Reversible O−O Bond Cleavage in Copper−Dioxygen Isomers: Impact of Anion Basicity

μ–η2:η2–peroxodicopper(II) (P) and bis(μ–oxo)dicopper(III) (O) complexes are valence isomers that differ by the degree of O2 reduction and the presence of an O−O bond.1,2 These isomers can exist in a measurable equilibrium with a small activation energy.3-6 This facile isomerization is significant to the processes of making and breaking an O–O bond, which are key steps in photosynthesis, respiration, and the catalytic cycle of tyrosinase, a binuclear copper enzyme that ortho-hydroxylates phenols. The characterized P species of oxygenated tyrosinase is accepted as the active oxidant in the oxygen atom transfer reaction, but a transient O-type species in which the O–O bond is cleaved prior to oxygen insertion cannot be overlooked.7 Understanding these steps in detail is important to the design of synthetic catalysts that use O2 as a terminal oxidant. A systematic study of the influence of the Lewis basicity of various anions, i.e. their coordinating ability, on the P/O equilibrium was undertaken as a model of substrate binding to the P core in tyrosinase.5,6 P/O mixtures were prepared with the ligand N,N,N′,N′-tetraethylpropane-1,3-diamine (TEPD) by injecting a CH2Cl2 solution of [(TEPD)Cu(CH3CN)n](X), where X− = SbF6−, CF3SO3−, TsO− (p-toluenesulfonate) or CH3SO3−,8 into a precooled, preoxygenated volume of CH2Cl2, tetrahydrofuran (THF) or acetone (−85°C, 1 atm O2, 1 mM in Cu). P and O isomers were stable only below −75°C and were identified by their characteristic charge-transfer absorptions (Table 1, Figure 1).1 In THF or CH2Cl2, [(TEPD)2Cu2O2](CF3SO3)2 exhibits rapid, reversible interconversion between equilibrium positions upon temperature change.9 A Van't Hoff analysis yields ΔH° = −4.3(2) kJ mol−1 and ΔS° = −24(2) J K−1 mol−1 for this P ⇔ O equilibrium in THF: O is favored enthalpically and P is favored entropically, as previously determined for other systems.4,5 Figure 1 (a) UV-Vis spectra of [(TEPD)2Cu2O2](X)2, with X− = SbF6−, CF3SO3− and CH3SO3− in THF at −85°C. (b) Addition of [N(n-Bu)4](PhCO2) (0–0.9 equivalent per dicopper species) to an acetone solution of ... Table 1 [(TEPD)2Cu2O2](X)2 solutions: UV-Vis features and P:O ratios More strongly coordinating counteranions bias the P:O equilibrium position towards P, from ∼10:90 with SbF6− to ∼100:0 with CH3SO3− (Figure 1a). The P:O ratio follows anion basicity regardless of size: e.g. CH3SO3− is slightly smaller than CF3SO3−, yet the more compact O isomer is not observed with CH3SO3−. Such a basicity effect is counter-intuitive, as more electron donation to the Cu2O2 core is anticipated to stabilize the higher oxidation state of the copper centers and hence favor the O isomer.10 Titration experiments with competing anions highlight the importance of anion basicity and reveal the existence of specific anion/dication interactions. Addition of a more coordinating anion Y− (CF3SO3−, TsO−, CH3SO3−, CF3CO2−, PhCO2−) to a preformed P/O solution with a “weaker” anion X− (SbF6−, CF3SO3−) results in a rapid, isosbestic isomerization in the direction O → P. Spectroscopically pure P species are obtained by addition of 1.0 equivalent of TsO−, CH3SO3−, CF3CO2− or PhCO2− per binuclear complex (Figure 1b).6,11 In all cases, no significant spectral changes occur upon addition of more than 1.0 equivalent of Y− per Cu2O2 species, and the final P:O ratio is the same as per direct oxygenation of [(TEPD)Cu(CH3CN)n](Y) (Y− = CF3SO3−, TsO− or CH3SO3−). In contrast, the reverse titration of a [(TEPD)2Cu2O2](Y)2 solution with a “weaker” X− anion is incomplete even with 200 