Copper coordinated ligand thioether-S and NO2− oxidation: relevance to the CuM site of hydroxylases

Abstract

In order to gain insight into the coordination site and oxidative activity of the Cu_M site of hydroxylases such as peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM), we have synthesized, characterized and studied the oxidation chemistry of copper complexes chelated by tridentate N₂S_thioether, N₂O_sulfoxide or N₂O_sulfone donor sets. The ligands are those of N-2-methylthiophenyl-2′-pyridinecarboxamide (HL1), and the oxidized variants, N-2-methylsulfenatophenyl-2′-pyridinecarboxamide (HL1^SO), and N-2-methylsulfinatophenyl-2′-pyridinecarboxamide (HL1^SO2). Our studies afforded the complexes [(L1)Cu^II(H₂O)](ClO₄)·H₂O (1·H₂O), {[(L1^SO)Cu^II(CH₃CN)](ClO₄)}_n (2), [(L1)Cu^II(ONO)] (3), [(L1^SO)Cu^II(ONO)]_n (4), [(L1)Cu^II(NO₃)]_n (5), [(L1^SO)Cu^II(NO₃)]_n (6) and [(L1^SO2)Cu^II(NO₃)] (7). Complexes 1 and 3 were described in a previous publication (Inorg. Chem., 2013, 52, 11084). The X-ray crystal structures revealed either distorted octahedral (in 2, 4–6) or square-pyramidal (in 1, 3) coordination geometry around Cu^II ions of the complexes. In the presence of H₂O₂, conversion of 1 → 2, 3–5 → 6 and 6 → 7 occurs quantitatively via oxidation of thioether-S and/or Cu(II) coordinated NO₂⁻ ions. Thioether-S oxidation of L1 also occurs when [L1]⁻ is reacted with [Cu^I(CH₃CN)₄](ClO₄) in DMF under O₂, albeit low in yield (20%). Oxidations of thioether-S and NO₂⁻ were monitored by UV-Vis spectroscopy. Recovery of the sulfur oxidized ligands from their metal complexes allowed for their characterization by elemental analysis, ¹H NMR, FTIR and mass spectrometry.