Incorporation of a Tethered Alcohol Enables Efficient Mechanically Triggered Release in Aprotic Environments.

Polymers that release small molecules in response to mechanical force are promising for a wide variety of applications. While offering a general platform for mechanically triggered release, previous mechanophore designs based on masked 2-furylcarbinol derivatives are limited to polar protic solvent environments for efficient release of the chemical payload. Here, we report a masked furfuryl carbonate mechanophore incorporating a tethered primary alcohol that enables efficient release of a hydroxycoumarin cargo in the absence of a protic solvent. Density functional calculations also implicate an intramolecular hydrogen bonding interaction between the tethered alcohol and the carbonyl oxygen of the carbonate that reduces the activation barrier for carbonate fragmentation leading to molecular release. This new mechanophore design expands the generality of the masked 2-furylcarbinol platform for mechanically triggered release, enabling the implementation of this strategy in a wider range of chemical environments.

Mechanically Triggered Release of Functionally Diverse Molecular Payloads from Masked 2-Furylcarbinol Derivatives.

Polymers that release functional small molecules in response to mechanical force are appealing targets for drug delivery, sensing, catalysis, and many other applications. Mechanically sensitive molecules called mechanophores are uniquely suited to enable molecular release with excellent selectivity and control, but mechanophore designs capable of releasing cargo with diverse chemical functionality are limited. Here, we describe a general and highly modular mechanophore platform based on masked 2-furylcarbinol derivatives that spontaneously decompose under mild conditions upon liberation via a mechanically triggered reaction, resulting in the release of a covalently installed molecular payload. We identify key structure-property relationships for the reactivity of 2-furylcarbinol derivatives that enable the mechanically triggered release of functionally diverse molecular cargo with release kinetics being tunable over several orders of magnitude. In particular, the incorporation of an electron-donating phenoxy group on the furan ring in combination with an α-methyl substituent dramatically lowers the activation barrier for fragmentation, providing a highly active substrate for molecular release. Moreover, we find that phenoxy substitution enhances the thermal stability of the mechanophore without adversely affecting its mechanochemical reactivity. The generality and efficacy of this molecular design platform are demonstrated using ultrasound-induced mechanical force to trigger the efficient release of a broad scope of cargo molecules, including those bearing alcohol, phenol, alkylamine, arylamine, carboxylic acid, and sulfonic acid functional groups.

Validation of the CoGEF Method as a Predictive Tool for Polymer Mechanochemistry.

The development of force-responsive molecules called mechanophores is a central component of the field of polymer mechanochemistry. Mechanophores enable the design and fabrication of polymers for a variety of applications ranging from sensing to molecular release and self-healing materials. Nevertheless, an insufficient understanding of structure-activity relationships limits experimental development, and thus computation is necessary to guide the structural design of mechanophores. The constrained geometries simulate external force (CoGEF) method is a highly accessible and straightforward computational technique that simulates the effect of mechanical force on a molecule and enables the prediction of mechanochemical reactivity. Here, we use the CoGEF method to systematically evaluate every covalent mechanophore reported to date and compare the predicted mechanochemical reactivity to experimental results. Molecules that are mechanochemically inactive are also studied as negative controls. In general, mechanochemical reactions predicted with the CoGEF method at the common B3LYP/6-31G* level of density functional theory are in excellent agreement with reactivity determined experimentally. Moreover, bond rupture forces obtained from CoGEF calculations are compared to experimentally measured forces and demonstrated to be reliable indicators of mechanochemical activity. This investigation validates the CoGEF method as a powerful tool for predicting mechanochemical reactivity, enabling its widespread adoption to support the developing field of polymer mechanochemistry. Secondarily, this study provides a contemporary catalog of over 100 mechanophores developed to date.

Designing naphthopyran mechanophores with tunable mechanochromic behavior.

Mechanochromic molecular force probes conveniently report on stress and strain in polymeric materials through straightforward visual cues. We capitalize on the versatility of the naphthopyran framework to design a series of mechanochromic mechanophores that exhibit highly tunable color and fading kinetics after mechanochemical activation. Structurally diverse naphthopyran crosslinkers are synthesized and covalently incorporated into silicone elastomers, where the mechanochemical ring-opening reactions are achieved under tension to generate the merocyanine dyes. Strategic structural modifications to the naphthopyran mechanophore scaffold produce dramatic differences in the color and thermal electrocyclization behavior of the corresponding merocyanine dyes. The color of the merocyanines varies from orange-yellow to purple upon the introduction of an electron donating pyrrolidine substituent, while the rate of thermal electrocyclization is controlled through electronic and steric factors, enabling access to derivatives that display both fast-fading and persistent coloration after mechanical activation and subsequent stress relaxation. In addition to identifying key structure-property relationships for tuning the behavior of the naphthopyran mechanophore, the modularity of the naphthopyran platform is demonstrated by leveraging blends of structurally distinct mechanophores to create materials with desirable multicolor mechanochromic and complex stimuli-responsive behavior, expanding the scope and accessibility of force-responsive materials for applications such as multimodal sensing.

Mechanically Triggered Small Molecule Release from a Masked Furfuryl Carbonate.

Stimuli-responsive polymers that release small molecules under mechanical stress are appealing targets for applications ranging from drug delivery to sensing. Here, we describe a modular mechanophore design platform for molecular release via a mechanically triggered cascade reaction. Mechanochemical activation of a furan-maleimide Diels-Alder adduct reveals a latent furfuryl carbonate that subsequently decomposes under mild conditions to release a covalently bound cargo molecule. The computationally guided design of a reactive secondary furfuryl carbonate enables the decomposition and release to proceed quickly at room temperature after unmasking via mechanical force. This general strategy is demonstrated using ultrasound-induced mechanical activation to release a fluorogenic coumarin payload from a polymer incorporating a chain-centered mechanophore.