Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro

The telomeric single-strand DNA binding protein protection of telomeres 1 (POT1) protects telomeres from rapid degradation in Schizosaccharomyces pombe and has been implicated in positive and negative telomere length regulation in humans. Human POT1 appears to interact with telomeres both through direct binding to the 3' overhanging G-strand DNA and through interaction with the TRF1 duplex telomere DNA binding complex. The influence of POT1 on telomerase activity has not been studied at the molecular level. We show here that POT1 negatively effects telomerase activity in vitro. We find that the DNA binding activity of POT1 is required for telomerase inhibition. Furthermore, POT1 is incapable of inhibiting telomeric repeat addition to substrate primers that are defective for POT1 binding, suggesting that in vivo, POT1 likely affects substrate access to telomerase.     

Yotiao protein, a ligand for the NMDA receptor, binds and targets cAMP-dependent protein kinase II(1)

A yeast two-hybrid screen revealed that regulatory subunits (RII) of PKAII bind the Yotiao protein. Yotiao interacts with the NR1 subunit of the NMDA receptor. A purified C-terminal fragment of Yotiao binds PKAII, via an RII binding site constituted by amino acid residues 1452-1469, with a dissociation constant (K(d)) between 50 and 90 nM in vitro. A stable complex composed of Yotiao, RII and NR1 was immunoprecipitated from whole rat brain extracts. Immunostaining analysis disclosed that Yotiao, RIIbeta and NR1 colocalize in striatal and cerebellar neurons. Co-assembly of Yotiao/PKAII complexes with NR1 subunits may promote cAMP-dependent modulation of NMDA receptor activity at synapses, thereby influencing brain development and synaptic plasticity.     

Uranyl(VI), copper(II) and nickel(II) complexes derived from a new compartmental ligand

A new heptadentate compartmental ligand has been synthesized by condensation of 3-formylsalicylic acid and 1,5-diamino-3-thiapentane in methanol (H₄L_a). This Schiff base contains an inner N₂SO₂ and an outer O₂O₂ site and gives, by reaction with copper(II), nickel(II) and uranyl(VI) diacetate, mononuclear, homo- and heterobinuclear complexes. In the mononuclear copper and nickel complexes, the metal ion is in the inner N₂SO₂ site, while it is in the outer O₂O₂ for uranyl; a solvent molecule fills the fifth equatorial coordination position in this last complex. The physico-chemical properties of the compounds are discusscd on the basis of infrared, electronic and magnetic data and by comparison with the analogous complexes with the ligand obtained by reaction of 3- formylsalicylic acid and diethylenetriamine (H₄L_b). The mononuclear copper and the heterodinuclear copper-uranyl complexes show anomalously low magnetic moments.     

Kinetics of the accelerator ligand effect for the complex formation of Cd(II) ion with a cationic water-soluble porphyrin

A kinetic study of the acceleration activities of inorganic and organic ligands for the incorporation of a Cd(II) ion into 5,10,15,20-tetrakis(4-N-methylpyridyl)porphine (TMPyP) has been performed. The acceleration activities of the inorganic ions decreased in the order . The logarithmic values of the rate constants of the Cd-TMPyP formation were proportional to the values of the nucleophilic constant. This fact suggests that the acceleration of the Cd(II) incorporation into TMPyP is mainly due to the enhancement of the water exchange rate in the inner coordination sphere of the Cd(II)-accelerator complex. Furthermore, the acceleration effects of organic ligands increased with the hydrophobicities of the accelerator ligands. In addition, accelerators possessing negative charges, which are capable of interacting with the positive charges of the N-methylpyridyl groups of TMPyP, significantly enhanced the incorporation of Cd(II) into TMPyP. The rate constant of the metal ion exchange reaction of Cd(II) with Pb-TMPyP in the presence of bathophenanthroline sulfonic acid was 1 400 000-fold greater than the reaction of Cd(II) with TMPyP in the absence of an accelerator. The acceleration effect of organic ligands was due to the enhancement of the hydrophobic interaction and the electrostatic interaction between the Cd(II)-accelerator complex and Pb-TMPyP in the outer coordination sphere.     

Synthesis, crystal structure and magnetic properties of a mononuclear and a ferromagnetically coupled dinuclear nickel(II) complex derived from a hexadentate Schiff base ligand

Reactions with Ni^II of a hexadentate Schiff base ligand, L, prepared from the reaction of 2-benzoylpyridine with N,N′-bis-(3-aminopropyl) ethylenediamine in the 2:1 molar ratio are reported. Mixing of this ligand with Ni(NO₃)₂ affords the mononuclear complex [NiL](NO₃)₂ (1), whereas the presence of NaN₃ in the reaction system leads to the formation of the dinuclear complex [Ni₂(L)(N₃)₄] (2). Both adducts have been characterized by X-ray crystallography revealing distorted octahedral NiN₆ coordination environments around the Ni^II centers. The dinuclear complex contains terminal and end-on bridging azido ligands and displays Ni-N-Ni bridge angles of 101.1(2)° and 101.6(2)° and an intramolecular Ni?Ni separation of 3.330(1)Å. The bridges mediate ferromagnetic magnetic exchange interactions between the Ni^II centers of 2, leading to an S = 2 ground state. Fitting of bulk magnetization data provided the coupling constant J = +20.96 cm³ K mol⁻¹ (in the H = −2JS₁ · S₂ convention for the Heisenberg Spin Hamiltonian), as well as the parameters g = 2.17, D = 0.69 cm⁻¹ and TIP = 622 × 10⁻⁶ cm³ mol⁻¹.     

