title: Oxoiron(IV) Tetramethylcyclam Complexes with Axial Carboxylate Ligands: Effect of Tethering the Carboxylate on Reactivity.
abstract: Oxoiron(IV) species are implicated as reactive intermediates in nonheme monoiron oxygenases, often acting as the agent for hydrogen-atom transfer from substrate. A histidine is the most likely ligand trans to the oxo unit in most enzymes characterized thus far but is replaced by a carboxylate in the case of isopenicillin N synthase. As the effect of a trans carboxylate ligand on the properties of the oxoiron(IV) unit has not been systematically studied, we have synthesized and characterized four oxoiron(IV) complexes supported by the tetramethylcyclam (TMC) macrocycle and having a carboxylate ligand trans to the oxo unit. Two complexes have acetate or propionate axial ligands, while the other two have the carboxylate functionality tethered to the macrocyclic ligand framework by one or two methylene units. Interestingly, these four complexes exhibit substrate oxidation rates that differ by more than 100-fold, despite having Ep,cvalues for the reduction of the Fe═O unit that span a range of only 130 mV. Eyring parameters for 1,4-cyclohexadiene oxidation show that reactivity differences originate from differences in activation enthalpy between complexes with tethered carboxylates and those with untethered carboxylates, in agreement with computational results. As noted previously for the initial subset of four complexes, the logarithms of the oxygen atom transfer rates of 11 complexes of the FeIV(O)TMC(X) series increase linearly with the observed Ep,cvalues, reflecting the electrophilicity of the Fe═O unit. In contrast, no correlation with Ep,cvalues is observed for the corresponding hydrogen atom transfer (HAT) reaction rates; instead, the HAT rates increase as the computed triplet-quintet spin state gap narrows, consistent with Shaik's two-state-reactivity model. In fact, the two complexes with untethered carboxylates are among the most reactive HAT agents in this series, demonstrating that the axial ligand can play a key role in tuning the HAT reactivity in a nonheme iron enzyme active site.
authors.affiliation: Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Jennifer O
authors.initials: JO
authors.lastname: Bigelow
authors.affiliation: Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: England
authors.affiliation: Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Johannes E M N
authors.initials: JE
authors.lastname: Klein
authors.affiliation: Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Farquhar
authors.affiliation: Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Frisch
authors.affiliation: Department of Chemistry, Carnegie Mellon University , Pittsburgh, Pennsylvania 15213, United States.
authors.forename: Marlène
authors.initials: M
authors.lastname: Martinho
authors.affiliation: Institute of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem , 91904 Jerusalem, Israel.
authors.forename: Debasish
authors.initials: D
authors.lastname: Mandal
authors.affiliation: Department of Chemistry, Carnegie Mellon University , Pittsburgh, Pennsylvania 15213, United States.
authors.forename: Eckard
authors.initials: E
authors.lastname: Münck
authors.affiliation: Institute of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem , 91904 Jerusalem, Israel.
authors.forename: Sason
authors.identifier: http://orcid.org/0000-0001-7643-9421
authors.initials: S
authors.lastname: Shaik
authors.affiliation: Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Lawrence
authors.identifier: http://orcid.org/0000-0002-0989-2813
authors.initials: L
authors.lastname: Que