Carbon Dioxide: A Waste Product in the Catalytic Cycle of α-Ketoglutarate Dependent Halogenases Prevents the Formation of Hydroxylated By-Products

We present the first density functional theory study on α-ketoglutarate dependent halogenases and focus on the mechanism starting from the iron(IV)-oxo species. The studies show that the high-valent iron(IV)-oxo species reacts with substrates via an initial and rate determining hydrogen abstraction that is characterized by a large kinetic isotope effect (KIE) of 26.7 leading to a radical intermediate. This KIE value is in good agreement with experimental data. The reaction proceeds via two-state reactivity patterns on competing quintet and septet spin state surfaces with close lying hydrogen abstraction barriers. However, the septet spin radical intermediate gives very high barriers for hydroxylation and chlorination whereas the barriers on the quintet spin state surface are much lower. The calculations give extra information regarding the nature of the intermediates and a prediction of a new low-energy mechanism starting from the radical intermediate, whereby a waste product from an earlier step in the catalytic cycle (CO2) is recycled and takes the hydroxyl radical away to form bicarbonate via an OH trapping mechanism. As a consequence, this mechanism prevents the occurrence of hydroxylated byproduct and gives a rationale for the sole observance of halogenated products. By contrast, a direct halogenation reaction cannot compete with hydroxylation due to higher reaction barriers. Our findings support experimental work in the field and give a rationale for the lack of hydroxylation products in α-ketoglutarate dependent halogenases

Synthesis, Characterization, and Spectroscopic Studies of 2,6-Dimethylpyridyl-Linked Cu(I)–CNC Complexes: The Electronic Influence of Aryl Wingtips on Copper Centers

Six new Cu(I) complexes containing pincer ligands of the type 2,6-bis(3-alkyl/arylimidazol-2-ylidene) methylpyridine I(R/R′Ar) ĈN̂C, where R = trifluoroethyl (TFE) and R′ = 4-CF3, 4-NO2, 4-CN, 4-H, and 4-CH3, have been synthesized. These complexes, namely, [Cu(I(TFE)ĈN̂C)]PF6, 1-TFE; [Cu(ICF3Ar ĈN̂C]PF6, 2-CF3; [Cu(INO2Ar ĈN̂C)]PF6, 3-NO2; [Cu(ICNAr ĈN̂C]PF6, 4-CN; [Cu(IHAr ĈN̂C)]2(PF6)2, 5-H; and [Cu(ICH3Ar ĈN̂C)]2(PF6)2, 6-CH3, were fully characterized by 1H, 13C, and HMBC NMR spectroscopy, elemental analysis, electrochemical studies, and single-crystal X-ray crystallography. The crystallographic data revealed different structures and copper nuclearities for the complexes bearing aryl wingtips with electron-withdrawing (2-CF3, 3-NO2, and 4-CN) and electron-donating (5-H and 6-CH3) substituents. The solution-phase conductivity measurements in acetonitrile revealed a mix-electrolyte behavior for these complexes, supporting the presence of both mono- and binuclear forms of each complex. The fast monomer–dimer equilibrium of the Cu–CNC complexes at room temperature is reflected in their simple 1H NMR spectra in acetonitrile. However, both mono- and binuclear forms were identifiable in 1H diffusion-ordered spectroscopy (DOSY) at low temperatures. The dynamic behavior of these complexes in solution was further examined by variable-temperature 1H NMR (VT 1H NMR) experiments, and the relevant thermodynamic parameters were determined. The process was also probed by one-dimensional rotating-frame Overhauser enhancement spectroscopy (1D ROESY) experiments to elucidate the coexisting species in solution. The 2,6-dimethylpyridyl-linked Cu–CNC complexes also presented a quasi-reversible Cu(II)/Cu(I) couple in cyclic voltammetry studies, wherein a clear influence of the aryl wingtips on the E1/2 values was observed. Furthermore, the percent buried volumes (% Vbur) of the complexes were calculated, showing a similar steric hindrance around copper in all complexes. These findings support the importance of electronic effects, induced by the aryl wingtips, on the preferred coordination geometry, copper nuclearity, and redox properties of the Cu–CNC complexes

Cu(I) Complexes of Pincer Pyridine-Based N‑Heterocyclic Carbenes with Small Wingtip Substituents: Synthesis and Structural and Spectroscopic Studies

