Dioxygen reactivity of copper and heme-copper complexes possessing an imidazole-phenol cross-link

Recent spectroscopic, kinetics, and structural studies on cytochrome c oxidases (CcOs) suggest that the histidine-tyrosine cross-link at the heme a3-CuB binuclear active site plays a key role in the reductive O2-cleavage process. In this report, we describe dioxygen reactivity of copper and heme/Cu assemblies in which the imidazole-phenol moieties are employed as a part of copper ligand LN4OH (2-{4-[2-(bis-pyridin-2-ylmethyl-amino)-ethyl]-imidazol-1-yl}-4,6-di -tert-butyl-phenol). Stopped-flow kinetic studies reveal that low-temperature oxygenation of [CuI(LN4OH)]+ (1) leads to rapid formation of a copper-superoxo species [CuII(LN4OH)(O2-)]+ (1a), which further reacts with 1 to form the 2:1 Cu:O2 adduct, peroxo complex [{CuII(LN4OH)}2(O2(2-))]2+ (1b). Complex 1b is also short-lived, and a dimer Cu(II)-phenolate complex [CuII(LN4O-)]2(2+) (1c) eventually forms as a final product in the later stage of the oxygenation reaction. Dioxygen reactivities of 1 and its anisole analogue [CuI(LN4OMe)]+ (2) in the presence of a heme complex (F8)FeII (3) (F8 = tetrakis(2,6,-difluorotetraphenyl)-porphyrinate) are also described. Spectroscopic investigations including UV-vis, 1H and 2H NMR, EPR, and resonance Raman spectroscopies along with spectrophotometric titration reveal that low-temperature oxygenation of 1/3 leads to formation of a heme-peroxo-copper species [(F8)FeIII-(O2(2-))-CuII(LN4OH)]+ (4), nu(O-O) = 813 cm(-1). Complex 4 is an S = 2 spin system with strong antiferromagnetic coupling between high-spin iron(III) and copper(II) through a bridging peroxide ligand. A very similar complex [(F8)FeIII-(O2(2-))-CuII(LN4OMe)]+ (5) (nu(O-O) = 815 cm(-1)) can be generated by utilizing the anisole compound 2, which indicates that the cross-linked phenol moiety in 4 does not interact with the bridging peroxo group between heme and copper. This investigation thus reveals that a stable heme-peroxo-copper species can be generated even in the presence of an imidazole-phenol group (i.e., possible electron/proton donor source) in close proximity. Future studies are needed to probe key factors that can trigger the reductive O-O cleavage in CcO model compounds.     

Tridentate copper ligand influences on heme-peroxo-copper formation and properties: reduced, superoxo, and mu-peroxo iron/copper complexes

In cytochrome c oxidase synthetic modeling studies, we recently reported a new mu-eta2:eta2-peroxo binding mode in the heteronuclear heme/copper complex [(2L)Fe(III)-(O2(2-))-CuII]+ (6) which is effected by tridentate copper chelation (J. Am. Chem. Soc. 2004, 126, 12716). To establish fundamental coordination and O2-reactivity chemistry, we have studied and describe here (i) the structure and dioxygen reactivity of the copper-free compound (2L)FeII (1), (ii) detailed spectroscopic properties of 6 in comparisons with those of known mu-eta2:eta1 heme-peroxo-copper complexes, (iii) formation of 6 from the reactions of [(2L)FeIICuI]+ (3) and dioxygen by stopped-flow kinetics, and (iv) reactivities of 6 with CO and PPh3. In the absence of copper, 1 serves as a myoglobin model compound possessing a pyridine-bound five-coordinate iron(II)-porphyrinate which undergoes reversible dioxygen binding. Oxygenation of 3 below -60 degrees C generates the heme-peroxo-copper complex 6 with strong antiferromagnetic coupling between high-spin iron(III) and copper(II) to yield an S = 2 spin system. Stopped-flow kinetics in CH2Cl2/6% EtCN show that dioxygen reacts with iron(II) first to form a heme-superoxide moiety, [(EtCN)(2L)FeIII-(O2-)...CuI(EtCN)]+ (5), which further reacts with Cu(I) to generate 6. Compared to those properties of a known mu-eta2:eta1-heme-peroxo-copper complex, 6 has a significantly diminished resonance Raman nu(O-O) stretching frequency at 747 cm(-1) and distinctive visible absorptions at 485, 541, and 572 nm, all of which seem to be characteristics of a mu-eta2:eta2-heme-peroxo-copper system. Addition of CO or PPh3 to 6 yields a bis-CO adduct of 3 or a PPh(3) adduct of 5, the latter with a remaining FeIII-(O2-) moiety.     

