Efficient and specific strand scission of DNA by a dinuclear copper complex: comparative reactivity of complexes with linked tris(2-pyridylmethyl)amine moieties

The compound [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4) (D(1) = dinucleating ligand with two tris(2-pyridylmethyl)amine units covalently linked in their 5-pyridyl positions by a -CH(2)CH(2)- bridge) selectively promotes cleavage of DNA on oligonucleotide strands that extend from the 3' side of frayed duplex structures at a site two residues displaced from the junction. The minimal requirements for reaction include a guanine in the n (i.e. first unpaired) position of the 3' overhang adjacent to the cleavage site and an adenine in the n position on the 5' overhang. Recognition and strand scission are independent of the nucleobase at the cleavage site. The necessary presence of both a reductant and dioxygen indicates that the intermediate responsible for cleavage is produced by the activation of dioxygen by a copper(I) form of the dinuclear complex. The lack of sensitivity to radical quenching agents and the high level of site selectivity in scission suggest a mechanism that does not involve a diffusible radical species. The multiple metal center exhibits a synergy to promote efficient cleavage as compared to the action of a mononuclear analogue [Cu(II)(TMPA)(H(2)O)](ClO(4))(2) (TMPA = tris(2-pyridylmethyl)amine) and [Cu(OP)(2)](2+) (OP = 1,10-phenanthroline) at equivalent copper ion concentrations. The dinuclear complex, [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4), is even capable of mediating efficient specific strand scission at concentrations where [Cu(OP)(2)](2+) does not detectably modify DNA. The unique coordination and reactivity properties of [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4) are critical for its efficiency and site selectivity since an analogue, [Cu(II)(2)(DO)(Cl(2))](ClO(4))(2), where DO is a dinucleating ligand very similar to D(1), but with a -CH(2)OCH(2)- bridge, exhibits only nonselective cleavage of DNA. The differences in the reactivity of these two complexes with DNA and their previously established interaction with dioxygen suggest that specific strand scission is a function of the orientation of a reactive intermediate.     

Electrocatalytic O2 reduction by covalently immobilized mononuclear copper(I) complexes: evidence for a binuclear Cu2O2 intermediate

A Cu(I) complex of 3-ethynyl-phenanthroline covalently immobilized onto an azide-modified glassy carbon surface is an active electrocatalyst for the four-electron (4-e) reduction of O(2) to H(2)O. The rate of O(2) reduction is second-order in Cu coverage at moderate overpotential, suggesting that two Cu(I) species are necessary for efficient 4-e reduction of O(2). Mechanisms for O(2) reduction are proposed that are consistent with the observations for this covalently immobilized system and previously reported results for a similar physisorbed Cu(I) system.     

Hydroxyl radical is the active species in photochemical DNA strand scission by bis(peroxo)vanadium(V) phenanthroline

Bis(peroxo)vanadium(V) complexes are widely investigated as anticancer agents. They exert their antitumor and cyctotoxic effects through inhibition of tyrosine phosphatases and DNA cleavage, respectively. The latter process remains poorly understood. The mechanism of DNA cleavage by NH(4)[(phen)V(O)(eta(2)-O(2))(2)] (phen = 1,10-phenanthroline) was investigated. Kinetic studies on DNA cleavage revealed that the complex is a single-strand nicking agent with no specificity. EPR experiments using 2,2,6,6-tetramethyl-4-piperidone (TMP) and 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) as spin-traps for singlet oxygen and hydroxyl radical, respectively, implicated hydroxyl radical production upon photodecomposition of bis(peroxo)vanadium(V). This was corroborated by benzoate inhibition of DNA strand scission and stoichiometric oxidation of 2-propanol to acetone upon irradiation of bis(peroxo)vanadium(V) phenanthroline. High-resolution polyacrylamide gel analysis of the vanadium cleavage reaction and [Fe(II)EDTA](2)(-)/H(2)O(2) resulted in comigration of "ladder" pattern bands, which superimposed when both reactions were run on the same lane. These findings identify hydroxyl radical produced from the photooxidation of the peroxo ligand on vanadium as the active species in DNA cleavage.     

