By using a biomimetic approach, our goal is to understand the active site of metalloproteins and particularly the key structural features required to obtain a specific activity such as, for example, the reduction of dioxygen in water. Our current research concerning the mechanism of dioxygen activation by cytochrome c oxidase perfectly illustrates this philosophy. Indeed, the recent resolution of the X-ray structure of the enzyme (see below) has generated a plethora of biomimetic studies, but few models incorporate all the structural features of the active site: (1) a heme possessing an intramolecular fifth ligand, (2) a flexible triaza ligand for copper I/II coordination, and finally (3) a mimic of Tyr244.
In the past decade, we have developed small synthetic metal complexes that incorporate the essence of the binding site of CcO in their own structure, giving rise to a particularly useful family of functionalized porphyrins: the “Arbor” porphyrins or “tren-capped” porphyrins (see selected examples below). These biomimetic models are functional analogs and so, able to reduce dioxygen in water via a 4e- / 4 H+ process. Additionally, The “iron-only” complexes of these tren-capped porphyrins were shown to be even more efficient than the iron-copper complexes and selective. Recently, new generations of ligands for cytochrome c oxidase mimicking have been designed. These porphyrins are functionalized with both an internal nitrogen base on one side and a triaza (N3) or a triaza-phenol (N3O) moiety on the other side, attached to the macrocycle by various spacers. The reactivity toward dioxygen as well as spectroscopic characterization of these models are currently under investigation.
In the course of our research, we also developed models to probe the influence of an apical carboxylic group on dioxygen affinity (see selected example below). According to the Pauling hypothesis, a hydrogen bond or even a dipole-dipole interaction with the superoxo complex is expected to increase the dioxygen affinity of the heme. Such a hydrogen bond has also been evidenced in heme oxygenase proteins. Thus, the influence of a hanging carboxylic group on the stability of the dioxygen adduct can be directly and easily studied since the obtained iron(II) complexes are five coordinate. These complexes were found to bind reversibly dioxygen without oxidation over several weeks, as shown by CO trapping experiments, and further studies towards dioxygen affinity are under investigation.