Dicopper peroxo complexes: low temperature stopped-flow reaction kinetics of [(BQPA)CuI]+ and [(Me2-TMPA)CuI]+.

In the last 20 years, the reaction of many different CuI complexes and with dioxygen has been described. There is quite a big variety in their coordination geometry and most of them have been characterized by X-ray crystallography. Beyond structural information, stopped-flow kinetics experiments have provided additional mechanistic insights. In the particular systems [(BQPA)CuI]+ and [(Me2-TMPA)CuI]+ a new equilibrium between the two species trans-mu-1,2-peroxo and bis-mu-oxo is demonstrated. In the case of [(BQPA)CuI]+ the two species are in an equilibrium, presumably via the transient superoxo species. The reaction of [(Me2-TMPA)CuI]+ with dioxygen leads to the parallel formation of both species. The kinetically preferred trans-mu-peroxo species is then isomerised to the thermodynamically more stable bis-mu-oxo species.

Formation, characterization, and reactivity of bis(mu-oxo)dinickel(III) complexes supported by a series of bis[2-(2-pyridyl)ethyl]amine ligands.

Bis(mu-oxo)dinickel(III) complexes supported by a series of bis[2-(2-pyridyl)ethyl]amine ligands have been successfully generated by treating the corresponding bis(mu-hydroxo)dinickel(II) complexes or bis(mu-methoxo)dinickel(II) complex with an equimolar amount of H(2)O(2) in acetone at low temperature. The bis(mu-oxo)dinickel(III) complexes exhibit a characteristic UV-vis absorption band at approximately 410 nm and a resonance Raman band at 600-610 cm(-1) that shifted to 570-580 cm(-1) upon (18)O-substitution. Kinetic studies and isotope labeling experiments using (18)O(2) imply the existence of intermediate(s) such as peroxo dinickel(II) in the course of formation of the bis(mu-oxo)dinickel(III) complex. The bis(mu-oxo)dinickel(III) complexes supported by the mononucleating ligands (L1(X) = para-substituted N,N-bis[2-(2-pyridyl)ethyl]-2-phenylethylamine; X = OMe, Me, H, Cl) gradually decompose, leading to benzylic hydroxylation of the ligand side arm (phenethyl group). The kinetics of the ligand hydroxylation process including kinetic deuterium isotope effects (KIE), p-substituent effects (Hammett plot), and activation parameters (Delta H(H)(*) and Delta S(H)(*)) indicate that the bis(muxo)dinickel(III) complex exhibits an ability of hydrogen atom abstraction from the substrate moiety as in the case of the bis(mu-oxo)dicopper(III) complex. Such a reactivity of bis(mu-oxo)dinickel(III) complexes has also been suggested by the observed reactivity toward external substrates such as phenol derivatives and 1,4-cyclohexadiene. The thermal stability of the bis(mu-oxo)dinickel(III) complex is significantly enhanced when the dinucleating ligand with a longer alkyl strap is adopted instead of the mononucleating ligand. In the m-xylyl ligand system, no aromatic ligand hydroxylation occurred, showing a sharp contrast with the reactivity of the (mu-eta(2):eta(2)-peroxo)dicopper(II) complex with the same ligand which induces aromatic ligand hydroxylation via an electrophilic aromatic substitution mechanism. Differences in the structure and reactivity of the active oxygen complexes between the nickel and the copper systems are discussed on the basis of the detailed comparison of these two systems with the same ligand.

(F(8)TPP)Fe(II)/O(2) reactivity studies [F(8)TPP = tetrakis(2,6-difluorophenyl)porphyrinate(2-)]: spectroscopic (UV-Visible and NMR) and kinetic study of solvent-dependent (Fe/O(2) = 1:1 or 2:1) reversible O(2)-reduction and ferryl formation.