Zinc and copper complexes of prodigiosin: implications for copper-mediated double-strand DNA cleavage

[reaction: see text] Zinc(II) and copper(II) complexes of prodigiosin (1) have been characterized. All N-atoms of 1 bind Cu(II) to generate 5: the complex exhibits regiospecific oxidation of the C-pyrrole. In contrast, coordination by Zn(II) to 1 produces Zn(1)(2) (8), a 4-coordinate tetrahedral complex. The influence of these binding geometries on Cu-mediated double-strand (ds) DNA cleavage by 1 is discussed.     

Stereoselective [3+2+2] cycloaddition utilizing optically active binuclear Fischer carbene complexes with alkynes

The reaction of optically active α,β-unsaturated binuclear Fischer carbene complexes with alkynes gave planar chiral cycloheptatriene chromium complexes via [3+2+2] cycloaddition with high diastereoselectivity.     

ESR study of weak exchange interactions in binuclear copper(ii) complexes with 2-hydroxyacetophenone acyldihydrazones

The binuclear copper(ii) complexes with 2-hydroxyacetophenone acyldihydrazones (H₄L) Cu₂L·2Py were studied by ESR spectroscopy. In these complexes, the coordination polyhedra are linked via the polymethylene chain containing from one to five units. In the complexes based on acyldihydrazones of malonic, succinic, glutaric, and adipic acids, weak spin-spin exchange interactions occur between the paramagnetic centers. An increase in the length of the polymethylene chain to five units hinders exchange interactions, and the ESR spectrum of the corresponding complex has a signal typical of monomeric copper(ii) complexes.     

The novel azomethine ligands for binuclear copper(II) complexes with ferro- and antiferromagnetic properties

A series of novel binuclear ferro- and antiferromagnetic Cu(2+) chelates of structurally broadly varied Schiff bases (derived from o-tosylamino(hydroxyl)benzaldehydes and monoalkylated o-phenylenediamine, o-aminophenol, o-aminothiophenol, 1,2-diaminobenzimidazole, 1-aminobenzimidazoline-2-thione) and β-diketimines (derived from 2,6-di-i-Pr-aniline) has been prepared. The tautomerism of the ligands and structureof their copper complexes have been studied with the use of IR, ¹H NMR EPR and EXAFS spectroscopy. Molecular and crystal structure of a β-diketimine copper dimer has been determined by X-ray crystallography. The magnetic measurements (2–300?K) performed for all the complexes showed that the ferro- and antiferromagnetic character of the exchange interaction depends both on the structure of the coordination site (origin of the ligating centers) and the structure of the ligands (in particular, on the type of the cycle annelated to the bridging fragment). Whereas S-binding metal chelates 13 (X?=?NTs, Y?=?S, R?=?H) are diamagnetic, the complexes 15 with annelated azole moieties are ferromagnetic.     

DNA cleavage by the photolysis of cyclopentadienyl metal complexes: mechanistic studies and sequence selectivity of strand scission by CpW(CO)3CH3

[Reaction: see text]. The photolysis of CpW(CO)3Me has been shown to produce methyl radicals and to cleave DNA in a single-stranded manner, and preliminary evidence implicated a carbon-centered radical in this process. In this work, the mechanism of strand scission in this reaction was determined to occur by hydrogen atom abstraction from the 4'- and 5'-positions of the deoxyribose moiety of the backbone of DNA. Additionally, in a side reaction that does not lead to frank strand scission, all four bases of DNA are methylated under these conditions; however, none of these base or backbone modifications lead to the formation of abasic sites.     

The solution structure of [Cu(aq)]2+ and its implications for rack-induced bonding in blue copper protein active sites

