Nitric oxide reactivity of copper(II) complexes of bidentate amine ligands: effect of substitution on ligand nitrosation

Three copper(ii) complexes with bidentate ligands L(1), L(2) and L(3) [L(1), N,N(/)-dimethylethylenediamine; L(2), N,N(/)-diethylethylenediamine and L(3), N,N(/)-diisobutylethylenediamine], respectively, were synthesized as their perchlorate salts. The single crystal structures for all the complexes were determined. The nitric oxide reactivity of the complexes was studied in acetonitrile solvent. The formation of thermally unstable [Cu(II)-NO] intermediate on reaction of the complexes with nitric oxide in acetonitrile solution was observed prior to the reduction of copper(II) centres to copper(I). The reduction was found to result with a simultaneous mono- and di-nitrosation at the secondary amine sites of the ligand. All the nitrosation products were isolated and characterized. The ratio of the yield of mono- and di-nitrosation product was found to be dependent on the N-substitution present in the ligand framework.     

Galactose oxidase models: solution chemistry, and phenoxyl radical generation mediated by the copper status

Galactose oxidase (GO) is an enzyme that catalyzes two-electron oxidations. Its active site contains a copper atom coordinated to a tyrosyl radical, the biogenesis of which requires copper and dioxygen. We have recently studied the properties of electrochemically generated mononuclear Cu(II)-phenoxyl radical systems as model compounds of GO. We present here the solution chemistry of these ligands under various copper and dioxygen statuses: N(3)O ligands first chelate Cu(II), leading, in the presence of base, to [Cu(II)(ligand)(CH(3)CN)](+) complexes (ortho-tert-butylated ligands) or [(Cu(II))(2)(ligand)(2)](2+) complexes (ortho-methoxylated ligands). Excess copper(II) then oxidizes the complex to the corresponding mononuclear Cu(II)-phenoxyl radical species. N(2)O(2) tripodal ligands, in the presence of copper(II), afford directly a copper(II)-phenoxyl radical species. Addition of more than two molar equivalents of copper(II) affords a Cu(II)-bis(phenoxyl) diradical species. The donor set of the ligand directs the reaction towards comproportionation for ligands possessing an N(3)O donor set, while disproportionation is observed for ligands possessing an N(2)O(2) donor set. These results are discussed in the light of recent results concerning the self-processing of GO. A path involving copper(II) disproportionation is proposed for oxidation of the cross-linked tyrosinate of GO, supporting the fact that both copper(I) and copper(II) activate the enzyme.     

Tale of a twist: magnetic and optical switching in copper(II) semiquinone complexes

An intermediate (C) that is observed in both phenol hydroxylation and catechol oxidation with the side-on peroxide species [Cu(2)O(2)(DBED)(2)](2+) (DBED = N(1),N(2)-di-tert-butylethane-1,2-diamine) is identified as a copper(II) semiquinone species ([1](+)) through independent synthesis and characterization. The reaction of the redox-active 3,5-di-tert-butylquinone ligand with [(DBED)Cu(I)(MeCN)](+) yields a copper(II) semiquinone [1](+) complex with a singlet ground state and an intense purple chromophore (ε(580) ~ 3500 M(-1) cm(-1)). All other copper(II) semiquinone complexes characterized to date are paramagnetic and weakly colored (ε(800) ~ 500 M(-1) cm(-1)). Antiferromagnetic coupling between the Cu(II) center and the semiquinone radical in [1](+) is characterized by paramagnetic (1)H NMR and SQUID magnetometry. Comparative X-ray crystal structures along with density functional theory calculations correlate the geometric structures of copper(II) semiquinone complexes with their magnetic and optical properties. The unique observable properties of [1](+) originate from an increase in the overlap of the Cu 3d and semiquinone π orbitals resulting from a large rhombic distortion in the structure with a twist of 51°, attributable to the large isotropic demands of the tert-butyl substituents of the DBED ligand. Independent characterization of [1](+) allows the spectroscopic yields of intermediate C to be quantified in this intriguing hydroxylation reaction.     

