In this study, a manganese(IV) oxide-mediator (MnO2-mediator) system for the abatement of sulfonamide antibiotics was evaluated. Two simple model humic constituents, syringaldehyde (SA) and acetosyringone (AS), could promote the transformation of sulfonamides at pH 5-8. Two additional potential mediators, tannic acid and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonate (ABTS), had negligible enhancement on the transformation of sulfonamides by MnO2. The enhancing effect was attributed to the reaction of the oxidized mediator (i.e., phenoxy radical or benzoquinone-like compounds) produced from the oxidation of the mediators by MnO2 with SMX. Thereby cross-coupling products from sulfamethoxazole (SMX) with oxidized SA were formed in the MnO2-SA system, which was confirmed by liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry. Coexisting metal ions (i.e., Ca(II), Mg(II) and Mn(II)) showed inhibitory effects in the order of Mn(II)> Ca(II)> Mg(II). For repetitive runs of the MnO2-SA-SMX system, MnO2 lost its oxidative capacity due to the sorption of Mn(II) on the reactive sites of the MnO2 surface. A full regeneration of partially deactivated MnO2 by oxidation of the sorbed Mn(II) with Mn(VII) could be achieved. (C) 2019 Elsevier Ltd. All rights reserved.