Bioorthogonal catalysis in complex media: Consequences of using polymeric scaffold materials on catalyst stability and activity

Bioorthogonal catalysis using transition-metal-based complexes (TMCs) is a promising approach for converting substrates to desired products in complex cellular media. Notably, the in situ activation of prodrugs or synthesis of active drugs with the aim to complement existing treatments in diseases such as cancer has received significant attention. Whereas the focus has initially been on optimizing ligands to enhance the activity and stability of the metal complexes, more recently the benign effects of compartmentalization of the catalyst into homogeneous or heterogeneous scaffolds have been unveiled. Such tailor-made carrier materials not only afford active catalysts but also permit to guide the catalyst to the site of interest in in vivo applications. This review will emphasize the potential of synthetic amphiphilic polymers that form compartmentalized nanostructures for TMCs. The use of amphiphilic polymers is well established in the field of nanomedicine for i.e. drug delivery purposes, but their application as homogeneous carrier materials for TMCs has been less well explored. Since synthetic polymers are readily functionalized with ligands and targeting moieties, they can act as versatile catalysts carriers. After a short overview of the state-of-the-art in bioorthogonal catalysis using ligand-based TMCs, we summarize the advances in using homogeneous natural polymers as scaffolds and synthetic heterogeneous carrier materials for bioorthogonal catalysis. We end this review by highlighting the recent advances of catalysis in complex media using TMCs embedded in nanostructures formed by amphiphilic synthetic polymers. The combination of polymer science and homogeneous catalysis with the field of nanomedicine may open up new opportunities for advancing the exciting field of bioorthogonal catalysis for therapeutic applications.