David P. Goldberg

Unprecedented Rate Enhancements of Hydrogen-Atom Transfer to a Manganese(V)―Oxo Corrolazine Complex

The reactivity of high-valent metal–oxo species is critical to the functioning of a large class of metalloenzymes. In heme enzymes, the identity of the proximal ligand is believed to have an important effect on the generation, stability, and substrate reactivity of these intermediates. For example, the proximal cysteinate ligand in cytochrome P450 (Cyt-P450) has been suggested to increase the oxidizing power of the enzyme toward hydrocarbon (C H) substrates by enhancing the basicity (i.e. the affinity for H) of the [(porphC)Fe(O)] intermediate, thereby increasing the driving force of hydrogen-atom transfer (HAT). Beyond Cyt-P450, it is of considerable interest to elucidate the factors that control metal–oxo HAT reactions because of the fundamental importance of this chemistry to both biological and synthetic processes. Only recently has limited information become available on the kinetics of HAT reactions for either heme or nonheme iron/manganese–oxo complexes. Even fewer of these studies have systematically determined the effects of ancillary ligands on the kinetics of HAT reactions. For example, the influence of axial ligands trans to the oxo group, which is of particular relevance to heme proteins, has only recently been described for discrete iron–oxo complexes. 7, 8] No similar study has yet appeared for analogous manganese–oxo complexes. In earlier work, principles of ligand design were used to prepare a porphyrinoid ligand that stabilizes high-valent transition metals. 12] This ligand, which contains a ringcontracted porphyrin nucleus and a 3 charge, provided rare access to a stable manganese(V)–oxo complex, [(TBP8Cz)Mn (O)] (1; TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato ). Herein, we take advantage of the stability of 1 to determine the influence of axial donors on the kinetics of HAT for a discrete Mn(O) species. The addition of anionic axial ligands (X ) to this manganese(V)–oxo complex leads to unprecedented rate enhancements in HAT reactions. Computational studies (density functional theory, DFT) were performed that successfully reproduce the experimental findings, thus providing a comprehensive theoretical framework in which these unprecedented influences on reactivity can be understood. In a previous study it was shown that mixing 1 with excess 9,10-dihydroanthracene (DHA) at room temperature led to the isosbestic conversion of 1 into 2 (see Scheme 1). The data for this reaction, together with similar reactions involving substituted phenols, were consistent with the mechanism shown in Scheme 1. Complex 1 abstracts a hydrogen atom from the substrate in the rate-determining step, thus leading to a postulated Mn(OH) intermediate which is not observed, but is then consumed in a second, fast HAT step to give [(TBP8Cz)Mn ] (2).

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

Addition of the Lewis acid Zn(2+) to (TBP(8)Cz)Mn(V)(O) induces valence tautomerization, resulting in the formation of [(TBP(8)Cz(+•))Mn(IV)(O)-Zn(2+)]. This new species was characterized by UV-vis, EPR, the Evans method, and (1)H NMR and supported by DFT calculations. Removal of Zn(2+) quantitatively restores the starting material. Electron-transfer and hydrogen-atom-transfer reactions are strongly influenced by the presence of Zn(2+).

Recent advances in the chemistry of corroles and core-modified corroles

The aim of this review is to highlight recent progress in the chemistry of corroles and core-modified corroles. Emphasis is put on the synthetic and coordination aspects of corroles with meso substituents and corrolazines.

Catalytic Reactivity of a Meso-N-Substituted Corrole and Evidence for a High-Valent Iron−Oxo Species

It is shown that an iron(III) meso-N-substituted corrole (TBP(8)Cz)Fe(III) (1) (TBP(8)Cz = octakis(4-tert-butylphenyl)corrolazinato), is a potent catalyst for the oxidation of alkenes in the presence of pentaflouroiodosylbenzene (C(6)F(5)IO) as oxidant. In the case of cyclohexene, complex 1 performs on a par with one of the best porphyrin catalysts ((TPPF(20))FeCl), exhibiting rapid turnover and a high selectivity for epoxide (CzFe(III)/C(6)F(5)IO/cyclohexene (1:100:1000) in CH(2)Cl(2)/CH(3)OH (3:1 v:v) gives 33 turnovers of epoxide in <2 min). Reaction rates for 1 are greatly enhanced compared to other Fe or Mn corroles under similar catalytic conditions, consistent with an increase in the electrophilicity of a high-valent iron-oxo intermediate induced by meso-N substitution. Reaction of dark-green 1 (lambda(max) = 440, 611, 747 nm) under single-turnover-like conditions at -78 degrees C leads to the formation of a new dark-brown species (2) (lambda(max) = 396, 732, 843 nm). The Fe(III) complex 1 is restored upon the addition of 2 equiv of ferrocene to 2, or by the addition of 1 equiv of PPh(3), which concomitantly yields OPPh(3). In addition, complex 2 reacts with excess cyclohexene at -42 degrees C to give 1. Complex 2 was also characterized by EPR spectroscopy, and all of the data are consistent with 2 being an antiferromagnetically coupled iron(IV)-oxo pi-cation-radical complex. Rapid-mixing stopped-flow UV-vis studies show that the low-temperature complex 2 is generated as a short-lived intermediate at room temperature.

