Intramolecular Charge Transfer and Biomimetic Reaction Kinetics in Galactose Oxidase Model Complexes

One-electron oxidation of two structurally similar CuII−diphenolate complexes, 1 and 2, creates EPR-silent CuII−phenoxyl complexes [1]+ and [2]+ that mimic the oxidized form of the enzyme galactose oxidase (GOase). Both model complexes display novel NIR absorptions assigned to phenolate−phenoxyl charge transfer that resemble a tyrosinate−tyrosyl charge-transfer band observed in the enzymatic system. [1]+ and [2]+ react with benzyl alcohol to form 0.5 equivs of benzaldehyde per complex; biomimetic reduction to CuI−phenol complexes is not observed, but such species may exist transiently. Initial kinetic studies show that [2]+ reacts faster with benzyl alcohol than does [1]+, despite being a significantly weaker oxidant (ΔE° = 370 mV). This acceleration is ascribed to mechanistic differences:  [2]+ appears to bind substrate prior to the rate-determining step. Large, nonclassical kinetic isotope effects confirm C−H bond cleavage as the rate-determining step in the reactions of both [1]+ and [2]+ with benzyl alcohol, as is the case for GOase

Covalent Heterogenization of a Discrete Mn(II) Bis-Phen Complex by a Metal-Template/Metal-Exchange Method: An Epoxidation Catalyst with Enhanced Reactivity

Considerable attention has been devoted to the immobilization of discrete epoxidation catalysts onto solid supports due to the possible benefits of site isolation such as increased catalyst stability, catalyst recycling, and product separation. A synthetic metal-template/metal-exchange method to imprint a covalently attached bis-1,10-phenanthroline coordination environment onto high-surface area, mesoporous SBA-15 silica is reported herein along with the epoxidation reactivity once reloaded with manganese. Comparisons of this imprinted material with material synthesized by random grafting of the ligand show that the template method creates more reproducible, solution-like bis-1,10-phenanthroline coordination at a variety of ligand loadings. Olefin epoxidation with peracetic acid shows the imprinted manganese catalysts have improved product selectivity for epoxides, greater substrate scope, more efficient use of oxidant, and higher reactivity than their homogeneous or grafted analogues independent of ligand loading. The randomly grafted manganese catalysts, however, show reactivity that varies with ligand loading while the homogeneous analogue degrades trisubstituted olefins and produces trans-epoxide products from cis-olefins. Efficient recycling behavior of the templated catalysts is also possible

Hydrogen Atom Abstraction by a Mononuclear Ferric Hydroxide Complex: Insights into the Reactivity of Lipoxygenase

The lipoxygenase mimic [FeIII(PY5)(OH)](CF3SO3)2 is synthesized from the reaction of [FeII(PY5)(MeCN)](CF3SO3)2 with iodosobenzene, with low-temperature studies suggesting the possible intermediacy of an Fe(IV) oxo species. The Fe(III)−OH complex is isolated and identified by a combination of solution and solid-state methods, including EPR and IR spectroscopy. [FeIII(PY5)(OH)]2+ reacts with weak X−H bonds in a manner consistent with hydrogen-atom abstraction. The composition of this complex allows meaningful comparisons to be made with previously reported Mn(III)−OH and Fe(III)−OMe lipoxygenase mimics. The bond dissociation energy (BDE) of the O−H bond formed upon reduction to [FeII(PY5)(H2O)]2+ is estimated to be 80 kcal mol-1, 2 kcal mol-1 lower than that in the structurally analogous [MnII(PY5)(H2O)]2+ complex, supporting the generally accepted idea that Mn(III) is the thermodynamically superior oxidant at parity of coordination sphere. The identity of the metal has a large influence on the entropy of activation for the reaction with 9,10-dihydroanthracene; [MnIII(PY5)(OH)]2+ has a 10 eu more negative ΔS⧧ value than either [FeIII(PY5)(OH)]2+ or [FeIII(PY5)(OMe)]2+, presumably because of the increased structural reorganization that occurs upon reduction to [MnII(PY5)(H2O)]2+. The greater enthalpic driving force for the reduction of Mn(III) correlates with [MnIII(PY5)(OH)]2+ reacting more quickly than [FeIII(PY5)(OH)]2+. Curiously, [FeIII(PY5)(OMe)]2+ reacts with substrates only about twice as fast as [FeIII(PY5)(OH)]2+, despite a 4 kcal mol-1 greater enthalpic driving force for the methoxide complex

Mechanistic Insights from Reactions between Copper(II)−Phenoxyl Complexes and Substrates with Activated C−H Bonds

