Iron: Models of Proteins with Dinuclear Active Sites

Abstract

This article focuses on recent developments in the area of synthetic model compounds for diiron enzymes. The archetypical enzyme in this class is soluble methane monooxygenase, a protein capable of hydroxylating methane as well as many other substrates. The article includes new diiron enzymes for which the X‐ray structures have been determined. These developments allow for synthetic chemists to focus on new coordination modes for model compounds. The versatility of the diiron site provides new challenges for modeling. The synthetic approaches are organized based on ligand types and assembly modes. These categories include the use of chelating ligands to generate mononuclear iron sites that are then coupled together by bridging ligands to generate the dinuclear site. Employment of trispyridyl ligands, used extensively by Que's group, is next addressed and separated from chelating ligands owing to their popularity and versatility. New developments in binucleating ligands first seen several decades ago are treated next and this is followed by the employment of bulky carboxylate ligands, mainly pioneered by Lippard's group, to control nuclearity and structure. The final topic is a new approach introduced by Lippard's group in which metal‐spanning ligands referred to as “platform ligands” are used to create syn nitrogen coordination. Overall, new developments have been in the area of reactivity where functional models have been developed. Although the goal of catalytically oxidizing external alkane and aromatic substrates under ambient conditions with dioxygen is coming closer to reality, this is yet to be achieved. The modeling approach will continue to provide valuable insights into catalytic mechanisms of dinuclear enzymes and will help in the development of green catalysts.

Assembly of a mononuclear ferrous site using a bulky aldehyde-imidazole ligand

“…Enzymes containing non-heme iron sites are abundant in nature [1–6]. For mononuclear non-heme iron sites, enzymatic functions include a variety of oxygen activating functions [7].…”