Six new Cu­(I) complexes with pincer N-heterocyclic carbene (NHC) ligands of the type 2,6-bis­(3-alkylimidazol-2-ylidene)­pyridine, I­(R)^CNC, and 2,6-bis­(3-alkylimidazol-2-ylidene)­methylpyridine, I­(R)^{C^N^C}, where R = Me, Et, and ⁱPr have been synthesized using Cu precursors and bis­(imidazolium) salts. All of these compounds, namely, [Cu₂(IMe^CNC)₂]­(PF₆)₂, <b>1</b>; [Cu₂(IEt^CNC)₂]­(PF₆)₂, <b>2</b>; [Cu₂(IⁱPr^CNC)₂]­(PF₆)₂, <b>3</b>; [Cu­(IMe^{C^N^C})]­(PF₆), <b>4</b>; [Cu­(IEt^{C^N^C})]­(PF₆), <b>5</b>; and [Cu­(IⁱPr^{C^N^C})]­(PF₆), <b>6</b>, have been characterized by ¹H and ¹³C NMR spectroscopies, elemental analysis, solution conductivity, and electrochemical studies. Single crystal X-ray structures were obtained for all complexes except <b>1</b>. The crystallographic data reveal a binuclear structure containing two Cu atoms at a close distance, 2.622–2.811 Å for all the complexes except <b>5</b>, which shows a unique mononuclear structure. Spatial syn arrangement of ethyl groups and extensive π–π stacking in the solid state accounts for the mononuclear structure of complex <b>5</b>. A pseudolinear coordination geometry about metal centers consisting of two Cu–carbene bonds, as well as weak Cu–pyridine interactions, exist among all the complexes independent of their ligand. Solution-state conductivity data reveal a dominant 1:2 electrolyte behavior for <b>1</b>–<b>3</b> but 1:1 electrolyte for <b>4</b>–<b>6</b>, consistent with the sustainable binuclear structure in solutions of Cu­(I)–I­(R)^CNC complexes. Cyclic voltammetry and differential pulse voltammetry studies reveal an irreversible and two quasi-reversible peaks for the one-electron oxidation of solvent-bound and solvent-free binuclear and mononuclear Cu-NHC species in complexes <b>1</b>–<b>3</b>. In contrast, the reversible Cu­(II)/Cu­(I) couples of <b>4</b>–<b>6</b> at potentials close to that of complexes with tripodal polydentate NHC scaffolds indicate the electronic and structural flexibility of I­(R)^{C^N^C} ligands to accommodate both Cu­(I) and Cu­(II) ions

Cu(I) Complexes of Pincer Pyridine-Based N‑Heterocyclic Carbenes with Small Wingtip Substituents: Synthesis and Structural and Spectroscopic Studies

Six new Cu­(I) complexes with pincer N-heterocyclic carbene (NHC) ligands of the type 2,6-bis­(3-alkylimidazol-2-ylidene)­pyridine, I­(R)^CNC, and 2,6-bis­(3-alkylimidazol-2-ylidene)­methylpyridine, I­(R)^{C^N^C}, where R = Me, Et, and ⁱPr have been synthesized using Cu precursors and bis­(imidazolium) salts. All of these compounds, namely, [Cu₂(IMe^CNC)₂]­(PF₆)₂, <b>1</b>; [Cu₂(IEt^CNC)₂]­(PF₆)₂, <b>2</b>; [Cu₂(IⁱPr^CNC)₂]­(PF₆)₂, <b>3</b>; [Cu­(IMe^{C^N^C})]­(PF₆), <b>4</b>; [Cu­(IEt^{C^N^C})]­(PF₆), <b>5</b>; and [Cu­(IⁱPr^{C^N^C})]­(PF₆), <b>6</b>, have been characterized by ¹H and ¹³C NMR spectroscopies, elemental analysis, solution conductivity, and electrochemical studies. Single crystal X-ray structures were obtained for all complexes except <b>1</b>. The crystallographic data reveal a binuclear structure containing two Cu atoms at a close distance, 2.622–2.811 Å for all the complexes except <b>5</b>, which shows a unique mononuclear structure. Spatial syn arrangement of ethyl groups and extensive π–π stacking in the solid state accounts for the mononuclear structure of complex <b>5</b>. A pseudolinear coordination geometry about metal centers consisting of two Cu–carbene bonds, as well as weak Cu–pyridine interactions, exist among all the complexes independent of their ligand. Solution-state conductivity data reveal a dominant 1:2 electrolyte behavior for <b>1</b>–<b>3</b> but 1:1 electrolyte for <b>4</b>–<b>6</b>, consistent with the sustainable binuclear structure in solutions of Cu­(I)–I­(R)^CNC complexes. Cyclic voltammetry and differential pulse voltammetry studies reveal an irreversible and two quasi-reversible peaks for the one-electron oxidation of solvent-bound and solvent-free binuclear and mononuclear Cu-NHC species in complexes <b>1</b>–<b>3</b>. In contrast, the reversible Cu­(II)/Cu­(I) couples of <b>4</b>–<b>6</b> at potentials close to that of complexes with tripodal polydentate NHC scaffolds indicate the electronic and structural flexibility of I­(R)^{C^N^C} ligands to accommodate both Cu­(I) and Cu­(II) ions

