Tetraphenylethene-Based\nMolecular Cage with Coenzyme\nFAD: Conformationally Isomeric Complexation toward Photocatalysis-Assisted\nPhotodynamic Therapy

Flavin adenine dinucleotide (FAD),\nserving as a light-absorbing\ncoenzyme factor, can undergo conformationally isomeric complexation\nwithin different enzymes to form various enzyme–coenzyme complexes,\nwhich exhibit photocatalytic functions that play a crucial role in\nphysiological processes. Constructing an artificial photofunctional\nsystem using FAD or its derivatives can not only develop biocompatible\nphotocatalytic systems with excellent activities but also further\nenhance our understanding of the role of FAD in biological systems.\nHere, we demonstrate a supramolecular approach for constructing an\nartificial enzyme–coenzyme-type host–guest complex with\nphotoinduced catalytic function in water. First, we have designed\nand synthesized a water-soluble tetraphenylethene (TPE)-based octacationic\nmolecular cage (<b>1</b>) with a large and flexible cavity,\nwhich can adaptively encapsulate with two FAD molecules with “U-shaped”\nconformation (<i>u</i>FAD) to form a 1:2 host–guest\ncomplex (<b>1</b>⊃<i>u</i>FAD<sub>2</sub>)\nin water. Second, based on the conformationally isomeric complexation\nof FAD within <b>1</b>, the <b>1</b>⊃<i>u</i>FAD<sub>2</sub> complex facilitates electron and energy transfers\nto molecular oxygen upon the white-light illumination, efficiently\nproducing reactive oxygen species (ROS) such as superoxide radical\n(O<sub>2</sub><sup>•–</sup>) and singlet oxygen (<sup>1</sup>O<sub>2</sub>). To our knowledge, the <b>1</b>⊃<i>u</i>FAD<sub>2</sub> complex acts as a photocatalyst to achieve\nthe highest turnover frequency (TOF) of 35.6 min<sup>–1</sup> for the photocatalytic oxidation reaction of NADH via a photoinduced\nsuperoxide radical catalysis mechanism in an aqueous medium. At last,\ncombining the cytotoxic effects of ROS and the disruption of the intracellular\nredox balance involving NADH, <b>1</b>⊃<i>u</i>FAD<sub>2</sub> as a supramolecular photosensitizer displays an excellent\noxygen-independent photocatalysis-assisted photodynamic therapy in\nhypoxic tumors.