Fine-tuning of copper(I)-dioxygen reactivity by 2-(2-pyridyl)ethylamine bidentate ligands

Copper(I)-dioxygen reactivity has been examined using a series of 2-(2-pyridyl)ethylamine bidentate ligands (R1)Py1(R2,R3). The bidentate ligand with the methyl substituent on the pyridine nucleus (Me)Py1(Et,Bz) (N-benzyl-N-ethyl-2-(6-methylpyridin-2-yl)ethylamine) predominantly provided a (mu-eta(2):eta(2)-peroxo)dicopper(II) complex, while the bidentate ligand without the 6-methyl group (H)Py1(Et,Bz) (N-benzyl-N-ethyl-2-(2-pyridyl)ethylamine) afforded a bis(mu-oxo)dicopper(III) complex under the same experimental conditions. Both Cu(2)O(2) complexes gradually decompose, leading to oxidative N-dealkylation reaction of the benzyl group. Detailed kinetic analysis has revealed that the bis(mu-oxo)dicopper(III) complex is the common reactive intermediate in both cases and that O[bond]O bond homolysis of the peroxo complex is the rate-determining step in the former case with (Me)Py1(Et,Bz). On the other hand, the copper(I) complex supported by the bidentate ligand with the smallest N-alkyl group ((H)Py1(Me,Me), N,N-dimethyl-2-(2-pyridyl)ethylamine) reacts with molecular oxygen in a 3:1 ratio in acetone at a low temperature to give a mixed-valence trinuclear copper(II, II, III) complex with two mu(3)-oxo bridges, the UV-vis spectrum of which is very close to that of an active oxygen intermediate of lacase. Detailed spectroscopic analysis on the oxygenation reaction at different concentrations has indicated that a bis(mu-oxo)dicopper(III) complex is the precursor for the formation of trinuclear copper complex. In the reaction with 2,4-di-tert-butylphenol (DBP), the trinuclear copper(II, II, III) complex acts as a two-electron oxidant to produce an equimolar amount of the C[bond]C coupling dimer of DBP (3,5,3',5'-tetra-tert-butyl-biphenyl-2,2'-diol) and a bis(mu-hydroxo)dicopper(II) complex. Kinetic analysis has shown that the reaction consists of two distinct steps, where the first step involves a binding of DBP to the trinuclear complex to give a certain intermediate that further reacts with the second molecule of DBP to give another intermediate, from which the final products are released. Steric and/or electronic effects of the 6-methyl group and the N-alkyl substituents of the bidentate ligands on the copper(I)-dioxygen reactivity have been discussed.     

mu-eta2:eta2-peroxodicopper(II) complex with a secondary diamine ligand: a functional model of tyrosinase

The activation of dioxygen (O(2)) by Cu(I) complexes is an important process in biological systems and industrial applications. In tyrosinase, a binuclear copper enzyme, a mu-eta(2):eta(2)-peroxodicopper(II) species is accepted generally to be the active oxidant. Reported here is the characterization and reactivity of a mu-eta(2):eta(2)-peroxodicopper(II) complex synthesized by reacting the Cu(I) complex of the secondary diamine ligand N,N'-di-tert-butyl-ethylenediamine (DBED), [(DBED)Cu(MeCN)](X) (1.X, X = CF(3)SO(3)(-), CH(3)SO(3)(-), SbF(6)(-), BF(4)(-)), with O(2) at 193 K to give [[Cu(DBED)](2)(O(2))](X)(2) (2.X(2)). The UV-vis and resonance Raman spectroscopic features of 2 vary with the counteranion employed yet are invariant with change of solvent. These results implicate an intimate interaction of the counteranions with the Cu(2)O(2) core. Such interactions are supported further by extended X-ray absorption fine structure (EXAFS) analyses of solutions that reveal weak copper-counteranion interactions. The accessibility of the Cu(2)O(2) core to exogenous ligands such as these counteranions is manifest further in the reactivity of 2 with externally added substrates. Most notable is the hydroxylation reactivity with phenolates to give catechol and quinone products. Thus the strategy of using simple bidentate ligands at low temperatures provides not only spectroscopic models of tyrosinase but also functional models.     