In this report, we describe in detail the O(2)-binding chemistry of the metalloporphyrin (F(8)TPP)Fe(II) (1). This complex was synthesized from aqueous dithionite reduction of (F(8)TPP)Fe(III)-Cl (X-ray structure reported: C(55)H(36)ClF(8)FeN(4)O; a = 13.6517(2) A, b = 13.6475(2) A, c = 26.3896(4), alpha = 90 degrees, beta = 89.9776(4) degrees, gamma = 90 degrees; monoclinic, P2(1)/c, Z = 4). Complex 1 crystallizes from toluene/heptane solvent system as a bis(toluene) solvate, (F(8)TPP)Fe(II).(C(7)H(8))(2), with ferrous ion in the porphyrin plane (C(58)H(36)F(8)FeN(4); a = 20.9177(2) A, b = 11.7738(2) A, c = 19.3875(2), alpha = 90 degrees, beta = 108.6999(6) degrees, gamma = 90 degrees; monoclinic, C2/c, Z = 4; Fe-N(4)(av) = 2.002 A; N-Fe-N (all) = 90.0 degrees ). Close metal-arene contacts are also observed at 3.11-3.15 A. Upon oxygenation of 1 at 193 K in coordinating solvents, UV-visible and (2)H and (19)F NMR spectroscopies revealed the presence of a reversibly formed dioxygen adduct, formulated as the heme-superoxo complex (S)(F(8)TPP)Fe(III)-(O(2)(-)) (2) (S = solvent) [(i) tetrahydrofuran (THF) solvent: UV-visible, 416 (Soret), 536 nm; (2)H NMR: delta(pyrrole) 8.9 ppm; (ii) EtCN solvent: UV-visible, 414 (Soret), 536 nm; (iii) acetone solvent: UV-visible, 416 (Soret), 537 nm; (2)H NMR: delta(pyrrole) 8.9 ppm]. Dioxygen-uptake manometry (THF, 193 K) revealed an O(2):1 oxygenation stoichiometry of 1.02:1, consistent with the heme-superoxo formulation of 2. Stopped-flow UV-visible spectrophotometry studies of the (F(8)TPP)Fe(II) (1)/O(2) reaction in EtCN and THF solvents were able to provide kinetic and thermodynamic insight into the reversible formation of 2 [(i) EtCN: Delta H degrees = -40 +/- 5 kJ/mol; Delta S degrees = -105 +/- 23 J/(K mol); k(1) = (5.57 +/- 0.04) x 10(3) M(-)(1) s(-)(1) (183 K); Delta H(++) = 38.6 +/- 0.2 kJ/mol; Delta S(++) = 42 +/- 1 J/(K mol); (ii) THF: Delta H* = -37.5 +/- 0.4 kJ/mol; Delta S* = -109 +/- 2 J/(K mol)]. The (F(8)TPP)Fe(II) (1)/O(2) reaction was also examined at reduced temperatures in noncoordinating solvents (toluene, CH(2)Cl(2)), where UV-visible and (2)H and (19)F NMR spectroscopies also revealed the presence of a reversibly formed adduct, formulated as the peroxo-bridged dinuclear complex [(F(8)TPP)Fe(III)](2)-(O(2)(2)(-)) (3) [CH(2)Cl(2): UV-visible, 414 (Soret), 535 nm; (2)H NMR, delta(pyrrole) 17.5 ppm]. Dioxygen-uptake spectrophotometric titrations revealed a stoichiometry of 2 (F(8)TPP)Fe(II) (1) per O(2) upon full formation of 3. Addition of a nitrogenous base, 4-(dimethylamino)pyridine, to a cold solution of 3 in dichloromethane gave rapid formation of the iron(IV)-oxo ferryl species (DMAP)(F(8)TPP)Fe(IV)==O (4), based upon UV-visible [417 (Soret), 541 nm] and (2)H NMR (delta(pyrrole) = 3.5 ppm) spectroscopic characterization. These detailed investigations into the O(2)-adducts and "ferryl" species formed from (F(8)TPP)Fe(II) (1) may be potentially important for a full understanding of our ongoing heme-copper oxidase model studies, which employ 1 or similar "tethered" (i.e., covalently attached Cu-chelate) porphyrin analogues in heme/Cu heterobinuclear systems.

