Tyrosinase enzymes (Ty), found in nearly all aerobic life forms, oxidize substrates through a binuclear copper active site that activates dioxygen. The resulting side-on peroxide Cu^II species converts tyrosine to melanins for pigment formation in animals and plants.

Daniel P. Stack, Stanford University, CA, USA, and colleagues have shown that the simplest synthetic active-site analogue (pictured) can be formed by a self-assembly process. Substituted imidazoles, CuI, and O₂ organize in solution at a temperature of –145 °C. The substrate reactivity is similar to that of Ty but apparently proceeds through a mechanism not postulated for the biological oxidation.  The researchers charaterized a high-valent bis-Cu^III bis-oxide intermediate.

While the assembly and Cu^III identification are surprising, the stability and facile reactivity reveal a detail of Ty chemistry: The tertiary protein structure may not be needed, e.g., to impose structural constraints or induce function, since the active-site core is innately reactive.

• Simplest Monodentate Imidazole Stabilization of the oxy-Tyrosinase Cu₂O₂ Core: Phenolate Hydroxylation through a Cu^III Intermediate,
  Linus Chiang, William Keown, Cooper Citek, Erik C. Wasinger, T. Daniel P. Stack,
  Angew. Chem. Int. Ed. 2016.
  DOI: 10.1002/anie.201605159