self-regulation of an exothermic reaction in a 3-dimensional material via autonomously oscillating catalytic hydrogels is described.

In Chapter 4, we report the design, synthesis and characterization of self-healing magnetic nanocomposites prepared from readily available commodity monomers. These multi-functional materials demonstrate robust mechanical properties, with a Young's modulus of 70 MPa and over 500% extensibility. The magnetic nanocomposites also show self-healing ability, achieving 46% recovery of extensibility in 5 hours in ambient conditions while retaining high magnetic actuation with a commodity magnet.

RNA-based therapeutics has garnered tremendous attention due to their potential to revolutionize vaccination, protein replacement therapies, and the treatment of genetic diseases. However, safe and efficient RNA delivery is still a critical challenge for widespread therapeutic applications. In this dissertation, we developed a variety of biodegradable molecular carriers for the delivery of various RNA, including siRNA, mRNA, and CRISPR-Cas9 machinery.

Chapter 1 provides a concise introduction to gene therapy and RNA therapy, along with critical challenges and strategies for developing RNA delivery vehicles. It also summarizes different categories of current RNA delivery materials and previous work completed in our lab.

Chapter 2 describes the design and development of a multivalent peptide-functionalized bioreducible polymer system for universal, safe, and efficient delivery of various RNAs of different lengths and structures. This work provides a novel promising vector system for universal RNA delivery, which may speed up the clinical application of RNA therapy and allow for the co-delivery of multiple RNAs.

Chapter 3 describes a series of peptide-functionalized bioreducible amphiphilic vectors for safe and efficient siRNA delivery. It also discusses the details of vector design and the correlations between chemical structures and biological functions.

Chapter 4 explores a family of poly(thymine) peptide nucleic acid-functionalized bioreducible polymers for mRNA delivery. This work provides a novel strategy for mRNA delivery by introducing hydrogen-binding into RNA-vector complexation.

In Chapter 5, I discussed another research project in my Ph.D. study, which is developing hybrid organic-inorganic quantum dot superlattices for next-generation photovoltaics. This work provides a hybrid quantum dot-molecular wire approach to construct highly-ordered nanocrystal films, which brings in significantly enhanced charge transport.

The pursuit of dynamic molecular interactions to control macroscopic properties of polymers represents an exciting new direction to materials science. This new paradigm gives power to bottom-up rational design of materials to imbue remarkable macroscopic responses such as biomimetic adaptiveness, self-healing, and reprocessability. Thus, there is a critical need to establish a clear link between the mechanical and dynamic properties of advanced polymeric materials and the thermodynamic and kinetic parameters of its small molecule constituents, which is the goal of this dissertation.

In Chapter 2, we set out to directly correlate the fundamental mechanical properties of advanced dynamic materials to its individual molecular constituents. We used multi-cyclic single-molecule force spectroscopy (SMFS), paired with the unique capability of SMFS to derive the shape profile and the kinetic and thermodynamic parameters of the energy landscape of modular rupture and refolding, to characterize a titin-mimicking modular polymer. We found that a steep dissociative pathway accounted for the high plateau modulus, while a shallow associative well explained the slow dynamic recovery and energy-dissipative hysteresis.

In Chapter 3, we used variable small molecule kinetics to rationally design and directly correlate the advanced dynamic properties of dynamically crosslinked materials. Specifically, we crosslinked diol-based polymers with two variants of telechelic di-boronic esters, whose rates of transesterification vary by five orders of magnitude. It was found that the highly dynamic nature of the fast exchanging boronic ester imbued efficient self-healing and enhanced malleability, while the relatively inert nature of the slow exchanging boronic ester demonstrated little self-healing capability as well as diminished malleability, though both variants showed excellent reprocessibility at elevated temperatures.

In Chapter 4, we furthered the concept of Chapter 3 by moving to a dynamically crosslinked thermoset design. This was achieved through poly-condensation of telechelic boronic acids with multivalent diols. Though unfortunately the kinetic variability of boronic acid exchange and its emergent effect on bulk material was inconclusive, a boronic ester-based vitrimer material was nevertheless described, with a robust match between activation energies of molecular exchange and bulk material flow.

