Abstract
Bioorthogonal bond-cleavage reactions have evolved into powerful tools for chemical biology, representing a promising strategy for achieving controlled release of molecules under physiologically relevant conditions, even in living organisms. Since their discovery, significant efforts have been invested in the development and understanding of the underlying chemistries to enhance the click-to-release performance, biocompatibility, and stability of bioorthogonal tools. In this review, we aim to provide a concise overview of click-triggered bioorthogonal bond-cleavage reactions, with an emphasis on the mechanisms and characteristics of the most commonly applied click-to-release chemistries.