The structure of [Cu(aq)]2+ has been investigated by using full multiple-scattering theoretical (MXAN) analysis of the copper K-edge X-ray absorption (XAS) spectrum and density functional theory (DFT) to test both ideal Td and square-planar four-coordinate, five-coordinate square-pyramidal, and six-coordinate octahedral [Cu(aq)]2+ models. The best fit was an elongated five-coordinate square pyramid with four Cu-O(eq) bonds (2 x 1.98 +/- 0.03 A and 2 x 1.95 +/- 0.03 A) and a long Cu-O(ax) bond (2.35 +/- 0.05 A). The four equatorial ligands were D2d-distorted from the mean equatorial plane by +/-(17 +/- 4) degrees, so that the overall symmetry of [Cu(H2O)5]2+ is C2v. The four-coordinate MXAN fit was nearly as good, but the water ligands (4 x 1.96 +/- 0.02 A) migrated +/-(13 +/- 4) degrees from the mean equatorial plane, making the [Cu(H2O)4]2+ model again D2d-distorted. Spectroscopically calibrated DFT calculations were carried out on the C2v elongate square-pyramidal and D2d-distorted four-coordinate MXAN copper models, providing comparative electronic structures of the experimentally observed geometries. These calculations showed 0.85e spin on Cu(II) and 0.03e electron spin on each of the four equatorial water oxygens. All covalent bonding was restricted to the equatorial plane. In the square-pyramidal model, the electrostatic Cu-O(ax) bond was worth only 96.8 kJ mol(-1), compared to 304.6 kJ mol(-1) for each Cu-O(eq) bond. Both MXAN and DFT showed the potential well of the axial bond to be broad and flat, allowing large low-energy excursions. The irregular geometry and D2d-distorted equatorial ligand set sustained by unconstrained [Cu(H2O)5]2+ warrants caution in drawing conclusions regarding structural preferences from small molecule crystal structures and raises questions about the site-structural basis of the rack-induced bonding hypothesis of blue copper proteins. Further, previously neglected protein folding thermodynamic consequences of the rack-bonding hypothesis indicate an experimental disconfirmation.     

Selective interactions of a few acridinium derivatives with single strand DNA: study of photophysical and DNA binding interactions

Novel acridinium derivatives 1-3, wherein steric factors have been varied systematically through substitution at the ninth position of the acridinium ring, were synthesized and their interactions with single strand and double strand DNA have been investigated through photophysical, biophysical, and microscopic techniques. The acridinium derivative 1 exhibited quantitative fluorescence yields (phi f approximately =1) and high lifetime of 35 ns, while significantly lower fluorescence yields of 0.11 and 0.02 and lifetimes of 3.5 and 1.2 ns were observed for 2 and 3, respectively. The derivatives 1 and 2 having 2-methylphenyl and 2,4-dimethylphenyl substituents at the ninth position of the acridinium ring showed selective interactions with single strand DNA (ssDNA) with association constants of KssDNA = 6.3-6.6 x 10(4) M(-1), while negligible interactions were observed with double strand DNA (dsDNA). In contrast, the derivative 3 with 2,6-dimethylphenyl substitution showed negligible interactions with both ssDNA and dsDNA. Studies with a series of 19-mer oligonucleotides indicate that these derivatives exhibit significant selectivity for the sequences rich in guanosine (ca. 3-fold) as compared to the cytosine-rich sequences. These derivatives with high water solubility and the ability to distinguish between ssDNA and dsDNA through changes in fluorescence emission can be used as fluorescent probes for understanding the role of ssDNA in various biological processes and to study various DNA-ligand interactions.     

Three new binuclear copper(II) complexes with isonicotinic acid N-oxide: syntheses,crystal structures and properties

Three new copper(II) complexes with isonicotinic acid N-oxide (HL) and 1,10-phenanthroline (phen) as ligands, [Cu(L)(phen)(H₂O)]₂(NO₃)₂···2H₂O (1), [Cu(L)(phen)(H₂O)]₂(ClO₄)₂···2H₂O (2), and [Cu(L)(phen)Br]₂- [Cu(L)(phen)(H₂O)]₂Br₂···6H₂O (3) have been synthesized and structurally characterized. The structures of all three complexes feature a Cu₂ dimer formed by two Cu(II) ions interconnected by two bridging ligands. Each copper(II) ion has a distorted square pyramidal coordination geometry with elongated axial coordination by an aqua ligand or halogen anion. The isonicotinic acid N-oxide anion is bidentate, being coordinated to two Cu(II) ions through its N-O oxygen and one of its carboxylate oxygen atoms. Magnetic susceptibility measurements show a Curie–Weiss paramagnetic behavior characteristic of one unpaired electron for a copper(II) ion for all three complexes.     