Cu(I) Complexes of Pincer Pyridine-Based N‑Heterocyclic Carbenes with Small Wingtip Substituents: Synthesis and Structural and Spectroscopic Studies

Six new Cu­(I) complexes with pincer N-heterocyclic carbene (NHC) ligands of the type 2,6-bis­(3-alkylimidazol-2-ylidene)­pyridine, I­(R)^CNC, and 2,6-bis­(3-alkylimidazol-2-ylidene)­methylpyridine, I­(R)^{C^N^C}, where R = Me, Et, and ⁱPr have been synthesized using Cu precursors and bis­(imidazolium) salts. All of these compounds, namely, [Cu₂(IMe^CNC)₂]­(PF₆)₂, <b>1</b>; [Cu₂(IEt^CNC)₂]­(PF₆)₂, <b>2</b>; [Cu₂(IⁱPr^CNC)₂]­(PF₆)₂, <b>3</b>; [Cu­(IMe^{C^N^C})]­(PF₆), <b>4</b>; [Cu­(IEt^{C^N^C})]­(PF₆), <b>5</b>; and [Cu­(IⁱPr^{C^N^C})]­(PF₆), <b>6</b>, have been characterized by ¹H and ¹³C NMR spectroscopies, elemental analysis, solution conductivity, and electrochemical studies. Single crystal X-ray structures were obtained for all complexes except <b>1</b>. The crystallographic data reveal a binuclear structure containing two Cu atoms at a close distance, 2.622–2.811 Å for all the complexes except <b>5</b>, which shows a unique mononuclear structure. Spatial syn arrangement of ethyl groups and extensive π–π stacking in the solid state accounts for the mononuclear structure of complex <b>5</b>. A pseudolinear coordination geometry about metal centers consisting of two Cu–carbene bonds, as well as weak Cu–pyridine interactions, exist among all the complexes independent of their ligand. Solution-state conductivity data reveal a dominant 1:2 electrolyte behavior for <b>1</b>–<b>3</b> but 1:1 electrolyte for <b>4</b>–<b>6</b>, consistent with the sustainable binuclear structure in solutions of Cu­(I)–I­(R)^CNC complexes. Cyclic voltammetry and differential pulse voltammetry studies reveal an irreversible and two quasi-reversible peaks for the one-electron oxidation of solvent-bound and solvent-free binuclear and mononuclear Cu-NHC species in complexes <b>1</b>–<b>3</b>. In contrast, the reversible Cu­(II)/Cu­(I) couples of <b>4</b>–<b>6</b> at potentials close to that of complexes with tripodal polydentate NHC scaffolds indicate the electronic and structural flexibility of I­(R)^{C^N^C} ligands to accommodate both Cu­(I) and Cu­(II) ions

Cu(I) Complexes of Pincer Pyridine-Based N‑Heterocyclic Carbenes with Small Wingtip Substituents: Synthesis and Structural and Spectroscopic Studies

