Substrate Sulfoxidation by an Iron(IV)-Oxo Complex: Benchmarking Computationally Calculated Barrier Heights to Experiment

High-valent metal-oxo oxidants are common reactive species in synthetic catalysts as well as heme and nonheme iron enzymes. In general, they efficiently react with substrates through oxygen atom transfer, and for a number of cases, experimental rate constants have been determined. However, because these rate constants are generally measured in a polar solution, it has been found difficult to find computational methodologies to reproduce experimental trends and reactivities. In this work, we present a detailed computational study into para-substituted thioanisole sulfoxidation by a nonheme iron­(IV)-oxo complex. A range of density functional theory methods and basis sets has been tested for their suitability to describe the reaction mechanism and compared with experimentally obtained free energies of activation. It is found that the enthalpy of activation is reproduced well, but all methods overestimate the entropy of activation by about 50%, for which we recommend a correction factor. The effect of solvent and dispersion on the barrier heights is explored both at the single-point level and also through inclusion in geometry optimizations, and particularly, solvent is seen as highly beneficial to reproduce experimental free energies of activation. Interestingly, in general, experimental trends and Hammett plots are reproduced well with almost all methods and procedures, and only a systematic error seems to apply for these chemical systems. Very good agreement between experiment and theory is found for a number of different methods, including B3LYP and PBE0, and procedures that are highlighted in the paper

Mechanism of S-Oxygenation by a Cysteine Dioxygenase Model Complex

In this work, we present the first computational study on a biomimetic cysteine dioxygenase model complex, [Fe^II(LN₃S)]⁺, in which LN₃S is a tetradentate ligand with a bis(imino)pyridyl scaffold and a pendant arylthiolate group. The reaction mechanism of sulfur dioxygenation with O₂ was examined by density functional theory (DFT) methods and compared with results obtained for cysteine dioxygenase. The reaction proceeds via multistate reactivity patterns on competing singlet, triplet, and quintet spin state surfaces. The reaction mechanism is analogous to that found for cysteine dioxygenase enzymes (Kumar, D.; Thiel, W.; de Visser, S. P. <i>J. Am. Chem. Soc.</i> <b>2011</b>, <i>133</i>, 3869–3882); hence, the computations indicate that this complex can closely mimic the enzymatic process. The catalytic mechanism starts from an iron(III)–superoxo complex and the attack of the terminal oxygen atom of the superoxo group on the sulfur atom of the ligand. Subsequently, the dioxygen bond breaks to form an iron(IV)–oxo complex with a bound sulfenato group. After reorganization, the second oxygen atom is transferred to the substrate to give a sulfinic acid product. An alternative mechanism involving the direct attack of dioxygen on the sulfur, without involving any iron–oxygen intermediates, was also examined. Importantly, a significant energetic preference for dioxygen coordinating to the iron center prior to attack at sulfur was discovered and serves to elucidate the function of the metal ion in the reaction process. The computational results are in good agreement with experimental observations, and the differences and similarities of the biomimetic complex and the enzymatic cysteine dioxygenase center are highlighted

Noticiero de Vigo : diario independiente de la mañana: Ano XXVIII Número 11530 - 1913 setembro 21