Copper(I) and copper(II) complexes possessing cross-linked imidazole-phenol ligands: structures and dioxygen reactivity

Catalytic reduction of O2 to H2O, and coupling to membrane proton translocation, occurs at the heterobinuclear heme a3-CuB active site of cytochrome c oxidase. One of the CuB ligated histidines is cross-linked to a neighboring tyrosine (C-N bond; tyrosine C6 and histidine epsilon-nitrogen), and the protic residue of this cross-linked His-Tyr moiety is proposed to participate as both an electron and a proton donor in the catalytic dioxygen reduction event. To provide insight into the chemistry of such a moiety, we have synthesized and characterized tetra- and tridentate pyridylalkylamine chelate ligands {LN4OR and LN3OR (R = H or Me)}, which include an imidazole-phenol (or anisole) cross-link and their copper(I/II) complexes. [CuI(LN4OH)]B(C6F5)4 (1) reacts with dioxygen at -80 degrees C in THF, forming an unstable trans-mu-1,2-peroxodicopper(II)complex, which subsequently converts to a dimeric copper(II)-phenolate complex [{Cu(LN4O-)}2](B(C6F5)4)2 (5a). The close analogue [CuI(LN4OMe)]B(C6F5)4 (3) binds dioxygen reversibly at -80 degrees C in tetrahydrofuran. Stopped-flow kinetics of the reaction [CuI(LN3OH)]ClO4 (2) with O2 in CH2Cl2 indicate a steady formation of the purple dimeric product [{Cu(LN3O-)}2](ClO4)2 (5b), which has been analyzed in the temperature range from -40 to +20 degrees C, DeltaH = -9.6 (6) kJ mol-1, DeltaS = -168 (2) J mol-1 K-1 (k(-40 degrees C) = 1.05(4) x 106 and k(+20 degrees C) = 4.6(2) x 105 M-2 s-1). The X-ray crystal structures of 1, [CuII(LN3OH)(MeOH)(OClO3-)](ClO4) (4), 5a, and 5b are reported.     

Reaction of a copper-dioxygen complex with nitrogen monoxide (*NO) leads to a copper(II)-peroxynitrite species

A discrete peroxynitrite-copper(II) complex, [(TMG3tren)CuII(-OONO)]+ (3), has been generated in solution (ESI-MS, m/z = 565.15; tetragonal EPR) by reacting *NO(g) with superoxo complex [(TMG3tren)CuII(O2*-)]+ (2). Complex 3 undergoes a thermal transformation to give CuII-nitrite complex [(TMG3tren)CuII(-ONO)]+ (4) (X-ray) along with ca. 0.5 molar equiv dioxygen. A DFT calculation derived structure with cyclic bidentate k2-O,O'-OONO bound peroxynitrite moiety and dx2-y2 ground state is proposed. Experiments using 18O2 suggest that the adjacent peroxo oxygen atoms in 3 are derived from molecular oxygen. Further, 18O2 containing 3 undergoes O-O bond cleavage to form singly 18-O-labeled 4. The results suggest the viability of biological CuI/O2/(*NO) peroxynitrite formation and chemistry, that is, not coming from free superoxide plus *NO reaction.     

Superoxo, peroxo, and hydroperoxo complexes formed from reactions of rhodium porphyrins with dioxygen: thermodynamics and kinetics

Rhodium(II) porphyrin complexes react with dioxygen to form terminal superoxo and bridged mu-peroxo complexes. Equilibrium constants for dioxygen complex formation with rhodium(II) tetramesitylporphyrin ((TMP)Rh*) and a m-xylyl-tethered dirhodium(II) diporphyrin complex (*Rh(m-xylyl)Rh*) are reported. (TMP)Rh-H reacts with oxygen to form a transient hydroperoxy complex ((TMP)Rh-OOH), which reacts on to form the rhodium(II) complex ((TMP)Rh*) and water. Kinetic studies for reactions of (TMP)Rh-H with O2 suggest a near concerted addition of dioxygen to the (TMP)Rh-H unit. Reactivity studies for mixtures of H2/O2 and CH4/O2 with the dirhodium(II) complex (*Rh(m-xylyl)Rh*) are reported.     

Copper(I)-dioxygen reactivity of [(L)Cu(I)](+) (L = tris(2-pyridylmethyl)amine): kinetic/thermodynamic and spectroscopic studies concerning the formation of Cu-O2 and Cu2-O2 adducts as a function of solvent medium and 4-pyridyl ligand substituent variations