Synthesis, spectroscopy and redox behaviors of 4,6-di-t-Bu-, 4-Me-6-t-Bu- and 4-t-Bu-2-nitrosophenolato copper(II) complexes; Characterization of radical species generated by PPh3

The synthesis, spectroscopy (IR, UV-Vis, ESR), magnetic and thermal behaviors, as well electrochemistry and reactivity towards PPh3 of alkyl-substituted bis(2-nitrosophenolato)copper(II) complexes, CuLx2, where Lx = 4,6-di-t-Bu-2-nitrosophenolato (L1), 4-CH3-6-t-Bu-2-nitrosophenolato (L2), 4-t-Bu-2-nitrosophenolato (L3) mono-anion ligands, are presented. The solid-state and solution ESR spectra showed an axially symmetric g-tensors with gII > g 2.03 indicating that the unpaired electron is located in the dx2 - y2orbital. When CuLx2 complexes were treated with an excess of PPh3 in air or under vacuum in toluene (or other solutions) at 300K, as confirmed by UV-Vis and ESR examination, without formation of PPh3 adduct of the complexes, the immediately generation of semiquinone type radical species and reduction of Cu(II) to Cu(I) were observed. In the case of CuL(1)(2) the further conversion of the generated primary radical species to secondary bis(PPh3)2(phenoxazinolato)Cu(I) semiquinone type radical was detected. The cyclic voltammetry (CV) of CuLx2 exhibited two successive quasi-reversible ligand centered reductions and two irreversible metal and ligand centered oxidation processes. Electrochemical behaviors were interpreted in terms of the existence two-valence tautomeric nitroso and oximato isomers of CuLx2 in solution.     

Oxidative double dehalogenation of tetrachlorocatechol by a bio-inspired CuII complex: formation of chloranilic acid

Copper(II) complexes of the potentially tripodal N,N,O ligand 3,3-bis(1-methylimidazol-2-yl)propionate (L1) and its conjugate acid HL1 have been synthesised and structurally and spectroscopically characterised. The reaction of equimolar amounts of ligand and CuII resulted in the complexes [Cu(L1)]n(X)n (X=OTf-, PF6(-); n=1,2), for which a new bridging coordination mode of L1 is inferred. Although these complexes showed moderate catecholase activity in the oxidation of 3,5-di-tert-butylcatechol, surprising reactivity with the pseudo-substrate tetrachlorocatechol was observed. A chloranilato-bridged dinuclear CuII complex was isolated from the reaction of [Cu(L1)]n(PF6)n with tetrachlorocatechol. This stoichiometric oxidative double dehalogenation of tetrachlorocatechol to chloranilic acid by a biomimetic copper(II) complex is unprecedented. The crystal structure of the product, [Cu2(ca)Cl2(HL1)2], shows a bridging bis-bidentate chloranilato (ca) ligand and ligand L1 coordinated as its conjugate acid (HL1) in a tridentate fashion. Magnetic susceptibility studies revealed weak antiferromagnetic coupling (J= -35 cm(-1)) between the two copper centres in the dinuclear complex. Dissolution of the green complex [Cu2(ca)Cl2(HL1)2] resulted in the formation of new pink-purple mononuclear compound [Cu(ca)(HL1)(H2O)], the crystal structure of which was determined. It showed a terminal bidentate chloranilato ligand and N,N-bidentate coordination of ligand HL1, which illustrates the flexible coordination chemistry of ligand L1.     

