Carboxylate coordination chemistry of a mononuclear Ni(II) center in a hydrophobic or hydrogen bond donor secondary environment: relevance to acireductone dioxygenase

A series of Ni(II) carboxylate complexes, supported by a chelate ligand having either secondary hydrophobic phenyl groups (6-Ph2TPA, N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine) or hydrogen bond donors (bnpapa, N,N-bis((6-neopentylamino-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine), have been prepared and characterized. X-ray crystallographic studies of [(6-Ph2TPA)Ni(O2C(CH2)2SCH3)]ClO4.CH2Cl2 (4.CH2Cl2) and [(6-Ph2TPA)Ni(O2CCH2SCH3)]ClO(4).1.5CH2Cl2 (5.1.5CH2Cl2) revealed that each complex contains a distorted octahedral Ni(II) center and a bidentate carboxylate ligand. A previously described benzoate complex ([(6-Ph2TPA)Ni(O2CPh)]ClO4 (3)) has similar structural characteristics. Recrystallization of dry powdered samples of 3, 4.0.5CH2Cl2, and 5 from wet organic solvents yielded a second series of crystalline Ni(II) carboxylate complexes having a coordinated monodentate carboxylate ligand ([(6-Ph2TPA)Ni(H2O)(O2CPh)]ClO4 (6), [(6-Ph2TPA)Ni(H2O)(O2C(CH2)2SCH3)]ClO4.0.2CH2Cl2 (7.0.2CH2Cl2), [(6-Ph2TPA)Ni(H2O)(O2CCH2SCH3)]ClO4 (8)) which is stabilized by a hydrogen-bonding interaction with a Ni(II)-bound water molecule. In the cationic portions of 7.0.2CH2Cl2 and 8, weak CH/pi interactions are also present between the methylene units of the carboxylate ligands and the phenyl appendages of the 6-Ph2TPA ligands. A formate complex of the formulation [(6-Ph2TPA)Ni(H2O)(O2CH)]ClO4 (9) was isolated and characterized. The mononuclear Ni(II) carboxylate complexes [(bnpapa)Ni(O2CPh)]ClO4 (10), [(bnpapa)Ni(O2C(CH2)2SCH3)]ClO4 (11), [(bnpapa)Ni(O2CCH2SCH3)]ClO4 (12), and [(bnpapa)Ni(O2CH)]ClO4 (13) were isolated and characterized. Two crystalline solvate forms of 10 (10.CH3CN and 10.CH2Cl2) were examined by X-ray crystallography. In both, the distorted octahedral Ni(II) center is ligated by a bidentate benzoate ligand, one Ni(II)-bound oxygen atom of which accepts two hydrogen bonds from the supporting bnpapa chelate ligand. Spectroscopic studies of 10(-13) suggest that all contain a bidentate carboxylate ligand, even after exposure to water. The combined results of this work enable the formulation of a proposed pathway for carboxylate product release from the active site Ni(II) center in acireductone dioxygenase.     

Mechanistic studies of the O2-dependent aliphatic carbon-carbon bond cleavage reaction of a nickel enolate complex

