Control of Tetrazine Bioorthogonal Reactivity by Rotaxanation
Rotaxanation is an efficient method to control the tetrazine-mediated inverse electron demand Diels-Alder (IEDDA) reaction. Tetrazine rotaxanes were synthesized in high yield by crown ether active template applied to the nucleophilic aromatic substitution of tetrazines. Kinetics of the bioorthogonal reaction with tetrazine rotaxanes were much slower than those with the corresponding threads. Interestingly, disassembly of the mechanical bond upon the application of the right stimulus activates IEDDA. Control of IEDDA in live cells was proved by means of a β-galactosidase sensitive tetrazine rotaxane: Enzymatic digestion allowed the Diels-Alder reaction, which resulted in a fluorescent compound.
Authors
- Romen Carrillo (ORCID: https://orcid.org/0000-0002-7078-300X)
- Jorge Pasán
- Diego Álvarez de la Rosa (ORCID: https://orcid.org/0000-0002-4324-2793)
- F.J. Lahoz (ORCID: https://orcid.org/0000-0001-8008-1696)
- Jimena Scoccia (ORCID: https://orcid.org/0000-0001-9296-3071)
- Teresa Giráldez (ORCID: https://orcid.org/0000-0002-4096-810X)
- Yaiza Pérez‐Pérez (ORCID: https://orcid.org/0000-0002-9363-4373)
- Lidia A. Pérez‐Márquez (ORCID: https://orcid.org/0000-0001-5719-1491)
- Nieves R. Paz (ORCID: https://orcid.org/0000-0001-8133-6099)
- David Tejedor (ORCID: https://orcid.org/0000-0003-3262-0776)
- Carlos Fumero‐Medina
Institutions
- Universidad de La Laguna (ES)
- Instituto de Productos Naturales y Agrobiología (ES)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2025-09-21
- DOI
- https://doi.org/10.1002/anie.202514796
- Primary Topic
- Click Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00