Synthesis and reactivity of copper(I) complexes with an ethylene-bridged bis(imidazolin-2-imine) ligand

A series of copper(I) complexes with a sterically hindered, bidentate ligand, BL iPr, derived from an N-heterocyclic carbene precursor have been isolated, characterized and their reactivity studied. The ethylene-bridged bis(imidazolin-2-imine) ligand (BL iPr) provides strongly donating N-donor atoms for the stabilization of a copper(I) metal center, priming it for reactivity. The complexes [(BL iPr)Cu(XyNC)]PF6 (4) and [(BL iPr)CuCl] (5) were characterized by X-ray crystallography and exhibit trigonal coordination at the copper centers. The reactivity of [(BL iPr)Cu]SbF6 toward dioxygen was studied at low temperature, indicating formation of a thermally sensitive intermediate with intense UV/Vis features and an isotope-sensitive vibration at 625 cm(-1) (599 cm(-1) with 18 O2). The intermediate is assigned as containing the bis(mu-oxo)dicopper(III) core, [2](PF6)2, and the related, stable hydroxo form was crystallized as [{(BL iPr)Cu}2(mu-OH)2](PF6)2, [3](PF6)2. The reactivity of 5 as a catalyst for the ATR polymerization of styrene was assessed in terms of reaction kinetics and polymer properties, with low PDI values achieved for polymers with molecular weights up to 30 000 g mol(-1).     

Synthesis, spectroscopic characterization and ESR studies on electron transfer reactions of bis[N-(2,6-di-tert-butyl-1-hydroxyphenyl)salicylaldiminato]-copper(II) complexes with PbO2 and PPh3

New bis[N-(2,6-di-t-butyl-1-hydroxyphenyl)salicylideneminato]copper(II) complexes bearing HO and CH3O substituents on the salicyaldehyde moiety were prepared, and their spectroscopic properties, as well as redox reactivity towards PbO2 and PPh3, examined by ESR and UV spectroscopy. In the process of synthesis of HO complexes unlike CH3O the oxidative C-C coupling of coordinated salicylaldimine ligands does not takes place. The powder ESR spectra of CH3O substituted complexes unlike of HO analogues are typical of a triplet state Cu(II) dimers with a half-field forbidden (deltaM = +/- 2) transition and the allowed transitions (AM = +/- 1) dimeric form of the complexes at 300 and 113 K. The one-electron oxidation of 3-CH3O and all of the OH complexes with PbO2 to give indophenoxyl type secondary radicals which are significantly different from those observed for analogues Cl, Br and NO2 substituted chelates. The presented complexes unlike their electron-withdrawing analogues are readily reduced by PPh3 via intramolecular electron transfer from ligand to copper(II) to give various radical intermediates as well as Cu(I) radical ligand compounds. The analysis of ESR spectra all of the complexes and radical intermediates are presented.     

Mononuclear and binuclear copper(I) complexes ligated by bis(3,5-diisopropyl-1-pyrazolyl)methane: insight into the fundamental coordination chemistry of three-coordinate copper(I) complexes with a neutral coligand

