I-Jui Hsu

Efficient Oxidation of Methane to Methanol by Dioxygen Mediated by Tricopper Clusters

Methane oxidation is extremely difficult chemistry to perform in the laboratory. The C H bond in CH4 has the highest bond energy (104 kcalmol ) amongst organic substrates. In nature, the controlled oxidation of organic substrates is mediated by an important class of enzymes known as monooxygenases and dioxygenases, and the methane monooxygenases are unique in their capability to mediate the facile conversion of methane to methanol. With a turnover frequency approaching 1 s , the particulate methane monooxygenase (pMMO) is the most efficient methane oxidizer discovered to date. Given the current interest in developing a laboratory catalyst suitable for the conversion of methane to methanol on an industrial scale, there is strong impetus to understand how pMMO works and to develop functional biomimetics of this enzyme. pMMO is a complex membrane protein consisting of three subunits (PmoA, PmoB, and PmoC) and many copper cofactors. Inspired by the proposal that the catalytic site might be a tricopper cluster, we have recently developed a series of tricopper complexes that are capable of supporting facile catalytic oxidation of hydrocarbons. We show herein that these model tricopper complexes can mediate efficient catalytic oxidation of methane to methanol as well. The oxidation of CH4 mediated by the tricopper complex [CuCuCu(7-N-Etppz)] in acetonitrile (ACN), where 7-NEtppz corresponds to the ligand 3,3’-(1,4-diazepane-1,4diyl)bis[1-(4-ethylpiperazine-1-yl)propan-2-ol], is summarized in Figure 1A. A single turnover (turnover number; TON= 0.92) is obtained when this CuCuCu complex is activated by excess dioxygen in the presence of excess CH4 (Figure 1B). The reaction is complete within ten minutes, clearly indicating that the oxidation is very rapid. In accordance with the single turnover, the kinetics of the overall process is pseudo first-order with respect to the concentration of the fully reduced tricopper complex with a rate constant k1= 0.065 min 1 (Figure 1B, inset). If we assume that the kinetics is limited by the dioxygen activation of the CuCuCu cluster with the subsequent O-atom transfer to the substrate molecule being rapid, then k1=k2·[O2]0, and from the solubility of oxygen in ACN at 25 8C (8.1 mm), we obtain the bimolecular rate constant k2 of 1.33 10 m 1 s 1 for the dioxygen activation of the CuCuCu cluster. This second-order rate constant is similar to values that we have previously determined for the dioxygen activation of other model tricopper clusters at room temperature. The process can be made catalytic by adding the appropriate amounts of H2O2 to regenerate the spent catalyst after O-atom transfer from the activated tricopper complex to CH4. This multiple-turnover reaction is depicted in Figure 1C. In these experiments, the [CuCuCu(7-N-Etppz)] catalyst is activated by O2 as in the single-turnover experiment described earlier, but the spent catalyst is regenerated by twoelectron reduction by a molecule of H2O2 (Figure 2A). Because the effective turnover number (TON), or the total equivalent of products formed over the time course of the experiment, peaks at approximately six when the turnover is initiated with 20 equivalents of H2O2, it is evident that abortive cycling begins to kick in when the steady-state concentration of the H2O2 concentration exceeds approximately ten equivalents. When the steady-state H2O2 concentration is above this level, reductive abortion of the activated catalyst becomes competitive with the O-atom transfer to methane to produce methanol. In this case, the rate of O-atom transfer is limited by the relatively low solubility of CH4 in ACN under ambient conditions of temperature and pressure (Figure 2B). The [CuCuCu(7-N-Etppz)] complex also mediates the catalytic oxidation of normal C2–C6 alkanes (data not shown) [*] Prof. Dr. S. I. Chan, Y.-J. Lu, Dr. P. Nagababu, Dr. S. Maji, M.-C. Hung, P. D. Minh, J. C.-H. Lai, K. Y. Ng, Prof. Dr. S. S.-F. Yu Institute of Chemistry, Academia Sinica Nankang, Taipei 11529 (Taiwan) E-mail: sunneychan@yahoo.com sfyu@gate.sinica.edu.tw

Relative Binding Affinity of Thiolate, Imidazolate, Phenoxide, and Nitrite Toward the {Fe(NO)2} Motif of Dinitrosyl Iron Complexes (DNICs): The Characteristic Pre-Edge Energy of {Fe(NO)2}9 DNICs