The reactivities of two copper(II)−phenoxyl analogues of the oxidized, active form of the metalloenzyme galactose oxidase, [1tBu2]+ and [2tBu2]+, have been studied using the substrates benzyl alcohol and 9,10-dihydroanthracene, for a total of four reactions. The reaction stoichiometries in all cases show a 2:1 ratio of oxidant to benzaldehyde or anthracene product, indicating that [1tBu2]+ and [2tBu2]+ behave ultimately as only one-electron oxidants, but the reaction kinetics each indicate that only a single copper(II)−phenoxyl complex is involved in the rate-determining step. For each substrate, rate laws indicate that [1tBu2]+ and [2tBu2]+ react by different mechanisms:  one proceeds by a simple bimolecular reaction, while the other first enters into a substrate-binding equilibrium before subsequently reacting by an intramolecular reaction. The reactions proceeding by the latter mechanism have faster overall rates, which correlates to a lower entropic barrier for the substrate-binding mechanism. Correlation of the reaction rates with the C−H bond dissociation energies of substrates as well as significant deuterium kinetic isotope effects indicates that the rate-determining steps involve hydrogen atom abstraction from the activated C−H bonds. A variable-temperature study (268−308 K) of the nonclassical KIE of the [1tBu2]+/benzyl alcohol reaction (kH/kD = 15 at 298 K) failed to show evidence for quantum tunneling. The rapid sequence by which a second 1 equiv of copper(II)−phenoxyl oxidant completes the reaction after the rate- and product-determining hydrogen atom abstraction step cannot be probed kinetically. Comparisons are made to the reactivities of other copper(II)−phenoxyl complexes reported in the literature and to galactose oxidase itself

A Tris(μ-hydroxy)tricopper(II) Complex as a Model of the Native Intermediate in Laccase and Its Relationship to a Binuclear Analogue

The reaction of a copper(I) complex with a sterically demanding secondary diamine ligand and O2 yields a tris(μ-hydroxy)tricopper(II) complex. This complex is a structural model of the proposed native intermediate in multicopper oxidases, with interesting structural, magnetic, and solution properties

Ligand and pH Influence on Manganese-Mediated Peracetic Acid Epoxidation of Terminal Olefins

Nineteen MnII complexes were screened for the catalytic epoxidation of terminal olefins using peracetic acid. Few of these complexes are efficient catalysts at pH < 2, but many are effective at 1 mol % catalyst loading at pH 4. With 0.1 mol % loading, four complexes epoxidize 1-octene in ∼80% yield in 5 min. The relative reactivity of the catalysts toward different olefins was probed using a multicomponent intermolecular competition reaction

Detailed Evaluation of the Geometric and Electronic Structures of One-Electron Oxidized Group 10 (Ni, Pd, and Pt) Metal(II)-(Disalicylidene)diamine Complexes

The geometric and electronic structures of a series of one-electron oxidized group 10 metal salens (Ni, Pd, Pt) have been investigated in solution and in the solid state. Ni (1) and Pd (2) complexes of the tetradentate salen ligand N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine (H2Salcn) have been examined along with the Pt (3) complex of the salen ligand N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-ethylenediamine (H2Salen). All three oxidized compounds exist as ligand radical species in solution and in the solid state. The solid state structures of [1]+ and [3]+ exhibit a symmetric coordination sphere contraction relative to the neutral forms. By contrast, the coordination sphere of the Pd derivative [2]+ exhibits a pronounced asymmetry in the solid state. In solution, the oxidized derivatives display intense low-energy NIR transitions consistent with their classification as ligand radical compounds. Interestingly, the degree of communication between the phenolate moieties depends strongly on the central metal ion, within the Ni, Pd, and Pt series. Electrochemical measurements and UV−vis−NIR spectroscopy, in conjunction with density functional theory calculations provide insights into the degree of delocalization of the one-electron hole in these systems. The Pd complex [2]+ is the least delocalized and is best described as a borderline Class II/III intervalence complex based on the Robin−Day classification system. The Ni [1]+ and Pt [3]+ analogues are Class III (fully delocalized) intervalence compounds. Delocalization is dependent on the electronic coupling between the redox-active phenolate ligands, mediated by overlap between the formally filled metal dxz orbital and the appropriate ligand molecular orbital. The degree of coupling increases in the order Pd < Ni < Pt for the one-electron oxidized group 10 metal salens

C−H Bond Activation by a Ferric Methoxide Complex: Modeling the Rate-Determining Step in the Mechanism of Lipoxygenase

