Methimazole (MMI) is an anti-thyroid drug that also shows potential as an antioxidant and for regulating copper homeostasis in neurodegenerative diseases. When methimazole is treated with CuBF4, copper is reduced and oxidized methimazole disulfide (MMIDS) is formed. Under air-free conditions, these reactions yield a variety of Cu(I) complexes, including [Cu2(MMIDS)3][BF4]2, [Cu2(MMI)6][BF4]2, and [Cu2(MMI)2(MMIDS)2][BF4]2, demonstrating the coordination versatility and reversibility of methimazole disulfide bond formation in the presence of electron-rich Cu(I). In these dinuclear complexes, Cu(I) ions are stabilized by the bridging MMI or MMIDS ligands, and the tertiary structure is stabilized by π-π interactions of the imidazole rings. The disulfide bond lengths (2.06-208 Å) and dihedral C-S-S angles of these complexes are remarkably similar to cysteine-derived disulfide bonds. When Cu(I) or Cu(II) salts are treated with methimazole in air, a sulfur atom of the methimazole disulfide is extruded, resulting in coordination of the monosulfide, diimidazole (MMIMS) to Cu(II) in complexes of the formulae [Cu(MMIMS)2(OH2)][CH3SO4]2, [Cu(MMIMS)2(OH2)2][NO3]2, Cu(MMIMS)(SO4)(CH3OH), and Cu(MMIMS)(SO4)(DMSO), depending on solvent and the copper salt. In some of these products, the extruded sulfur is oxidized to sulfate or methylsulfate, demonstrating the complexity of these redox reactions and their oxygen dependence.

Copper-thione complexes are truly complex: Redox and sulfur extrusion reactions

255th National Meeting (2018)

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