Oxoiron(IV) Tetramethylcyclam Complexes with Axial Carboxylate Ligands: Effect of Tethering the Carboxylate on Reactivity

Jennifer O. Bigelow, Jason England, Johannes E.M.N. Klein, Erik R. Farquhar, Jonathan R. Frisch, Marlène Martinho, Debasish Mandal, Eckard Münck, Sason Shaik, Lawrence Que

Research output: Contribution to journalArticle

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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,c values 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,c values, reflecting the electrophilicity of the FeO unit. In contrast, no correlation with Ep,c values 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.

Original languageEnglish (US)
Pages (from-to)3287-3301
Number of pages15
JournalInorganic Chemistry
Volume56
Issue number6
DOIs
StatePublished - Mar 20 2017

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tethering
carboxylates
reactivity
Hydrogen
Ligands
Atoms
ligands
hydrogen atoms
enzymes
Oxidation
Oxygenases
Propionates
Substrates
Enzymes
oxidation
histidine
Histidine
Reaction rates
logarithms
Enthalpy

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Oxoiron(IV) Tetramethylcyclam Complexes with Axial Carboxylate Ligands : Effect of Tethering the Carboxylate on Reactivity. / Bigelow, Jennifer O.; England, Jason; Klein, Johannes E.M.N.; Farquhar, Erik R.; Frisch, Jonathan R.; Martinho, Marlène; Mandal, Debasish; Münck, Eckard; Shaik, Sason; Que, Lawrence.

In: Inorganic Chemistry, Vol. 56, No. 6, 20.03.2017, p. 3287-3301.

Research output: Contribution to journalArticle

Bigelow, JO, England, J, Klein, JEMN, Farquhar, ER, Frisch, JR, Martinho, M, Mandal, D, Münck, E, Shaik, S & Que, L 2017, 'Oxoiron(IV) Tetramethylcyclam Complexes with Axial Carboxylate Ligands: Effect of Tethering the Carboxylate on Reactivity', Inorganic Chemistry, vol. 56, no. 6, pp. 3287-3301. https://doi.org/10.1021/acs.inorgchem.6b02659
Bigelow, Jennifer O. ; England, Jason ; Klein, Johannes E.M.N. ; Farquhar, Erik R. ; Frisch, Jonathan R. ; Martinho, Marlène ; Mandal, Debasish ; Münck, Eckard ; Shaik, Sason ; Que, Lawrence. / Oxoiron(IV) Tetramethylcyclam Complexes with Axial Carboxylate Ligands : Effect of Tethering the Carboxylate on Reactivity. In: Inorganic Chemistry. 2017 ; Vol. 56, No. 6. pp. 3287-3301.
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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,c values 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,c values, reflecting the electrophilicity of the FeO unit. In contrast, no correlation with Ep,c values 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.",
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T1 - Oxoiron(IV) Tetramethylcyclam Complexes with Axial Carboxylate Ligands

T2 - Effect of Tethering the Carboxylate on Reactivity

AU - Bigelow, Jennifer O.

AU - England, Jason

AU - Klein, Johannes E.M.N.

AU - Farquhar, Erik R.

AU - Frisch, Jonathan R.

AU - Martinho, Marlène

AU - Mandal, Debasish

AU - Münck, Eckard

AU - Shaik, Sason

AU - Que, Lawrence

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N2 - 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,c values 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,c values, reflecting the electrophilicity of the FeO unit. In contrast, no correlation with Ep,c values 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.

AB - 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,c values 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,c values, reflecting the electrophilicity of the FeO unit. In contrast, no correlation with Ep,c values 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.

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