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.