The generation of a new high-valent iron terminal imido complex prepared with a corrolazine macrocycle is reported. The reaction of [Fe^III(TBP₈Cz)] (TBP₈Cz = octakis­(4<i>-tert</i>-butylphenyl)­corrolazinato) with the commercially available chloramine-T (Na⁺TsNCl^–) leads to oxidative N-tosyl transfer to afford [Fe^IV(TBP₈Cz^+•)­(NTs)] in dichloromethane/acetonitrile at room temperature. This complex was characterized by UV–vis, Mössbauer (δ = −0.05 mm s^–1, Δ<i>E</i>_Q = 2.94 mm s^–1), and EPR (X-band (15 K), <i>g</i> = 2.10, 2.00) spectroscopies, and together with reactivity patterns and DFT calculations has been established as an iron­(IV) species antiferromagnetically coupled with a Cz-π-cation-radical (<i>S</i>_total = ¹/₂ ground state). Reactivity studies with triphenylphosphine as substrate show that [Fe^IV(TBP₈Cz^+•)­(NTs)] is an efficient NTs transfer agent, affording the phospharane product Ph₃PNTs under both stoichiometric and catalytic conditions. Kinetic analysis of this reaction supports a bimolecular NTs transfer mechanism with rate constant of 70(15) M^–1 s^–1. These data indicate that [Fe^IV(TBP₈Cz^+•)­(NTs)] reacts about 100 times faster than analogous Mn terminal arylimido corrole analogues. It was found that two products crystallize from the same reaction mixture of Fe^III(TBP₈Cz) + chloramine-T + PPh₃, [Fe^IV(TBP₈Cz)­(NPPh₃)] and [Fe^III(TBP₈Cz)­(OPPh₃)], which were definitively characterized by X-ray crystallography. The sequential production of Ph₃PNTs, Ph₃PNH, and Ph₃PO was observed by ³¹P NMR spectroscopy and led to a proposed mechanism that accounts for all of the observed products. The latter Fe^III complex was then rationally synthesized and structurally characterized from Fe^III(TBP₈Cz) and OPPh₃, providing an important benchmark compound for spectroscopic studies. A combination of Mössbauer and EPR spectroscopies led to the characterization of both intermediate spin (<i>S</i> = ³/₂) and low spin (<i>S</i> = ¹/₂) Fe^III corrolazines, as well as a formally Fe^IV corrolazine which may also be described by its valence tautomer Fe^III(Cz^+•)

Generation of a High-Valent Iron Imido Corrolazine Complex and NR Group Transfer Reactivity

The generation of a new high-valent iron terminal imido complex prepared with a corrolazine macrocycle is reported. The reaction of [Fe^III(TBP₈Cz)] (TBP₈Cz = octakis­(4<i>-tert</i>-butylphenyl)­corrolazinato) with the commercially available chloramine-T (Na⁺TsNCl^–) leads to oxidative N-tosyl transfer to afford [Fe^IV(TBP₈Cz^+•)­(NTs)] in dichloromethane/acetonitrile at room temperature. This complex was characterized by UV–vis, Mössbauer (δ = −0.05 mm s^–1, Δ<i>E</i>_Q = 2.94 mm s^–1), and EPR (X-band (15 K), <i>g</i> = 2.10, 2.00) spectroscopies, and together with reactivity patterns and DFT calculations has been established as an iron­(IV) species antiferromagnetically coupled with a Cz-π-cation-radical (<i>S</i>_total = ¹/₂ ground state). Reactivity studies with triphenylphosphine as substrate show that [Fe^IV(TBP₈Cz^+•)­(NTs)] is an efficient NTs transfer agent, affording the phospharane product Ph₃PNTs under both stoichiometric and catalytic conditions. Kinetic analysis of this reaction supports a bimolecular NTs transfer mechanism with rate constant of 70(15) M^–1 s^–1. These data indicate that [Fe^IV(TBP₈Cz^+•)­(NTs)] reacts about 100 times faster than analogous Mn terminal arylimido corrole analogues. It was found that two products crystallize from the same reaction mixture of Fe^III(TBP₈Cz) + chloramine-T + PPh₃, [Fe^IV(TBP₈Cz)­(NPPh₃)] and [Fe^III(TBP₈Cz)­(OPPh₃)], which were definitively characterized by X-ray crystallography. The sequential production of Ph₃PNTs, Ph₃PNH, and Ph₃PO was observed by ³¹P NMR spectroscopy and led to a proposed mechanism that accounts for all of the observed products. The latter Fe^III complex was then rationally synthesized and structurally characterized from Fe^III(TBP₈Cz) and OPPh₃, providing an important benchmark compound for spectroscopic studies. A combination of Mössbauer and EPR spectroscopies led to the characterization of both intermediate spin (<i>S</i> = ³/₂) and low spin (<i>S</i> = ¹/₂) Fe^III corrolazines, as well as a formally Fe^IV corrolazine which may also be described by its valence tautomer Fe^III(Cz^+•)

Generation of a High-Valent Iron Imido Corrolazine Complex and NR Group Transfer Reactivity