By using the neutral bidentate nitrogen-containing ligand, bis(3,5-diisopropyl-1-pyrazolyl)methane (L1' '), the copper(I) complexes [Cu(L1' ')2](CuCl2) (1CuCl2), [Cu(L1' ')2](ClO4) (1ClO4), [Cu(L1' ')]2(ClO4)2 (2ClO4), [Cu(L1' ')]2(BF4)2 (2BF4), [Cu(L1' ')(NCMe)](PF6) (3PF6), [Cu(L1' ')(PPh3)](ClO4) (4ClO4), [Cu(L1' ')(PPh3)](PF6) (4PF6), [{Cu(L1' ')(CO)}2(mu-ClO4)](ClO4) (5ClO4), and the copper(II) complexes [{Cu(L1' ')}2(mu-OH)2(mu-ClO4)2] (6), and [Cu(L1' ')Cl2] (7) were systematically synthesized and fully characterized by X-ray crystallography and by IR and 1H NMR spectroscopy. In the case of copper(II), ESR spectroscopy was also applied. In comparison with the related neutral tridentate ligand L1', bis-chelated copper(I) complexes and binuclear linear-coordinated copper(I) complexes are easy to obtain with L1' ', like 1CuCl2, 1ClO4, 2ClO4, and 2BF4. Importantly, stronger and bulkier ligands such as acetonitrile (3PF6) and especially triphenylphosphine (4ClO4 and 4PF6) generate three-coordinate structures with a trigonal-planar geometry. Surprisingly, for the smaller ligand carbon monoxide, a mononuclear three-coordinate structure is very unstable, leading to the formation of a binuclear complex (5ClO4) with one bridging perchlorate anion, such that the copper(I) centers are four-coordinate. The same tendency is observed for the copper(II) bis(mu-hydroxo) compounds 6, which is additionally bridged by two perchlorate anions. Both copper(II) complexes 6 and 7 were obtained by molecular O2 oxidation of the corresponding copper(I) complexes. A comparison of the new copper(I) triphenylphosphine complexes 4ClO4 and 4PF6 with corresponding species obtained with the related tridentate ligands L1' and L1 (8ClO4 and 9, respectively) reveals surprisingly small differences in their spectroscopic properties. Density functional theory (DFT) calculations are used to shed light on the differences in bonding in these compounds and the spectral assignments. Finally, the reactivity of the different bis(pyrazolyl)methane complexes obtained here toward PPh3, CO, and O2 is discussed.     

Six-coordinate titanium complexes of a tripodal aminetris(phenoxide) ligand: synthesis, structure, and dynamics

The five-coordinate titanium(IV) alkoxide LTi(O(t)Bu) (LH(3) = tris(2-hydroxy-3,5-di-tert-butylbenzyl)amine) is protonolyzed readily by the conjugate acids of monoanionic bidentate ligands, both symmetrical (tropolone, acetylacetone, di-p-toluoylmethane) and unsymmetrical (8-hydroxyquinoline, salicylaldehyde, 2,6-diformyl-p-cresol, anthrarufin). The geometry of these complexes, which is pseudo-octahedral with the tripodal ligand adopting a chiral, propeller-like conformation, has been confirmed in four cases by X-ray crystallography. Variable-temperature NMR spectroscopy indicates that the six-coordinate complexes undergo two dynamic processes. First, the ligands undergo a twisting motion that results in racemization, a process which is over 10(4) times faster than in five-coordinate complexes. The rate acceleration upon binding of an equatorial ligand is ascribed to steric repulsions with one of the cis phenoxides; the dynamics of a binuclear dibenzyl phosphate-bridged compound, which has a unique conformation of the tripodal ligand, indicates that flexing the cis phenoxide is the rate-limiting step in racemization. Second, the complexes undergo a process that interchanges the inequivalent arms of the tripodal ligand. This process involves a trigonal twist that shifts the bidentate ligand between clefts in the tripod. The intermediate geometry in the reaction appears to be a transition state and not a long-lived intermediate, as judged from the relative rates of interconversion of tripod arms and chelate ends in the ditoluoylmethane complex. Tripod arm interchange takes place without partial dissociation of the bidentate chelate, a reaction that has been observed on a slower time scale in one case.     

Structure and DNA cleavage properties of two copper(II) complexes of the pyridine-pyrazole-containing ligands mbpzbpy and Hmpzbpya