Dynamic materials including self-healing polymers and vitrimers have huge potential for improving current material’s performance, lifetime and processability. In this thesis, we have synthesized a self-healing system by incorporating zinc amide interaction and a vitrimer system via transesterification of boronic esters. Chapter 1 provides a brief introduction to the background of self-healing polymers and vitrimers. Chapter 2 details the design and development of a zinc amide self-healing polymer system. Chapter 3 discusses attempts to synthesize a catalyst free, tunable boronic ester vitrimer.

Despite promising potentials for disease treatment, clinical application of RNAi is greatly limited by the lack of safe and effective delivery vectors. In this dissertation, we aim to achieve efficient siRNA delivery by developing novel synthetic biomaterials through rational molecular design and in-depth structure-property study.

Chapter 1 introduces the background of siRNA delivery. Major challenges in synthetic vector design are discussed, followed by current approaches to overcome these obstacles. Several successful synthetic vectors are surveyed with an emphasis on materials with dendritic architectures.

Chapter 2 describes dendronized polymer (denpol) for efficient siRNA delivery. The denpol architecture combines multivalency of dendrons and flexibility of polymer backbone to achieve strong siRNA binding. Through in vitro screening of a focused denpol library, we identified that histidine and aromatic amino acid functionalized denpols achieved high delivery efficiency with minimum cytotoxicity. Fluorescence trafficking study revealed that aromatic groups enhanced cell uptake and histidine helped endosomal escape. Such combination could also be applied to other systems. Chapter 3 describes tryptophan and histidine functionalized dendritic polyglycerol for siRNA delivery. And chapter 4 investigates the application of tryptophan-histidine combination on a novel bolaamphiphile structure. Compared to normal amphiphiles, bolaamphiphiles do not disrupt cell membrane and thus greatly reduces toxicity. The molecular structure of bolaamphiphiles determines their self-assembly behavior with siRNA and subsequent biological activity. The optimal dendron bolaamphiphile achieved effective silencing at low siRNA concentration.

Chapter 5 highlights the importance of formulation process in delivery. In a stimuli-responsive nanogel system, we found that only in situ cross-linking could effectively encapsulate siRNA and achieve functional delivery.

Chapter 6 describes a novel Ru catalytic system for polyamide synthesis. All the biomaterials we developed in previous chapters are based on polyamides, as the amide bonds provide good chemical stability while maintain biodegradability. Current syntheses of polyamides involve harsh conditions and/or produce stoichiometric amount of toxic waste. We developed the first catalytic polyamidation by dehydrogenation of diols and diamines to achieve high atomic economy with no waste generation. The high catalytic selectivity also offers the opportunity to efficiently incorporate polyamines into the polymer backbone without tedious protection/deprotection steps.

Polymers have become a ubiquitous part of our lives, filling diverse applications ranging from aerospace to children’s toys. With over three hundred million tons of plastics being produced annually, it’s crucial to increase their usable lifespan and reduce their relegation to waste. As such, it is necessary to move away from traditional commodity polymers and steer towards new structural designs that make the polymers more recyclable and more resistant toward deterioration and failure. For wider adoption, these new structural designs should be thermally stable, resistant to additives, and can resist/repair damage. The incorporation of dynamic covalent chemistries into polymers offer an attractive route towards our dream of limitless recyclability. Dynamic covalent bonds allow for the shuffling of crosslink points between disparate polymer backbones, allowing for benefits such as self-healing, moldability, and malleability within static materials. The incorporation of dynamic covalent chemistries provides a platform for the next generation of green materials by imparting recyclability in traditionally un-recyclable materials. Chapter 1 of this thesis will provide the reader with an overview of the field for understanding the most meaningful contributions to the field of dynamic covalent chemistries in polymer networks.

Chapter 2 describes my work towards developing a robust self-healing polymer by incorporating both dynamic covalent chemistry and supramolecular interactions via sterically hindered thiourea linkages. In model compounds studies I found that tuning the bulkiness of the thiourea linkage led to the tunability of the association and dissociation equilibrium. When transferred to polymers, these findings led to the generation of both high molecular weight polymers and efficient self-healing at ambient temperatures.