The synthesis, characterization, and transformation of the anionic {Fe(NO)(2)}(9) dinitrosyl iron complexes (DNICs) [(NO)(2)Fe(ONO)(2)](-) (1), [(NO)(2)Fe(OPh)(2)](-) (2), [(NO)(2)Fe(OPh)(C(3)H(3)N(2))](-) (3) (C(3)H(3)N(2) = imidazolate), [(NO)(2)Fe(OPh)(-SC(4)H(3)S)](-) (4), [(NO)(2)Fe(p-OPhF)(2)](-) (5), and [(NO)(2)Fe(SPh)(ONO)](-) (6) were investigated. The binding affinity of ligands ([SPh](-), [-SC(4)H(3)S](-), [C(3)H(3)N(2)](-), [OPh](-), and [NO(2)](-)) toward the {Fe(NO)(2)}(9) motif follows the ligand-displacement series [SPh](-) approximately [-SC(4)H(3)S](-) > [C(3)H(3)N(2)](-) > [OPh](-) > [NO(2)](-). The findings, the pre-edge energy derived from the 1s --> 3d transition in a distorted T(d) environment of the Fe center falling within the range of 7113.4-7113.8 eV for the anionic {Fe(NO)(2)}(9) DNICs, implicate that the iron metal center of DNICs is tailored to minimize the electronic changes accompanying changes in coordinated ligands. Our results bridging the ligand-substitution reaction study and X-ray absorption spectroscopy study of the electronic richness of the {Fe(NO)(2)}(9) core may point the way to understanding the reasons for natures choice of combinations of cysteine, histidine, and tyrosine in protein-bound DNICs and rationalize that most DNICs characterized/proposed nowadays are bound to the proteins almost through the thiolate groups of cysteinate/glutathione side chains in biological systems.

Discrimination of mononuclear and dinuclear dinitrosyl iron complexes (DNICs) by S K-edge X-ray absorption spectroscopy: insight into the electronic structure and reactivity of DNICs.

In addition to probing the formation of dinitrosyl iron complexes (DNICs) by the characteristic Fe K-edge pre-edge absorption energy ranging from 7113.4 to 7113.8 eV, the distinct S K-edge pre-edge absorption energy and pattern can serve as an efficient tool to unambiguously characterize and discriminate mononuclear DNICs and dinuclear DNICs containing bridged-thiolate and bridged-sulfide ligands. The higher Fe-S bond covalency modulated by the stronger electron-donating thiolates promotes the Fe → NO π-electron back-donation to strengthen the Fe-NO bond and weaken the NO-release ability of the mononuclear DNICs, which is supported by the Raman ν(Fe-NO) stretching frequency. The Fe-S bond covalency of DNICs further rationalizes the binding preference of the {Fe(NO)(2)} motif toward thiolates following the trend of [SEt](-) > [SPh](-) > [SC(7)H(4)SN](-). The relative d-manifold energy derived from S K-edge XAS as well as the Fe K-edge pre-edge energy reveals that the electronic structure of the {Fe(NO)(2)}(9) core of the mononuclear DNICs [(NO)(2)Fe(SR)(2)](-) is best described as {Fe(III)(NO(-))(2)}(9) compared to [{Fe(III)(NO(-))(2)}(9)-{Fe(III)(NO(-))(2)}(9)] for the dinuclear DNICs [Fe(2)(μ-SEt)(μ-S)(NO)(4)](-) and [Fe(2)(μ-S)(2)(NO)(4)](2-).

Anionic Roussin’s Red Esters (RREs) syn-/anti-[Fe(µ-SEt)(NO)2]2−: the Critical Role of Thiolate Ligands in Regulating the Transformation of RREs into Dinitrosyl Iron Complexes and the Anionic RREs

