Oxidation of Biologically Relevant Chalcogenones and Their Cu(I) Complexes: Insight into Selenium and Sulfur Antioxidant Activity

Abstract

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 = <i>N</i>,<i>N</i>′-dimethylimidazole selone or thione] were treated with H₂O₂ and the products analyzed by ¹H, ¹³C­{¹H}, and ⁷⁷Se­{¹H} 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