Isocyanide binding to the copper(I) centers of the catalytic core of peptidylglycine monooxygenase (PHMcc).

Binding of the Cu(I)-specific ligands 2,6-dimethylphenyl isocyanide (DIMPI) and isopropyl isocyanide (IPI) to the reduced form of peptidylglycine monooxygenase (PHM) is reported. Both ligands bind to the methionine-containing CuM center, eliciting FTIR bands at 2,138 and 2,174 cm(-1), respectively, but appear unable to coordinate at the histidine-containing CuH center in the wild-type enzyme. This chemistry parallels that previously observed for CO binding to the reduced PHM catalytic core (PHMcc). However, in contrast to the CO chemistry, peptide substrate binding did not induce binding of the isocyanide at CuH. XAS confirmed the binding of DIMPI at CuM via the observation of a short Cu-C interaction at 1.87 A and by the lengthening of the Cu-S(methionine) bond length by 0.06 A. Similarly, FTIR studies on DIMPI binding to the M314I and H172A mutant forms of reduced PHMcc confirmed the assignment of the 2,138-cm(-1) IR band as a CuM-DIMPI complex, but surprisingly also showed DIMPI binding to CuH, as indicated by a band at 2,148 cm(-1). An inorganic complex, [Cu(1,2-Me2Im)2(DIMPI)](PF6), was synthesized and its crystal structure was determined as a model for the interaction of isocyanides with imidazole-containing Cu(I) complexes. Comparison of EXAFS data for the protein and model suggests that DIMPI probably binds to CuM in a tilted fashion, similar to that of ethyl isocyanide binding to myoglobin.

Copper(I) complexes, copper(I)/O(2) reactivity, and copper(II) complex adducts, with a series of tetradentate tripyridylalkylamine tripodal ligands.

Copper(I) and copper(II) complexes possessing a series of related ligands with pyridyl-containing donors have been investigated. The ligands are tris(2-pyridylmethyl)amine (tmpa), bis[(2-pyridyl)methyl]-2-(2-pyridyl)ethylamine (pmea), bis[2-(2-pyridyl)ethyl]-(2-pyridyl)methylamine (pmap), and tris[2-(2-pyridyl)ethyl]amine (tepa). The crystal structures of the protonated ligand H(tepa)ClO(4), the copper(I) complexes [Cu(pmea)]PF(6) (1b-PF(6)), [Cu(pmap)]PF(6) (1c-PF(6)), and copper(II) complexes [Cu(pmea)Cl]ClO(4).H(2)O (2b-ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4).H(2)O (2c-ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4) (2c-ClO(4)), and [Cu(pmea)F](2)(PF(6))(2) (3b-PF(6)) were determined. Crystal data: H(tepa)ClO(4), formula C(21)H(25)ClN(4)O(4), triclinic space group P1, Z = 2, a = 10.386(2) A, b = 10.723(2) A, c = 11.663(2) A, alpha = 108.77(3) degrees, beta = 113.81(3) degrees, gamma = 90.39(3) degrees; 1b-PF(6), formula C(19)H(20)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a = 14.413(3) A, b = 16.043(3) A, c = 18.288(4) A, alpha = beta = gamma = 90 degrees; (1c-PF(6)), formula C(20)H(22)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a = 13.306(3) A, b = 16.936(3) A, c = 19.163(4) A, alpha = beta = gamma = 90 degrees; 2b-ClO(4).H(2)O, formula C(19)H(22)Cl(2)CuN(4)O(5), triclinic space group P1, Z = 4, a = 11.967(2) A, b = 12.445(3) A, c = 15.668(3) A, alpha = 84.65(3) degrees, beta = 68.57(3) degrees, gamma = 87.33(3) degrees; 2c-ClO(4).H(2)O, formula C(20)H(24)Cl(2)CuN(4)O(5), monoclinic space group P2(1)/c, Z = 4, a = 11.2927(5) A, b = 13.2389(4) A, c = 15.0939(8) A, alpha = gamma = 90 degrees, beta = 97.397(2) degrees; 2c-ClO(4), formula C(20)H(22)Cl(2)CuN(4)O(4), monoclinic space group P2(1)/c, Z = 4, a = 8.7682(4) A, b = 18.4968(10) A, c = 13.2575(8) A, alpha = gamma = 90 degrees, beta = 94.219(4) degrees; 3b-PF(6), formula [C(19)H(20)CuF(7)N(4)P](2), monoclinic space group P2(1)/n, Z = 2, a = 11.620(5) A, b = 12.752(5) A, c = 15.424(6) A, alpha = gamma = 90 degrees, beta = 109.56(3) degrees. The oxidation of the copper(I) complexes with dioxygen was studied. [Cu(tmpa)(CH(3)CN)](+) (1a) reacts with dioxygen to form a dinuclear peroxo complex that is stable at low temperatures. In contrast, only a very labile peroxo complex was observed spectroscopically when 1b was reacted with dioxygen at low temperatures using stopped-flow kinetic techniques. No dioxygen adduct was detected spectroscopically during the oxidation of 1c, and 1d was found to be unreactive toward dioxygen. Reaction of dioxygen with 1a-PF(6), 1b-PF(6), and 1c-PF(6) at ambient temperatures leads to fluoride-bridged dinuclear copper(II) complexes as products. All copper(II) complexes were characterized by UV-vis, EPR, and electrochemical measurements. The results manifest the dramatic effects of ligand variations and particularly chelate ring size on structure and reactivity.