The mononuclear nickel(II) enolate complex [(6-Ph(2)TPA)Ni(PhC(O)C(OH)C(O)Ph]ClO(4) (I) was the first reactive model complex for the enzyme/substrate (ES) adduct in nickel(II)-containing acireductone dioxygenases (ARDs) to be reported. In this contribution, the mechanism of its O(2)-dependent aliphatic carbon-carbon bond cleavage reactivity was further investigated. Stopped-flow kinetic studies revealed that the reaction of I with O(2) is second-order overall and is ～80 times slower at 25 °C than the reaction involving the enolate salt [Me(4)N][PhC(O)C(OH)C(O)Ph]. Computational studies of the reaction of the anion [PhC(O)C(OH)C(O)Ph](-) with O(2) support a hydroperoxide mechanism wherein the first step is a redox process that results in the formation of 1,3-diphenylpropanetrione and HOO(-). Independent experiments indicate that the reaction between 1,3-diphenylpropanetrione and HOO(-) results in oxidative aliphatic carbon-carbon bond cleavage and the formation of benzoic acid, benzoate, and CO:CO(2) (～12:1). Experiments in the presence of a nickel(II) complex gave a similar product distribution, albeit benzil [PhC(O)C(O)Ph] is also formed, and the CO:CO(2) ratio is ～1.5:1. The results for the nickel(II)-containing reaction match those found for the reaction of I with O(2) and provide support for a trione/HOO(-) pathway for aliphatic carbon-carbon bond cleavage. Overall, I is a reasonable structural model for the ES adduct formed in the active site of Ni(II)ARD. However, the presence of phenyl appendages at both C(1) and C(3) in the [PhC(O)C(OH)C(O)Ph](-) anion results in a reaction pathway for O(2)-dependent aliphatic carbon-carbon bond cleavage (via a trione intermediate) that differs from that accessible to C(1)-H acireductone species. This study, as the first detailed investigation of the O(2) reactivity of a nickel(II) enolate complex of relevance to Ni(II)ARD, provides insight toward understanding the chemical factors involved in the O(2) reactivity of metal acireductone species.     

Glyoxalase I-type hemithioacetal isomerization reactivity of a mononuclear Ni(II) deprotonated amide complex

The synthesis, characterization, and hemithioacetal isomerization reactivity of a mononuclear Ni(II) deprotonated amide complex, [(bppppa-)Ni]ClO4.CH3OH (1, bppppa- = monoanion of N,N-bis-[(6-phenyl-2-pyridyl)methyl]-N-[(6-pivaloylamido-2-pyridyl)methyl]amine), are reported. Complex 1 was characterized by X-ray crystallography, 1H NMR, UV-vis, FTIR, and elemental analysis. Treatment of 1 with an equimolar amount of the hemithioacetal PhC(O)CH(OH)SCD3 in dry acetonitrile results in the production of the thioester PhCH(OH)C(O)SCD3 in approximately 60% yield. This reaction is conveniently monitored via 2H NMR spectroscopy. A protonated analogue of 1, [(bppppa)Ni](ClO4)2 (2), is unreactive with the hemithioacetal, thus indicating the requirement of the anionic chelate ligand in 1 for hemithioacetal isomerization reactivity. Complex 1 is unreactive with the thioester product, PhCH(OH)C(O)SCD3, which indicates that the pKa value for the PhCH(OH)C(O)SCD3 proton of the thioester must be significantly higher than the pKa value of the C-H proton of the hemithioacetal (PhC(O)CH(OH)SCD3). Complex 1 is the first well-characterized Ni(II) coordination complex to exhibit reactivity relevant to Ni(II)-containing E. coli glyoxalase I. Treatment of NiBr2.2H2O with PhC(O)CH(OH)SCD3 in the presence of 1-methylpyrrolidine also yields thioester product, albeit the reaction is slower and involves the formation of multiple -SCD3 labeled species, as detected by 2H NMR spectroscopy. The results of this study provide the first insight into hemithioacetal isomerization promoted by a synthetic Ni(II) coordination complex versus a simple Ni(II) ion.     

Comparing a mononuclear Zn(II) complex with hydrogen bond donors with a dinuclear Zn(II) complex for catalysing phosphate ester cleavage

Introducing ligand based hydrogen bond donors to increase the activity of a mononuclear Zn(II) complex for catalysing phosphate ester cleavage can be a more effective strategy than making the dinuclear analogue.     

Reactivity of mononuclear alkylperoxo copper(II) complex. O-O bond cleavage and C-H bond activation

A detailed reactivity study has been carried out for the first time on a new mononuclear alkylperoxo copper(II) complex, which is generated by the reaction of copper(II) complex supported by the bis(pyridylmethyl)amine tridentate ligand containing a phenyl group at the 6-position of the pyridine donor groups and cumene hydroperoxide (CmOOH) in CH3CN. The cumylperoxo copper(II) complex thus obtained has been found to undergo homolytic cleavage of the O-O bond and induce C-H bond activation of exogenous substrates, providing important insights into the catalytic mechanism of copper monooxygenases.     