The generation of a new high-valent iron terminal imido complex prepared with a corrolazine macrocycle is reported. The reaction of [Fe^III(TBP₈Cz)] (TBP₈Cz = octakis­(4<i>-tert</i>-butylphenyl)­corrolazinato) with the commercially available chloramine-T (Na⁺TsNCl^–) leads to oxidative N-tosyl transfer to afford [Fe^IV(TBP₈Cz^+•)­(NTs)] in dichloromethane/acetonitrile at room temperature. This complex was characterized by UV–vis, Mössbauer (δ = −0.05 mm s^–1, Δ<i>E</i>_Q = 2.94 mm s^–1), and EPR (X-band (15 K), <i>g</i> = 2.10, 2.00) spectroscopies, and together with reactivity patterns and DFT calculations has been established as an iron­(IV) species antiferromagnetically coupled with a Cz-π-cation-radical (<i>S</i>_total = ¹/₂ ground state). Reactivity studies with triphenylphosphine as substrate show that [Fe^IV(TBP₈Cz^+•)­(NTs)] is an efficient NTs transfer agent, affording the phospharane product Ph₃PNTs under both stoichiometric and catalytic conditions. Kinetic analysis of this reaction supports a bimolecular NTs transfer mechanism with rate constant of 70(15) M^–1 s^–1. These data indicate that [Fe^IV(TBP₈Cz^+•)­(NTs)] reacts about 100 times faster than analogous Mn terminal arylimido corrole analogues. It was found that two products crystallize from the same reaction mixture of Fe^III(TBP₈Cz) + chloramine-T + PPh₃, [Fe^IV(TBP₈Cz)­(NPPh₃)] and [Fe^III(TBP₈Cz)­(OPPh₃)], which were definitively characterized by X-ray crystallography. The sequential production of Ph₃PNTs, Ph₃PNH, and Ph₃PO was observed by ³¹P NMR spectroscopy and led to a proposed mechanism that accounts for all of the observed products. The latter Fe^III complex was then rationally synthesized and structurally characterized from Fe^III(TBP₈Cz) and OPPh₃, providing an important benchmark compound for spectroscopic studies. A combination of Mössbauer and EPR spectroscopies led to the characterization of both intermediate spin (<i>S</i> = ³/₂) and low spin (<i>S</i> = ¹/₂) Fe^III corrolazines, as well as a formally Fe^IV corrolazine which may also be described by its valence tautomer Fe^III(Cz^+•)

Rationalization of the Barrier Height for <i>p</i>‑Z-styrene Epoxidation by Iron(IV)-Oxo Porphyrin Cation Radicals with Variable Axial Ligands

A versatile class of heme monoxygenases involved in many vital functions for human health are the cytochromes P450, which react via a high-valent iron­(IV) oxo heme cation radical species called Compound I. One of the key reactions catalyzed by these enzymes is CC epoxidation of substrates. We report here a systematic study into the intrinsic chemical properties of substrate and oxidant that affect reactivity patterns. To this end, we investigated the effect of styrene and para-substituted styrene epoxidation by Compound I models with either an anionic (chloride) or neutral (acetonitrile) axial ligand. We show, for the first time, that the activation enthalpy of the reaction is determined by the ionization potential of the substrate, the electron affinity of the oxidant, and the strength of the newly formed C–O bond (approximated by the bond dissociation energy, BDE_OH). We have set up a new valence bond model that enables us to generalize substrate epoxidation reactions by iron­(IV)-oxo porphyrin cation-radical oxidants and make predictions of rate constants and reactivities. We show here that electron-withdrawing substituents lead to early transition states, whereas electron-donating groups on the olefin substrate give late transition states. This affects the barrier heights in such a way that electron-withdrawing substituents correlate the barrier height with BDE_OH, while the electron affinity of the oxidant is proportional to the barrier height for substrates with electron-donating substituents

Synthesis and Ligand Non-Innocence of Thiolate-Ligated (N₄S) Iron(II) and Nickel(II) Bis(imino)pyridine Complexes

