Incorporation of a self-immolative spacer enables mechanically triggered dual payload release.

Polymers that release functional small molecules in response to mechanical force are promising materials for a variety of applications including drug delivery, catalysis, and sensing. While many different mechanophores have been developed that enable the triggered release of a variety of small molecule payloads, most mechanophores are limited to one specific payload molecule. Here, we leverage the unique fragmentation of a 5-aryloxy-substituted 2-furylcarbinol derivative to design a novel mechanophore capable of the mechanically triggered release of two distinct cargo molecules.

Multimechanophore Polymers for Mechanically Triggered Small Molecule Release with Ultrahigh Payload Capacity.

Polymers that release small molecules in response to mechanical force are promising for a variety of applications including drug delivery, catalysis, and sensing. While a number of mechanophores have been developed for the release of covalently bound payloads, existing strategies are either limited in cargo scope or, in the case of more general mechanophore designs, are restricted to the release of one or two cargo molecules per polymer chain. Herein, we introduce a nonscissile mechanophore based on a masked 2-furylcarbinol derivative that enables the preparation of multimechanophore polymers with ultrahigh payload capacity.

Anomalous photochromism and mechanochromism of a linear naphthopyran enabled by a polarizing dialkylamine substituent.

In contrast to common angular naphthopyrans that exhibit strong photochromic and mechanochromic behavior, constitutionally isomeric linear naphthopyrans are typically not photochromic, due to the putative instability of the completely dearomatized merocyanine product. The photochemistry of linear naphthopyrans is thus relatively understudied compared to angular naphthopyrans, while the mechanochromism of linear naphthopyrans remains completely unexplored. Here we demonstrate that the incorporation of a polarizing dialkylamine substituent enables photochromic and mechanochromic behavior from polymers containing a novel linear naphthopyran motif.

Naphthopyran molecular switches and their emergent mechanochemical reactivity.

Naphthopyran molecular switches undergo a ring-opening reaction upon external stimulation to generate intensely colored merocyanine dyes. Their unique modularity and synthetic accessibility afford exceptional control over their properties and stimuli-responsive behavior. Commercial applications of naphthopyrans as photoswitches in photochromic ophthalmic lenses have spurred an extensive body of work exploring naphthopyran-merocyanine structure-property relationships.

Remote control of mechanochemical reactions under physiological conditions using biocompatible focused ultrasound.

External control of chemical reactions in biological settings with spatial and temporal precision is a grand challenge for noninvasive diagnostic and therapeutic applications. While light is a conventional stimulus for remote chemical activation, its penetration is severely attenuated in tissues, which limits biological applicability. On the other hand, ultrasound is a biocompatible remote energy source that is highly penetrant and offers a wide range of functional tunability.

Competitive Activation Experiments Reveal Significantly Different Mechanochemical Reactivity of Furan-Maleimide and Anthracene-Maleimide Mechanophores.

During the past two decades, our understanding of mechanochemical reactivity has advanced considerably. Nevertheless, an incomplete knowledge of structure-activity relationships and the principles that govern mechanochemical transformations limits molecular design. The experimental development of mechanophores has thus benefited from simple computational tools like CoGEF, from which quantitative metrics like rupture force can be extracted to estimate reactivity.

Validation of an Accurate and Expedient Initial Rates Method for Characterizing Mechanophore Reactivity.

Understanding structure-mechanochemical reactivity relationships is important for informing the rational design of new stimuli-responsive polymers. To this end, establishing accurate reaction kinetics for mechanophore activation is a key objective. Here, we validate an initial rates method that enables the accurate and rapid determination of rate constants for ultrasound-induced mechanochemical transformations.

Mechanically gated formation of donor-acceptor Stenhouse adducts enabling mechanochemical multicolour soft lithography.

Stress-sensitive molecules called mechanophores undergo productive chemical transformations in response to mechanical force. A variety of mechanochromic mechanophores, which change colour in response to stress, have been developed, but modulating the properties of the dyes generally requires the independent preparation of discrete derivatives. Here we introduce a mechanophore platform enabling mechanically gated multicolour chromogenic reactivity.

Mechanical Force Enables an Anomalous Dual Ring-Opening Reaction of Naphthodipyran.

Multimodal mechanophores that exhibit complex mechanochromic behavior beyond the typical binary response are capable of distinguishing between multiple stress states through discrete changes in color. Naphthodipyran photoswitches contain two pyran rings fused to a central naphthalene core and represent a potentially promising framework for multimodal reactivity. However, the concurrent ring opening of both pyran moieties has previously proven inaccessible via photochemical activation.

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.

Examining the Impact of Relative Mechanophore Activity on the Selectivity of Ultrasound-Induced Mechanochemical Chain Scission.

Despite recent advances in polymer mechanochemistry, a more complete understanding of the factors that dictate the ultrasound-induced mechanochemical activation efficiency of mechanophores is necessary. Here, we examine how the identity of a mechanophore, and hence its unique force-coupled reactivity, affects the competition between mechanophore activation and nonspecific polymer backbone scission. Polymers incorporating distinct mechanophores but with putatively similar "chain-centeredness" exhibit widely different mechanochemical activation efficiencies.