O2 Activation by Bis(imino)pyridine Iron(II)-Thiolate Complexes

The new iron(II)-thiolate complexes [((iPr)BIP)Fe(II)(SPh)(Cl)] (1) and [((iPr)BIP)Fe(II)(SPh)(OTf)] (2) [BIP = bis(imino)pyridine] were prepared as models for cysteine dioxygenase (CDO), which converts Cys to Cys-SO(2)H at a (His)(3)Fe(II) center. Reaction of 1 and 2 with O(2) leads to Fe-oxygenation and S-oxygenation, respectively. For 1 + O(2), the spectroscopic and reactivity data, including (18)O isotope studies, are consistent with an assignment of an iron(IV)-oxo complex, [((iPr)BIP)Fe(IV)(O)(Cl)](+) (3), as the product of oxygenation. In contrast, 2 + O(2) results in direct S-oxygenation to give a sulfonato product, PhSO(3)(-). The positioning of the thiolate ligand in 1 versus 2 appears to play a critical role in determining the outcome of O(2) activation. The thiolate ligands in 1 and 2 are essential for O(2) reactivity and exhibit an important influence over the Fe(III)/Fe(II) redox potential.

Activation of Dioxygen by Iron and Manganese Complexes: A Heme and Nonheme Perspective.

The rational design of well-defined, first-row transition metal complexes that can activate dioxygen has been a challenging goal for the synthetic inorganic chemist. The activation of O2 is important in part because of its central role in the functioning of metalloenzymes, which utilize O2 to perform a number of challenging reactions including the highly selective oxidation of various substrates. There is also great interest in utilizing O2, an abundant and environmentally benign oxidant, in synthetic catalytic oxidation systems. This Perspective brings together recent examples of biomimetic Fe and Mn complexes that can activate O2 in heme or nonheme-type ligand environments. The use of oxidants such as hypervalent iodine (e.g., ArIO), peracids (e.g., m-CPBA), peroxides (e.g., H2O2) or even superoxide is a popular choice for accessing well-characterized metal-superoxo, metal-peroxo, or metal-oxo species, but the instances of biomimetic Fe/Mn complexes that react with dioxygen to yield such observable metal-oxygen species are surprisingly few. This Perspective focuses on mononuclear Fe and Mn complexes that exhibit reactivity with O2 and lead to spectroscopically observable metal-oxygen species, and/or oxidize biologically relevant substrates. Analysis of these examples reveals that solvent, spin state, redox potential, external co-reductants, and ligand architecture can all play important roles in the O2 activation process.

Electron- and Hydride-Transfer Reactivity of an Isolable Manganese(V)−Oxo Complex

