Binding of Reactive Oxygen Species at Fe-S Cubane Clusters

Reactive oxygen species (ROS) play an important role in the biochemistry of the cell and occur in degenerative processes as well as in signal transduction. Iron-sulfur proteins are particularly oxygen-sensitive and their inorganic cofactors frequently undergo ROS-induced decomposition reactions. As experimental knowledge about these processes is still incomplete we present here a quantum chemical study of the relative energetics for the binding of the most relevant ROS to [Fe4S4] clusters. We find that cubane clusters with one uncoordinated Fe atom (as found, for instance, in aconitase) bind all oxygen derivatives considered, whereas activation of triplet O2 to singlet O2 is required for binding to valence-saturated iron centers in these clusters. The radicals NO and OH feature the most exothermic binding energies to Fe atoms. Direct sulfoxidation of coordinating cysteine residues is only possible by OH or H2O2 as attacking agents. The thermodynamic picture of ROS binding to iron-sulfur clusters established here can serve as a starting point for studying reactivity-modulating effects of the cluster-embedding protein environment on ROS-induced decomposition of iron-sulfur proteins.