Models for Nonheme Iron Intermediates:  Structural Basis for Tuning the Spin States of Fe(TPA) Complexes

Our efforts to model the oxygen activation chemistry of nonheme iron enzymes have yielded transient intermediates with novel properties. These properties can be dramatically affected by the introduction of a 6-methyl substituent on the pendant pyridines of the tetradentate ligand TPA (TPA = tris(2-pyridylmethyl)amine). A series of Fe(TPA) complexes has thus been synthesized and characterized to provide the structural basis for these dramatic effects. The following complexes have been obtained: Fe(L)(CH3CN)2(ClO4)2 (1, L = TPA; 2, L = 6-MeTPA; 3, L = 6-Me2TPA; 4, L = 6-Me3TPA) and Fe(L)(acac)(ClO4)2 (5, L = TPA; 6, L = 5-Me3TPA; 7, L = 6-MeTPA). As indicated by 1H NMR and/or EPR, 1, 5, and 6 with no 6-methyl substituent are low spin, while complexes 2, 3, 4, and 7 with at least one 6-methyl substituent are all high spin, with higher redox potentials than their low-spin counterparts. The ligands with 6-methyl substituents thus favor a metal center with a larger ionic radius, i.e., FeII over FeIII and high spin over low spin. Careful scrutiny of the crystal structures of 1, 4, 6, and 7 reveals that one hydrogen of the 6-methyl group is only 2.7 Å away from the metal center in the high-spin complexes. Its presence thus prevents the pyridine nitrogen from forming an Fe−N bond shorter than 2.1 Å as required for an iron center to adopt a low-spin configuration. This steric effect of the 6-methyl substituent serves as a simple but very useful ligand design tool to tune the electronic properties of the metastable alkylperoxoiron(III) species derived from the reactions of 1−4 with tert-butyl hydroperoxide. These intermediates serve as models for low-spin and high-spin peroxoiron(III) species in the reaction cycles of the antitumor drug bleomycin and lipoxygenase, respectively. Similar principles apply in the design of nonheme diiron(II) complexes that reversibly bind dioxygen and of high-valent bis(μ-oxo)diiron complexes that model the high-valent intermediates in the redox cycles of nonheme diiron enzymes such as methane monooxygenase and ribonucleotide reductase.