Six new Cu­(I) complexes with pincer N-heterocyclic carbene (NHC) ligands of the type 2,6-bis­(3-alkylimidazol-2-ylidene)­pyridine, I­(R)^CNC, and 2,6-bis­(3-alkylimidazol-2-ylidene)­methylpyridine, I­(R)^{C^N^C}, where R = Me, Et, and ⁱPr have been synthesized using Cu precursors and bis­(imidazolium) salts. All of these compounds, namely, [Cu₂(IMe^CNC)₂]­(PF₆)₂, <b>1</b>; [Cu₂(IEt^CNC)₂]­(PF₆)₂, <b>2</b>; [Cu₂(IⁱPr^CNC)₂]­(PF₆)₂, <b>3</b>; [Cu­(IMe^{C^N^C})]­(PF₆), <b>4</b>; [Cu­(IEt^{C^N^C})]­(PF₆), <b>5</b>; and [Cu­(IⁱPr^{C^N^C})]­(PF₆), <b>6</b>, have been characterized by ¹H and ¹³C NMR spectroscopies, elemental analysis, solution conductivity, and electrochemical studies. Single crystal X-ray structures were obtained for all complexes except <b>1</b>. The crystallographic data reveal a binuclear structure containing two Cu atoms at a close distance, 2.622–2.811 Å for all the complexes except <b>5</b>, which shows a unique mononuclear structure. Spatial syn arrangement of ethyl groups and extensive π–π stacking in the solid state accounts for the mononuclear structure of complex <b>5</b>. A pseudolinear coordination geometry about metal centers consisting of two Cu–carbene bonds, as well as weak Cu–pyridine interactions, exist among all the complexes independent of their ligand. Solution-state conductivity data reveal a dominant 1:2 electrolyte behavior for <b>1</b>–<b>3</b> but 1:1 electrolyte for <b>4</b>–<b>6</b>, consistent with the sustainable binuclear structure in solutions of Cu­(I)–I­(R)^CNC complexes. Cyclic voltammetry and differential pulse voltammetry studies reveal an irreversible and two quasi-reversible peaks for the one-electron oxidation of solvent-bound and solvent-free binuclear and mononuclear Cu-NHC species in complexes <b>1</b>–<b>3</b>. In contrast, the reversible Cu­(II)/Cu­(I) couples of <b>4</b>–<b>6</b> at potentials close to that of complexes with tripodal polydentate NHC scaffolds indicate the electronic and structural flexibility of I­(R)^{C^N^C} ligands to accommodate both Cu­(I) and Cu­(II) ions

Cu(I) Complexes of Pincer Pyridine-Based N‑Heterocyclic Carbenes with Small Wingtip Substituents: Synthesis and Structural and Spectroscopic Studies

Six new Cu­(I) complexes with pincer N-heterocyclic carbene (NHC) ligands of the type 2,6-bis­(3-alkylimidazol-2-ylidene)­pyridine, I­(R)^CNC, and 2,6-bis­(3-alkylimidazol-2-ylidene)­methylpyridine, I­(R)^{C^N^C}, where R = Me, Et, and ⁱPr have been synthesized using Cu precursors and bis­(imidazolium) salts. All of these compounds, namely, [Cu₂(IMe^CNC)₂]­(PF₆)₂, <b>1</b>; [Cu₂(IEt^CNC)₂]­(PF₆)₂, <b>2</b>; [Cu₂(IⁱPr^CNC)₂]­(PF₆)₂, <b>3</b>; [Cu­(IMe^{C^N^C})]­(PF₆), <b>4</b>; [Cu­(IEt^{C^N^C})]­(PF₆), <b>5</b>; and [Cu­(IⁱPr^{C^N^C})]­(PF₆), <b>6</b>, have been characterized by ¹H and ¹³C NMR spectroscopies, elemental analysis, solution conductivity, and electrochemical studies. Single crystal X-ray structures were obtained for all complexes except <b>1</b>. The crystallographic data reveal a binuclear structure containing two Cu atoms at a close distance, 2.622–2.811 Å for all the complexes except <b>5</b>, which shows a unique mononuclear structure. Spatial syn arrangement of ethyl groups and extensive π–π stacking in the solid state accounts for the mononuclear structure of complex <b>5</b>. A pseudolinear coordination geometry about metal centers consisting of two Cu–carbene bonds, as well as weak Cu–pyridine interactions, exist among all the complexes independent of their ligand. Solution-state conductivity data reveal a dominant 1:2 electrolyte behavior for <b>1</b>–<b>3</b> but 1:1 electrolyte for <b>4</b>–<b>6</b>, consistent with the sustainable binuclear structure in solutions of Cu­(I)–I­(R)^CNC complexes. Cyclic voltammetry and differential pulse voltammetry studies reveal an irreversible and two quasi-reversible peaks for the one-electron oxidation of solvent-bound and solvent-free binuclear and mononuclear Cu-NHC species in complexes <b>1</b>–<b>3</b>. In contrast, the reversible Cu­(II)/Cu­(I) couples of <b>4</b>–<b>6</b> at potentials close to that of complexes with tripodal polydentate NHC scaffolds indicate the electronic and structural flexibility of I­(R)^{C^N^C} ligands to accommodate both Cu­(I) and Cu­(II) ions

Valence Tautomerism in a High-Valent Manganese–Oxo Porphyrinoid Complex Induced by a Lewis Acid

Addition of the Lewis acid Zn2+ to (TBP8Cz)­MnV(O) induces valence tautomerization, resulting in the formation of [(TBP8Cz+•)­MnIV(O)–Zn2+]. This new species was characterized by UV–vis, EPR, the Evans method, and 1H NMR and supported by DFT calculations. Removal of Zn2+ quantitatively restores the starting material. Electron-transfer and hydrogen-atom-transfer reactions are strongly influenced by the presence of Zn2+

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