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The reaction sequences that drive these tools are complex, and thus prone to an array of dead\u2010end intermediates that reduce their release\/cleavage efficiency. Here, we redirect that complexity to explore yet another aspect of tetrazine (Tz)\/\n                    <jats:italic>trans<\/jats:italic>\n                    \u2010cyclooctene (TCO) click\u2010to\u2010release. By exchanging the carbamate linkage of established release Tzs for an anilinium leaving group, post\u2010click tautomerization is accelerated and temporally synchronized, generating an intermediate capable of trapping thiols rapidly and in high yields. Further integration of an orthogonal azide into the Tz hub enables a one\u2010pot multi\u2010component reaction that allows straightforward combinatorial synthesis of densely functionalized architectures. Leveraging both click and release, the resulting process converts a Tz\/TCO pair into a ternary scaffold on demand, readily incorporating fluorophores, chelators, cleavable drugs, proteins, oligonucleotides, and more. This modular cascade assembly offers a rapid and versatile platform for functionalization of biomolecules and small molecule targeting vectors, with immediate potential in imaging, theranostics, and multivalent bioconjugate design.\n                  <\/jats:p>","DOI":"10.1002\/anie.8598826","type":"journal-article","created":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:22:38Z","timestamp":1791109358000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Click\u2010to\u2010Release Reactivity of Quaternary Anilinium Tetrazines Enables Cascade Assembly of Multifunctional Biomolecular Scaffolds"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7712-1818","authenticated-orcid":false,"given":"Markus","family":"Staudt","sequence":"first","affiliation":[{"name":"Department of Drug Design and Pharmacology University of Copenhagen  Copenhagen Denmark"},{"name":"Institute of Applied Synthetic Chemistry  Vienna Austria"},{"name":"Center for Systems Biology and Cancer Institute Massachusetts General Hospital Research Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2662-9803","authenticated-orcid":false,"given":"Christian B. 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