equivalents of X− per dimer.12 Overall, these experiments suggest that each dicationic Cu2O2 species is associated with one anion intimately.13 Extended X-ray Absorption Fine Structure (EXAFS) analysis of a frozen THF solution of [(TEPD)2Cu2O2](CH3SO3)2 provides structural evidence of the close association between the anion and the Cu2O2 core in this spectroscopically pure P species. The EXAFS data are consistent with a side-on peroxo-bridged copper dimer having four Cu–N/O14 interactions at 1.94 A, one Cu−O at 2.26 A, and one Cu···Cu at 3.51 A (Figure 2a).1 The scattering atom at 2.26 A is required for a good fit and is ascribed to a CH3SO3− oxygen atom,15 consistent with the titration experiments. Coordination of CH3SO3− would place the sulfur atom within 3.3–3.8 A of the copper centers, which corresponds to the poorly fitted region in the 4-component model. A 5-component EXAFS fit with a Cu···S interaction at a refined distance of 3.47 A16 provides a better match to the data (Figure 2b, Table S1). The dual requirement for a Cu−O interaction at 2.26 A and a Cu···S interaction at 3.47 A in the EXAFS fit establishes that the CH3SO3− anion is well-ordered at close range from the Cu2O2 core. Figure 2 EXAFS data (inset) and Fourier transforms with offset fit residuals (bottom) of [(TEPD)2Cu2O2](CH3SO3)2 (−). (a) 4-component fit (- - -); (b) 5-component fit (- - -): 4 Cu–N/O = 1.94 A, 1 Cu−O = 2.26 A, 6 Cu···C ... Density Functional Theory (DFT) calculations17 support the EXAFS structure. A plausible model consists of the association between a [(TEPD)2Cu2O2]2+ molecule and one CH3SO3− anion, in accord with the experimental 1:1 anion-to-dimer stoichiometry. Electronic optimization of this model with a Cu···Cu distance fixed to the experimental value of 3.51 A converges to the P species depicted in Figure 3. The CH3SO3− anion bridges the two copper(II) ions through axial positions, a ligation mode documented for the weaker triflate anion in copper dimers.18 The calculated distances about the copper ions agree closely with the EXAFS results, notably for the axial oxygen atoms. The Cu2O2 core exhibits a slight butterfly distortion with a dihedral angle of ∼150° between the two CuO2 planes that may account for the weak feature at ∼500 nm in the UV-Vis spectrum of this P species (Figure 1a).19 Figure 3 DFT-optimized geometry of {[(TEPD)2Cu2O2](CH3SO3)}+. Cu−Oeq = 1.94 A (avg), Cu−N = 2.02 A (avg), Cu−Oax = 2.26 A, Cu···C = 2.87 A (avg), Cu···S = 3.36 ... The axial ligation mode of the anion is substantiated experimentally. The ∼600 nm charge-transfer feature of the P isomers shifts to lower energies by 12% as the basicity of the counteranion increases from CF3SO3− to PhCO2− (Table 1). Since this transition originates from the out-of-plane π* orbital of the peroxo moiety, this large shift strongly suggests that the anion is positioned above the Cu2O2 plane. This indirect characterization of the anion-core association may become useful for probing substrate binding to a P core. In conclusion, axial binding of an anion induces an electronic/electrostatic, not steric, preference for the P isomer: the O−O bond is not cleaved with an anion positioned axially on the Cu centers. In oxytyrosinase, although the substrate presumably approaches the P core from above,20 its subsequent deprotonation yields a phenolate anion, which is much more basic than the anions used here. Such a strong ligand can potentially redefine the equatorial planes of the copper centers with minimal reorganization of the O2-derived ligands. Such change could trigger O−O bond cleavage and yield a reactive O-type species, as suggested recently.7