On the reactivity of strained seven- and eight-membered rings in click chemistry

Summary

The research described in this dissertation embodies the development of new click reagents, the development of new click and declick methodologies for application in bioconjugations and a detailed study of their kinetics. The new click methodologies allow for the attachment of payloads onto antibodies or tumor cell surfaces, whereas the declick methodologies allow for induced release of that payload. The fundamental chemical investigations towards such functional molecules are performed by means of rational design and acquired by means of synthetic organic chemistry. Another main topic is the analysis of the driving forces behind certain types of click chemistries (i.e., SPOCQ and SPAAC). This dissertation therefore comprises an interplay between synthetic and physical organic chemistry in unveiling the role of strained bonds in click chemistry.