A bioinspired model for copper monooxygenase: direct aromatic hydroxylation using O₂

A novel copper(I) complex, [Cu^I(L)(CH₃CN)]CF₃SO₃ (1) (L = 1,1,2-tri(pyridin-2-yl)propan-1-ol), has been synthesized, characterized, and investigated as a bioinspired model for copper monooxygenases. Under aerobic conditions in CH₃CN, complex 1 undergoes conversion to a dicopper complex, [(Cu^IIL)(Cu^IIL H)(SO₃CF₃)₂]·CF₃SO₃·H₂O (2), whose molecular structure reveals a Cu-Cu distance of 2.96 Å. A dicopper(II) complex, [(LCu^II)₂(SO₃CF₃)₂] (3), has been synthesized for comparison, which exhibits a similar Cu-Cu distance of 2.97 Å. EPR spectroscopy has ascertained the solution-state geometries of complexes 2 and 3, which displayed g_∥ > g_⊥ values, indicative of distorted square pyramidal geometries consistent with their solid-state structures. Complex 1 selectively hydroxylates benzene in the presence of O₂ and Et₃N, affording 7% phenol based on the substrate, without any side products. However, the use of H₂O₂ as the oxygen source under identical conditions significantly increases the phenol yield to 19%. The catalytically active intermediates generated by the reaction of complex 1 with dioxygen showed an O (π*σ) → Cu ligand-to-metal charge transfer (LMCT) transition at 360 nm and a d-d transition at 650 nm. These spectral features are more pronounced with H₂O₂, showing a new LMCT transition at 360 nm and a very weak d-d transition at 689 nm. This is supported by solution FT-IR spectroscopy, which showed an O-O stretching frequency at 890 cm^-1 (DFT spectra at 829 cm^-1), corresponding to a Cu-OOH intermediate. The structure of the [(L)Cu^II-OOH]⁺ species was optimized by DFT calculations. Kinetic isotope effect (KIE) studies using C₆H₆/C₆D₆ (1 : 1) (k_H/k_D = 1.03) and isotopic labeling experiments using H₂¹⁸O₂ support our proposed mechanism of benzene hydroxylation. In contrast, dinuclear complexes 2 and 3 exhibited poor benzene hydroxylation activity even with H₂O₂ and yielded only 4% and 6% phenol, respectively, along with by-products such as biphenyl and quinone under identical conditions.