Biomimetic Studies of Dioxygen Activation at Nonheme Iron Centers

Nature has designed enzymes that can activate dioxygen (O 2) at iron centers to unleash the oxidizing powers stored in O 2, which can be used for a wide array of physiologically important cellular functions including biosynthesis, bioremediation and catabolism. Reactive oxoiron intermediates are often generated as the active species from O2 activation at nonheme iron centers to initiate selective and efficient substrate oxidation while other undesirable consequences of O2 activation are avoided in enzymatic cycles. My thesis is focused on biomimetic studies of dioxygen activation at nonheme iron centers to better understand the mechanisms and regulation of nonheme-iron-promoted dioxygen activation. An unprecedented near-quantitative formation of a mononuclear oxoiron(IV) intermediate from its Fe(II) precursor and stoichiometric H 2O2 is reported here. This novel result, coupled with an in-depth kinetic analysis, establishes unequivocally a direct reaction between our iron(II) complex and H2O 2 that results in heterolytic cleavage of the O-O bond. This process is facilitated by a base catalyst, which helps to shuttle a proton from the proximal oxygen to the distal oxygen. The study of a simple synthetic model complex demonstrates the feasibility of heterolytic O-O bond cleavage at nonheme iron(II) centers, and provides a nice illustration of a solution used by Nature to ensure the high-yield formation of oxoiron(IV) species while avoiding the generation of damaging hydroxyl radicals from O-O bond cleavage. A previously proposed but undetected FeIII-OOH intermediate supported by tetramethylcyclam ligand was generated by protonating its conjugate base and characterized in detail by various spectroscopic methods. This FeIII -OOH species converts quantitatively to an FeIV=O complex via O-O bond cleavage, which represents the first well-documented example of such a conversion. This conversion is promoted by two factors: the strong FeIII-OOH bond that inhibits Fe-O bond lysis and the addition of protons that facilitates O-O bond cleavage. This example provides a synthetic precedent for O-O bond cleavage of high-spin nonheme iron(III)-peroxo intermediates, and also lends credence to the involvement of a FeIII-OOH intermediate during O2 activation. While protons play a critical role during the O-O bond cleavage in last two aspects of work presented in this thesis, we also found that Lewis acids such as Sc3+ can replace H+ to promote O2 activation at ferrous centers supported by a series of cyclam-based ligands. Interestingly, a scandium-bound peroxo intermediate was accessed and characterized. This intermediate can then decay into a high-valent FeIV=O intermediate via O-O bond lysis, substantiating our proposed mechanism in which Sc 3+ can replace H+ to promote the O-O bond cleavage step during O2 activation. The last aspect of my research focuses on synthetic dinuclear iron(II)iron(III) and iron(II)manganese(II) clusters for dioxygen activation, the analogs of which were recently discovered in the active sites of somes enzymes. These centers deviate from the well established nonheme diiron active sites. Novel dinuclear iron(II)iron(III) and iron(II)manganese(II) complexes supported by a dinucleating ligand have been synthesized and spectroscopically characterized. A new protocol has been developed to better understand the EPR/Mossbauer data and electronic structures of diiron(II,III) complexes. The reactivity of a mangananese(II)iron(II) complex towards dioxygen was also discovered; an oxygenated intermediate was generated and characterized. This work can provide structural and/or mechanistic insights into the less well-known O2-activating iron(II)iron(III) and iron(II)manganese(II) clusters in enzymes.