Catalytic phenol hydroxylation with dioxygen: extension of the tyrosinase mechanism beyond the protein matrix.

A pinnacle of bio-inorganic chemistry is the ability to leverage insights gleaned from metalloenzymes toward the design of small analogs capable of effecting catalytic reactivity outside the context of the natural system.[1,2] Structural mimicry of active sites is an attempt to insert a synthetic catalyst into an enzymatic mechanism. Such a mechanism evolves by selection pressures for efficiency and traverses an energetic path with barriers and wells neither too high nor too deep in energy – a critical factor of catalytic turnover.[3] An advantage of metalloenzymes over small metal complexes is the site-isolation of the metal center in the protein matrix with its attendant ability to attenuate destructive decay processes – reaction sinks. This protection provides access to thermal regimes that allows barriers and wells to be traversed. Synthetic complexes too must avoid any deleterious reactions, often necessitating deliberate incorporation of protective superstructures.[4,5] Such limitations make reproducing enzymatic catalytic reactivity in a synthetic complex with native substrates a significant challenge, as evidenced by the dearth of good examples, despite decades of effort.