The DNA-cleavage properties of the two copper(II) complexes, [Cu(mbpzbpy)Br(2)](H(2)O)(2.5) (1) and [Cu(mpzbpya)Cl](CH(3)OH) (2), obtained from the ligands 6,6'-bis(3,5-dimethyl-N-pyrazolmethyl)-2,2'-bipyridine) (mbpzbpy) and 6'-(3,5-dimethyl-N-pyrazolmethyl)-2,2'-bipyridine-6-carboxylic acid) (Hmpzbpya), respectively, are reported. Upon coordination to Cu(II) chloride in methanol, one arm of the ligand mbpzbpy is hydrolyzed to form mpzbpya. Under the same experimental conditions, the reaction of mbpzbpy with CuBr(2) does not lead to ligand hydrolysis. The ligand mpzbpya is coordinated to a copper(ii) ion generating a CuN(3)OCl chromophore, resulting in a distorted square-pyramidal environment, whereas with the N(4) mbpzbpy ligand, the Cu(II) ion is four-coordinated in a distorted square planar geometry. Both complexes promote the oxidative DNA cleavage of phiX174 phage DNA in the absence of reductant. The oxidative nature of the DNA cleavage reaction has been confirmed by religation and cell-transformation experiments. Studies using standard radical scavengers suggest the involvement of hydroxyl radicals in the oxidative cleavage of DNA. Although both compounds do convert form I (supercoiled) DNA to form II (nicked, relaxed form), only complex 1 is able to produce small amounts of form III (linearized DNA). This observation may be explained either by the attack of the copper(ii) complexes to only one single strand of DNA, or by a single cleavage event. Statistical analysis of relative DNA quantities present after the treatment with both copper(ii) complexes supports a random mode of DNA cleavage.     

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.     

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.     

Cu(I)-amido complexes in the Ullmann reaction: reactions of Cu(I)-amido complexes with iodoarenes with and without autocatalysis by CuI

A series of Cu(I)-amido complexes both lacking ancillary ligands and containing 1,10-phenanthroline (phen) as ancillary ligand have been prepared. These complexes react with iodoarenes to form arylamine products, and this reactivity is consistent with the intermediacy of such complexes in catalytic Ullmann amination reactions. The stoichiometric reactions of the Cu(I)-amido complexes with iodoarenes are autocatalytic, with the free CuI generated during the reaction serving as the catalyst. Such autocatalytic behavior was not observed for reactions of iodoarenes with copper(I) amidates, imidates, or phenoxides. The selectivity of these complexes for two sterically distinct aryl halides under various conditions imply that the autocatalytic reaction proceeds by forming highly reactive [CuNPh(2)](n) lacking phen. Reactions with radical probes imply that the reactions of phen-ligated Cu(I)-amido complexes with iodoarenes occur without the intermediacy of aryl radicals. Density functional theory calculations on the oxidative addition of iodoarenes to Cu(I) species are consistent with faster reactions of iodoarenes with CuNPh(2) species lacking phen in DMSO than reactions of iodoarenes with LCuNPh(2) in which L = phen. The free-energy barrier computed for the reaction of PhI with (DMSO)CuNPh(2) was 21.8 kcal/mol, while that for the reaction of PhI with (phen)CuNPh(2) was 33.4 kcal/mol.     

Modeling Tyrosinase Monooxygenase Activity. Spectroscopic and Magnetic Investigations of Products Due to Reactions between Copper(I) Complexes of Xylyl-Based Dinucleating Ligands and Dioxygen: Aromatic Ring Hydroxylation and Irreversible Oxidation Products

