Mechanochemical Release of <i>N</i>‐Heterocyclic Carbenes from Flex‐Activated Mechanophores

Shen, Hang; Larsen, Michael B.; Roessler, Allison G.; Zimmerman, Paul M.; Boydston, Andrew J.

doi:10.1002/anie.202100576

Cited by 45 publications

(41 citation statements)

References 68 publications

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“… 14 , 15 Boydston has developed mechanophores based on a flex-activation manifold demonstrating release of a benzyl furfuryl ether molecule via a mechanically induced cycloelimination reaction 16 , 17 and the release of N-heterocyclic carbenes. 18 Notably, each approach uses a judiciously designed mechanophore to release a specific compound upon mechanical activation, which consequently limits the scope of molecules that can be released. Small-molecule release has also been achieved through the mechanically triggered heterolytic scission and subsequent depolymerization of poly( o -phthalaldehyde) to regenerate its constituent monomers.…”

Section: Introductionmentioning

confidence: 99%

“…Several mechanophores have been designed to achieve the mechanically triggered release of functional organic molecules, although the scope of molecules that can be released is still relatively limited. Moore and Craig have designed mechanophores based on gem -dichlorocyclopropane motifs that undergo mechanochemical rearrangement reactions with subsequent release of HCl. , Boydston has developed mechanophores based on a flex-activation manifold demonstrating release of a benzyl furfuryl ether molecule via a mechanically induced cycloelimination reaction , and the release of N-heterocyclic carbenes . Notably, each approach uses a judiciously designed mechanophore to release a specific compound upon mechanical activation, which consequently limits the scope of molecules that can be released.…”

Section: Introductionmentioning

confidence: 99%

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

Zeng

Husic

et al. 2021

ACS Cent. Sci.

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zeng

Husic

et al. 2021

ACS Cent. Sci.

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“…The addition of liquid PITC to the PMA network was thought to plasticize the polymer and thus improve its durability. To demonstrate the adaptability of employed NHCs, NHC‐CDIs based on 1,3‐bis(2,6‐diisopropylphenyl)imidazolidin‐2‐ylidene (SIPr) were incorporated into the PMA network 11 b and 0.4 % of the mechanophore was activated after compression at 7400 bar for 10 minutes [26] . The approach of flex activation was also used by the group of Kilian and co‐workers, who incorporated oxanorbornadiene 6 into a double network hydrogel consisting of two interpenetrated networks.…”

Section: Molecular Release Systemsmentioning

confidence: 99%

Release of Molecular Cargo from Polymer Systems by Mechanochemistry

Küng

Göstl

Schmidt

2022

Chemistry A European J

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The design and manipulation of (multi)functional materials at the nanoscale holds the promise of fuelling tomorrow's major technological advances. In the realm of macromolecular nanosystems, the incorporation of force‐responsive groups, so called mechanophores, has resulted in unprecedented access to responsive behaviours and enabled sophisticated functions of the resulting structures and advanced materials. Among the diverse force‐activated motifs, the on‐demand release or activation of compounds, such as catalysts, drugs, or monomers for self‐healing, are sought‐after since they enable triggering pristine small molecule function from macromolecular frameworks. Here, we highlight examples of molecular cargo release systems from polymer‐based architectures in solution by means of sonochemical activation by ultrasound (ultrasound‐induced mechanochemistry). Important design concepts of these advanced materials are discussed, as well as their syntheses and applications.

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“…Several approaches are being used where stimuli‐responsive systems addressed by, for example, light, 6,7 electromagnetic fields, 8 pH, 9 or redox, 10 allow to control the delivery and release of therapeutic agents. Recently, concepts in polymer mechanochemistry were exploited to activate or release drugs 11–16 and other molecules 17–27 by ultrasound (US) 28,29 . Therefore, shear force is exerted on polymer chains to activate a mechanochemically latent site (the mechanophore) at a higher rate compared to the remaining bonds in the polymer 30–34 …”

Section: Introductionmentioning

confidence: 99%

Microgels as drug carriers for sonopharmacology

Zou

Zhao

Fan

et al. 2022

Journal of Polymer Science

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The ultrasound‐induced cleavage of covalent and non‐covalent bonds to activate drugs (sonopharmacology) is a promising concept to gain control over the action of active pharmaceutical ingredients by an external trigger. Previously, linear polymer architectures bearing drug payloads were exploited for drug release by using the principles of polymer mechanochemistry. In this work, the carrier design is altered by the polymer topology to improve the ultrasound‐triggered release of covalently anchored drugs from polymer scaffolds. We use microgels crosslinked by mechanoresponsive disulfides and copolymerized with Diels‐Alder adducts of furylated payload molecules and acetylenedicarboxylate. Force‐induced thiol formation induces a Michael‐type addition liberating the payload from the microgels. The use of microgels significantly reduces sonication times compared to linear polymer chains and shields the cargo efficiently from non‐triggered activation using ultrasound that produces inertial cavitation at a frequency of 20 kHz as model condition.

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Mechanochemical Release of N‐Heterocyclic Carbenes from Flex‐Activated Mechanophores

Cited by 45 publications

References 68 publications

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

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

Release of Molecular Cargo from Polymer Systems by Mechanochemistry

Microgels as drug carriers for sonopharmacology

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