The kinetic and thermodynamic behavior of O(2)-binding to Cu(I) complexes can provide fundamental understanding of copper(I)/dioxygen chemistry, which is of interest in chemical and biological systems. Here we report stopped-flow kinetic investigations of the oxygenation reactions of a series of tetradentate copper(I) complexes [(L(R))Cu(I)(MeCN)](+) (1(R), R=H, Me, tBu, MeO, Me(2)N) in propionitrile (EtCN), tetrahydrofuran (THF), and acetone. The syntheses of 4-pyridyl substituted tris(2-pyridylmethyl)amine ligands (L(R)) and copper(I) complexes are detailed. Variations of ligand electronic properties are manifested in the electrochemistry of 1(R) and nu(CO) of [(L(R))Cu(I)-CO](+) complexes. The kinetic studies in EtCN and THF show that the O(2)-reactions of 1(R) follow the reaction mechanism established for oxygenation of 1(H) in EtCN (J. Am. Chem. Soc. 1993, 115, 9506), involving reversible formation (k(1)/k(-1)) of [(L(R))Cu(II)(O(2-))](+) (2(R)), which further reacts (k(2)/k(-2)) with 1(R) to form the 2:1 Cu(2)O(2) complex [[(L(R))Cu(II)](2)(O(2)(2-))](2+) (3(R)). In EtCN, the rate constants for formation of 2(R) (k(1)) are not dramatically affected by the ligand electronic variations. For R = Me and tBu, the kinetic and thermodynamic parameters are very similar to those of the parent complex (1(H)); e.g., k(1) is in the range 1.2 x 10(4) to 3.1 x 10(4) M(-1) s(-1) at 183 K. With the stronger donors R = MeO and Me(2)N, more significant effects were observed, with the expected increase in thermodynamic stability of resultant 2(R) and 3(R) complexes, and decreased dissociation rates. The modest ligand electronic effects manifested in EtCN are due to the competitive binding of solvent and dioxygen to the copper centers. In THF, a weakly coordinating solvent, the formation rate for 2(H) is much faster (>/=100 times) than that in EtCN, and the thermodynamic stabilities of both the 1:1 (K(1)) and 2:1 (beta = K(1)K(2)) copper-dioxygen species are much higher than those in EtCN (e.g., for 2(H), deltaH(o) (K(1))=-41 kJ mol(-1) in THF versus -29.8 kJ mol(-1) in EtCN; for 3(H), deltaH(o) (beta)=-94 kJ mol(-1) in THF versus -77 kJ mol(-1) in EtCN). In addition, a more significant ligand electronic effect is seen for the oxygenation reactions of 1(MeO) in THF compared to that in EtCN; the thermal stability of superoxo- and peroxocopper complexes are considerably enhanced using L(MeO) compared to L(H). In acetone as solvent, a different reaction mechanism involving dimeric copper(I) species [(L(R))(2)Cu(I)(2)](2+) is proposed for the oxygenation reactions, supported by kinetic analyses, electrical conductivity measurements, and variable-temperature NMR spectroscopic studies. The present study is the first systematic study investigating both solvent medium and ligand electronic effects in reactions forming copper-dioxygen adducts.     

Density functional study of the O2 binding to [CuI(TPAR)]+ (TPA = tris(2-pyridylmethyl)amine) in THF and EtCN

Density functional theory using the B3LYP hybrid functional has been employed to study the formation of [Cu(II)(TPA(H))(O2-)]+ and [Cu(II)(TPA(MeO))(O2-)]+ (TPA = tris(2-pyridylmethyl)amine) in two different solvents, THF and EtCN. The thermodynamics of solvent coordination as well as that of the overall reactions with O2 has been computed. The formations of [Cu(II)(TPA(H))(O2-)]+ in THF and of [Cu(II)(TPA(MeO))(O2-)]+ in both THF and EtCN are found to be initiated from the [Cu(I)(TPA(R))]+ species, that is, the Cu complex possessing an empty coordination site. In contrast, the formation of [Cu(II)(TPA(H))(O2-)]+ in EtCN is found to be initiated from the [Cu(I)(TPA(H))(EtCN)]+ species, that is, one solvent molecule being coordinated to Cu(I). In general, good agreement is found between theoretical and experimental results. The high accuracy of the B3LYP functional in reproducing experimental thermodynamic data for the present type of transition metal complexes is demonstrated by the fact that the differences between measured and computed thermodynamic parameters (DeltaG degree, DeltaH degrees , and -TDeltaS degree, in most cases are less than 2.0 kcal mol(-1). An attempt was made to investigate the kinetics of the formation of [Cu(II)(TPA(H))(O2-)]+ in THF and EtCN. Computed free energies of activation, DeltaG, are in good agreement with experimental results. However, an analysis of the partitioning of the free energy barriers in enthalpic and entropic contributions indicates that the computationally studied reaction pathway might differ from the one observed experimentally.     

