Coordination-Driven Design of Single-Atom Nanozymes: Bridging Mechanistic Insights and Multimetal Applications

Abstract

Single-atom nanozymes (SANs) represent a transformative frontier in artificial enzymes, addressing limitations of natural enzymes and conventional nanomaterial-based catalysts. Natural enzymes are fragile and costly, and traditional nanozymes often lack well-defined active sites. Our research leverages single-atom catalysis to engineer highly efficient and stable enzyme mimics for biosensing and environmental remediation.

SANs exhibit a diverse range of enzyme-like activities, including peroxidase, catalase, oxidase (OXD), and superoxide dismutase (SOD) mimetic functions. By focusing on atomically dispersed metal centers, SANs maximize atomic utilization and provide well-defined active sites, enabling unprecedented control over catalytic performance, e.g., copper-based systems that exhibit remarkable OXD-like activity mimicking galactose oxidase.

To decode the active site and clarify the underlying catalytic mechanism, we combined experimental techniques and theoretical modeling. Kinetic assays revealed ultrahigh substrate affinity and catalytic efficiency, and advanced characterization provided direct evidence for high-valent metal-oxo intermediate formation, mirroring natural heme-containing enzymes. However, this pathway is not universal; SAN mechanisms are highly coordination-dependent, with alternative routes including surface-confined redox cycling, radical-mediated processes, and metal–ligand cooperative pathways. Density functional theory calculations confirmed that the precise electronic structure and coordination environment endowed the SANs with biomimetic catalytic mechanisms.

These mechanistic insights formed the bedrock for rational design principles: judicious choice of metal, strategic selection of support materials, and precise control of the coordination environment. Using MOF-derived and wet-chemistry approaches, we developed a zinc-centered SAN (Zn-SAN) that mimics the CO₂ hydration activity of carbonic anhydrase and bimetallic Cu/Zn-SANs mimicking SOD, with enhanced stability and recyclability.

SANs offer robust, cost-effective platforms for sensitive biosensing, controlled ROS generation for antibacterial treatments, and CO₂ capture and conversion, with applications in point-of-care diagnostics, food safety monitoring, and therapeutics. Challenges in long-term stability, scalable synthesis, and ultrahigh selectivity remain, but integrating AI and advanced computational design promises to accelerate discovery toward multifunctional SANs with cascade catalytic capabilities.

Rather than a discrete subclass of nanozymes, SANs should be viewed as atomically engineered catalytic materials bridging heterogeneous catalysis and biological redox chemistry. Continued integration of operando characterization, theoretical modeling, and rational coordination design will be essential for establishing structure–mechanism–function relationships that guide translational applications.