An enzymatic acetal/hemiacetal conversion for the physiological temperature activation of the alkoxyamine C–ON bond homolysis

Albalat, Muriel; Audran, Gérard; Holzritter, Maxence; Marque, Sylvain R. A.; Mellet, Philippe; Vanthuyne, Nicolas; Voisin, Pierre

doi:10.1039/d0qo00559b

Cited by 11 publications

(9 citation statements)

References 51 publications

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“…Chemical, [88][89][90] biological, [91,92] or plasmonic [93,94] stimuli are relatively new as triggers for dynamic alkoxyamine bond dissociation. Although these stimuli have not been exploited in alkoxyamine-based CANs, they were already successfully utilized in NMP or as smart alkoxyamines.…”

Section: Other Stimulimentioning

confidence: 99%

Covalent Adaptable Networks Based on Dynamic Alkoxyamine Bonds

Jia

Delaittre

Tsotsalas

2022

Macro Materials & Eng

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Covalent adaptable networks (CANs) introduce a new paradigm to polymer science, by making static network polymers dynamic and thereby recyclable, reprocessable, and self‐healing. The critical feature in CANs is the presence of dynamic covalent linkages within the network structure. A variety of such linkages are introduced into CANs, making the respective networks responsive to various stimuli, such as light, temperature, or pH. Here, CANs based on alkoxyamines as dynamic covalent bonds are reviewed. Alkoxyamines uniquely combine the ability to dynamically form, break, and reform covalent bonds with the possibility to initiate reversible‐deactivation radical polymerization. Polymer networks based on alkoxyamines are therefore both adaptive and quasi‐living, able to remodel the network structure by nitroxide‐exchange reactions (NER) and extend the network structure by nitroxide‐mediated polymerization (NMP). In this review, the concepts behind CANs are first introduced and the properties of nitroxides and derived alkoxyamines are discussed. A special focus is set on the ability to tune the response of alkoxyamines to different stimuli, through alteration of their structure. In addition, possible side reactions during dynamic bond exchange and limitations for polymerization are critically reviewed. Subsequently, examples of alkoxyamine‐based CANs responsive to different stimuli, such as temperature, light, or chemical triggers, are discussed. Properties and applications of CANs based on alkoxyamines are then discussed. Finally, an outlook is provided on challenges that need to be addressed as well as opportunities that lie within these “living” CANs.

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Section: Other Stimulimentioning

confidence: 99%

Covalent Adaptable Networks Based on Dynamic Alkoxyamine Bonds

Jia

Delaittre

Tsotsalas

2022

Macro Materials & Eng

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“…Kinetics of 22 (●) and 24 (■) in the absence (red) and presence (blue) of subtilisin A (1.5 mM) in buffer (pH 7.4) solution at 37 °C. Adapted with permission from ref . Copyright 2020 Royal Society of Chemistry.…”

Section: Tools For Smart Applicationsmentioning

confidence: 99%

“…Interestingly, at 37 °C, in the presence of subtilisin A, 64 mixed acetal 22 and 24 are hydrolyzed into their corresponding aldehydes 23 and 25, affording t max values of 1500 and 500 s, respectively (Figure 23), whereas t 1/2 values of 42 million years and 330 years are expected in the absence of enzymatic activation (Scheme 3). 1 Such a large switch is due to the combination of polar, stabilization, steric, and solvent effects.…”

Section: Smart Alkoxyamines As Theranostic Agents For the Treatment O...mentioning

confidence: 99%

Smart Alkoxyamines: A New Tool for Smart Applications

2020

Self Cite

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In 1986, Rizzardo et al. discovered the nitroxide-mediated polymerization which relies on the reversibility of homolysis of the C−ON bond of alkoxyamine R 1 R 2 NOR 3 , a unique property of these molecules. This discovery has generated a tremendous endeavor in the field of polymer chemistry. Alkoxyamines have been used as initiators/controllers for nitroxidemediated polymerization. Moreover, photoexcitable alkoxyamines that dissociate under light at different wavelengths have also been developed for polymer chemistry. Over the past few years, alkoxyamines have started to be used in materials sciences. In many cases (e.g., self-healing polymers), the development of smart materials requires the use of smart building blocks, that is, molecules or systems whose properties and/or structures change upon external stimuli. Alkoxyamines exhibit a unique property: reversible homolysis (i.e., homolysis of the C−ON bond into alkyl R 3 • and nitroxyl R 1 R 2 NO• radicals and reformation via the coupling of these two species). Until now, this property has been controlled only by changes in temperatures or by light irradiation. Chemical and/or biochemical control of the homolysis event would open new gates for the application of these molecules in different fields such as biology and medicine. Thus, the concept of smart alkoxyamines is discussed and exemplified via the activation of alkoxyamines using chemical or/and biochemical changes amplifying the polar, steric, and stabilization effects. In situ activation is also discussed. It is shown that (i) increasing the electron-withdrawing properties of the alkyl fragment weakens the C−ON bond and thus favors homolysis but is opposite for the nitroxyl fragment; (ii) increasing the steric hindrance on the nonactive site affords dramatic conformation changes which weaken the C−ON bond; and (iii) increasing the stabilization of the released alkyl radical weakens the C−ON bond. Solvent effects and intramolecular hydrogen bonding are also discussed. Reactions used to highlight our purpose are either reversible or nonreversible and used under conditions that are as mild as possible (temperatures below 40 °C and atmospheric pressure). For example, a several (thousands of millions of) millions of orders of magnitude enhancement of the homolysis rate constant is observed upon enzymatic hydrolysis at 37 °C, meaning that a shift from a stable alkoxyamine (t 1/2 = 42 000 milleniums) to a highly labile alkoxyamine (t max = 1500 s for 35% conversion) is achieved. Applications of this concept are discussed for safe NMP initiators and for theranostic agents.

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“…In the last decade, the concept of smart alkoxyamines has been developed. 1 These are highly stable alkoxyamines with half-lives of several hundred years, which can be selectively transformed into highly labile species with half-lives of seconds or minutes through chemical, 2-5 photochemical [6][7][8][9] or biochemical 10,11 events. Such alkoxyamines have interesting properties for potential applications in industry, e.g., safe storage of initiators for radical polymerizations, 5,12 or in biology, e.g., drugs for cancer or parasites.…”

Section: Introductionmentioning

confidence: 99%

“…Such alkoxyamines have interesting properties for potential applications in industry, e.g., safe storage of initiators for radical polymerizations, 5,12 or in biology, e.g., drugs for cancer or parasites. 10,11,[13][14][15][16][17][18] While the focus of these studies has been on triggering alkoxyamine homolysis, to form a nitroxide and carbon-centred radical, recently it has been shown that upon oxidation, through electrochemical [19][20][21][22][23] or photoredox 24,25 methods, alkoxyamines can spontaneously undergo mesolytic cleavage instead. Depending on the leaving group and other species present, this process can yield nitroxides and carbocations, or alternatively oxoamoniums and carbon-centred radicals.…”

Section: Introductionmentioning

confidence: 99%