Related Experiment Video
Updated: Aug 18, 2025

Depolymerizable Olefinic Polymers Based on Fused-Ring Cyclooctene Monomers
Published on: December 16, 2022
Readily Accessible Strained Difunctionalized trans-Cyclooctenes with Fast Click and Release Capabilities
Daan Sondag1, Luuk Maartense1, Heleen de Jong1
1Institute for Molecules and Materials, Radboud University, 6525 AJ, Nijmegen, Netherlands.
Abstract:
The click reaction between a functionalized trans-cyclooctene (TCO) and a tetrazine (Tz) is a compelling method for bioorthogonal conjugation in combination with payload releasing capabilities. However, the synthesis of difunctionalized TCOs remains challenging. As a result, these compounds are poorly accessible, which impedes the development of novel applications. In this work, the scalable and accessible synthesis of a new bioorthogonal difunctionalized TCO is reported in only four single selective high yielding steps starting from commercially available compounds. The TCO-Tz click reaction was assessed and revealed excellent kinetic rates and subsequently payload release was shown with various functionalized derivatives. Tetrazine triggered release of carbonate and carbamate payloads was demonstrated up to 100 % release efficiency and local drug release was shown in a cellular toxicity study which revealed a >20-fold increase in cytotoxicity.
More Related Videos
09:45Accessing Valuable Ligand Supports for Transition Metals: A Modified, Intermediate Scale Preparation of 1,2,3,4,5-Pentamethylcyclopentadiene
Published on: March 20, 2017
10:17Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Related Concept Videos
Cycloaddition Reactions: Overview
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Cycloaddition Reactions: MO Requirements for Thermal Activation
Thermal and Photochemical Electrocyclic Reactions: Overview
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry