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

Abstract

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 $\tilde {\nu}$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 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.

Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure–reactivity correlations

“…CuL OL 2 and CuBIMZ were measured in dichloromethane and exhibited absorption maxima at λ = 340 nm and λ = 610 nm for CuL OL 2 and λ = 333 nm as well as λ = 600 nm for CuBIMZ. The slight shift of the π σ * → d x 2 −y 2 charge transfer transition to higher energies was also noticed for copper(I) complexes with bidentate bis(oxazoline) ligands [67]. In contrast, no µ-η 2 :η 2 -peroxo-dicopper(II) complex could be found for CuL imz 1 in tetrahydrofuran, dichloromethane, and acetone.…”

Acid/base triggered interconversion of μ-η2:η2-peroxido and bis(μ-oxido) dicopper intermediates capped by proton-responsive ligands

“…29 By spectroscopic means we demonstrated that several ligands, R,H BOXs (Scheme 1B), reversibly bind to dioxygen to form μ-η 2 :η 2 -peroxidodicopper( ii ) complexes, both in solution and in the solid state; the thermodynamic and kinetic parameters of the P core formation have been determined. 29 Furthermore, we have shown that certain free bis(oxazoline)s, R,H BOXs, exist as an equilibrium mixture between the diimine and iminoenamine tautomers. 30 The latter are reminiscent of β-diketimines used extensively as anionic ligands after deprotonation, which led us to consider R,H BOXs as proton responsive ligands.…”

“…Reactions of R,R′ BOX with [Cu(MeCN) 4 ]ClO 4 in tetrahydrofuran (THF) gave the air sensitive copper( i ) complexes [( R,R′ BOX)Cu(MeCN)]ClO 4 , 1 (R = R′ = Me), 2 (R = Me, R′ = H), 3 (R = R′ = H) 29 as colourless compounds (see ESI†). Oxygenation of 1 , 2 and 3 in THF at 193 K led to deep purple coloured solutions of [{ R,R′ BOX(THF)Cu} 2 (μ-η 2 :η 2 -O 2 )](ClO 4 ) 2 , P 4 (R = R′ = Me), P 5 (R = Me, R′ = H) and P 6 (R = R′ = H) with intense optical features around 330 nm ( ε ≈ 20 × 10 3 M –1 cm –1 ) and 500 nm ( ε ≈ 1 × 10 3 M –1 cm –1 ).…”

“…, from an occupied in-plane d xy (Cu II )/π*(O 2 2– )/d xy (Cu II ) bonding orbital combination into its antibonding counterpart), typically observed for μ-η 2 :η 2 peroxido complexes. 26,29,32 The shallow absorption band at 535 nm is assigned to an intra-core π* → σ* transition ( i.e. , from the out-of-plane π* of the O 2 2– ligand into the in-plane d xy (Cu II )/π*(O 2 2– )/d xy (Cu II ) antibonding orbital combination).…”

“…33–38 Most of the metric parameters of P 4 and P 5 are in excellent agreement with those derived from Cu K-edge extended X-ray absorption fine structure (EXAFS) data, for the corresponding P cores obtained with the capping ligands t Bu,H BOX ( t Bu,H P ) and H,H BOX ( H,H P ). 29 …”