Balancing acceleration and turnover in [1 + 1] tetra-imine bis-calix[4]pyrrole reactor for Huisgen cycloadditions

Tailored molecular cages can confine reactive partners and enhance their reaction rates. However, for bimolecular reactions, product inhibition is commonly observed. We report a tetra-imine bis-calix[4]pyrrole cage with two chemically non-equivalent polar hemispheres that promote azide-alkyne Huisge...

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Detalles Bibliográficos
Autores: Li, Yifan, Aragay, Gemma, Ballester, Pablo
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:dnet:recercat____::b068a258b1dad28a8ea2d3eb873905f6
Acceso en línea:https://hdl.handle.net/2072/489522
https://doi.org/10.1038/s41467-026-72315-w
Access Level:acceso abierto
Palabra clave:Química
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Descripción
Sumario:Tailored molecular cages can confine reactive partners and enhance their reaction rates. However, for bimolecular reactions, product inhibition is commonly observed. We report a tetra-imine bis-calix[4]pyrrole cage with two chemically non-equivalent polar hemispheres that promote azide-alkyne Huisgen cycloadditions. This cage forms 1:1 and 1:2 complexes with para-substituted pyridine-N-oxides, including ternary hetero-complexes with an azide and an alkyne moiety into proximity. Here, we show that cage confinement accelerates the regioselective formation of 1,4-triazoles. A global kinetic model allows the determination of the intra-vessel rate constant (kintra) without direct quantification of the “Michaelis” ternary complex. Modest acceleration is observed for one pair of reactants, yet the cage can still turn over because the product is weakly bound. Extending the azide linker by one methylene dramatically enhances acceleration and introduces product inhibition. Comparisons with a related octa-imine cage reveal how subtle geometric changes tune the balance between transition-state stabilization and product release.