The anionic syn-/ anti-[Fe(mu-SEt)(NO) 2] 2 (-) ( 2a) were synthesized and characterized by IR, UV-vis, EPR, and X-ray diffraction. The geometry of the [Fe(mu-S) 2Fe] core is rearranged in going from [{Fe(NO) 2} (9)-{Fe(NO) 2} (9)] Roussins red ester [Fe(mu-SEt)(NO) 2] 2 ( 1a) (Fe...Fe distance of 2.7080(5) A) to the [{Fe(NO) 2} (9)-{Fe(NO) 2} (10)] complex 2a (Fe...Fe distance of 2.8413(6) A) to minimize the degree of Fe...Fe interaction to stabilize complex 2a. On the basis of X-ray absorption (Fe K- and L-edge), EPR and SQUID, complex 2a is best described as the anionic [{Fe(NO) 2} (9)-{Fe(NO) 2} (10)] Roussins red ester with the fully delocalized mixed-valence core. The complete bridged-thiolate cleavage yielded DNIC [(EtS) 2Fe(NO) 2] (-) ( 3a) in the reaction of 2 equiv of [EtS] (-) and complex 1a, whereas reaction of 2 equiv of [(t)BuS] (-) with [Fe(micro-S (t)Bu)(NO) 2] 2 (1b) gave DNIC [((t)BuS) 2Fe(NO) 2] (-) (3b) and the anionic Roussins red ester [Fe(mu-S (t)Bu)(NO) 2] 2 (-) (2b) through bridged-thiolate cleavage in combination with reduction. In contrast to the inertness of DNIC 3b toward complex 1b, nucleophile DNIC 3a induces the reduction of complex 1a to produce the anionic Roussins red ester 2a. Interestingly, dissolution of complex 3a in MeOH at 298 K finally led to the formation of a mixture of complexes 2a and 3a, in contrast to the dynamic equilibrium of complexes 3b and 1b observed in dissolution of complex 3b in MeOH. These results illustrate the aspect of how the steric structures of nucleophiles ([EtS] (-) vs [ (t)BuS] (-) and [(EtS) 2Fe(NO)2](-) vs [((t)BuS) 2Fe(NO)2] (-)) function to determine the reaction products.

Insight into the dinuclear {Fe(NO)2}10{Fe(NO)2}10 and mononuclear {Fe(NO)2}10 dinitrosyliron complexes.

The reversible redox transformations [(NO)(2)Fe(S(t)Bu)(2)](-) ⇌ [Fe(μ-S(t)Bu)(NO)(2)](2)(2-) ⇌ [Fe(μ-S(t)Bu)(NO)(2)](2)(-) ⇌ [Fe(μ-S(t)Bu)(NO)(2)](2) and [cation][(NO)(2)Fe(SEt)(2)] ⇌ [cation](2)[(NO)(2)Fe(SEt)(2)] (cation = K(+)-18-crown-6 ether) are demonstrated. The countercation of the {Fe(NO)(2)}(9) dinitrosyliron complexes (DNICs) functions to control the formation of the {Fe(NO)(2)}(10){Fe(NO)(2)}(10) dianionic reduced Roussins red ester (RRE) [PPN](2)[Fe(μ-SR)(NO)(2)](2) or the {Fe(NO)(2)}(10) dianionic reduced monomeric DNIC [K(+)-18-crown-6 ether](2)[(NO)(2)Fe(SR)(2)] upon reduction of the {Fe(NO)(2)}(9) DNICs [cation][(NO)(2)Fe(SR)(2)] (cation = PPN(+), K(+)-18-crown-6 ether; R = alkyl). The binding preference of ligands [OPh](-)/[SR](-) toward the {Fe(NO)(2)}(10){Fe(NO)(2)}(10) motif of dianionic reduced RRE follows the ligand-displacement series [SR](-) > [OPh](-). Compared to the Fe K-edge preedge energy falling within the range of 7113.6-7113.8 eV for the dinuclear {Fe(NO)(2)}(9){Fe(NO)(2)}(9) DNICs and 7113.4-7113.8 eV for the mononuclear {Fe(NO)(2)}(9) DNICs, the {Fe(NO)(2)}(10) dianionic reduced monomeric DNICs and the {Fe(NO)(2)}(10){Fe(NO)(2)}(10) dianionic reduced RREs containing S/O/N-ligation modes display the characteristic preedge energy 7113.1-7113.3 eV, which may be adopted to probe the formation of the EPR-silent {Fe(NO)(2)}(10)-{Fe(NO)(2)}(10) dianionic reduced RREs and {Fe(NO)(2)}(10) dianionic reduced monomeric DNICs in biology. In addition to the characteristic Fe/S K-edge preedge energy, the IR ν(NO) spectra may also be adopted to characterize and discriminate [(NO)(2)Fe(μ-S(t)Bu)](2) [IR ν(NO) 1809 vw, 1778 s, 1753 s cm(-1) (KBr)], [Fe(μ-S(t)Bu)(NO)(2)](2)(-) [IR ν(NO) 1674 s, 1651 s cm(-1) (KBr)], [Fe(μ-S(t)Bu)(NO)(2)](2)(2-) [IR ν(NO) 1637 m, 1613 s, 1578 s, 1567 s cm(-1) (KBr)], and [K-18-crown-6 ether](2)[(NO)(2)Fe(SEt)(2)] [IR ν(NO) 1604 s, 1560 s cm(-1) (KBr)].

