Design and synthesis of mechanoresponsive materials and multivalent polymer-peptide conjugates

Functional polymers have been studied extensively due to their versatility and ability to yield diverse materials with desirable properties. Polymers that are functionalized intrinsically are made using several strategies including specially designed monomers and post polymerization functionalization. This thesis focuses on two examples of intrinsic functionalization. First, mechanophores are incorporated into polymers and impart function when materials are subjected to mechanical force. Second, multivalent polymer-peptide conjugates (mPPCs) are synthesized by the post polymerization modification of a polymer backbone with peptides and interact with amyloid beta to inhibit its aggregation. These examples of functionalized polymers elucidate structure-reactivity relationships which will be beneficial to future research and prove useful in biomedical applications. The mechanophore hypothesis posits that force drives productive and selective chemical change. In chapter two of this thesis, the effect of regiochemistry on the mechanochemical reactivity of a naphthopyran mechanophore is examined. A series of constitutional isomers was evaluated computationally, then synthesized and incorporated into a crosslinked polymer matrix. Experiments revealed three mechanochemically active isomers which differ in their sensitivity to force. This work revealed the importance of the alignment between the direction of applied force and the scissile bond within the naphthopyran mechanophore. Further, this study highlighted the structure-reactivity relationships which govern naphthopyran mechanochromism. The third chapter of this thesis details the remote generation of light using high-intensity focused ultrasound (HIFU) as a remote force trigger for a dioxetane based mechanophore. Remotely generating light is potentially useful in biomedical applications such as optogenetics where light is needed inside biological systems. In this study, dioxetane mechanophores were incorporated in polymer matrices. HIFU was then used as a source of force to trigger light generation through the activation of the dioxetane mechanophore. Light intensity was increased by optimizing sample components and preparation. The final chapter of this thesis focuses on the synthesis and characterization of mPPCs. These polymers are functionalized post polymerization with peptide ligands. We demonstrate that mPPCs are a compelling general strategy to inhibit the aggregation of amyloid beta. To highlight this we vary peptide inhibitor, polymer molecular weight, and substitution percentage. We find that a negatively charged ligand leads to more effective mPPCs when compared to neutral ligands, and is most effective at 7% substitution regardless of molecular weight. Molecular dynamics simulations and dynamic light scattering measurements reveal interesting structural characteristics and interactions that enhance our understanding of structure-property relationships present in the system. Ultimately this work will lead to the improvement of inhibitors as it increases our fundamental understanding of a complex system.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Halmes, Abigail Joy

Contributors dc:contributor

• Moore, Jeffrey S
• Sottos, Nancy R
• Braun, Paul V
• Zimmerman, Steven C

• Functional Polymers
• Mechanophore
• Mechanochromic
• Naphthopyran
• Dioxetane
• mPPC
• Multivalent
• Amyloid

Statement dc:rights

• Copyright 2020 Abigail Halmes

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/108237

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/108237