Nonbonding Ammonium Stabilizing Manganese-Oxygen σ-Bond by Manipulating Spin Electrons to Regulate Enzymatic...

The bonding strategy cannot effectively address the inherent limitations of layered nanozymes, resulting in their failure to maintain stability within the tumor microenvironment (TME). Herein, ammonium (NH₄⁺)-intercalated δ-MnO₂ nanozymes (N-MnO₂) were constructed through the acid-base neutralization strategy. Due to interlayer van der Waals interactions, the NH₄⁺ is stabilized in a nonbonded configuration. Significantly, nonbonding NH₄⁺ exhibits unique electron-manipulating capabilities, enabling precise regulation of Mn 3d spin electrons from a high-spin state (t_2g³e_g¹) to low-spin (t_2g⁴e_g⁰) configurations. The controlled spin-state redistribution prevents electron occupation in the e_g antibonding orbitals (σ*), thereby significantly enhancing the stability of the Mn-O σ-bond and suppressing Jahn-Teller (J-T) distortions in the [MnO₆] octahedra of layered MnO₂. This dual nonbonding stabilization mechanism effectively resists structural disruption by endogenous glutathione (GSH, a scavenger of superoxide radicals), which can enhance the enzyme-mimetic activity. Furthermore, the nonbonding NH₄⁺ in N-MnO₂ maintains a dynamic Mn³⁺/Mn⁴⁺ equilibrium, endowing the nanozyme with dual catalase-like and oxidase-like activities. This can catalyze cascade enzymatic reactions (H₂O₂ → O₂ → O₂^•-) to sufficiently enrich O₂^•-. Consequently, it is demonstrated that N-MnO₂ possesses enhanced cascade catalytic performance within the complex TME for tumor-specific therapy.