Stability properties of dioxygen-iron(II) porphyrins: an overview from simple complexes to myoglobin

Abstract

The reversible and stable binding of molecular oxygen to iron(II) is not a simple process. Although it has been possible to synthesize a class of O 2-binding porphyrins by the introduction of certain steric restraints to prevent the formation of an oxygen-bridged dimer, small heme complexes are mostly oxidized very rapidly and irreversibly by O 2. In cases of myoglobin and hemoglobin, each heme iron atom is embedded in its protein matrix so as to be unable to form such a dimer. Nevertheless, the oxygenated form is still oxidized to the ferric met-species, at a slow but considerable rate, with the generation of superoxide anion. Kinetic and thermodynamic studies of the stability of native oxymyoglobin have revealed that its autoxidation proceeds through a pathway quite different from that of the simple heme complexes. The FeO 2 center of myoglobin is always subject to nucleophilic attack by an entering water molecule with strong proton assistance from the distal histidine (E 7), which acts as a catalytic residue. This center is also open to the attack of an entering hydroxide anion. These reactions can cause irreversible displacement of the bound dioxygen from MbO 2 in the form of O 2 − so that the iron is converted to the ferric met-form. Myoglobin has thus evolved with a globin moiety that can protect the FeO 2 center from easy access of a water molecule and its conjugate anionic species. These new features of the stability of MbO 2 are of primary importance, not only for a full understanding of the nature of FeO 2 bonding, but also for planning new molecular designs for synthetic oxygen carriers which may be able to function in aqueous solutions under physiological conditions.