Further insights into the spectroscopic properties, electronic structure, and kinetics of formation of the heme-peroxo-copper complex [(F8TPP)FeIII-(O2(2-)-CuII(TMPA)]+

In the further development and understanding of heme-copper O2-reduction chemistry inspired by the active-site chemistry in cytochrome c oxidase, we describe a dioxygen adduct, [(F8TPP)FeIII-(O22-)-CuII(TMPA)](ClO4) (3), formed by addition of O2 to a 1:1 mixture of the porphyrinate-iron(II) complex (F8TPP)FeII (1a) {F8TPP = tetrakis(2,6-difluorophenyl)porphyrinate dianion} and the copper(I) complex [(TMPA)CuI(MeCN)](ClO4) (1b) {TMPA = tris(2-pyridylmethyl)amine}. Complex 3 forms in preference to heme-only or copper-only binuclear products, is remarkably stable {t1/2 (RT; MeCN) approximately 20 min; lambda max = 412 (Soret), 558 nm; EPR silent}, and is formulated as a peroxo complex on the basis of manometry {1a/1b/O2 = 1:1:1}, MALDI-TOF mass spectrometry {16O2, m/z 1239 [(3 + MeCN)+]; 18O2, m/z 1243}, and resonance Raman spectroscopy {nu(O-O) = 808 cm-1; Delta16O2/18O2 = 46 cm-1; Delta16O2/16/18O2 = 23 cm-1}. Consistent with a mu-eta2:eta1 bridging peroxide ligand, two metal-O stretching frequencies are observed {nu(Fe-O) = 533 cm-1, nu(Fe-O-Cu) = 511 cm-1}, and supporting normal coordinate analysis is presented. 2H and 19F NMR spectroscopies reveal that 3 is high-spin {also muB = 5.1 +/- 0.2, Evans method} with downfield-shifted pyrrole and upfield-shifted TMPA resonances, similar to the pattern observed for the structurally characterized mu-oxo complex [(F8TPP)FeIII-O-CuII(TMPA)]+ (4) (known S = 2 system, antiferromagnetically coupled high-spin FeIII and CuII). M?ssbauer spectroscopy exhibits a sharp quadrupole doublet (zero field; delta = 0.57 mm/s, |DeltaEQ| = 1.14 mm/s) for 3, with isomer shift and magnetic field dependence data indicative of a peroxide ligand and S = 2 formulation. Both UV-visible-monitored stopped-flow kinetics and M?ssbauer spectroscopic studies reveal the formation of heme-only superoxide complex (S)(F8TPP)FeIII-(O2-) (2a) (S = solvent molecule) prior to 3. Thermal decomposition of mu-peroxo complex 3 yields mu-oxo complex 4 with concomitant release of approximately 0.5 mol O2 per mol 3. Characterization of the reaction 1a/1b + O2 --> 2 --> 3 --> 4, presented here, advances our understanding and provides new insights to heme/Cu dioxygen-binding and reduction.     

An iron-peroxo porphyrin complex: new synthesis and reactivity toward a Cu(II) complex giving a heme-peroxo-copper adduct

Side-on eta2-peroxo-iron porphyrins are strong nucleophiles. In cytochrome P450-like aromatase and other enzymes, such species are postulated as the active oxidants. In cytochrome c oxidase, hemea3-peroxo, hemea3-hydroperoxo, or hemea3-(mu-peroxo)-copper species are proposed as transient intermediates forming prior to O-O bond cleavage. In this report, we describe (1) a facile method for reduction of a heme-O2 species [(F8TPP)FeIII(O2-)(S)] (2), generating the ferric peroxo porphyrin complex [(F8TPP)FeIII(O22-)]- (3) (UV-vis, THF: lambdamax = 435 (Soret), 540(sh), 561; EPR: g = 8.7, 4.2), and (2) that this can be subsequently reacted with a ligand-copper(II) complex, [CuII(TMPA)-(CH3CN)](ClO4)2 (4), affording a heme-peroxo-copper heterobinuclear compound, [(F8TPP)FeII(O22-)-CuII(TMPA)](ClO4) (5). Generation of [(F8TPP)FeIII(O22-)]- (3) using cobaltocene as a one-electron reductant was monitored by UV-vis, EPR, and 1H NMR spectroscopies. Reaction between 3 and 4 was followed by UV-vis spectroscopy, and the product 5 could be precipitated and characterized. Coordination by copper(II) in 5 makes possible further reduction of the mu-peroxo complex by cobaltocene yielding the mu-oxo analogue, [(F8TPP)FeIII(O2-)-CuII(TMPA)](ClO4) (6).     

Efficient photodissociation of O2 from synthetic heme and heme/M (M = Fe, Cu) complexes

Single wavelength excitation (lambdaex = 355 or 532 nm) of low-temperature stabilized (198 K) synthetic heme-dioxygen and heme-dioxygen/M complexes, where M = copper or iron in a non-heme environment, results in the dissociation of dioxygen as indicated by the generation of the ferrous heme (Soret band, 427 nm) and the bleaching of the ferric-superoxide (FeIII(O2-)) 410-nm Soret band in the transient absorption difference spectrum. Dioxygen rebinds to the four heme complexes studied with comparable rate constants ( approximately 6-9 x 105 M-1 s-1). However, the quantum yield for complete dissociation of O2 from our simplest heme-O2 complex (F8)FeIII(O2-) (phi = 0.60) is higher than the other complexes measured (phi = approximately 0.2-0.3) as well as that for oxy-myoglobin (phi = 0.3).     