Dicopper(I) complexes of unsymmetrical binucleating ligands and their dioxygen reactivities.

The design, synthesis, and characterization of binuclear copper(I) complexes and investigations of their dioxygen reactivities are of interest in understanding fundamental aspects of copper/O2 reactivity and in modeling copper enzyme active-site chemistry. In the latter regard, unsymmetrical binuclear systems are of interest. Here, we describe the chemistry of new unsymmetrical binuclear copper complexes, starting with the binucleating ligand UN2-H, possessing a m-xylyl moiety linking a bis[2-(2-pyridyl)ethyl]amine (PY2) tridentate chelator and a 2-[2-(methylamino)ethyl]pyridine bidentate group. Dicopper(I) complexes of UN2-H, [Cu2(UN2-H)]2+ (1), as PF6- and ClO4- salts, are synthesized. These react with O2 (Cu:O2 = 2:1, manometry) resulting in the hydroxylation of the xylyl moiety, producing the phenoxohydroxodicopper(II) complex [Cu2(UN2-O-)(OH-)(CH3CN)]2+ (2). Compound 2(PF6)2 is characterized by X-ray crystallography, which reveals features similar to those of a structure described previously (Karlin, K. D.; et al. J. Am. Chem. Soc. 1984, 106, 2121-2128) for a symmetrical binucleating analogue having two tridentate PY2 moieties; here a CH3CN ligand replaces one pyridylethyl arm. Isotope labeling from a reaction of 1 using 18O2 shows that the ligand UN2-OH, extracted from 2, possesses an 18O-labeled phenol oxygen atom. Thus, the transformation 1 + O2-->2 represents a monooxygenase model system. [CuI2(UN2-OH)(CH3CN)]2+ (3), a new binuclear dicopper(I) complex with an unsymmetrical coordination environment is generated either by reduction of 2 with diphenylhydrazine or in reactions of cuprous salts with UN2-OH. Complex 3 reacts with O2 at -80 degrees C, producing the (mu-1,1-hydroperoxo)dicopper(II) complex [CuII2(UN2-O-)(OOH-)]2+ (4) (lambda max 390 nm (epsilon 4200 M-1 cm-1), formulated on the basis of the stoichiometry of O2 uptake by 3 (Cu:O2 = 2:1, manometry), its reaction with PPh3 giving O=PPh3 (85%), and comparison to previously studied close analogues. Discussions include the relevance and comparison to other copper bioinorganic chemistry.

