Nitrile oxide-mediated cycloaddition: a metal-free click platform for precision macromolecular materials

Abstract

Nitrile oxide-mediated cycloaddition has emerged as a powerful metal-free click strategy in polymer science, owing to its high efficiency, mild reaction conditions, and excellent compatibility with alkene- and alkyne-decorated macromolecular systems. Beyond their conventional role as transient dipoles for constructing N–O heterocycles, nitrile oxides have evolved into versatile linking modules, now widely employed in polymer synthesis, functionalisation, cross-linking, and surface modification. Furthermore, they hold considerable promise for protein conjugation, the design of precise macromolecular architectures, and the fabrication of advanced polymeric materials. This review presents a polymer-focused overview of nitrile oxide click chemistry, highlighting key applications in click polymerisation, post-polymerisation functionalisation, network construction, surface engineering, and protein bioconjugation.