Models for amide ligation in nonheme iron enzymes

Lipoxygenase and isopenicillin N synthase belong to an emerging class of mononuclear nonheme iron(II) enzymes involved in dioxygen activation.(1) Though these two enzymes catalyze very different reactions, they possess common structural features. Crystal structures(2,3) of these enzymes (Figure 1) show the divalent metal centers to be coordinated to a 2-His-1-carboxylate facial triad(1c) as well as an amide Ligand. These enzymes represent the first examples of amide ligation to iron in biology, a feature not anticipated by prior spectroscopic studies. The amide ligand appears to play a role in catalysis, as indicated by site-directed mutagenesis studies of the two (4,5) To determine the effects of an amide ligand an enzymes. the properties of an iron center, we have synthesized iron complexes of the tetradentate ligand bis(2-pyridylmethyl)glycinamide(BPh4). [Fe-II(BPGm)(0(2)CCH(3))(CH3OH)](BPh4) (1) represents the first example of a complex with a ligand combination that corresponds closely to the coordination environments found for the metal centers in lipoxygenase and isopenicillin N synthase. For comparison, we also report the structures of [Fe-II(TPA)(O2CC(CH3)(3))(CH3OH)](BPh4) (2, TPA = tris(2-pyridylmethyl)amine) and [Fe-2(III)(mu-O)(mu-O2CCH3)-(BPGm)(2)](ClO4)(3) (3) and their properties.