biostudies-literatureGody GEuropean Research CouncilMonash UniversityLicella Pty. Ltd.Royal SocietyUniversity of WarwickAustralian Research Council4061-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC4846186biostudies-literatureUnknown138(12)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 adJournal of the American Chemical SocietyA New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine--Tertiary Isocyanate Coupling for Polymer Ligation.PMC4846186WM130055LP100200339TUSUPO - 647106Maschmeyer TRoberts DAGody GPerrier SfalseA 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 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 ad2016-01-01T00:00:00Z2016 Mar2025-04-04T18:34:58.581Z2019-03-27T02:12:28ZS-EPMC48461862692762410.1021/jacs.5b11831