Hydroxyl radical damage to DNA causes disease, and sulfur and selenium antioxidant coordination to hydroxyl-radical-generating Cu+ is one mechanism for their observed DNA damage prevention. To determine how copper binding results in antioxidant activity, biologically relevant selone and thione ligands and Cu+ complexes of the formula [Tpm*Cu(L)](+) [Tpm* = tris(3,5-dimethylpyrazolyl)methane; L = N,N'-dimethylimidazole selone or thione] were treated with H2O2 and the products analyzed by H-1, C-13{H-1}, and Se-77{H-1} NMR spectroscopy, mass spectrometry, and X-ray crystallography. Upon H2O2 treatment, selone and thione binding to Cu+ prevents oxidation to Cu2+; instead, the chalcogenone ligand is oxidized. Thus, copper coordination by sulfur and selenium compounds can provide targeted sacrificial antioxidant activity.