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 e nzymes have yielded transient intermediates with novel properties. The se 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 o btained: [Fe(L)(CH3CN)(2)](ClO4)(2) (1, L = TPA; 2, L = 6-MeTPA; 3, L = 6-Me(2)TPA; 4, L = 6-Me(3)TPA) and [Fe(L)(acac)](ClO4)(2) (5, L = TP A; 6, L = 5-Me(3)TPA; 7, L = 6-MeTPA). As indicated by H-1 NMR and/or EPR, 1, 5, and 6 wish no 6-methyl substituent are low spin, while comp lexes 2, 3, 4, and 7 with at least one 6-methyl substituent are all hi gh spin, with higher redox potentials than their low-spin counterparts . The ligands with 6-methyl substituents thus favor a metal center wit h a larger ionic radius, i.e., Fe-II over Fe-III and high spin over lo w spin. Careful scrutiny of the crystal structures of 1, 4, 6, and 7 r eveals that one hydrogen of the 6-methyl group is only 2.7 Angstrom aw ay 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 Angstrom as required for an iron center to adopt a low-spin confi guration. This steric effect of the 6-methyl substituent serves as a s imple but very useful ligand design tool to tune the electronic proper ties of the metastable alkylperoxoiron(III) species derived from the r eactions of 1-4 with tert-butyl hydroperoxide. These intermediates ser ve as models for low-spin and high-spin peroxoiron(III) species in the reaction cycles of the antitumor drug bleomycin and lipoxygenase, res pectively. Similar principles apply in the design of nonheme diiron(II ) complexes that reversibly bind dioxygen and of high-valent bis(mu-ox o)diiron complexes that model the high-valent intermediates in the red ox cycles of nonheme diiron enzymes such as methane monooxygenase and ribonucleotide reductase.