BOX Ligands in Biomimetic Copper‐Mediated Dioxygen Activation: A Hemocyanin Model

The μ-η2:η2-peroxodicopper(II) core found in the oxy forms of the active sites of type III dicopper proteins have been a key target for bioinorganic model studies. Here, it is shown that simple bis(oxazoline)s (BOXs), which are classified among the so-called “privileged ligands”, provide a suitable scaffold for supporting such biomimetic copper/dioxygen chemistry. Three derivatives R,HBOX-Me2 (R = H, Me, tBu) with different backbone substituents have been used. Their bis(oxazoline)-copper(I) complexes bind dioxygen to yield biomimetic μ-η2:η2-peroxodicopper(II) species. O2 can be reversibly released upon an increase in temperature. Their formation kinetics have been studied under cryo-stopped-flow conditions for the tBu derivative, giving activation parameters ΔH‡on = (2.27 ± 0.18) kcal mol–1, ΔS‡on = (–46.3 ± 0.8) cal K–1 mol–1 for the binding event and ΔH‡off = (11.7 ± 1.9) kcal mol–1, ΔS‡off = (–16.1 ± 8.2) cal K–1 mol–1 for the release of O2, as well as thermodynamic parameters ΔH° = (–10.0 ± 1.7) kcal mol–1 and ΔS° = (–32.7 ± 7.4) cal K–1 mol–1 for this equilibrium. The μ-η2:η2-peroxodicopper(II) complexes have been isolated as surprisingly stable solids and investigated in depth by a variety of methods, both in solution and in the solid state. Resonance Raman spectroscopy revealed a characteristic isotope-sensitive stretch O–O = 731–742 cm–1 (Δ[18O2] ≈ –39 cm–1) and an intense feature around 280 cm–1 diagnostic for the fundamental symmetric Cu2O2 core vibration. A slight butterfly-shape of the Cu2O2 core has been derived from EXAFS data and DFT calculations. SQUID magnetic data evidenced strong antiferromagnetic coupled CuII2 (–2J ≥ 1000 cm–1). Thermal degradation in solution yields bis(hydroxo)-bridged [(tBu,HBOX-Me2)(L)Cu(OH)]2(PF6)2 (L = H2O, MeCN or THF); whereas in the case of H,HBOX-Me2, ligand oxygenation has been detected. Preliminary reactivity studies with the substrate 2,4-di-tert-butylphenol indicate the formation of the C–C coupling product 3,3′,5,5′-tetra-tert-butyl-2,2′-biphenol, whereas ortho-hydroxylation was not observed. The copper(I) complex [(tBu,HBOX-Me2)Cu(MeCN)]PF6 as well as two dicopper(II) complexes [(L)(tBu,HBOX-Me2)Cu(OH)]2(PF6)2 have been characterised by single-crystal X-ray diffraction. Considering the vast number of known BOX derivatives, a rich and versatile Cu/O2 chemistry based on this platform is anticipated.

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