Molecular Design of Advanced Mechanophore Scaffolds for Triggered Release

Author: Tseng, Yu-Ling

Year: 2027

Degree: Dissertation (Ph.D.)

Advisor: Robb, Maxwell J.

Committee Members: Stoltz, Brian M.; Wei, Lu; Fu, Gregory C.; Robb, Maxwell J.

Option: Chemistry

DOI: 10.7907/v4zf-pp67

Abstract

In the field of polymer mechanochemistry, mechanical force is harnessed to drive productive chemical transformations within stress sensitive molecules termed as mechanophores. Mechanophores designed to release functional small molecules have garnered significant attention for their broad utility in drug delivery, catalysis, and sensing. This dissertation explores advanced molecular design strategies to expand the scope of mechanically triggered release, focusing on diversifying cargo compatibility and drastically amplifying payload capacity.

A central focus of this work is the development of a modular masked 5-aryloxy-substituted 2-furylcarbinol mechanophore. In Chapter 1, this platform is utilized to covalently conjugate an adamantylidene-phenoxy-1,2-dioxetane chemiluminophore payload. By incorporating this conjugate into poly(methyl acrylate) and poly(ethylene glycol) backbones, ultrasound-induced mechanochemical activation initiates a cascade fragmentation that generates intense green luminescence across both organic and aqueous media. Chapter 2 expands the utility of this 2-furylcarbinol architecture to enable the triggered liberation of two distinct payload molecules. By integrating a self-immolative spacer, the mechanophore successfully releases dual payloads. The specific release profile, whether simultaneous or step-wise, can be finely tuned by altering the relative attachment sites of the payloads.

While single-mechanophore architectures are highly functional, they are inherently bottlenecked by a maximum release capacity of one or two payloads per polymer chain, restricting overall material efficiency. To address this stoichiometric limitation, Chapter 3 details the development of a water-soluble multimechanophore polymer architecture with ultrahigh payload capacity. By rationally engineering both the mechanophore monomer and a cyclooctene comonomer, the resulting polymer achieves excellent aqueous solubility. Upon mechanical activation, this multi-payload design demonstrates a remarkable 106-fold enhancement in payload release efficiency in an aqueous environment relative to traditional single-mechanophore systems.

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