Light Switchable\nBioorthogonal Reaction Manifold for\nModulation of Hydrogel Properties

Chemical reaction systems that can\noccur via multiple\npathways\nin a controllable fashion are highly attractive for advanced materials\napplications and biological research. In this report, we introduce\na bioorthogonal reaction manifold based on a chalcone pyrene (<b>CPyr</b>) moiety that can undergo either red-shifted photoreversible\n[2 + 2] cycloaddition or thiol-Michael addition click reaction. By\ncoupling the <b>CPyr</b> to a water-soluble poly(ethylene glycol)\nend group, we demonstrate the efficient polymer dimerization and cleavage\nby blue light (λ = 450 nm) and UV light (λ = 340 nm),\nrespectively. In the absence of light, <b>CPyr</b> rapidly reacts\nwith thiols in aqueous environments, enabling fast and efficient polymer\nend-group functionalization. The chemical reaction manifold was further\nemployed in polymer cross-linking for the preparation of hydrogels\nwhose stiffness and morphology can be modulated by different photonic\nfields or the addition of a thiol cross-linker. The photoreversible\ncycloaddition and thiol-Michael addition click reaction can be used\nin conjunction for spatial and temporal conjugation of a streptavidin\nprotein. Both cross-linking conditions are nontoxic to various cell\nlines, highlighting their potential in biomaterials applications.