%0 Journal Article %T Using the High-Entropy Approach to Obtain Multimetal Oxide Nanozymes: Library Synthesis, In Silico Structure-Activity, and Immunoassay Performance. %A Phan-Xuan T %A Schweidler S %A Hirte S %A Schüller M %A Lin L %A Khandelwal A %A Wang K %A Schützke J %A Reischl M %A Kübel C %A Hahn H %A Bello G %A Kirchmair J %A Aghassi-Hagmann J %A Brezesinski T %A Breitung B %A Dailey LA %J ACS Nano %V 18 %N 29 %D 2024 Jul 23 %M 38985736 %F 18.027 %R 10.1021/acsnano.4c03053 %X High-entropy nanomaterials exhibit exceptional mechanical, physical, and chemical properties, finding applications in many industries. Peroxidases are metalloenzymes that accelerate the decomposition of hydrogen peroxide. This study uses the high-entropy approach to generate multimetal oxide-based nanozymes with peroxidase-like activity and explores their application as sensors in ex vivo bioassays. A library of 81 materials was produced using a coprecipitation method for rapid synthesis of up to 100 variants in a single plate. The A and B sites of the magnetite structure, (AA')(BB'B'')2O4, were substituted with up to six different cations (Cu/Fe/Zn/Mg/Mn/Cr). Increasing the compositional complexity improved the catalytic performance; however, substitutions of single elements also caused drastic reductions in the peroxidase-like activity. A generalized linear model was developed describing the relationship between material composition and catalytic activity. Binary interactions between elements that acted synergistically or antagonistically were identified, and a single parameter, the mean interaction effect, was observed to correlate highly with catalytic activity, providing a valuable tool for the design of high-entropy-inspired nanozymes.