Structure and EPR spectra of binuclear copper(II) complexes with acyldihydrazones of benzenedicarboxylic acids and 5-substituted 2-hydroxyacetophenones

Binuclear copper(II) complexes with acyldihydrazones of 1,3- or 1,4 benzenedicarboxylic acid and 5-methyl- or 5-bromo-2-hydroxyacetophenone in which coordination polyhedra are connected by an aromatic bridge have been synthesized and studied. The structure of the copper(II) complex with diacylhydrazone of isophthalic acid and 2-hydroxy-5-methylacetophenone (H₄L) of composition [Cu₂L · 3Py] was studied by X-ray diffraction. The crystals are monoclinic: a = 12.1996(12) Å, b = 17.7295(17) Å, c = 17.9339(17) Å, β = 109.7450(10)°, space group P2₁/n, Z = 4. The complex is of the “dimer of dimers” type and contains two binuclear subunits that bind together into a centrosymmetric dimer owing to the coordination of the copper cation to the phenoxyl oxygen atom of a neighboring binuclear molecule to form the Cu₂O₂ moiety, in which the copper atoms are 3.409 Å apart. The distance between the copper(II) cations in the binuclear subunit is 8.56 atoms (2N + O) of the doubly deprotonated acylhydrazone moiety and the nitrogen atom of the pyridine molecule. One of the copper cation is additionally coordinated to an extra pyridine molecule so that its coordination sphere is completed to a tetragonal pyramid. The second copper atom is involved in additional interaction with the phenoxyl oxygen atom of the neighboring molecule. The EPR spectra of solutions of the binuclear complexes show an isotropic signal of four HFS lines (g _o = 2.065–2.143, a _Cu = 52.1–66.5 × 10^?4 cm^?1) typical of mononuclear copper(II) complexes.     

Mono- and binuclear copper(II) complexes of saccharin with 2-pyridinepropanol synthesis,spectral, thermal and structural characterization

Mono- and binuclear copper(II) saccharinate (sac) complexes containing 2-pyridinepropanol (pypr) have been prepared and characterized by elemental analyses, i.r., u.v.–vis., magnetic measurements and single crystal X-ray diffraction. The copper(II) ion in trans-[Cu(pypr)₂(sac)₂] has –1 site symmetry and is octahedrally coordinated by two bidentate neutral pypr (N, O) and two sac (O) ligands. The binuclear copper(II) complex, [Cu₂(-pypr)₂(sac)₂], is built up around a centre of symmetry and contains two strongly distorted square–planar coordinated copper(II) ions bridged by two alkoxo groups of the deprotonated pypr ligand, which also coordinates to the copper(II) ions through its nitrogen. In contrast to the mononuclear complex, the sac ligands in the binuclear complex is N-coordinated. The binuclear complex exhibits diamagnetic behaviour. The i.r. spectra and thermal decompositions of both complexes are described.     

Mechanistic implications of the active species involved in the oxidation of hydrocarbons by iron complexes of pyrazine-2-carboxylic acid

The reactivity towards H(2)O(2) of the complexes [Fe(pca)(2)(py)(2)].py (1) and Na(2){[Fe(pca(3))](2)O}.2H(2)O.CH(3)CN (2) (where pca(-) is pyrazine-2-carboxylate) and their catalytic activity in the oxidation of hydrocarbons is reported. Addition of H(2)O(2) to 1 results in the formation of a dinuclear Fe(III)-(mu-O)-Fe(III) species characterized spectroscopically and by cyclic voltammetry. By contrast, treatment of 2 with H(2)O(2) results in the formation of mononuclear iron(II) complexes, [Fe(pca)(2)(solvent)(2)]. The experimental results indicate that the catalytic activity of the starting complexes 1 and 2 is strongly dependent on the species formed in solution.     

N,N'-二(3-氨丙基)草酰胺合铜的双核Cu(II)-Zn(II)配合物的合成和结构

合成和表征了三个异核配合物: [Cu(oxpn)Zn(bpy)2](ClO4)2·1/2H2O(1),[Cu(oxpn)Zn-(phen)2](ClO4)2·2H2O(2), [Cu(oxpn)Zn(NO2-phen)2](ClO4)2·2H2O(3)[bpy=2,2'-联吡啶、phen=1,10-菲咯啉、NO2-phen=5-硝基-1,10-菲咯啉、oxpn=N,N'-二(3-氨丙基)草酰胺阴离子], 2的晶体属单斜晶系, P2/n空间群, 晶胞参数: a=1.5061(3), b=1.2924(3), c=2.2802(3)nm, β=108.42(2)°, V=4.1869nm^3,Z=4, Dm=1.409g/cm^3, μ=12.812cm^-^1, F(000)=1812, 最终的偏离因子R=0.093,Rw=0.099。结构分析证实, 配合物具有扩充的草酰胺桥联结构, Cu(II)及Zn(II)的配位环境分别为平面四边形和畸变的八面体构型, 阳离子的对称性近似为C2v。此外, 本文还指派了配合物的电子光谱, 并对EPR、有效磁矩等数据进行了讨论。     

