Supramolecular photodynamic agents for simultaneous oxidation of NADH and generation of superoxide radical

Given that Type-I photosensitizers (PSs) have hypoxia tolerance, developing general approaches to prepare Type-I PSs is of great importance, but remains a challenge. Here, we report a supramolecular strategy for the preparation of Type-I photodynamic agents, which simultaneously generate strong oxidizing cationic radicals and superoxide radicals, by introducing electron acceptors to the existing Type-II PSs. As a proof-of-concept, three electron acceptors were designed and co-assembled with a classical PS to produce quadruple hydrogen-bonded supramolecular photodynamic agents. The photo-induced electron transfer from the PS to the adjacent electron acceptor occurs efficiently, leading to the generation of a strong oxidizing PS^+• and an anionic radical of the acceptor, which further transfers an electron to oxygen to form O₂^-•. In addition, these photodynamic agents induce direct photocatalytic oxidation of NADH with a turnover frequency as high as 53.7 min^-1, which offers an oxygen-independent mechanism to damage tumors.