Lipoxygenases are mononuclear non-heme iron enzymes that regio- and stereospecifcally convert 1,4-pentadiene subunit-containing fatty acids into alkyl peroxides. The rate-determining step is generally accepted to be hydrogen atom abstraction from the pentadiene subunit of the substrate by an active ferric hydroxide species to give a ferrous water species and an organic radical. Reported here are the synthesis and characterization of a ferric model complex, [FeIII(PY5)(OMe)](OTf)2, that reacts with organic substrates in a manner similar to the proposed enzymatic mechanism. The ligand PY5 (2,6-bis(bis(2-pyridyl)methoxymethane)pyridine) was developed to simulate the histidine-dominated coordination sphere of mammalian lipoxygenases. The overall monoanionic coordination provided by the endogenous ligands of lipoxygenase confers a strong Lewis acidic character to the active ferric site with an accordingly positive reduction potential. Incorporation of ferrous iron into PY5 and subsequent oxidation yields a stable ferric methoxide species that structurally and chemically resembles the proposed enzymatic ferric hydroxide species. Reactivity with a number of hydrocarbons possessing weak C−H bonds, including a derivative of the enzymatic substrate linoleic acid, scales best with the substrates' bond dissociation energies, rather than pKa's, suggesting a hydrogen atom abstraction mechanism. Thermodynamic analysis of [FeIII(PY5)(OMe)](OTf)2 and the ferrous end-product [FeII(PY5)(MeOH)](OTf)2 estimates the strength of the O−H bond in the metal bound methanol in the latter to be 83.5 ± 2.0 kcal mol-1. The attenuation of this bond relative to free methanol is largely due to the high reduction potential of the ferric site, suggesting that the analogously high reduction potential of the ferric site in LO is what allows the enzyme to perform its unique oxidation chemistry. Comparison of [FeIII(PY5)(OMe)](OTf)2 to other coordination complexes capable of hydrogen atom abstraction shows that, although a strong correlation exists between the thermodynamic driving force of reaction and the rate of reaction, other factors appear to further modulate the reactivity

C−H Bond Activation by a Ferric Methoxide Complex: Modeling the Rate-Determining Step in the Mechanism of Lipoxygenase

Lipoxygenases are mononuclear non-heme iron enzymes that regio- and stereospecifcally convert 1,4-pentadiene subunit-containing fatty acids into alkyl peroxides. The rate-determining step is generally accepted to be hydrogen atom abstraction from the pentadiene subunit of the substrate by an active ferric hydroxide species to give a ferrous water species and an organic radical. Reported here are the synthesis and characterization of a ferric model complex, [FeIII(PY5)(OMe)](OTf)2, that reacts with organic substrates in a manner similar to the proposed enzymatic mechanism. The ligand PY5 (2,6-bis(bis(2-pyridyl)methoxymethane)pyridine) was developed to simulate the histidine-dominated coordination sphere of mammalian lipoxygenases. The overall monoanionic coordination provided by the endogenous ligands of lipoxygenase confers a strong Lewis acidic character to the active ferric site with an accordingly positive reduction potential. Incorporation of ferrous iron into PY5 and subsequent oxidation yields a stable ferric methoxide species that structurally and chemically resembles the proposed enzymatic ferric hydroxide species. Reactivity with a number of hydrocarbons possessing weak C−H bonds, including a derivative of the enzymatic substrate linoleic acid, scales best with the substrates' bond dissociation energies, rather than pKa's, suggesting a hydrogen atom abstraction mechanism. Thermodynamic analysis of [FeIII(PY5)(OMe)](OTf)2 and the ferrous end-product [FeII(PY5)(MeOH)](OTf)2 estimates the strength of the O−H bond in the metal bound methanol in the latter to be 83.5 ± 2.0 kcal mol-1. The attenuation of this bond relative to free methanol is largely due to the high reduction potential of the ferric site, suggesting that the analogously high reduction potential of the ferric site in LO is what allows the enzyme to perform its unique oxidation chemistry. Comparison of [FeIII(PY5)(OMe)](OTf)2 to other coordination complexes capable of hydrogen atom abstraction shows that, although a strong correlation exists between the thermodynamic driving force of reaction and the rate of reaction, other factors appear to further modulate the reactivity

Simple Iron Catalyst for Terminal Alkene Epoxidation

A μ-oxo-iron(III) dimer, [((phen)2(H2O)FeIII)2(μ-O)](ClO4)4, is an efficient epoxidation catalyst for a wide range of alkenes, including terminal alkenes, using peracetic acid as the oxidant. Low catalyst loadings, in situ catalyst preparation from common reagents, fast reaction times (<5 min at 0 °C), and enhanced reaction performance at high substrate concentrations combine to create a temporally and synthetically efficient procedure for alkene epoxidation