Rearranging Spin Electrons\nby Axial-Ligand-Induced\nOrbital Splitting to Regulate Enzymatic Activity of Single-Atom Nanozyme\nwith Destructive d−π Conjugation

Most of the nanozymes have been obtained based on trial\nand error,\nfor which the application is usually compromised by enzymatic activity\nregulation due to a vague catalytic mechanism. Herein, a hollow axial\nMo–Pt single-atom nanozyme (H-MoN₅@PtN₄/C) is constructed by a two-tier template capture strategy. The axial\nligand can induce Mo 4d orbital splitting, leading to a rearrangement\nof spin electrons (↑ ↑ → ↑↓) to\nregulate enzymatic activity. This creates catalase-like activity and\nenhances oxidase-like activity to catalyze cascade enzymatic reactions\n(H₂O₂ → O₂ → O₂^•–), which can overcome tumor hypoxia and accumulate cytotoxic superoxide\nradicals (O₂^•–). Significantly,\nH-MoN₅@PtN₄/C displays destructive d−π\nconjugation between the metal and substrate to attenuate the restriction\nof orbitals and electrons. This markedly improves enzymatic performance\n(catalase-like and oxidase-like activity) of a Mo single atom and\nperoxidase-like properties of a Pt single atom. Furthermore, the H-MoN₅@PtN₄/C can deplete overexpressed glutathione (GSH)\nthrough a redox reaction, which can avoid consumption of ROS (O₂^•– and ^•OH). As\na result, H-MoN₅@PtN₄/C can overcome limitations\nof a complex tumor microenvironment (TME) for tumor-specific therapy\nbased on TME-activated catalytic activity.