Peptide-bound dinitrosyliron complexes (DNICs) and neutral/reduced-form Roussin's red esters (RREs/rRREs): understanding nitrosylation of [Fe-S] clusters leading to the formation of DNICs and RREs using a de novo design strategy.

This manuscript describes the interaction of low-molecular-weight DNICs with short peptides designed to explore the stability and structure of DNIC-peptide/RRE-peptide constructs. Although characterization of protein-bound and low-molecular-weight DNICs is possible via EPR, XAS, and NRVS, this study demonstrates that the combination of aqueous IR ν(NO) and UV-vis spectra can serve as an efficient tool to characterize and discriminate peptide-bound DNICs and RREs. The de novo chelate-cysteine-containing peptides KC(A)(n)CK-bound (n = 1-4) dinitrosyliron complexes KC(A)(n)CK-DNIC (CnA-DNIC) and monodentate-cysteine-containing peptides KCAAK-/KCAAHK-bound Roussins red esters (RREs) KCAAK-RRE/KCAAHK-RRE were synthesized and characterized by aqueous IR, UV-vis, EPR, CD, XAS, and ESI-MS. In contrast to the inertness of chelate-cysteine-containing peptide-bound DNICs toward KCAAK/KCAAHK, transformation of KCAAK-RRE/KCAAHK-RRE into CnA-DNIC triggered by CnA and reversible transformation between CnA-DNIC and CnA-RRE via {Fe(NO)(2)}(9)-{Fe(NO)(2)}(10) reduced-form peptide-bound RREs demonstrate that the {Fe(NO)(2)}(9) motif displays a preference for chelate-cysteine-containing peptides over monodentate-cysteine-containing peptides. Also, this study may signify that nitrosylation of [Fe-S] proteins generating protein-bound RREs, reduced protein-bound RREs, or protein-bound DNICs are modulated by both the oxidation state of iron and the chelating effect of the bound proteins of [Fe-S] clusters.

Insight into one-electron oxidation of the {Fe(NO)2}9 dinitrosyl iron complex (DNIC): aminyl radical stabilized by [Fe(NO)2] motif.

A reversible redox reaction ({Fe(NO)(2)}(9) DNIC [(NO)(2)Fe(N(Mes)(TMS))(2)](-) (4) ⇄ oxidized-form DNIC [(NO)(2)Fe(N(Mes)(TMS))(2)] (5) (Mes = mesityl, TMS = trimethylsilane)), characterized by IR, UV-vis, (1)H/(15)N NMR, SQUID, XAS, single-crystal X-ray structure, and DFT calculation, was demonstrated. The electronic structure of the oxidized-form DNIC 5 (S(total) = 0) may be best described as the delocalized aminyl radical [(N(Mes)(TMS))(2)](2)(-•) stabilized by the electron-deficient {Fe(III)(NO(-))(2)}(9) motif, that is, substantial spin is delocalized onto the [(N(Mes)(TMS))(2)](2)(-•) such that the highly covalent dinitrosyl iron core (DNIC) is preserved. In addition to IR, EPR (g ≈ 2.03 for {Fe(NO)(2)}(9)), single-crystal X-ray structure (Fe-N(O) and N-O bond distances), and Fe K-edge pre-edge energy (7113.1-7113.3 eV for {Fe(NO)(2)}(10) vs 7113.4-7113.9 eV for {Fe(NO)(2)}(9)), the (15)N NMR spectrum of [Fe((15)NO)(2)] was also explored to serve as an efficient tool to characterize and discriminate {Fe(NO)(2)}(9) (δ 23.1-76.1 ppm) and {Fe(NO)(2)}(10) (δ -7.8-25.0 ppm) DNICs. To the best of our knowledge, DNIC 5 is the first structurally characterized tetrahedral DNIC formulated as covalent-delocalized [{Fe(III)(NO(-))(2)}(9)-[N(Mes)(TMS)](2)(-•)]. This result may explain why all tetrahedral DNICs containing monodentate-coordinate ligands isolated and characterized nowadays are confined in the {Fe(NO)(2)}(9) and {Fe(NO)(2)}(10) DNICs in chemistry and biology.

