Strain-promoted click reaction

Scheme 7.45 Formation of a cross-linked polymer coating on an alkyne-functionalized substrate using strain-promoted click reaction.

As click chemistry requires catalytic copper, which is toxic to cells, in vivo applications have so far been restricted. To overcome this limitation, Bertozzi and coworkers introduced a second generation of click chemistry that is based on a strain-promoted reaction between a cyclooctyne and an azide moiety [31]. This reaction has been further improved over the past years and is a hot topic in ligation chemistry [32, 33]. 

POC-click is formed by thermo-cross-linking the mixture of pre-POC-N (azide-containing POC prepolymer) and pre-POC-Al (alkyne-containing POC prepolymer) the process applies synchronous binary cross-link mechanism, esterification, and thermal click reaction, and the residual azide groups on the surface of POC-click film or scaffold paved the way of surface bioconjugation through strain-promoted alkyne-azide cycloaddition (SPAAC), another copper-free click reaction. 

R. Manova, T.A. van Beek, H. Zuilhof, Surface functionalization by strain- promoted alkyne-azide click reactions, Angew. Chem. Int. Ed. 50(2011)5428-5430. 

Strain-promoted azide-alkyne cycloaddition (SPAAC), since its inception in 2004, has firmly established itself as a powerful click chemistry tool. The commercial access of starting materials, its ease of operation, the nowadays practical reaction... 

Shelbourne M, Chen X, Brown T, El-Sagheer AH (2011) Fast copper-free click DNA ligation by the ring-strain promoted alkyne-azide cycloaddition reaction. Chem Commun 47(22) 6257-6259. doi 10.1039/clccl0743g... 

Describe the main criteria that should be satis ed for a reaction to be called a click reaction How would you justify the inclusion of the following reactions into the pantheon of click reactions (a) Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions (b) strain-promoted azide-alkyne coupling (SPAAC) reactions (c) Diels-Alder (DA) cycloaddition reactions (d) thiol-ene (TE) reactions and (e) thiol-yne (TY) reactions ... 

Generation of chemical patterns with photoreactive polymers photo-Diels-Alder surface anchoring followed by azide-alkyne click reaction to immobilize fluorescent dyes, (a) SPAAC strain-promoted azide-alkyne cycloaddition and (b) CuAAC Cu(l)-catalyzed azide-alkyne cycloaddition. (Source Adapted with permission from Reference [36d].)... 

Sequential click strategies were utihzed by Zhang, Cheng, and coworkers to precisely construct new surfactants based on polyhedral oligomeric silsesquiox-ane (POSS), tethering cychc polymers [109]. The general synthetic approach involves different types of click chemistries sequentially performed strain-promoted azide-alkyne cycloaddition (SPAAC), CuAAC for POSS—polymer conjugation, and thiol-ene reactions for POSS surface functionalization. 

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