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 Δ H^‡_on = (2.27 ± 0.18) kcal mol^-1, Δ S^‡_on = (-46.3 ± 0.8) cal K^-1 mol^-1 for the binding event and Δ H^‡_off = (11.7 ± 1.9) kcal mol^-1, Δ S^‡_off = (-16.1 ± 8.2) cal K^-1 mol^-1 for the release of O₂, as well as thermodynamic parameters Δ H° = (-10.0 ± 1.7) kcal mol^-1 and Δ S° = (-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 $\tilde {\nu}$_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 Cu^II₂ (-2 J ≥ 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. [ABSTRACT FROM AUTHOR]