The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies

Abstract

The bioinorganic chemistry of iron is central to life processes. Organisms must recruit iron from their environment, control iron storage and trafficking within cells, assemble the complex, iron-containing redox cofactors of metalloproteins, and manage a myriad of biochemical transformations by those enzymes. The coordination chemistry and the variable oxidation states of iron provide the essential mechanistic machinery of this metabolism. Our current understanding of several aspects of the chemistry of iron in biology are discussed with an emphasis on the oxygen activation and transfer reactions mediated by heme and nonheme iron proteins and the interactions of amphiphilic iron siderophores with lipid membranes.

Figure 1

Iron(III) protoporphyrin IX with a cysteinate as the axial ligand (1), which is typical of cytochrome P450, CPO, and NOS enzymes. The active oxygen species of these proteins and related heme enzymes is an oxoiron(IV)porphyrin cation radical (2), often called compound I.

Scheme 1

Consensus catalytic cycle for oxygen activation and transfer by cytochrome P450.

Figure

Structures 9–12.

Scheme 2

Pathways for oxygen atom transfer from the active ferryl species 7 of heme-thiolate enzymes such as cytochrome P450 to form the product alcohol coordinated to the ferric, resting form of the protein (8).

Figure 2

Energy level diagram and reaction coordinate for the hydroxylation of methane by a ferryl-porphyrin cation radical (7). This figure is adapted from ref. .

Figure 3

Representation of a synthetic electron-transfer assembly in a vesicle bilayer, showing a membrane-spanning porphyrin, an amphiphilic zinc porphyrin recruiter, and an associated cytochrome c.

Figure 4

Molecular models of the iron complexes of marinobactin E, mycobactin J, and rhizobactin 1021 showing the similarities in their amphiphilic structures. NMR data showing the line-broadening effect of Fe-marinobactin E on the choline methyl proton resonances. Proposed molecular mechanism of iron acquisition by marinobactin E (cf. ref. 76).