Multi-stimuli responsive trigger for temporally controlled depolymerization of self-immolative polymers

Nichol, Meghan F.; Clark, Kyle D.; Dolinski, Neil D.; Alaniz, Javier Read de

doi:10.1039/c9py00301k

Cited by 18 publications

(16 citation statements)

References 31 publications

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“…For example, preliminary kinetic studies performed on a small-molecule model compound reveal that the release of a primary alcohol from our earlier furfuryl carbonate substrate occurs with a half-life of approximately 4 days, or nearly 100× slower than the release of hydroxycoumarin ( Figure S1 ). We reasoned that the addition of an electron-donating substituent 31 at the 3-position of the furan would further suppress the activation barrier for fragmentation since this substituent is in resonance with the furfuryl carbocation, potentially enabling the efficient release of even more challenging payloads such as amines 32 under mild conditions.…”

Section: Resultsmentioning

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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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: Resultsmentioning

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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“…Recently, de Alaniz and co-workers reported the first example of reversible ‘pausing’ of a self-immolative depolymerisation reaction in response to temperature changes. 13 This work highlights an important advantage of dynamically responsive self-immolation: the ability to switch the cascade between active and paused states ensures that payload delivery proceeds only under specific environmental conditions and slows or ceases entirely if those conditions suddenly change. Considering the paucity of reported examples, there are unexplored opportunities for dynamically controlling self-immolation kinetics using transient or fluctuating signals.…”

Section: Introductionmentioning

confidence: 96%

Dynamic pH responsivity of triazole-based self-immolative linkers

et al. 2020

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Gating the release of chemical payloads in response to transient signals is an important feature of 'smart' delivery systems. Herein, we report a triazole-based self-immolative linker that can be reversibly paused or slowed and restarted throughout its elimination cascade in response to pH changes in both organic and organic-aqueous solvents. The linker is conveniently prepared using the alkyne-azide cycloaddition reaction, which introduces a 1,4-triazole ring that expresses a pH-sensitive intermediate during its elimination sequence. Using a series of model compounds, we demonstrate that this intermediate can be switched between active and dormant states depending on the presence of acid or base, cleanly gating the release of payload in response to a fluctuating external stimulus.

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“…Recently, de Alaniz and co-workers reported the rst example of reversible 'pausing' of a self-immolative depolymerisation reaction in response to temperature changes. 13 This work highlights an important advantage of dynamically responsive self-immolation: the ability to switch the cascade between active and paused states ensures that payload delivery proceeds only under specic environmental conditions and slows or ceases entirely if those conditions suddenly change. Considering the paucity of reported examples, there are unexplored opportunities for dynamically controlling self-immolation kinetics using transient or uctuating signals.…”

Section: Introductionmentioning

confidence: 96%

Dynamic pH responsivity of triazole-based self-immolative linkers

Roberts

Pilgrim²,

Dell³

et al. 2020

Preprint

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The Cu(I)-catalyzed azide-alkyne ‘click’ reaction is used to generate triazole-based self-immolative linkers that can be reversibly paused and restarted throughout their elimination cascades. The formed 1,4-triazole ring expresses a pH-sensitive intermediate that can be switched dynamically between active and dormant states depending on the presence of acid or base, cleanly gating the release of payload in response to pH changes.<br>

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Multi-stimuli responsive trigger for temporally controlled depolymerization of self-immolative polymers

Abstract: The design and development of a multi-stimuli trigger enables temporal control over trigger cleavage and subsequent depolymerization of self-immolative polymer.

Cited by 18 publications

References 31 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

Dynamic pH responsivity of triazole-based self-immolative linkers

Dynamic pH responsivity of triazole-based self-immolative linkers

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