Entropy-Encoded Electronic Reconstruction in High-Entropy Nanozymes Enables Cofactor-Free Monooxygenase-Like Catalysis.

Abstract

Flavin-dependent monooxygenases (FMOs) catalyze redox reactions central to antibiotic degradation and metabolic detoxification, yet replicating their intricate cofactor-dependent electron transfer in synthetic systems has remained elusive. Here, we report an electronic modulation strategy that enables cofactor-free FMO-like catalysis within a high-entropy alloy nanozyme (HEAzyme-Cu_1.5). We induce localized electron cloud enrichment that shifts Cu 3d orbitals toward the Fermi level, establishing a self-sustained redox channel without flavin cofactors. This atomic-scale entropy-driven alignment bridges the functional gap between natural cofactor-dependent enzymes and artificial catalysts, demonstrating for the first time that complex redox cascades traditionally confined to biological systems can be reconstructed purely by materials design. This entropy-driven electronic reconfiguration enables near-zero barrier O₂ activation and rapid hydroxylation with a kinetic constant. Integrating this multifunctional HEAzyme into a portable hydrogel sensor platform achieves real-time antibiotic detection down to 11-25 nM and > 90% degradation within 20 min in complex water samples. This work establishes a universal design principle for programmable enzyme mimetics, where atomic-scale entropy, electronic-state alignment, and multimetal cooperation converge to emulate and transcend biological catalysis. Such entropy-encoded redox systems offer a transformative route toward intelligent bioinspired materials for environmental remediation, green synthesis, and metabolic engineering.