Dioxygen-binding kinetics and thermodynamics of a series of dicopper(I) complexes with bis[2-(2-pyridyl)ethyl]amine tridendate chelators forming side-on peroxo-bridged dicopper(II) adducts.

Copper-dioxygen interactions are of interest due to their importance in biological systems as reversible O2- carriers, oxygenases, or oxidases and also because of their role in industrial and laboratory oxidation processes. Here we report on the kinetics (stopped-flow, -90 to 10 degrees C) of O2-binding to a series of dicopper(I) complexes, [Cu2(Nn)(MeCN)2]2+ (1Nn) (-(CH2)n- (n = 3-5) linked bis[(2-(2-pyridyl)ethyl]amine, PY2) and their close mononuclear analogue, [(MePY2)Cu(MeCN)]+ (3), which form mu-eta 2:eta 2-peroxodicopper(II) complexes [Cu2(Nn)-(O2)]2+ (2Nn) and [(MePY2)Cu]2(O2)]2+ (4), respectively. The overall kinetic mechanism involves initial reversible (k+,open/k-,open) formation of a nondetectable intermediate O2-adduct [Cu2(Nn)(O2)]2+ (open), suggested to be a CuI...CuII-O2- species, followed by its reversible closure (k+,closed/k-,closed) to form 2Nn. At higher temperatures (253 to 283 K), the first equilibrium lies far to the left and the observed rate law involves a simple reversible binding equilibrium process (kon,high = (k+,open/k-,open)(k+,closed)). From 213 to 233 K, the slow step in the oxygenation is the first reaction (kon,low = k+,open), and first-order behavior (in 1Nn and O2) is observed. For either temperature regime, the delta H++ for formation of 2Nn are low (delta H++ = -11 to 10 kJ/mol; kon,low = 1.1 x 10(3) to 4.1 x 10(3) M-1 s-1, kon,high = 2.2 x 10(3) to 2.8 x 10(4) M-1 s-1), reflecting the likely occurrence of preequilibria. The delta H degree ranges between -81 and -84 kJ mol-1 for the formation of 2Nn, and the corresponding equilibrium constant (K1) increases (3 x 10(8) to 5 x 10(10) M-1; 183 K) going from n = 3 to 5. Below 213 K, the half-life for formation of 2Nn increases with, rather than being independent of, the concentration of 1Nn, probably due to the oligomerization of 1Nn at these temperatures. The O2 reaction chemistry of 3 in CH2Cl2 is complicated, including the presence of induction periods, and could not be fully analyzed. However, qualitative comparisons show the expected slower intermolecular reaction of 3 with O2 compared to the intramolecular first-order reactions of 1Nn. Due to the likelihood of the partial dimerization of 3 in solution, the t1/2 for the formation of 4 remains constant with increasing complex concentration rather than decreasing. Acetonitrile significantly influences the kinetics of the O2 reactions with 1Nn and 3. For 1N4, the presence of MeCN inhibits the formation of a previously (Jung et al, J. Am. Chem. Soc. 1996, 118, 3763-3764) observed intermediate. Small amounts of added MeCN considerably slow the oxygenation rates of 3, inhibit its full formation to 4, and increase the length of the induction period. The results for 1Nn and their mononuclear analogue 3 are presented, and they are compared with each other as well as with other dinucleating dicopper(I) systems.

Dioxygen-activating bio-inorganic model complexes.