Generation and characterization of [(P)M-(X)-Co(TMPA)]n+ assemblies; P = Porphyrinate, M = FeIII and CoIII, X = O2-, OH-, O2(2-), and TMPA = tris(2-pyridylmethyl)amine

With the established chemistry of bridged [(porphyrinate)FeIII-X-CuII(ligand)]n+ [X = O2- (oxo), OH- (hydroxo), O22- (peroxo)] complexes, we investigated the effect of cobalt ion substitution for copper or copper and iron. Thus, in this report, the generation and characterization of new mu-oxo, micro-hydroxo, and micro-peroxo (micro-X) assemblies of [(porphyrinate)MIII-X-CoII/III(TMPA)]n+ assemblies is described, where M = FeIII or CoIII and TMPA = tris(2-pyridylmethyl)amine. The mu-oxo complex [(F8TPP)FeIII-O-CoII(TMPA)]+ (1, F8TPP = tetrakis(2,6-difluorphenyl)porphyrinate) was isolated by an acid-base self-assembly reaction of a 1:1 mixture of (F8TPP)FeIII-OH and [CoII(TMPA)(MeCN)]2+ upon addition of triethylamine. The crystal structure of 1.2C4H10O proved the presence of an unsupported Fe-O-Co moiety; angleFe-O-Co = 171.6 degrees and d(Fe...Co) = 3.58 A. Complex 1 was further characterized by UV-vis (lambdamax = 437 (Soret) and 557 nm), 1H NMR [delta 40.6 (pyrrole-H), 8.8 and 8.7 (m-phenyl-H), 8.0 (p-phenyl-H), 4.4 (PY-4H), 2.6 (PY-3H), 1.0 (PY-5H), -1.1 (PY-6H), and -2.7 (TMPA-CH2-) ppm], electrospray ionization (ESI) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometric methods, Evans method NMR (microeff = 3.1), and superconducting quantum interference device (SQUID) susceptometry (J = -114 cm-1, S = 1). The micro-hydroxo analogue [(F8TPP)FeIII-(OH)-CoII(TMPA)]+ (2) [UV-vis lambdamax = 567 nm; delta 78 ppm (pyrrole-H); Evans NMR microeff = 3.7] was generated by addition of 1 equiv of triflic acid to 1. The protonation is completely reversible, and 1 is regenerated from 2 by addition of triethylamine. While (F8TPP)FeII/[CoII(TMPA)(MeCN)]2+/O2 chemistry does not lead to a stable micro-peroxo species, a dicobalt micro-peroxo complex [(TPP)CoIII-(O22-)-CoIII(TMPA)]2+ (3, TPP = meso-tetraphenylporphyrinate) forms from a reaction of O2 with a 1:1 mixture of the CoII precursor components at -80 degrees C [UV-vis lambdamax = 435 (Soret), 548, and 583 (weak) nm; silent EPR spectrum; diamagnetic NMR spectrum]. The oxygenation/deoxygenation equilibrium is reversible; warming solutions of 3 releases approximately 1 equiv of O2 and the reduced complexes are reformed.     

Dioxygen reactivity of a copper(I) complex with a N3S thioether chelate; peroxo-dicopper(II) formation including sulfur-ligation

Employing a tetradentate N3S(thioether) ligand, LN3S, dioxygen reactivity of a copper(I) complex, [(LN3S)CuI]+ (1) was examined. In CH2Cl2, acetone (at -80 degrees C), or 2-methyltetrahydrofuran (at -128 degrees C), 1 reacts with O2 producing the end-on bound peroxodicopper(II) complex [{(LN3S)CuII}2(mu-1,2-O2(2-))]2+ (2), the first reported copper-dioxygen adduct with sulfur (thioether) ligation. Its absorption spectrum contains an additional low-energy feature (but not a Cu-S CT band) compared to the previously well-characterized N4 ligand complex, [{(TMPA)CuII}2(mu-1,2-O2(2-))]2+ (3) (TMPA = tris(2-pyridylmethyl)amine). Resonance Raman spectroscopy confirms the peroxo formulation {nu(O-O) = 817 cm-1 (16-18O2 Delta = 46 cm-1) and nu(Cu-O) = 545 cm-1 (16-18O2 Delta = 26 cm-1), in close analogy to that known for 3 {nu(O-O) = 827 cm-1 and nu(Cu-O) = 561 cm-1}. Direct evidence for thioether ligation comes from EXAFS spectroscopy {Cu K-edge; Cu-S = 2.4 A}.     

