Bridging The Catalytic Turnover Gap Between Single-Atom Iron Nanozymes and Natural Enzymes by Engineering the First And Second Shell Coordination.

Single-atom nanozymes (SAzyme) constitute a promising category of enzyme-mimicking materials with outstanding catalytic performance. The performance of SAzymes has been improved through modification of the coordination environments around the metal center. However, the catalytic turnover rates of SAzymes, which are key measures of the effectiveness of active site modifications, remain lower than those of natural enzymes, especially in peroxidase-reactions. Here, we report on the first and second shell coordination tuning strategy that yields SAzymes with structures and activities analogous to those of natural enzymes. The optimized SAzyme exhibited a turnover rate of 52.7 s -1 and a catalytic efficiency of 6.97 × 10 5 M -1 s -1 . A computational study revealed that axial S-ligands induce an alternative reaction mechanism and SO 2 -functional groups provide hydrogen bonds to reduce the activation energy. Additionally, SAzyme showed superior anti-tumor ability in vitro and in vivo. Our results demonstrate the validity of coordination engineering strategies and the carcinostatic potential of SAzymes. This article is protected by copyright. All rights reserved.