Simplest Monodentate Imidazole Stabilization of the oxy-Tyrosinase Cu2 O2 Core: Phenolate Hydroxylation through a Cu(III) Intermediate.

Tyrosinases are ubiquitous binuclear copper enzymes that oxygenate to Cu(II) 2 O2 cores bonded by three histidine Nτ-imidazoles per Cu center. Synthetic monodentate imidazole-bonded Cu(II) 2 O2 species self-assemble in a near quantitative manner at -125 °C, but Nπ-ligation has been required. Herein, we disclose the syntheses and reactivity of three Nτ-imidazole bonded Cu(II) 2 O2 species at solution temperatures of -145 °C, which was achieved using a eutectic mixture of THF and 2-MeTHF. The addition of anionic phenolates affords a Cu(III) 2 O2 species, where the bonded phenolates hydroxylate to catecholates in high yields. Similar Cu(III) 2 O2 intermediates are not observed using Nπ-bonded Cu(II) 2 O2 species, hinting that Nτ-imidazole ligation, conserved in all characterized Ty, has functional advantage beyond active-site flexibility. Substrate accessibility to the oxygenated Cu2 O2 core and stabilization of a high oxidation state of the copper centers are suggested from these minimalistic models.