Enhanced reactivity of 2-rhodaoxetanes through a labile acetonitrile ligand

New cationic, square-planar, ethene complexes [(Rbpa)RhI(C2H4)]+ [2a]--[2c]+ (Rbpa = N-alkyl-N,N-di(2-pyridylmethyl)amine; [2a]+: alkyl =R=Me; [2b]+: R = Bu; [2c]+: R = Bz) have been selectively oxygenated in acetonitrile by aqueous hydrogen peroxide to 2-rhoda(III)oxetanes with a labile acetonitrile ligand, [(Rbpa)RhIII(kappa2-C,O-CH2CH2O-)(MeCN)]+, [3a]+-[3c]+. The rate of elimination of acetaldehyde from [(Rbpa)RhIII(kappa2-C,O-CH2CH2O-)(MeCN)]+ increases in the order R = Me< R = Bu< R = Bz. Elimination of acetaldehyde from [(Bzbpa)RhIII(kappa2-C,O-CH2CH2O)(MeCN)]+ [3c]+, in the presence of ethene results in regeneration of ethene complex [(Bzbpa)RhI(C2H4)]+ [2c]+, and closes a catalytic cycle. In the presence of Z,Z-1,5-cyclooctadiene (cod) the corresponding cod complex [(Bzbpa)RhI(cod)]+ [6c]+ is formed. Further oxidation of [3c]+ by H2O2 results in the transient formylmethyl-hydroxy complex [(Bzbpa)RhIII(OH)[kappa1-C-CH2C(O)H]]+ [5c]+.     

Role of protons in superoxide reduction by a superoxide reductase analogue

Superoxide reduction by thiolate-ligated [FeII(SMe2N4(tren))]+ (1) involves two proton-dependent steps and a single peroxide intermediate, [FeIII(SMe2N4(tren))(OOH)]+ (2). An external proton donor is required, ruling out mechanisms involving H+ or H-atom abstraction from the ligand N-H. The initial protonation step affording 2 occurs with fairly basic proton donors (EtOH, MeOH, NH4+) in THF. More acidic proton donors are required to cleave the Fe-O(peroxide) bond in MeOH, and this occurs via a dissociative mechanism. Reaction rates are dependent on the pKa of the proton donor, and a common [FeIII(SMe2N4(tren))(MeOH)]2+ (3) intermediate is involved. Acetic acid releases H2O2 from 2 under pseudo-first-order conditions ([HOAc] = 138 mM, [2] = 0.49 mM) with a rate constant of 8.2 x 10(-4) s(-1) at -78 degrees C in MeOH. Reduction of 3 with Cp2Co regenerates the active catalyst 1.     

Photochemical production of a highly reactive porphyrin-iron-oxo species

Oxidation of 5,10,15,20-tetramesitylporphyrinatoiron(III) perchlorate, (TMP)FeIII(ClO4), with ferric perchlorate in acetonitrile gave a metastable species identified as (TMP)FeIV(ClO4)2 that decayed within seconds to the known isomeric species (TMP*+)FeIII(ClO4)2. Irradiation of the metastable species with 355 nm laser light gave a highly reactive transient that reacts with simple organic reductants (alkenes and arylalkanes) 5 orders of magnitude faster than known Compound I analogues, (TMP*+)FeIV(O)(X-).     

Redox couples of inducible nitric oxide synthase

We report direct electrochemistry of the iNOS heme domain in a DDAB film on the surface of a basal plane graphite electrode. Cyclic voltammetry reveals FeIII/II and FeII/I couples at -191 and -1049 mV (vs Ag/AgCl). Imidazole and carbon monoxide in solution shift the FeIII/II potential by +20 and +62 mV, while the addition of dioxygen results in large catalytic waves at the onset of FeIII reduction. Voltammetry at higher scan rates (with pH variations) reveals that the FeIII/II cathodic peak can be resolved into two components, which are attributable to FeIII/II couples of five- and six-coordinate hemes. Digital simulation of our experimental data implicates water dissociation from the heme as a gating mechanism for ET in iNOS.     

