Biosens Bioelectron. 2026 Mar 24;304:118638. doi: 10.1016/j.bios.2026.118638. Online ahead of print.

ABSTRACT

Iron-sulfur clusters play central roles in electron transfer and redox catalysis in natural enzymes, yet their direct mimicry in nanozymes remains largely unexplored. Here, we report that reduced graphene oxide embedded with Fe₂S₆ clusters (Fe-S-rGO), which resembles iron-sulfur clusters present in natural ferredoxin, show vivid enhancement in peroxidase-like catalytic efficiency (k_cat/K_m) over 400- and 5000-fold higher than that of natural horseradish peroxidase and undoped rGO, respectively, with negligible oxidase-like activity as well as excellent electrical conductivity. Density functional theory calculations reveal that the Fe₂S₆ active sites offer favorable adsorption and decomposition pathways for H₂O₂, rationalizing the bioinspired high activity. Leveraging these properties, Fe-S-rGO enabled ultrasensitive electrochemical detection of H₂O₂ across a wide dynamic range (10^-12 M ∼10^-4 M) with a detection limit of ∼70 fM. Furthermore, by integrating Fe-S-rGO with corresponding oxidase and esterase in cascade systems, choline and acetylcholine were quantified with outstanding sensitivity, achieving detection limits of ∼0.8 and ∼30 pM, respectively. By mimicking the inorganic redox centers of ferredoxin rather than traditional heme systems, this work uncovers a new paradigm in peroxidase-like nanozyme design and paves the way for highly selective biomimetic electrochemical sensors for diagnostics and point-of-care testing.

PMID:41895235 | DOI:10.1016/j.bios.2026.118638