Architectural Effects on Aqueous Self- Assembly of Bottlebrush Block Copolymers and Synthesis of Degradable Bottlebrush Polymers

Abstract

Bottlebrush polymers feature densely grafted side chains along a polymeric backbone. Due to their unusual topology, bottlebrush polymers are an emerging class of materials with unique physical properties and novel applications, including supersoft elastomers, residual-free adhesives, drug delivery or photonic crystals. Among these interesting applications, amphiphilic bottlebrush block copolymers (BCPs) and their solution self-assembly have attracted significant attention over the past decade due to their potentials as drug delivery carriers. Driven by microphase separation, amphiphilic bottlebrush BCPs self-assemble into various nanoaggregates with surface protrusions, including spherical micelles, ellipsoids, cylindrical micelles, and vesicles. Compared to their linear BCP analogues, bottlebrush BCPs exhibit significantly lower critical micelle concentrations and consequently form more stable nanoaggregates. While theoretical and experimental studies on cone-shaped amphiphiles have been widely studied, the solution self-assembly of cone-shaped (tapered) bottlebrush BCPs remains underexplored. To address this knowledge gap, this dissertation presents systematic studies of the aqueous self-assembly of tapered bottlebrush BCPs. A series of eight tapered and four cylindrical bottlebrush BCPs were synthesized via sequential addition of macromonomers ring-opening metathesis polymerization, featuring varying ratios of hydrophobic polystyrene (PS) and hydrophilic poly(acrylic acid) PAA side chains. The nanostructures formed by these bottlebrush BCPs in water were characterized using cryogenic transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS). Results reveal that most BCPs formed multiple nanostructures with surface protrusion, including spherical micelles, cylindrical micelles, and vesicles. Coarse-grained molecular dynamics simulations supported the interpretation of the experimental observations. Collectively, two distinct self-assembly pathways were identified. One pathway involves micelle fusion to form elliptical and cylindrical aggregates that, in some cases, fused further to form Y-junctions. The second pathway proceeded through micelle maturation into semi-vesicles, which subsequently developed into vesicles that, in some cases, fused further to form compound vesicles. Moreover, for the first time, larger spheres that are nanoaggregates with a core radius larger than the average core radius were identified by cryo-TEM tomography. These results provide the first experimental evidence for vesicle formation via semi-vesicle intermediates in bottlebrush BCPs. These findings highlight how structural parameters such as cone directionality govern self-assembly in these large, cone-shaped polymeric amphiphiles. Extending this work, the effects of cone angle on aqueous self-assembly were systematically investigated using six tapered bottlebrush BCPs—three with hydrophobic tips and three with hydrophobic bases— with estimated cone angles ranging from 6 o to 15o. Cylindrical bottlebrush BCPs with comparable molar masses were also synthesized for comparison. All bottlebrush BCPs maintained a constant mass ratio of hydrophobic PS to hydrophilic deuterated PAA side chains at approximately 50%. Moreover, deuteration of PAA side chains enabled us to employ contrast-variation SANS for characterization of core radius and shell thickness in spherical nanoaggregates. Cylindrical bottlebrush BCPs exhibited similar distributions of self-assembled morphologies regardless of molecular weight. In contrast, tapered bottlebrush BCPs displayed a correlation between morphology distributions and cone angle. Tapered bottlebrush BCPs with a hydrophobic tip favored nearly exclusive formation of spherical micelles at low cone angles. The cone angle exerted a more pronounced effect on morphology in bottlebrush BCPs with hydrophobic bases. Despite similar hydrophobic contents, BCPs with lower cone angles exhibited high populations of spherical micelles, whereas those with higher cone angles led to larger spheres, ellipsoids, vesicles, and work-like structures. Characterization of the core radius and shell thickness by cryo-TEM and contrast-variation SANS showed good agreement between the two techniques, though some discrepancies were observed between theoretical predictions and experimental measurements. This work provides insights into how cone geometry governs the aqueous self-assembly behavior of bottlebrush BCPs. Bottlebrush polymers have received considerable interest as residual-free pressure-sensitive adhesives (PSAs). Due to their unique topology and entanglement suppression of entanglement, these polymers are naturally soft and flexible without needing chemical additives. This allows them to stick when pressed and peel off cleanly without leaving behind a gummy residue. Unfortunately, most bottlebrush polymers include all-carbon backbones and could contribute to plastic pollution following their intended use. Recent efforts have focused on developing methods to synthesize degradable bottlebrush polymers. However, these methods typically require specialty monomers or cannot make bottlebrush polymers with high molar mass. To address these challenges, we developed an approach that takes advantage of the alternating free-radical copolymerization of sulfur dioxide (SO2) and electron-rich alkenes, including cycloalkenes (e.g., norbornene). We prepared several types of norbornene macromonomers with side chain molecular weights up to 5 kg/mol and successfully copolymerized them with SO2. These poly(olefin sulfone) bottlebrush polymers featured various types of side chains, such as polyacrylates, polymethacrylates, polystyrene, and poly(lactic acid), attached to a poly(norbornene-alt-SO2) backbone and reached number-averaged molar masses of up to 1100 kg/mol. More importantly, these bottlebrush polymers were degradable. Degradation studies with a variety of bases revealed that the sulfone unit with removable protons on neighboring carbons enabled degradation of these high-molecular-weight polymers within hours. Moreover, a bottlebrush polymer synthesized using this approach exhibited pressure-sensitive adhesive properties with a peel strength of approximately 1200 N/m. Collectively, this work offers a versatile approach using inexpensive SO2 gas to synthesize degradable bottlebrush polymers with high molar mass, enabling end-of-life disposal following their intended applications.