Highly oxidized metal-oxo species

Oxidation of heme to Fe^IV=O oxoferryl state by O₂

Oxidizing power of biological high-valence metal complexes stems form one- or two-electron oxidation of a metal center, typically coupled to formation of a metal-oxo group. Perhaps the most common example is the iron-oxo species formed by oxidation of ferric Fe^III iron to ferryl Fe^IV=O state in many heme enzymes. Such heme ferryl-oxo species carries a potential of ~1V and can catalyze hydroxylation reactions which occur directly at the metal binding site.

Highly-oxidized metal-oxo groups are often structurally and functionally coupled to additional redox factors and groups in the protein vicinity, which store another highly oxidizing equivalent. Such redox groups can be reversibly oxidized to a radical state, but the nature of a particular group being oxidized may vary.

Non-heme iron center coordinated by residues in the active sitre of TauD can react with oxygen producing highly oxodized Fe^IV=O species.

In some cases additional electron is extracted from a cofactor associates with the metal itself. One well known example is oxidation of the porphyrin macrocycle to a cation radical such as commonly occurs in peroxidases. This ferryloxo porphyrin radical species packs another 1V of oxidizing power and is the key catalytic intermediate in cytochromes P-450, for example. Because of tight structural and electronic coupling with metal-oxo center, metal-oxo porphyrin radicals considered as one highly oxidized metal site.

Biological catalysis is a well-choreographed process which progresses from one stage to another along well defined route. We investigate both the kinetics of conversions and the molecular structures at individual steps. In addition to structures of isolated reactive species, our interests include local interactions in the vicinity of metal centers and the role of protein moiety in controlling and complementing transition metal chemistry. Such interactions include of hydrogen bonding, protonation, charge compensation, nature and geometry of ligands, etc. all of which control of reactivity of transient species.

A related group of redox-active sites is structurally more distinct from metal-oxo species. These redox sites include coordinated non-metal cofactors or amino acid side chains of the protein itself. Such protein-bound radical groups are often generated via reversible one-electron oxidation by a metal-oxo species and thus are functionally dependent. Identity and properties of amino-acid centered protein radicals is another research subject of our group.