A full account of a chemical system possessing features that mimic the reactivity aspects of tyrosinase is presented. Using dinucleating ligands with a m-xylyl spacer three new dicopper(I) complexes have been synthesized and their reactivity with dioxygen investigated. The six-membered chelate ring forming ligands provide only two nitrogen coordinations to each copper. The complexes [Cu(I)(2)L(CH(3)CN)(2)]X(2) (X = ClO(4)(-) (1a), SbF(6)(-) (1b)) and [Cu(I)(2)(L-NO(2))(CH(3)CN)(2)][SbF(6)](2) (1c) [L = alpha,alpha'-bis[N-methyl-N-(2-pyridylethyl)amino]-m-xylene; L-NO(2) = para-nitro derivative of L] have been characterized by IR and (1)H NMR spectroscopy. The reaction of O(2) with 1a-c in CH(2)Cl(2) or THF is instantaneous and causes stoichiometric xylyl hydroxylation reactions producing phenol products. Thus 1a produces phenoxo-/hydroxo-bridged product [Cu(II)(2)(L-O)(OH)][ClO(4)](2) (2a). The existence of putative peroxo-dicopper(II) species could not be detected even at -80 degrees C. A trend is observed for the extent of aromatic ring hydroxylation (298 K): CH(3)CN approximately DMF > CH(3)OH > CH(2)Cl(2). Cyclic voltammetric experiment of 1a in DMF reveals an appreciably low redox potential (E(1/2) = -0.26 V vs SCE) for the Cu(II)(2)/Cu(I)(2) redox process. Variable-temperature (25-300 K) magnetic susceptibility measurements establish that the copper(II) centers in 2a and the dihydroxo-bridged complex [Cu(II)(2)L'(OH)(2)][ClO(4)](2) (2b) [formed due to an impurity (L') present during the synthesis of L following Method A; L' = bis[alpha,alpha'-bis(N-methyl-N-(2-pyridylethyl)amino)-m-xylene]methylamine] are antiferromagnetically coupled, with 2a considerably more coupled than 2b. Reaction of 1a with O(2) in CH(2)Cl(2) (298 K) produces an additional unhydroxylated product of composition [Cu(II)(2)L(OH)(OH(2))][ClO(4)](3).2H(2)O.0.5HCl (3a). In agreement with its proposed hydroxo-/aquo-bridged structure, 3a is weakly antiferromagnetically coupled. In CH(3)CN solution, 3a rearranges to generate a doubly hydroxo-bridged species [Cu(II)(2)L(OH)(2)](2+). Using a solution-generated dicopper(I) complex of a closely similar ligand (L' ') providing five-membered chelate ring, the reactivity toward dioxygen was also investigated. It produces only an irreversibly oxidized product of composition Cu(II)(2)L' '(OH)(ClO(4))(3)(H(2)O)(2) (3b) (L' ' = alpha,alpha'-bis[N-methyl-N-(2-pyridylmethyl)amino]-m-xylene). For 3b the copper(II) centers are almost uncoupled.     

Synthesis,structural characterization,and anti-ulcerogenic activity of schiff base ligands derived from tryptamine and 5-chloro, 5-nitro, 3,5-ditertiarybutyl salicylaldehyde and their nickel(II), copper(II), and zinc(II) complexes

Ni(II), Cu(II), and Zn(II) complexes with bidentate Schiff bases derived from the condensation reaction of 5-chlorosalicylaldehyde, 5-nitrosalicylaldehyde, and 3,5 ditertiarybutyl-2-hydroxy benzaldehyde with tryptamine, have been reported. The ligands and complexes were characterized by elemental analysis, IR, ¹H NMR and UV–Vis spectroscopy as well as single crystal X-ray structure analysis whenever possible. The complexes were found to have the general formula [M(L)₂]. Spectral studies reveal that these Schiff bases were acting as bidentate ligands and co-ordinating to the metal center through deprotonated phenolate oxygen and azomethine nitrogen atoms. The Zn(II) complexes establish a tetrahedral geometry in a 1:2 metal to ligand stoichiometry, whereas a square planar geometry was proposed for the nickel and copper complexes, slightly distorted in the case of the latter.The antiulcer activity of 5-chlorosalicylaldehyde derivative and its nickel and copper complexes were evaluated in ethanol-induced gastric mucosal injury in rats. This Schiff base and its complexes promote ulcer protection as ascertained by the comparative decrease in ulcer areas, and inhibition of edema and leucocyte infiltration of the submucosal layer.     