Efficient plasmid DNA cleavage by a mononuclear copper(II) complex

The Cu(II) complex of the ligand all-cis-2,4,6-triamino-1,3,5-trihydroxycyclohexane (TACI) is a very efficient catalyst of the cleavage of plasmid DNA in the absence of any added cofactor. The maximum rate of degradation of the supercoiled plasmid DNA form, obtained at pH 8.1 and 37 degrees C, in the presence of 48 microM TACI.Cu(II), is 2.3 x 10(-3) s(-1), corresponding to a half-life time of only 5 min for the cleavage of form I (supercoiled) to form II (relaxed circular). The dependence of the rate of plasmid DNA cleavage from the TACI.Cu(II) complex concentration follows an unusual and very narrow bell-like profile, which suggests an high DNA affinity of the complexes but also a great tendency to form unreactive dimers. The reactivity of the TACI.Cu(II) complexes is not affected by the presence of several scavengers for reactive oxygen species or when measured under anaerobic conditions. Moreover, no degradation of the radical reporter Rhodamine B is observed in the presence of such complexes. These results are consistent with the operation of a prevailing hydrolytic pathway under the normal conditions used, although the failure to obtain enzymatic religation of the linearized DNA does not allow one to rule out the occurrence of a nonhydrolytic oxygen-independent cleavage. A concurrent oxidative mechanism becomes competitive upon addition of reductants or in the presence of high levels of molecular oxygen: under such conditions, in fact, a remarkable increase in the rate of DNA cleavage is observed.     

A highly reactive mononuclear Zn(II) complex for phosphodiester cleavage

The activity of a Zn(II) complex of a tetradentate, tripodal ligand for catalyzing phosphodiester cleavage is enhanced 750-fold by introducing three hydrogen bond donors to the ligand. Inhibition studies show that the Zn-aqua complex is the kinetically active form and that it binds the transition state with a formal dissociation constant of 3 x 108 M-1. The effect of these ligand modifications on the transition-state affinity is comparable to the rate acceleration provided by the metal ion itself. Overall, this mononuclear complex is more active than the most reactive dinuclear Zn(II) complexes reported to date.     

Disulfide bond cleavage induced by a platinum(II) methionine complex

The cleavage of a disulfide bond and the redox equilibrium of thiol/disulfide are strongly related to the levels of glutathione (GSH)/oxidized glutathione (GSSG) or mixed disulfides in vivo. In this work, the cleavage of a disulfide bond in GSSG induced by a platinum(II) complex [Pt(Met)Cl2] (where Met = methionine) was studied and the cleavage fragments or their platinated adducts were identified by means of electrospray mass spectrometry, high-performance liquid chromatography, and ultraviolet techniques. The second-order rate constant for the reaction between [Pt(Met)Cl2] and GSSG was determined to be 0.4 M(-1) s(-1) at 310 K and pH 7.4, which is 100- and 12-fold faster than those of cisplatin and its monoaqua species, respectively. Different complexes were formed in the reaction of [Pt(Met)Cl2] with GSSG, mainly mono- and dinuclear platinum complexes with the cleavage fragments of GSSG. This study demonstrated that [Pt(Met)Cl2] can promote the cleavage of disulfide bonds. The mechanistic insight obtained from this study may provide a deeper understanding on the potential involvement of platinum complexes in the intracellular GSH/GSSG systems.     