The electron-transfer and hydride-transfer properties of an isolated manganese(V)−oxo complex, (TBP8Cz)Mn(V)(O) (1) (TBP8Cz = octa-tert-butylphenylcorrolazinato) were determined by spectroscopic and kinetic methods. The manganese(V)−oxo complex 1 reacts rapidly with a series of ferrocene derivatives ([Fe(C5H4Me)2], [Fe(C5HMe4)2], and ([Fe(C5Me5)2] = Fc*) to give the direct formation of [(TBP8Cz)Mn(III)(OH)]− ([2-OH]−), a two-electron-reduced product. The stoichiometry of these electron-transfer reactions was found to be (Fc derivative)/1 = 2:1 by spectral titration. The rate constants of electron transfer from ferrocene derivatives to 1 at room temperature in benzonitrile were obtained, and the successful application of Marcus theory allowed for the determination of the reorganization energies (λ) of electron transfer. The λ values of electron transfer from the ferrocene derivatives to 1 are lower than those reported for a manganese(IV)−oxo porphyrin. The presumed one-electron-reduced intermediate, a Mn(IV) complex, was not observed during the reduction of 1. However, a Mn(IV) complex was successfully generated via one-electron oxidation of the Mn(III) precursor complex 2 to give [(TBP8Cz)Mn(IV)]+ (3). Complex 3 exhibits a characteristic absorption band at λ(max) = 722 nm and an EPR spectrum at 15 K with g(max)′ = 4.68, g(mid)′ = 3.28, and g(min)′ = 1.94, with well-resolved 55Mn hyperfine coupling, indicative of a d3 Mn(IV)S = 3/2 ground state. Although electron transfer from [Fe(C5H4Me)2] to 1 is endergonic (uphill), two-electron reduction of 1 is made possible in the presence of proton donors (e.g., CH3CO2H, CF3CH2OH, and CH3OH). In the case of CH3CO2H, saturation behavior for the rate constants of electron transfer (k(et)) versus acid concentration was observed, providing insight into the critical involvement of H+ in the mechanism of electron transfer. Complex 1 was also shown to be competent to oxidize a series of dihydronicotinamide adenine dinucleotide (NADH) analogues via formal hydride transfer to produce the corresponding NAD+ analogues and [2-OH]−. The logarithms of the observed second-order rate constants of hydride transfer (k(H)) from NADH analogues to 1 are linearly correlated with those of hydride transfer from the same series of NADH analogues to p-chloranil.

A Manganese(V)–Oxo π-Cation Radical Complex: Influence of One-Electron Oxidation on Oxygen-Atom Transfer

One-electron oxidation of Mn(V)-oxo corrolazine 2 affords 2(+), the first example of a Mn(V)(O) π-cation radical porphyrinoid complex, which was characterized by UV-vis, EPR, LDI-MS, and DFT methods. Access to 2 and 2(+) allowed for a direct comparison of their reactivities in oxygen-atom transfer (OAT) reactions. Both complexes are capable of OAT to PPh(3) and RSR substrates, and 2(+) was found to be a more potent oxidant than 2. Analysis of rate constants and activation parameters, together with DFT calculations, points to a concerted OAT mechanism for 2(+) and 2 and indicates that the greater electrophilicity of 2(+) likely plays a dominant role in enhancing its reactivity. These results are relevant to comparisons between Compound I and Compound II in heme enzymes.

Secondary coordination sphere influence on the reactivity of nonheme iron(II) complexes: an experimental and DFT approach.

The new biomimetic ligands N4Py2Ph (1) and N4Py2Ph,amide (2) were synthesized and yield the iron(II) complexes [FeII(N4Py2Ph)(NCCH3)](BF4)2 (3) and [FeII(N4Py2Ph,amide)](BF4)2 (5). Controlled orientation of the Ph substituents in 3 leads to facile triplet spin reactivity for a putative FeIV(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 FeIIIOOR species which decays without arene hydroxylation. These results provide new insights regarding the impact of secondary coordination sphere effects at nonheme iron centers.

Iron(II)-Thiolate S-Oxygenation by O2: Synthetic Models of Cysteine Dioxygenase

The synthesis of structural and functional models of the active site of the nonheme iron enzyme cysteine dioxygenase (CDO) is reported. A bis(imino)pyridine ligand scaffold was employed to synthesize a mononuclear ferrous complex, Fe(II)(LN(3)S)(OTf) (1), which contains three neutral nitrogen donors and one anionic thiolato donor. Complex 1 is a good structural model of the Cys-bound active site of CDO. Reaction of 1 with O(2) results in oxygenation of the thiolato sulfur, affording the sulfonato complex Fe(II)(LN(3)SO(3))(OTf) (2) under mild conditions. Isotope labeling studies show that O(2) is the sole source of O atoms in the product and that the reaction proceeds via a dioxygenase-type mechanism for two out of three O atoms added, analogous to the dioxygenase reaction of CDO. The zinc(II) analog, Zn(LN(3)S)(OTf) (4), was prepared and found to be completely unreactive toward O(2), suggesting a critical role for Fe(II) in the oxygenation chemistry observed for 1. To our knowledge, S-oxygenation mediated by an Fe(II)-SR complex and O(2) is unprecedented.