Enzyme-mimicking peripheral substituents beyond the second coordination sphere tune single-atom catalysts for periodate activation

Single-atom catalysts (SACs) are promising enzyme-mimetic active centers, yet mimicking long-range regulation by distal binding pockets in natural metalloenzymes remains challenging. Here, we synthesize conjugated organic SACs bearing tunable peripheral substituents beyond the second coordination sphere (denoted as R-FeSAC; R = F, H, or NH 2 ) to regulate periodate (PI) activation. F-FeSAC outperforms its H- and NH 2 -substituted counterparts because long-range electronic regulation reconfigures the Fe-site microenvironment and strengthens PI adsorption and activation. In situ Raman spectroscopy, galvanic oxidation assays, and electrochemical analyses show that R-FeSAC activates PI to form high-potential metastable intermediates, enabling a direct electron-transfer pathway (ETP) for selective pollutant removal through polymerization, rather than radical or singlet-oxygen pathways. Fluorine substitution reinforces Fe–O interaction with PI and accelerates electron-transfer kinetics through an electron-withdrawing effect. Consistent relationships among pollutant half-wave potentials ( φ 1/2 ), LUMO (catalyst/PI) –HOMO (pollutant) energy gaps, and degradation reactivity further support the ETP and indicate that pollutant electron-donating ability governs selectivity. Moreover, an F-functionalized membrane exhibits enhanced durability during continuous-flow operation, while a pilot-scale ETP reactor achieves efficient pollutant degradation in real wastewater without iodate leakage. These findings establish beyond-second-sphere peripheral functionalization as an enzyme-inspired strategy for PI activation and polymerization-mediated water purification.