Coenzyme-functionalized photo-redox catalysis for low-energy click labeling

Photo-redox catalysis has emerged as a new generation of biochemical protocols in proximity labeling, noninvasive therapy, ultrafast activation. However, the well-developed photocatalysts cannot simultaneously possess low-energy absorption and high excited potentials to initiate photochemical reactions. Herein, we develop new Ru-PCs as bio-photocatalyst exhibiting both green-light absorption and high E_red*. Ru-PCs cooperatively function with natural coenzyme riboflavin (RF) via an integrated proton-coupled electron transfer (PCET) process to in situ transform Ru-PCs with two distinct ligands and consecutively mediate redox between phenol substrates, excited photocatalysts and oxygen. One quaternized (Qn) ligand keeps the metal-to-ligand-charge-transfer (MLCT) and the other carbonylated (Cb) ligand reserves a proton transfer site. Irradiating RuQnCb bio-photocatalyst leads to a highly selective neolignan oxidative intermolecular cross-coupling reaction of [4 + 2] cyclization of two phenol modules in diluted serum. Photo-modification of proteins has been accomplished within several seconds green light irradiation in a 97 % yield, without non-target conjugations to natural groups.