The known iron­(II) complex [Fe^II(LN₃S)­(OTf)] (<b>1</b>) was used as starting material to prepare the new biomimetic (N₄S­(thiolate)) iron­(II) complexes [Fe^II(LN₃S)­(py)]­(OTf) (<b>2</b>) and [Fe^II(LN₃S)­(DMAP)]­(OTf) (<b>3</b>), where LN₃S is a tetradentate bis­(imino)­pyridine (BIP) derivative with a covalently tethered phenylthiolate donor. These complexes were characterized by X-ray crystallography, ultraviolet–visible (UV-vis) spectroscopic analysis, ¹H nuclear magnetic resonance (NMR), and Mössbauer spectroscopy, as well as electrochemistry. A nickel­(II) analogue, [Ni^II(LN₃S)]­(BF₄) (<b>5</b>), was also synthesized and characterized by structural and spectroscopic methods. Cyclic voltammetric studies showed <b>1</b>–<b>3</b> and <b>5</b> undergo a single reduction process with <i>E</i>_1/2 between −0.9 V to −1.2 V versus Fc⁺/Fc. Treatment of <b>3</b> with 0.5% Na/Hg amalgam gave the monoreduced complex [Fe­(LN₃S)­(DMAP)]⁰ (<b>4</b>), which was characterized by X-ray crystallography, UV-vis spectroscopic analysis, electron paramagnetic resonance (EPR) spectroscopy (<i>g =</i> [2.155, 2.057, 2.038]), and Mössbauer (δ = 0.33 mm s^–1; Δ<i>E</i>_Q = 2.04 mm s^–1) spectroscopy. Computational methods (DFT) were employed to model complexes <b>3</b>–<b>5</b>. The combined experimental and computational studies show that <b>1</b>–<b>3</b> are 5-coordinate, high-spin (<i>S</i> = 2) Fe^II complexes, whereas <b>4</b> is best described as a 5-coordinate, intermediate-spin (<i>S</i> = 1) Fe^II complex antiferromagnetically coupled to a ligand radical. This unique electronic configuration leads to an overall doublet spin (<i>S</i>_total = 1/2) ground state. Complexes <b>2</b> and <b>3</b> are shown to react with O₂ to give S-oxygenated products, as previously reported for <b>1</b>. In contrast, the monoreduced <b>4</b> appears to react with O₂ to give a mixture of sulfur oxygenates and iron oxygenates. The nickel­(II) complex <b>5</b> does not react with O₂, and even when the monoreduced nickel complex is produced, it appears to undergo only outer-sphere oxidation with O₂

Secondary Coordination Sphere Influence on the Reactivity of Nonheme Iron(II) Complexes: An Experimental and DFT Approach

The new biomimetic ligands N4Py^2Ph (<b>1</b>) and N4Py^2Ph,amide (<b>2</b>) were synthesized and yield the iron­(II) complexes [Fe^II(N4Py^2Ph)­(NCCH₃)]­(BF₄)₂ (<b>3</b>) and [Fe^II(N4Py^2Ph,amide)]­(BF₄)₂ (<b>5</b>). Controlled orientation of the Ph substituents in <b>3</b> leads to facile triplet spin reactivity for a putative Fe^IV(O) intermediate, resulting in rapid arene hydroxylation. Addition of a peripheral amide substituent within hydrogen-bond distance of the iron first coordination sphere leads to stabilization of a high-spin Fe^IIIOOR species which decays without arene hydroxylation. These results provide new insights regarding the impact of secondary coordination sphere effects at nonheme iron centers

Synthesis and Ligand Non-Innocence of Thiolate-Ligated (N₄S) Iron(II) and Nickel(II) Bis(imino)pyridine Complexes

