Separation before function: mechanistic criteria for enzyme-like activity in iron-based nanomaterials and minerals

Iron-based nanomaterials and minerals are often described as enzyme-like, yet the mechanistic distinction between true biocatalysis and passive sorption remains unclear. Recent studies show that bulk-phase iron oxides from soils and sediments can catalyze phosphorus transformations under laboratory conditions, highlighting their intrinsic chemical reactivity even when mechanisms remain unresolved. We propose a framework-separation before function-to define the physical and energetic criteria for assigning enzyme-like behavior in inorganic systems. Only systems exhibiting spatial and mechanistic separation of sorption, reaction, and diffusion, such as structurally constrained nanoscale iron oxides, allow reliable evaluation of biocatalytic activity. Reactions such as peroxidase- or catalase-like activity occur at localized active sites on nanoparticles with minimal structural alteration, illustrating how mechanistic context dictates measurement requirements. Distinguishing nanoscale from bulk-phase behavior reflects a fundamental difference in chemical logic, encompassing surface structure, redox potential, and electron mobility. Recognizing these distinctions is essential for accurate modeling, catalyst benchmarking, and material design. More broadly, the principle of "<i>separation before function</i>" underscores a general scientific logic: functional understanding requires prior isolation of components before integration, establishing mechanistic insight across catalysis, environmental chemistry, and prebiotic systems.