Title: Additive-Free Clicking for Polymer Functionalization and Coupling by Tetrazine–Norbornene Chemistry

Authors: Claire F. Hansell†, Pieter Espeel‡, Milan M. Stamenovi‡, Ian A. Barker†, Andrew P. Dove†, Filip E. Du Prez‡, and Rachel K. O’Reilly†

Journal: Journal of the American Chemical Society

Affiliation: †Department of Chemistry, University of Warwick, ‡Department of Organic Chemistry, Polymer Chemistry Research Group, Ghent University

“Click” chemistry was introduced by Sharpless and coworkers in 2001 and since then the applications seem to be never ending.  The term click chemistry describes a set of chemical reactions that are very high yielding with simple, mostly benign reagents and bi-products.  As with any reaction, the various click reactions have their pitfalls.  Some are limited by their efficiency, others by the necessary addition of catalyst.  This paper discusses the application of the click reaction between a tetrazine and a norbornene to functionalizing polymers – the first time this reaction has been reported for use in polymer synthesis.  This click reaction does not require a catalyst (nice because the removal of catalysts after reactions can be difficult) and is EXTREMELY efficient (although click reactions need to be efficient those used for coupling polymers must be extraordinarily so).

First the researchers examined the orthogonality of reaction between the tetrazine and norbornene.  In particular they examined any interference it might have with the thiocarbonyl functional group that is present as an end group in reversible addition-fragmentation chain transfer (RAFT) polymerizations.  The authors demonstrated the orthogonality by performing a reaction between a norbornene functionalized chain transfer agent and dipyridyltetrazine.  They used ¹H NMR to observe the reaction taking place without the loss of the thiocarbonate group.

The researchers synthesized a norbornenyl-functionalized poly(styrene) and poly(N-isopropylacrylamide) (PNIPAM) using a RAFT polymerization.  Additionally they modified commercially available polyethylene glycol (PEG) to include a tetrazine group.  These were then coupled together using click chemistry in organic solvent.  The authors found that the reactions between the small molecules, a modified polymer and a small molecule, and two polymers all occurred at very similar (high) rates.  To show the high utility of this reaction the authors also attempted to reaction the norbornenyl- functionalized PNIPAM and the tetrazine-modified PEG.  This was also successful.

This paper demonstrated the use of the tetrazine/norbornene click reaction in coupling polymers.  This reaction can be performed in both organic solvents and water.  The authors are currently investigating further applications for this method in polymer and material science.