The known iron­(II) complex [Fe^II(LN₃S)­(OTf)] (<b>1</b>) was used as starting material to prepare the new biomimetic (N₄S­(thiolate)) iron­(II) complexes [Fe^II(LN₃S)­(py)]­(OTf) (<b>2</b>) and [Fe^II(LN₃S)­(DMAP)]­(OTf) (<b>3</b>), where LN₃S is a tetradentate bis­(imino)­pyridine (BIP) derivative with a covalently tethered phenylthiolate donor. These complexes were characterized by X-ray crystallography, ultraviolet–visible (UV-vis) spectroscopic analysis, ¹H nuclear magnetic resonance (NMR), and Mössbauer spectroscopy, as well as electrochemistry. A nickel­(II) analogue, [Ni^II(LN₃S)]­(BF₄) (<b>5</b>), was also synthesized and characterized by structural and spectroscopic methods. Cyclic voltammetric studies showed <b>1</b>–<b>3</b> and <b>5</b> undergo a single reduction process with <i>E</i>_1/2 between −0.9 V to −1.2 V versus Fc⁺/Fc. Treatment of <b>3</b> with 0.5% Na/Hg amalgam gave the monoreduced complex [Fe­(LN₃S)­(DMAP)]⁰ (<b>4</b>), which was characterized by X-ray crystallography, UV-vis spectroscopic analysis, electron paramagnetic resonance (EPR) spectroscopy (<i>g =</i> [2.155, 2.057, 2.038]), and Mössbauer (δ = 0.33 mm s^–1; Δ<i>E</i>_Q = 2.04 mm s^–1) spectroscopy. Computational methods (DFT) were employed to model complexes <b>3</b>–<b>5</b>. The combined experimental and computational studies show that <b>1</b>–<b>3</b> are 5-coordinate, high-spin (<i>S</i> = 2) Fe^II complexes, whereas <b>4</b> is best described as a 5-coordinate, intermediate-spin (<i>S</i> = 1) Fe^II complex antiferromagnetically coupled to a ligand radical. This unique electronic configuration leads to an overall doublet spin (<i>S</i>_total = 1/2) ground state. Complexes <b>2</b> and <b>3</b> are shown to react with O₂ to give S-oxygenated products, as previously reported for <b>1</b>. In contrast, the monoreduced <b>4</b> appears to react with O₂ to give a mixture of sulfur oxygenates and iron oxygenates. The nickel­(II) complex <b>5</b> does not react with O₂, and even when the monoreduced nickel complex is produced, it appears to undergo only outer-sphere oxidation with O₂

Synthesis and Ligand Non-Innocence of Thiolate-Ligated (N₄S) Iron(II) and Nickel(II) Bis(imino)pyridine Complexes

The known iron­(II) complex [Fe^II(LN₃S)­(OTf)] (<b>1</b>) was used as starting material to prepare the new biomimetic (N₄S­(thiolate)) iron­(II) complexes [Fe^II(LN₃S)­(py)]­(OTf) (<b>2</b>) and [Fe^II(LN₃S)­(DMAP)]­(OTf) (<b>3</b>), where LN₃S is a tetradentate bis­(imino)­pyridine (BIP) derivative with a covalently tethered phenylthiolate donor. These complexes were characterized by X-ray crystallography, ultraviolet–visible (UV-vis) spectroscopic analysis, ¹H nuclear magnetic resonance (NMR), and Mössbauer spectroscopy, as well as electrochemistry. A nickel­(II) analogue, [Ni^II(LN₃S)]­(BF₄) (<b>5</b>), was also synthesized and characterized by structural and spectroscopic methods. Cyclic voltammetric studies showed <b>1</b>–<b>3</b> and <b>5</b> undergo a single reduction process with <i>E</i>_1/2 between −0.9 V to −1.2 V versus Fc⁺/Fc. Treatment of <b>3</b> with 0.5% Na/Hg amalgam gave the monoreduced complex [Fe­(LN₃S)­(DMAP)]⁰ (<b>4</b>), which was characterized by X-ray crystallography, UV-vis spectroscopic analysis, electron paramagnetic resonance (EPR) spectroscopy (<i>g =</i> [2.155, 2.057, 2.038]), and Mössbauer (δ = 0.33 mm s^–1; Δ<i>E</i>_Q = 2.04 mm s^–1) spectroscopy. Computational methods (DFT) were employed to model complexes <b>3</b>–<b>5</b>. The combined experimental and computational studies show that <b>1</b>–<b>3</b> are 5-coordinate, high-spin (<i>S</i> = 2) Fe^II complexes, whereas <b>4</b> is best described as a 5-coordinate, intermediate-spin (<i>S</i> = 1) Fe^II complex antiferromagnetically coupled to a ligand radical. This unique electronic configuration leads to an overall doublet spin (<i>S</i>_total = 1/2) ground state. Complexes <b>2</b> and <b>3</b> are shown to react with O₂ to give S-oxygenated products, as previously reported for <b>1</b>. In contrast, the monoreduced <b>4</b> appears to react with O₂ to give a mixture of sulfur oxygenates and iron oxygenates. The nickel­(II) complex <b>5</b> does not react with O₂, and even when the monoreduced nickel complex is produced, it appears to undergo only outer-sphere oxidation with O₂