Active Site Models for the Cu(A) Site of Peptidylglycine α-Hydroxylating Monooxygenase and Dopamine β-Monooxygenase

A mononuclear copper(II) superoxo species has been invoked as the key reactive intermediate in aliphatic substrate hydroxylation by copper monooxygenases such as peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM). We have recently developed a mononuclear copper(II) end-on superoxo complex using a N-[2-(2-pyridyl)ethyl]-1,5-diazacyclooctane tridentate ligand, the structure of which is similar to the four-coordinate distorted tetrahedral geometry of the copper-dioxygen adduct found in the oxy-form of PHM (Prigge, S. T.; Eipper, B. A.; Mains, R. E.; Amzel, L. M. Science2004, 304, 864-867). In this study, structures and physicochemical properties as well as reactivity of the copper(I) and copper(II) complexes supported by a series of tridentate ligands having the same N-[2-(2-pyridyl)ethyl]-1,5-diazacyclooctane framework have been examined in detail to shed light on the chemistry dictated in the active sites of mononuclear copper monooxygenases. The ligand exhibits unique feature to stabilize the copper(I) complexes in a T-shape geometry and the copper(II) complexes in a distorted tetrahedral geometry. Low temperature oxygenation of the copper(I) complexes generated the mononuclear copper(II) end-on superoxo complexes, the structure and spin state of which have been further characterized by density functional theory (DFT) calculations. Detailed kinetic analysis on the O(2)-adduct formation reaction gave the kinetic and thermodynamic parameters providing mechanistic insights into the association and dissociation processes of O(2) to the copper complexes. The copper(II) end-on superoxo complex thus generated gradually decomposed to induce aliphatic ligand hydroxylation. Kinetic and DFT studies on the decomposition reaction have suggested that C-H bond abstraction occurs unimolecularly from the superoxo complex with subsequent rebound of the copper hydroperoxo species to generate the oxygenated product. The present results have indicated that a superoxo species having a four-coordinate distorted tetrahedral geometry could be reactive enough to induce the direct C-H bond activation of aliphatic substrates in the enzymatic systems.     

Carbon-halogen bond activation mechanism by copper(I) complexes of (2-pyridyl)alkylamine ligands

The reaction of p-substituted benzyl halides ((Y)BnX; X = Cl, Br, and I; Y = p-substituent, OMe, t-Bu, Me, H, F, Cl, and NO(2)) and copper(I) complexes supported by a series of (2-pyridyl)alkylamine ligands has been investigated to shed light on the mechanism of copper(I) complex mediated carbon-halogen bond activation, including ligand effects on the redox reactivity of copper(I) complexes which are relevant to the chemistry. For both the tridentate ligand (Phe)L(Pym2) [N,N-bis(2-pyridylmethyl)-2-phenylethylamine] and tetradentate ligand TMPA [tris(2-pyridylmethyl)amine] complexes, the C-C coupling reaction of benzyl halides proceeded smoothly to give corresponding 1,2-diphenylethane derivatives and copper(II)-halide complex products. Kinetic analysis revealed that the reaction obeys second-order kinetics both on the copper complex and the substrate; rate = k[Cu](2)[(Y)BnX](2). A reaction mechanism involving a dinuclear copper(III)-halide organometallic intermediate is proposed, on the basis of the kinetic results, including observed electronic effects of p-substituents (Hammett plot) and the rate dependence on the BDE (bond dissociation energy) of the C-X bond, as well as the ligand effects.     

Self-recognition based on atropoisomerism with new chiral bidentate ligands and copper(I)

A new family of atropoisomeric bidentate ligands that have a dissymmetric benzimidazole-pyridine binding site has been synthesized. Aromatic rings, that is, naphthyl, tolyl and cumyl, were introduced in order to fine tune the complexation properties of the ligands. The tetrahedral copper(I) complexes L2Cu were prepared and the structure of the complex with the naphthyl-substituted ligand was established by X-ray diffraction. The behavior of the L2Cu complexes in solution was studied by 1H NMR spectroscopy. With the most crowded cumyl-derived ligand, ligand self-recognition based on chirality occured: 95% of the complex was present in solution as a racemate RRdelta/SSlambda, the heterochiral RSdelta/SRlambda isomers represented only 5 % of the mixture, and the RRlambda/SSdelta isomers were not detected. Owing to lower steric repulsions within the other L2Cu complexes (i.e., with the naphthyl- and tolyl-based ligands) the homorecognition is less pronounced, as diastereomeric excesses of 6 and 26% were measured, respectively.