Substituent-controlled phenoxy radicals drive cross-coupling transformation of tetracycline on δ-MnO2

Tetracycline (TC) is widely detected in natural waters, yet its transformation under environmentally relevant oxidative conditions remains poorly understood, because most previous studies have focused on engineered oxidation systems employing strong oxidants or external energy input. Here we show that humic-like phenolic moieties can act as active mediators to redirect δ-MnO 2 -driven TC transformation from slow direct oxidation to a phenoxy-radical-mediated coupling pathway. Screening of 18 humic-acid model compounds identified acetosyringone (AS) and syringaldehyde (SyrA) as the most effective co-reactants, increasing the apparent rate constants ( k obs ) of TC by about 8.5- and 5.9-fold, respectively. Analyses indicate that TC transformation is governed by syringyl-type phenoxy radicals generated via surface-mediated one-electron transfer on δ-MnO 2 , with reactivity controlled by the fraction of deprotonated phenolic precursors (ArO − ) over a near-neutral pH range. The structure-activity analysis further revealed that ortho‑methoxy and para-carbonyl functionalities favor radical stability and cross-reactivity, whereas para-carboxyl substitution biases the mediator toward self-coupling and unproductive oxidant consumption. These substituent-dependent trends provide molecular-level insight into how humic-like phenolics regulate TC transformation at Mn oxide interfaces.