Tetrazine-based inverse-electron-demand Diels–Alder reaction: a powerful tool for fabrication and functionalization of polymeric materials

Abstract

The advent of the click chemistry paradigm has profoundly transformed the design of functional polymeric materials. Among the various reactions in the click chemistry toolkit, the inverse electron demand Diels–Alder (IEDDA) reaction is particularly notable for its rapid kinetics, high specificity, and bioorthogonality. Of the different electron-deficient dienes, the tetrazine (Tz) building block has become the most extensively employed component in the IEDDA reaction-based synthesis and functionalization of polymeric materials. This review begins with an overview of the IEDDA reaction involving Tz, followed by a discussion of examples where the Tz moiety has been utilized as a reactive handle for polymer synthesis and functionalization. We then focus on the application of Tz-based IEDDA reactions in the development of functional hydrogels and surface modifications. The selected examples highlight the diversity and versatility of this highly efficient chemistry. This review aims not only to survey recent progress but also to demonstrate the significant potential of IEDDA chemistry in advancing the design of functional polymeric materials.