Cyano-bridged structures based on [MnIIN3O2-macrocycle)]2+: a synthetic, structural, and magnetic study

Reactions between the complex [MnII(L)]2+, where L is a N3O2 macrocyclic ligand, and different cyanometalate precursors such as [M(CN)n]m- (M(III) = Cr, Fe; M(II) = Fe, Ni, Pd, Pt) lead to cyano-bridged molecular assemblies exhibiting a variety of structural topologies. The reaction between [MnII(L)]2+ and [FeII(CN)6]4- forms a trinuclear complex with formula [(MnII(L)(H2O))2(FeII(micro-CN)2(CN)4)] x 2MeOH x 10H2O (1) which crystallizes in the triclinic space group P1. The reaction between [MnII(L)]2+ and [M(II)(CN)4]2-, where M(II) = Ni (2), Pd (3), Pt (4), gives rise to three isostructural linear chain compounds with stoichiometry [(MnII(L))(M(II)(micro-CN)2(CN)2)]n and which crystallize in the monoclinic space group C2/c. The self-assembly between [MnII(L)]2+ with [M(III)(CN)6]3-, where M(III) = Cr (5), Fe (6, 7, 8), forms three types of compounds. Compounds 5 and 6 are isostructural (monoclinic, space group P2(1)/n), and the structures comprise anionic linear chains [(MnII(L))(M(III)(micro-CN)2(CN)4)]n(n-) with cationic trinuclear complexes [(MnII(L)(H2O))2(M(III)(micro-CN)2(CN)4)]+ as counterions. Using an excess of K3[FeIII(CN)6], an analogous compound to 6 but with K+ as counterion is obtained (7), which crystallizes in the triclinic space group P1. Compound 8 consists of 2-D layers with formula [(MnII(L))3(FeIII(micro-CN)4(CN)2)(FeIII(micro-CN)2(CN)4)]n x 2nMeOH; it crystallizes in the monoclinic space group P2(1)/n. The magnetic properties were investigated for all samples. In particular, compound 5, which shows antiferromagnetic exchange interactions between Mn(II) and Cr(III) ions through cyanide bridging ligands, has been studied in detail; the magnetic exchange parameter amounts to J = -7.5(7) cm(-1). Compound 8 shows a magnetically ordered phase below 6.4 K which is confirmed by M?ssbauer spectroscopy; two hyperfine split spectra were observed below Tc from which IJI values of 2.1 and 1.6 cm(-1) could be deduced.     

Heme/Cu/O2 reactivity: change in FeIII-(O2 2-)-CuII unit peroxo binding geometry effected by tridentate copper chelation

A new heme-peroxo-copper complex structural type with mu-eta2:eta2 peroxo ligation has been generated utilizing a heterobinucleating ligand with bis(2-(2-pyridyl)ethyl)amine tridentate chelate for copper. Oxygenation of [(2L)FeIICuI]+ (1) at -80 degrees C in CH2Cl2/6%EtCN, 1 (lambdamax, 426, 530 nm) produces [(2L)FeIII-(O22-)-CuII)]+ (3) (lambdamax, 419, 488, 544, 575 nm). Stopped-flow kinetic/spectroscopic probing reveals that a superoxo complex, [(2L)FeIII-(O2-)...CuI(NCEt)]+ (2) (lambdamax = 544 nm), initially forms, k1 = 5.23 +/- 0.09 x 104 M-1 s-1 (-105 degrees C). Subsequent intramolecular reaction of the copper(I) ion in 2 occurs with k2 = 2.74 +/- 0.04 x 101 s-1 (-105 degrees C), producing 3. Resonance Raman spectroscopy (rR) confirms the peroxo assignment for 3; nu(O-O) = 747 cm-1 (Delta(18O2) = -40 cm-1). In an 16O-18O mixed isotope experiment a single band is observed at 730 cm-1. The low nu(O-O) value and the absence of a splitting of the 730 cm-1 band are indicative of a symmetrical binding of the peroxide group in a side-on mu-eta2:eta2 geometry. This conclusion is supported by X-ray absorption spectroscopy on 3. Copper K-edge EXAFS indicates a five-coordinate metal center: 2 N, 2.028(7) A; 2 O, 1.898(7) A; 1 N, 2.171(12) A. An outer-sphere Fe scatterer is found at 3.62(1) A. The iron center K-edge EXAFS fits to either a five- or six-coordinate metal center: 4 N(pyrrole), approximately 2.1 A; 1,2 O, approximately 1.9 A. A preedge feature (Fe(1s) --> Fe(3d) transition) at 7113.2(2) eV resembles that obtained for a eta2-peroxo ferric heme complex, being weaker and at approximately 1.5 eV lower energy than those found in five-coordinate (P)FeIII-X (in C4v symmetry) complexes. Arguments based on rR properties of relevant peroxo compounds also effectively point to the copper(II) ion in 3 as being side-on bound, leading to the very low O-O stretching frequency observed in comparison to those of heme-peroxo species or heme-peroxo-copper complexes with a tetradentate copper chelate. These investigations derive from interest in establishing relevant and/or fundamental O2 chemistry at heme-copper centers, in relation to heme-copper oxidase active-site chemistry.     