Self-activated DNA cleavage of a water-soluble mononuclear Cu(II) complex with polyquinolinyl ligand

The synthesis and characterization of a water-soluble mononuclear Cu(II) complex, [CuLCl₂]·2CH₃CH₂OH, where L = bis(2-quinolinyl methyl)benzyl-amine has been reported. L is a tridentate polyquinolinyl ligand, coordinated to Cu(II) via NNN donors. The central copper ion of 1 has N₃Cl₂ donor set in a distorted trigonal-bipyramidal geometry. The dimer existing in the solid state resulted from hydrogen bonds and π–π accumulation between two mononuclear units. The interaction of 1 with CT-DNA has been explored by absorption and emission titration methods, revealing partial intercalation between 1 and CT-DNA. Moreover, 1 could make pBR322 plasmid DNA cleaved by a self-activated oxidative process; hydroxyl radical and singlet oxygen may be the main reactive oxygen species species in the process. Complex 1 may quench the intrinsic fluorescence of bovine serum albumin in a static quenching process, which has been investigated by UV–visible and fluorescence spectroscopic methods. 1 also demonstrates potent cytotoxity against Hela cells with IC₅₀ value of 2.84 μM, which shows it to be a potential candidate as an anticancer metal-based drug.     

Photosensitized (electron transfer) carbon-carbon bond cleavage of radical cations : The diphenylmethyl system

The photosensitized (electron transfer) reaction of methyl 2,2-diphenylethyl ether (1), 1,1,2,2-tetraphenylethane (5), 2-methyl-1,1,2-triphenylpropane (6), and 2-methoxy-2-diphenylmethylnorbornane (11 endo and exo) with 1,4-dicyanobenzene (4) in acetonitrile-methanol leads to products indicating cleavage of an intermediate radical cation to give the diphenylmethyl radical and a carbocation. The diphenylmethyl radical is then reduced by the radical anion of the photosensitizer and protonated to yield diphenylmethane. The carbocation fragment reacts with methanol to yield ether and/or acetals. The effect of temperature on the efficiency of cleavage of 5 and 6 has been analyzed. The increase in efficiency observed at higher temperatures reflects an activation energy for the cleavage of the radical cations. In cases where no cleavage is observed, the activation energy for cleavage may be so high that back electron transfer from the radical anion of the pbotosensitizer is the dominant reaction. The C—C bond dissociation energies of the radical cations of 5 and 6 were estimated by analysis of the thermochemical cycle using the bond dissociation energies and the oxidation potentials of the neutral molecules and the oxidation potential of the diphenylmethyl and cumyl radicals. The direction of cleavage of the radical cation is explained in terms of the relative oxidation potentials of the two possible radicals.     

New synthetic routes to a disulfidodinickel(II) complex: characterization and reactivity of a Ni2(mu-eta2:eta2-S2) core

Activation of elemental sulfur by the monovalent nickel complex [PhTt (tBu)]Ni(CO) [PhTt(tBu)=phenyl{tris[(tert-butylmethyl)thio]methyl}borate] generates the disulfidodinickel(II) complex 2. This species is alternatively accessible via thermal decomposition of [PhTt (tBu)]Ni(SCPh3). Spectroscopic, magnetic, and X-ray diffraction studies establish that 2 contains a mu-eta(2):eta(2)-S2 ligand that fosters antiferromagnetic exchange coupling between the Ni (II) ions. This observation is in contrast to the lighter congener, oxygen, which strongly favors the bis(mu-oxo)dinickel(III) structure. 2 oxidizes PPh 3 to SPPh3 and reacts with O2, generating several products, one of which has been identified as [(PhTt (tBu))Ni]2(mu-S) (3).     

Nickel(II)-catalyzed diastereoselective [3+2] cycloaddition of N-tosyl-aziridines and aldehydes via selective carbon-carbon bond cleavage

An efficient and mild Ni(ClO(4))(2)-catalyzed [3+2] cycloaddition of N-tosylaziridines and aldehydes via C-C bond cleavage was developed. The cycloaddition reaction proceeds with high diastereoselectivity and regioselectivity leading to highly substituted 1,3-oxazolidines. Notably, this novel reaction can be easily expanded to gram level scale and the thermal conditions cannot achieve the same transformation.     

