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 the first-generation visible-light driven o-diones and vinyl ether photocycloadditon reaction (DVPC 1.0). Further optimization of the DVPC reaction was driven by the demand to find similar light-driven bioorthogonal reaction with broader substrate scope to include electron-rich alkenes with better stability than vinyl ether, increased rection rates and excitation with light of longer wavelength. We report here the second-generation DVPC (DVPC 2.0) between o-diones with vinyl amides in which the electron-withdrawing substitutions on the o-diones accelerated 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. Bi-functional bioorthogonal substrate containing both N-vinyl group and azide functionality was prepared, which allowed sequential bioorthogonal reaction on proteins with temporal control.