Iron chelation equilibria, redox, and siderophore activity of a saccharide platform ferrichrome analogue

A complete characterization of the aqueous solution Fe(III) and Fe(II) coordination chemistry of a saccharide-based ferrichrome analogue, 1-O-methyl-2,3,6-tris-O-[4-(N-hydroxy-N-ethylcarbamoyl)-n-butyryl]-alpha-D-glucopyranoside (H3LN236), is reported including relevant thermodynamic parameters and growth promotion activity with respect to both Gram-negative and Gram-positive bacterial strains. The saccharide platform is an attractive backbone for the design and synthesis of ferrichrome analogues because of its improved water solubility and hydrogen-bonding capabilities, which can potentially provide favorable receptor recognition and biological activity. The ligand deprotonation constants (pKa values), iron complex (FeIII(LN236) and FeII(LN236)1-) protonation constants (KFeHxL-236-N), overall Fe(III) and Fe(II) chelation constants (beta110), and aqueous solution speciation were determined by spectrophotometric and potentiometric titrations, EDTA competition equilibria, and cyclic voltammetry. Log betaIII110 = 31.16 and pFe = 26.1 for FeIII(LN236) suggests a high affinity for Fe(III), which is comparable to or greater than ferrichrome and other ferrichrome analogues. The E1/2 for the FeIII(LN236)/FeII(LN236)1- couple was determined to be -454 mV (vs NHE) from quasi-reversible cyclic voltammograms at pH 9. Below pH 6.5, the E1/2 shifts to more positive values and the pH-dependent E1/2 profile was used to determine the FeII(LN236)1- protonation constants and overall stability constant log betaII110 = 11.1. A comparative analysis of similar data for an Fe(III) complex of a structural isomer of this exocyclic saccharide chelator (H3LR234), including strain energy calculations, allows us to analyze the relative effects of the pendant arm position and hydroxamate moiety orientation (normal vs retro) on overall complex stability. A correlation between siderophore activity and iron coordination chemistry of these saccharide-hydroxamate chelators is made.     

Low-temperature UV-visible and NMR spectroscopic investigations of O(2) binding to ((6)L)Fe(II), a ferrous heme bearing covalently tethered axial pyridine ligands

In this report, we describe the reversible dioxygen reactivity of ((6)L)Fe(II) (1) [(6)L = partially fluorinated tetraphenylporphyrin with covalently appended TMPA moiety; TMPA = tris(2-pyridylmethyl)amine] using a combination of low-temperature UV-vis and multinuclear ((1)H and (2)H) NMR spectroscopies. Complex 1, or its pyrrole-deuterated analogue ((6)L-d(8))Fe(II) (1-d(8)), exhibits downfield shifted pyrrole resonances (delta 28-60 ppm) in all solvents utilized [CH(2)Cl(2), (CH(3))(2)C(O), CH(3)CN, THF], indicative of a five-coordinate high-spin ferrous heme, even when there is no exogenous axial solvent ligand present (i.e., in methylene chloride). Furthermore, ((6)L)Fe(II) (1) exhibits non-pyrrolic upfield and downfield shifted peaks in CH(2)Cl(2), (CH(3))(2)C(O), and CH(3)CN solvents, which we ascribed to resonances arising from the intra- or intermolecular binding of a TMPA-pyridyl arm to the ferrous heme. Upon exposure to dioxygen at 193 K in methylene chloride, ((6)L)Fe(II) (1) [UV-vis: lambda(max) = 433 (Soret), 529 (sh), 559 nm] reversibly forms a dioxygen adduct [UV-vis: lambda(max) = 422 (Soret), 542 nm], formulated as the six-coordinate low-spin [delta(pyrrole) 9.3 ppm, 193 K] heme-superoxo complex ((6)L)Fe(III)-(O(2)(-)) (2). The coordination of the tethered pyridyl arm to the heme-superoxo complex as axial base ligand is suggested. In coordinating solvents such as THF, reversible oxygenation (193 K) of ((6)L)Fe(II) (1) [UV-vis: lambda(max) = 424 (Soret), 542 nm] also occurs to give a similar adduct ((6)L)Fe(III)-(O(2)(-)) (2) [UV-vis: lambda(max) = 418 (Soret), 537 nm. (2)H NMR: delta(pyrrole) 8.9 ppm, 193 K]. Here, we are unable to distinguish between a bound solvent ligand or tethered pyridyl arm as axial base ligand. In all solvents, the dioxygen adducts decompose (thermally) to the ferric-hydroxy complex ((6)L)Fe(III)-OH (3) [UV-vis: lambda(max) = 412-414 (Soret), 566-575 nm; approximately delta(pyrrole) 120 ppm at 193 K]. This study on the O(2)-binding chemistry of the heme-only homonuclear ((6)L)Fe(II) (1) system lays the foundation for a more complete understanding of the dioxygen reactivity of heterobinuclear heme-Cu complexes, such as [((6)L)Fe(II)Cu(I)](+), which are models for cytochrome c oxidase.