Harnessing the Power of Force: Development of Mechanophores for Molecular Release.

Polymers that release small molecules in response to mechanical force are promising materials for a variety of applications ranging from sensing and catalysis to targeted drug delivery. Within the rapidly growing field of polymer mechanochemistry, stress-sensitive molecules known as mechanophores are particularly attractive for enabling the release of covalently bound payloads with excellent selectivity and control. Here, we review recent progress in the development of mechanophore-based molecular release platforms and provide an optimistic, yet critical perspective on the fundamental and technological advancements that are still required for this promising research area to achieve significant impact.

A modular approach to mechanically gated photoswitching with color-tunable molecular force probes.

Molecular force probes conveniently report on mechanical stress and/or strain in polymers through straightforward visual cues. Unlike conventional mechanochromic mechanophores, the mechanically gated photoswitching strategy decouples mechanochemical activation from the ultimate chromogenic response, enabling the mechanical history of a material to be recorded and read on-demand using light. Here we report a completely redesigned, highly modular mechanophore platform for mechanically gated photoswitching that offers a robust, accessible synthesis and late stage diversification through Pd-catalyzed cross-coupling reactions to precisely tune the photophysical properties of the masked diarylethene (DAE) photoswitch.

5-Aryloxy substitution enables efficient mechanically triggered release from a synthetically accessible masked 2-furylcarbinol mechanophore.

Polymers that release small molecules in response to mechanical force are attractive materials for a wide variety of applications. Here, we report a new mechanophore platform based on a masked 2-furylcarbinol derivative that incorporates a 5-aryloxy group, which serves as both an electron-rich substituent to accelerate molecular release and the position of polymer attachment proximal to the furan-maleimide junction. The mechanophore is readily synthesized and efficiently releases both phenol and arylamine payloads following mechanical activation.

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.

Generation of an Elusive Permanent Merocyanine via a Unique Mechanochemical Reaction Pathway.

We report the discovery of a 2-naphtho[1,2-]pyran mechanophore that produces a permanent merocyanine dye upon mechanochemical activation, in contrast to the reversible product generated photochemically. Experiments suggest that the irreversibility of the mechanically generated merocyanine is due to a unique reaction in which the scission of an ester C-O bond reveals a β-hydroxy ketone that locks the merocyanine through an intramolecular H-bonding interaction. In addition to demonstrating the reactivity using solution-phase ultrasonication, permanent merocyanine generation is also achieved in solid polymeric materials.

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.

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.

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.

Force-Dependent Multicolor Mechanochromism from a Single Mechanophore.

We report a bis-naphthopyran mechanophore that exhibits force-dependent changes in visible absorption. A series of polymers incorporating a chain-centered bis-naphthopyran mechanophore was synthesized and mechanically activated using ultrasonication. By varying the length of the polymer chains, the force delivered to the mechanophore is modulated systematically.

Spatially Selective and Density-Controlled Activation of Interfacial Mechanophores.

Mechanically sensitive molecules known as mechanophores have recently attracted much interest due to the need for mechanoresponsive materials. Maleimide-anthracene mechanophores located at the interface between poly(glycidyl methacrylate) (PGMA) polymer brushes and Si wafer surfaces were activated locally using atomic force microscopy (AFM) probes to deliver mechanical stimulation. Each individual maleimide-anthracene mechanophore exhibits binary behavior: undergoing a retro-[4 + 2] cycloaddition reaction under high load to form a surface-bound anthracene moiety and free PGMA or remaining unchanged if the load falls below the activation threshold.

Mechanochemical Regulation of a Photochemical Reaction.

We introduce the concept of mechanochemically gated photoswitching. Mechanical regulation of a photochemical reaction is exemplified using a newly designed mechanophore based on a cyclopentadiene-maleimide Diels-Alder adduct. Ultrasound-induced mechanical activation of the photochemically inert mechanophore in polymers generates a diarylethene photoswitch via a retro-[4 + 2] cycloaddition reaction that photoisomerizes between colorless and colored states upon exposure to UV and visible light.

Interfacial Mechanophore Activation Using Laser-Induced Stress Waves.

A new methodology is developed to activate and characterize mechanochemical transformations at a solid interface. Maleimide-anthracene mechanophores covalently anchored at a fused silica-polymer interface are activated using laser-induced stress waves. Spallation-induced mechanophore activation is observed above a threshold activation stress of 149 MPa.

Polymers with autonomous life-cycle control.

The lifetime of man-made materials is controlled largely by the wear and tear of everyday use, environmental stress and unexpected damage, which ultimately lead to failure and disposal. Smart materials that mimic the ability of living systems to autonomously protect, report, heal and even regenerate in response to damage could increase the lifetime, safety and sustainability of many manufactured items. There are several approaches to achieving these functions using polymer-based materials, but making them work in highly variable, real-world situations is proving challenging.