Dual-Bioorthogonal Molecular Tool: “Click-to-Release” and “Double-Click” Reactivity on Small Molecules and Material Surfaces

The development of reactive moieties that enable molecular control of bond-forming and bond-breaking reactions within complex media is highly important in materials and biomaterials research as it provides opportunities to carefully manipulate small molecules and material surfaces in a reliable manner. Despite recent advances in the realization of new ligation strategies and “click-and-release” systems, there has been little development of multifunctional moieties that feature a broad range of chemical capabilities. To address this challenge, we designed a molecular tool that can utilize four well-defined bioorthogonal chemistries interchangeably for the attachment, replacement, and release of molecules within a system: the Staudinger–Bertozzi ligation (SBL), perfluoroaryl azide Staudinger reaction (PFAA-SR), strain-promoted alkyne–azide cycloaddition (SPAAC), and strain-promoted alkyne–nitrone cycloaddition (SPANC). We demonstrate “click-to-release” and “double-click” reactivity on small molecules and go...