In Chapter 3 we report our discovery of a new silyl ether metathesis reaction and its application in vitrimer design. The incorporation of silyl ether crosslinks led to enhanced mechanical properties and significant creep resistance over unmodified polymers. Our silyl ether-based vitrimer represents the most thermally stable vitrimer reported to date, owing to the high thermal and oxidative stability of the Si-O bond.

In Chapter 4 we describe our developments towards a new fluoride catalyst for selective and rapid exchange of siloxanes, thereby expanding the scope of Si-O vitrimer chemistry. The field of vitrimers has largely focused on niche polymers with little attention into the expansion of vitrimer chemistry into commodity plastics. Here, I work on developing industrially relevant methods for preparing vitrimers from commodity polymers.

Chapter 5 summarizes our work towards the development of a generalized polymer compatibilizer using thermally reversible Diels-Alder chemistry. This compatibilizer uses thermally reversible mechanical interlocks to stabilize the phase separation of immiscible polymer blends. If successful, this work would provide both a new recycling method and a technique to produce novel polymer blends.

Drawing on inspiration from nature, transient, dynamic interactions can encode function into synthetic materials. Reversible interactions, such as dynamic covalent chemistry and transient noncovalent interactios can provide mechanisms for a host of functional applications such as self-healing, malleability, and energy dissipation. The effect of dynamic interactions on the emergent functional properties is a common thread throughout the thesis. The dissertation begins with an extensive introduction to self-healing polymer materials. Here, three main self-healing mechanisms are discussed including physical, vascular, and intrinsic based healing. A short exposition of polymerization techniques used in this thesis is also discussed briefly in the beginning.

In Chapter 2, I discuss my efforts toward the development of tunable boronic ester transesterification mediated self-healing and malleable materials. Small molecule model studies show that introduction of an amino-neighboring group accelerates the rate of transesterification of aryl boronic esters over five orders of magnitude. Telechelic boronic ester cross-linkers, one with the neighboring group and one without, are introduced to a poly-ol matrix and showed dramatic differences in dynamic properties. This study is the first self-healing system where the dynamicity of the healing motif has been systematically tuned based on small molecule experiments which directly relate to the emergent dynamic properties. In Chapter 3, the boronic ester transesterification reaction is further tuned to access to rates that are within the five orders of magnitude described in Chapter 2. Here, tuning the electronics on the aryl boronic ester and the sterics on the neighboring amine are varied and can be used successfully to finely tune the rate of transesterification. We believe that this fine tuning will provide a method by which bottom up approaches to dynamic materials can be pursued.

In Chapter 4, I then discuss polycyclooctene based thermoplastic elastomers. Here, by introducing different amounts of dihydroxylated cyclooctene in a polycyclooctene based polymer, the melting temperature and therefore crystallinity can be adjusted. The bulk mechanical properties show that the materials with intermediate diol are thermoplastic elastomers with interesting mechanical properties. By TEM, phase collapse is observed.

In Chapter 5, I discuss a hydrogen bonding-based self-healing nanocomposite system. Here, polymer grafted silica nanoparticles that contain amides are prepared. Three different approaches to controlling the graft density on particle surface are explored. Silica nanoparticles could indeed be functionalized with polymerization initiators and subsequent polymerizations could be completed. All three approaches, however, led to irreproducible and inconsistent results. This chapter largely serves as a cautionary tale about the intricacies of nanocomposite materials.

Finally, in chapter 6, I describe my contributions to a multi-university collaboration where nanocomposite polymer coating materials for blast-induced shockwave mitigation is explored. First, nanoparticles with acrylate polymers grafted from the surface are blended into a host polyurea matrix. When the acrylate polymers have urea units that can hydrogen bond to the host matrix, the materials are able to significantly dissipate energy. The second half of the chapter discusses the development of superlattice nanocomposite materials that have controlled center to center spacing for targeted frequency absorption. Throughout this thesis, I hope to convey that programming subtle molecular interactions can have dramatic impacts on the dynamic properties of bulk polymer materials.