Nickel(II)-catalyzed carbon-carbon bond formation reaction of functionalized organozinc reagents with aromatic aldehydes

In the presence of a silylating reagent and catalytic amount of Ni(acac)₂, organozinc halides reacted with aromatic aldehydes to give the corresponding dialkylation products in good to excellent yields under mild conditions.     

Synthesis, characterization and biological evaluation of mononuclear Co(II), Ni(II), Cu(II) and Pd(II) complexes with new N2O2 Schiff base ligands

New tetradentate N(2)O(2) donor Schiff bases and their mononuclear Co(II), Ni(II), Cu(II), and Pd(II) complexes were synthesized and characterized extensively by IR, (1)H-, (13)C-NMR, mass, ESR, conductivity measurements, elemental and thermal analysis. Specifically the magnetic and electronic spectral measurements demonstrate the octahedral structures of cobalt(II), nickel(II) complexes and square planar geometries of copper(II), palladium(II) complexes. All the ligands and complexes were screened for their in vitro antibacterial activity against two gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus) and two gram-negative bacteria (Escherichia coli, Klebsiella pneumonia). In this study, Pd(II) complexes exhibited potent antibacterial activity against B. subtilis, S. aureus whereas other metal complexes also exerted good activity towards all tested strains even than standard drugs streptomycin and ampicillin.     

Oxidative cleavage of DNA by a new ferromagnetic linear trinuclear copper(II) complex in the presence of H2O2/sodium ascorbate

A new trinuclear copper(II) complex has been synthesized and structurally characterized: [Cu(3)(L)(2)(HCOO)(2)(OH)(2)](infinity) (HL = (N-pyrid-2-ylmethyl)benzenesulfonylamide). In the complex, the central copper ion is six-coordinated. The coordination spheres of the terminal copper atoms are square pyramidal, the apical positions being occupied by a sulfonamido oxygen of the contiguous trimer. As a consequence, the complex can be considered a chain of trinuclear species. The three copper atoms are in a strict linear arrangement, and adjacent coppers are connected by a hydroxo bridge and a bidentate syn-syn carboxylato group. The mixed bridging by a hydroxide oxygen atom and a bidentate formato group leads to a noncoplanarity of the adjacent basal coordination planes with a dihedral angle of 61.4(2) degrees. Susceptibility measurements (2-300 K) reveal a strong ferromagnetic coupling, J = 79 cm(-1), leading to a quartet ground state that is confirmed by the EPR spectrum. The ferromagnetic coupling arises from the countercomplementarity of the hydroxo and formato bridges. The trinuclear complex cleaves DNA efficiently, in the presence of hydrogen peroxide/sodium ascorbate. tert-Butyl alcohol and sodium azide inhibit the oxidative cleavage, suggesting that the hydroxyl radical and singlet oxygen are involved in the DNA degradation.     

New reactivity of oxaziridine: Pd(II)-catalyzed aromatic C-H ethoxycarbonylation via C-C bond cleavage

A novel Pd(II)-catalyzed aromatic C-H ethoxycarbonylation with oxaziridine involving C-C bond cleavage is described. Various aromatic 2-phenylpyridines and related compounds as well as aryl ureas can be effectively ethoxycarbonylated. A catalytic cycle involving Pd(II) and Pd(IV) is proposed.     

Dimerization of 3-methylpent-2-en-4-yn-1-ol by diels-alder reaction with cleavage of a carbon-carbon bond

In this study, it was found that in the thermal reaction of Z-3-methylpent-2-en-4-yn-1-ol, two parallel processes occur — radical polymerization and formation of low-molecular-weight products by a nonradical pathway. The structure of the principal low-molecular-weight product was determined. It was shown that its formation by dimerization of the original alcohol presented an unusual path-way for the Diels-Adler reaction with elimination of one molecule of formaldehyde from two molecules of alcohol.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2050–2052, September, 1989.The authors express their gratitute to A. F. Bochkov and A. B. Gagarinov for helpful discussions on the results of this work, and also to A. D. Pershin for recording the proton NMR spectra.