Paramagnetic and diamagnetic binuclear copper(II) complexes with different bidentate exogenous bridges: synthesis, spectroscopy and magnetic properties

Summary Four binuclear Cu^II complexes, [Cu₂(L)(-X)], have been prepared and characterized, where H₃L is a 2:1 Schiff base derived from 2-hydroxy-1-naphthaldehyde and 1,3-diamino-2-propanol and X = 1,3-N₃ (1), C₃H₃N₂ (pyrazolate) (2), AcO (3) and PhCO₂ (4). The Cu^IIions are bridged by endogenous alkoxide and bidentate exogenous bridges. The variable-temperature magnetic analyses show that complexes (2)–(4) exhibit antiferro-magnetic coupling with the exchange integrals, 2J, from- 188 to -158 cm^-1. The -1,3-azide-bridged binuclear Cu^II complex (1) shows the essential features of diamagnetism through measurements of its variable-temperature susceptibility and e.p.r. spectra. The results suggest that (1) can act as a diamagnetic model for metazidohemocyanin.     

Studies on DNA binding behavior of biologically active Cu(II) complexes of Schiff bases containing acyl pyrazolones and 2-ethanolamine

Pyrazolone derivatives (Z)-4-((2-hydroxyethylimino)(p-tolyl)methyl)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one [PMP-EA] (1), (Z)-1-(3-chlorophenyl)-4-((2-hydroxyethylimino)(p-tolyl)methyl)-3-methyl-1H-pyrazol-5(4H)-one [MCPMP-EA] (2), and (Z)-4-((2-hydroxyethylimino)(p-tolyl)methyl)-3-methyl-1-p-tolyl-1H-pyrazol-5(4H)-one [PTPMP-EA] (3) have been synthesized and characterized. The molecular geometry of 2 has been determined by single-crystal X-ray study. These ligands exist in amine-one tautomeric form in the solid state. Three copper(II) complexes, [Cu(PMP-EA)(H₂O)₂] (4), [Cu(MCPMP-EA)(H₂O)₂] (5), and [Cu(PTPMP-EA)(H₂O)₂] (6), respectively, have been synthesized using these ligands and characterized by microanalytical data, molar conductivity, IR, UV–Visible, FAB-Mass, magnetic measurement, TG-DTA studies, and ESR spectral studies; Cu(II) is five-coordinated with [ML(H₂O)₂] composition. The interaction of the complexes with CT-DNA (calfthymus) was investigated using different methods. The results suggest that the copper complexes bind to DNA via intercalation and can quench the fluorescence intensity of EB bound to DNA.     

Structure-catalytic function relationship of SiO2-immobilized mononuclear Cu complexes: an EPR study

Mononuclear CuL and Cu(2L) complexes, where L is propyl-thiazol-2-ylmethylene-amine, covalently immobilized onto SiO2, can catalyze efficiently the oxidation of 3,5-di-t-butylcatechol (DTBC) to 3,5-di-t-butylquinone (DTBQ) by utilizing ambient O2 as oxidant. By increasing the loading of L on SiO2, the DTBQ formation can be improved up to 400% vs the homogeneous catalyst. Equally important is however that grafting per se at low loading is not adequate for an improved catalytic activity. Appropriate loadings have to be achieved, which then may result in significant catalytic performance. Based on EPR spectroscopy a theoretical method is developed, eq A12, for spin-spin distance estimation in heterogeneously dispersed surface complexes. Practical rules including error estimates are provided. By applying this method to the [SiO2-CuL] catalysts it is shown that mononuclear copper complexes fixed on SiO2 with Cu...Cu distances as short as 4.9 +/- 0.3 A are responsible for the improved catalytic activity. The present results demonstrate that mononuclear Cu complexes can have considerable catecholase activity, if the proper geometrical proximity can be fixed. Grafting on SiO2 may be an efficient method for engineering catalysts with improved performance.