The study of model compounds continues to significantly contribute to our understanding of the role of transition metals at the active sites of enzymes. Recent advances in the field include the use of mimics for enzymes that activate dioxygen, as dioxygen is not only manipulated in nature but also has industrial significance in metal-catalyzed oxidations of organics. Copper, nonheme and heme iron coordination complexes have been used to mimic reversible dioxygen-binding by the three classes of blood-oxygen carriers - hemocyanin, hemerythrin and hemoglobin/myoglobin - while functional mimics of oxygenases and oxidases with copper and iron have also provided key insights into important dioxygen activation processes.

Extended metal environments of cytochrome c oxidase structures.

The metals of the cytochrome c oxidase structures of the bovine heart mitochondrion (PDB code 1occ) and of the soil bacterium Paracoccus denitrificans (1arl) include a dicopper center (CuA), magnesium, two proximal hemes, a copper (CuB) atom, and a calcium. The mitochondrial structure also possesses a bound distant zinc ion. The extended environments of the metal sites are analyzed emphasizing residues of the second shell in terms of polarity, hydrophobicity, secondary structure, solvent accessibility, and H-bonding networks. A significant difference in the CuA metal environments concerns D-51 I in 1occ, absent from 1arl. The D-51 I appears to play an important role in the proton pumping pathway. Our analysis uncovers several statistically significant residue clusters, including a cysteine-histidine-tyrosine cluster overlapping the CuA-Mg complex; a histidine-acidic cluster enveloping the environment of Mg, the two hemes, and CuB; and on the protein surface a mixed charge cluster, which may help stabilize the quaternary structure and/or mediate docking to cytochrome c. These clusters may constitute possible pathways for electron transfer, for O2 diffusion, and for H2O movement. Many hydrogen bonding relations along the interface of subunits I and II demarcate this surface as a potential participant in proton pumping.

The extended environment of mononuclear metal centers in protein structures.

The objectives of this and the following paper are to identify commonalities and disparities of the extended environment of mononuclear metal sites centering on Cu, Fe, Mn, and Zn. The extended environment of a metal site within a protein embodies at least three layers: the metal core, the ligand group, and the second shell, which is defined here to consist of all residues distant less than 3.5 A from some ligand of the metal core. The ligands and second-shell residues can be characterized in terms of polarity, hydrophobicity, secondary structures, solvent accessibility, hydrogen-bonding interactions, and membership in statistically significant residue clusters of different kinds. Findings include the following: (i) Both histidine ligands of type I copper ions exclusively attach the Ndelta1 nitrogen of the histidine imidazole ring to the metal, whereas histidine ligands for all mononuclear iron ions and nearly all type II copper ions are ligated via the Nepsilon2 nitrogen. By contrast, multinuclear copper centers are coordinated predominantly by histidine Nepsilon2, whereas diiron histidine contacts are predominantly Ndelta1. Explanations in terms of steric differences between Ndelta1 and Nepsilon2 are considered. (ii) Except for blue copper (type I), the second-shell composition favors polar residues. (iii) For blue copper, the second shell generally contains multiple methionine residues, which are elements of a statistically significant histidine-cysteine-methionine cluster. Almost half of the second shell of blue copper consists of solvent-accessible residues, putatively facilitating electron transfer. (iv) Mononuclear copper atoms are never found with acidic carboxylate ligands, whereas single Mn2+ ion ligands are predominantly acidic and the second shell tends to be mostly buried. (v) The extended environment of mononuclear Fe sites often is associated with histidine-tyrosine or histidine-acidic clusters.

Metalloenzymes, structural motifs, and inorganic models.

Metalloenzymes effect a variety of important chemical transformations, often involving small molecule substrates or products such as molecular oxygen, hydrogen, nitrogen, and water. A diverse array of ions or metal clusters is observed at the active-site cores, but living systems use basic recurring structures that have been modified or tuned for specific purposes. Inorganic chemists are actively involved in the elucidation of the structure, spectroscopy, and mechanism of action of these biological catalysts, in part through a synthetic modeling approach involving biomimetic studies.