A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine-Tertiary Isocyanate Coupling for Polymer Ligation

Click reactions have provided access to an array of remarkably complex polymer architectures. However, the term "click" is often applied inaccurately to polymer ligation reactions that fail to respect the criteria that typify a true "click" reaction. With the purpose of providing a universal way to...

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Hauptverfasser: Gody, Guillaume, Roberts, Derrick, Maschmeyer, Thomas, Perrier, Sebastien
Weitere Verfasser: Biomolecular & Analytical Mass Spectrometry (BAMS)
Sprache:Englisch
Veröffentlicht: American Chemical Society 2019
Online-Zugang:https://demo7.dspace.org/handle/123456789/448
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author Gody, Guillaume
Roberts, Derrick
Maschmeyer, Thomas
Perrier, Sebastien
author2 Biomolecular & Analytical Mass Spectrometry (BAMS)
author_browse Biomolecular & Analytical Mass Spectrometry (BAMS)
Gody, Guillaume
Maschmeyer, Thomas
Perrier, Sebastien
Roberts, Derrick
author_facet Biomolecular & Analytical Mass Spectrometry (BAMS)
Gody, Guillaume
Roberts, Derrick
Maschmeyer, Thomas
Perrier, Sebastien
author_sort Gody, Guillaume
collection DSpace
description Click reactions have provided access to an array of remarkably complex polymer architectures. However, the term "click" is often applied inaccurately to polymer ligation reactions that fail to respect the criteria that typify a true "click" reaction. With the purpose of providing a universal way to benchmark polymer-polymer coupling efficiency at equimolarity and thus evaluate the fulfilment of click criteria, we report a simple one-pot methodology involving the homodicoupling of α-end-functionalized polymers using a small-molecule bifunctional linker. A combination of SEC analysis and chromatogram deconvolution enables straightforward quantification of the coupling efficiency. We subsequently employ this methodology to evaluate an overlooked candidate for the click reaction family: the addition of primary amines to α-tertiary isocyanates (α- t NCO). Using our bifunctional linker coupling strategy, we show that the amine-t NCO reaction fulfills the criteria for a polymer-polymer click reaction, achieving rapid, chemoselective, and quantitative coupling at room temperature without generating any byproducts. We demonstrate that amine-t NCO coupling is faster and more efficient than the more common amine-tertiary active ester coupling under equivalent conditions. Additionally, we show that the α-tNCO end group is unprecedentedly stable in aqueous media. Thus, we propose that the amine-t NCO ligation is a powerful new click reaction for efficient macromolecular coupling.
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spelling oai:localhost:123456789-4482021-04-07T16:30:12Z A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine-Tertiary Isocyanate Coupling for Polymer Ligation Gody, Guillaume Roberts, Derrick Maschmeyer, Thomas Perrier, Sebastien Biomolecular & Analytical Mass Spectrometry (BAMS) Click reactions have provided access to an array of remarkably complex polymer architectures. However, the term "click" is often applied inaccurately to polymer ligation reactions that fail to respect the criteria that typify a true "click" reaction. With the purpose of providing a universal way to benchmark polymer-polymer coupling efficiency at equimolarity and thus evaluate the fulfilment of click criteria, we report a simple one-pot methodology involving the homodicoupling of α-end-functionalized polymers using a small-molecule bifunctional linker. A combination of SEC analysis and chromatogram deconvolution enables straightforward quantification of the coupling efficiency. We subsequently employ this methodology to evaluate an overlooked candidate for the click reaction family: the addition of primary amines to α-tertiary isocyanates (α- t NCO). Using our bifunctional linker coupling strategy, we show that the amine-t NCO reaction fulfills the criteria for a polymer-polymer click reaction, achieving rapid, chemoselective, and quantitative coupling at room temperature without generating any byproducts. We demonstrate that amine-t NCO coupling is faster and more efficient than the more common amine-tertiary active ester coupling under equivalent conditions. Additionally, we show that the α-tNCO end group is unprecedentedly stable in aqueous media. Thus, we propose that the amine-t NCO ligation is a powerful new click reaction for efficient macromolecular coupling. 2019-04-26T08:57:04Z 2019-04-26T08:57:04Z 29/02/16 https://demo7.dspace.org/handle/123456789/448 en American Chemical Society
spellingShingle Gody, Guillaume
Roberts, Derrick
Maschmeyer, Thomas
Perrier, Sebastien
A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine-Tertiary Isocyanate Coupling for Polymer Ligation
title A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine-Tertiary Isocyanate Coupling for Polymer Ligation
title_full A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine-Tertiary Isocyanate Coupling for Polymer Ligation
title_fullStr A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine-Tertiary Isocyanate Coupling for Polymer Ligation
title_full_unstemmed A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine-Tertiary Isocyanate Coupling for Polymer Ligation
title_short A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine-Tertiary Isocyanate Coupling for Polymer Ligation
title_sort new methodology for assessing macromolecular click reactions and its application to amine tertiary isocyanate coupling for polymer ligation
url https://demo7.dspace.org/handle/123456789/448
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