Chemical bond characterization of a mixed-valence tri-cobalt complex, Co3(μ-admtrz)4(μ-OH)2(CN)6·2H2O.

Charge density study of a mixed-valence tri-cobalt compound, Co3(μ-admtrz)4(μ-OH)2(CN)6·2H2O (1) (admtrz = 3,5-dimethyl-4-amino-1,2,4-triazole), is investigated based on high resolution X-ray diffraction data and density functional theory (DFT) calculations. The molecular structure of this compound contains three cobalt atoms in a linear fashion, where two terminal ones are Co(III) at a low-spin (LS) state and a central one is Co(II) at a high-spin (HS) state with a total spin quantum number, S(total), of 3/2. It is centrosymmetric with the center of inversion located at the central Co atom (Co2). The Co2 ion is linked with each terminal cobalt (Co1) ion through two μ-admtrz ligands and a μ-OH ligand in a CoN4O2 coordination, where the Co1 is bonded additionally to three CN ligands with CoN2OC3 coordination. The combined experimental and theoretical charge density study identifies the different characters of two types of cobalt ions; more pronounced charge concentration and depletion features in the valence shell charge concentration (VSCC) are found in the Co(III) ion than in the Co(II) ion, and d-orbital populations also show the difference. According to topological properties associated with the bond critical point (BCP), the Co1-C(N) bond is the strongest among all the Co-ligand bonds in this compound; the Co-O is stronger than Co-N bond. Again Co1-O is stronger than Co2-O, so as the Co1-N being stronger than Co2-N bond. The electronic configuration of each type of Co atom is further characterized through magnetic measurement, Co-specific X-ray absorption near edge spectroscopy (XANES), and X-ray emission spectra (XES).

Resonant X-Ray Scattering and Absorption for the Global and Local Structures of Cu-modified Metallothioneins in Solution

With Cd and Zn metal ions removed from the native rabbit-liver metallothionein upon unfolding, Cu-modified metallothioneins (Cu-MTs) were obtained during refolding in solutions containing Cu(I) or Cu(II) ions. X-ray absorption near-edge spectroscopic results confirm the respectively assigned oxidation states of the copper ions in Cu(I)-MT and Cu(II)-MT. Global and local structures of the Cu-MTs were subsequently characterized by anomalous small-angle x-ray scattering (ASAXS) and extended x-ray absorption fine structure. Energy-dependent ASAXS results indicate that the morphology of Cu(II)-MT resembles that of the native MT, whereas Cu(I)-MT forms oligomers with a higher copper content. Both dummy-residue simulation and model-shape fitting of the ASAXS data reveal consistently rodlike morphology for Cu(II)-MT. Clearly identified Cu-S, Cu-O, and Cu-Cu contributions in the extended x-ray absorption fine structure analysis indicate that both Cu(I) and Cu(II) ions are bonded with O and S atoms of nearby amino acids in a four-coordination environment, forming metal clusters smaller than metal thiolate clusters in the native MT. It is demonstrated that a combination of resonant x-ray scattering and x-ray absorption can be particularly useful in revealing complementary global and local structures of metalloproteins due to the atom specific characteristics of the two techniques.

Mechanistic Studies of the Reaction of Ir(III) Porphyrin Hydride with 2,2,6,6-Tetramethylpiperidine-1-oxyl to an Unsupported Ir-Ir Porphyrin Dimer

Reaction of hydrido[5,10,15,20-tetrakis(p-tolyl)porphyrinato]iridium(III) (Ir(ttp)H) (1) with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) (2) at room temperature gave a 90% yield of the unsupported iridium(II) porphyrin dimer, Ir(II)(2)(ttp)(2) (3). Kinetic measurements revealed that the oxidation followed overall second-order kinetics: rate = k[Ir(ttp)H][TEMPO], k(25 °C) = 6.65 × 10(-4) M(-1). The entropy of activation (ΔS(‡) = -25.3 ± 2.5 cal mol(-1) K(-1)) and the kinetic isotope effect of 7.2 supported a bimolecular associative mechanism in the rate-determining hydrogen atom transfer from Ir(ttp)H to TEMPO.