Visible-light-driven bioorthogonal photoclick reaction of o-diones with vinyl amides

Abstract

Photo-initiated bioorthogonal reactions in the visible-light range allow spatiotemporal labeling or regulation in living systems, which however still remain scarce. To bridge this gap, we established a bioorthogonal o-dione and vinyl ether photocycloaddition (DVPC) reaction driven by visible light as the first-generation o-dione based bioorthogonal reaction (DVPC 1.0). Driven by the demand to expand substrate scope to include electron-rich alkenes with better stability, increased reaction rates and longer excitation wavelengths, herein we report the second-generation DVPC (DVPC 2.0) between o-diones and vinyl amides. Electron-withdrawing substitutions on the o-dione substrates in DVPC 2.0 were found to accelerate the reaction in aqueous solution by up to 50-fold. Some of the DVPC 2.0 substrates allowed two-photon excitation, which red-shifted the excitation wavelength to 700–800 nm. A bifunctional bioorthogonal substrate containing both an N-vinyl group and an azide functionality was prepared, which allowed sequential bioorthogonal reactions on proteins with temporal control.