Synthesis, X-ray crystal structure and magnetic study of a dicyanamido bridged 1D chain nickel(II) complex

Reaction of Ni(NO₃)₂ · 6H₂O and sodium dicyanamide (Nadca) yields a 1D infinite chain complex {[Ni(dien)(μ_1,5-dca)(H₂O)](NO₃)}_n (1) (where dien = diethylenetriamine). The coordination environment in complex 1 around the nickel(II) ions is distorted octahedron. Three nitrogen atoms of the ligand diethylenetriamine and an oxygen atom of H₂O molecule constitute the four coordination sites of the basal plane of the octahedron. Of two axial positions of the octahedron, one position is occupied by the nitrogen atom of a μ_1,5-dca anion the remaining coordination site is occupied by a nitrogen atom of another end-to-end bridging dca from an adjacent [Ni(dien)(μ_1,5-dca)(H₂O)] moiety, yielding 1D infinite chains which propagate parallel to crystallographic a-axis. No measurable magnetic interaction was evidenced through variable temperature magnetic susceptibility measurements (4-300 K). However, the magnetic susceptibility of the compound can be explained in terms of single-ion anisotropic model with zero-field splitting for nickel(II) ions.     

A novel trinuclear nickel(II) complex of an unsymmetrical tetradentate ligand involving bridging oxime and acetylacetone functions

A novel trinuclear nickel(II) complex, [Ni₃(L)₂(H₂O)₂](ClO₄)₂, where L is a bridging unsymmetrical tetradentate ligand, involving o-phenylenediamine, diacetyl monoxime and acetylacetone (H₂L = 4-[2-(3-hydroxy-1-methyl-but-2-enylideneamino)-phenylimino]-pentan-2-one oxime) has been synthesized and characterized structurally. In the complex, an octahedral Ni(II) centre is held in the middle by two square planar units with the aid of oxime and ketonic bridges.     

Synthesis, characterization, and DNA binding of a novel ligand and its Cu(II) complex

A novel naphthalene-2,3-diamine-2-salicylaldehyde (NS) ligand and its mononuclear copper(II) complex (CuNS) have been synthesized and structurally characterized. The UV–vis absorption and emission spectra of NS showed obvious changes on addition of Cu²⁺ solution. The interaction of the compounds with calf thymus DNA and G-quadruplex DNA were investigated by spectroscopic methods and thermal melting assay. The nucleolytic cleavage activity of the compounds was investigated on double-stranded circular pBR322 plasmid DNA and G-quadruplex DNA by electrophoretic mobility shift assay. The results show that CuNS has a greater ability to stabilize G-quadruplex DNA over calf-thymus DNA. The cytotoxicity of the compounds toward HpeG2 cancer cells was also studied, and they showed significant potential for antineoplastic effects.     

Cyanato bridged binuclear nickel(II) and copper(II) complexes with pyridylpyrazole ligand: Synthesis, structure and magnetic properties

Binuclear cyanate bridged nickel(II) complex [Ni(L)(NCO)]₂(PF₆)₂ (1) and copper(II) complex [Cu(L)(NCO)]₂(PF₆)₂ (2), where L is N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)aminomethylpyridine, a tetradentate N₄-coordinated ligand have been synthesized and characterized by physicochemical method. The structures of complexes 1 and 2 have been studied by single crystal X-ray diffraction analysis. The structure analysis reveals that both nickel(II) and copper(II) center are coordinated in distorted octahedral fashion and coordination mode of cyanate ligand is end-to-end (μ-1,3) for complex 1 but it is double end-on (μ-1,1) mode for complex 2. The variable temperature magnetic susceptibility data, measured from 2 to 300 K, show weak antiferromagnetic interaction with J value −6.2(1) cm⁻¹ for complex 1, whereas complex 2 has very weak ferromagnetic interaction with J value +0.5(1) cm⁻¹.     

Equilibrium and structural studies of copper and nickel complexes with a pentadentate ligand providing amide, amine and pyridyl nitrogen donors. Crystal structure of the dinuclear nickel(II) complex

A novel potentially pentadentate ligand 1,7-bis(2-pyridylcarbamoyl)-1,4,7-triazaheptane (pycdien) has been synthesised as its trihydrochloride salt; its protonation constants and the stability constants of the copper(II) and nickel(II) chelates have been determined by potentiometric and spectrophotometric techniques. Amide groups deprotonation allows the formation of [M(pycdienH₋₁)]⁺ and [M(pycdienH₋₂)] (M = Cu or Ni) species in all cases, whereas the detection of the complexes of the neutral or the protonated forms of the ligand depends on the nature of the metal ions. In the solid state, mononuclear complexes {[Cu(pycdienH)](ClO₄)₂Cl (1) and [Cu(pycdien)](ClO₄)₂ (2)} and dinuclear compounds {[Cu₂(pycdienH₋₂)₂] · H₂O (3) and [Ni₂(pycdienH₋₂)₂(OH₂)₂] · 6H₂O (4)} have been synthesised and characterised by spectroscopic techniques. X-ray crystal determination shows that the dimeric [Ni₂(pycdienH₋₂)₂ (OH₂)₂] · 6H₂O (4) crystallizes in the triclinic space group , and each nickel(II) center resides in a octahedral geometry generated by the N_pyridyl, N_amido, N_amine portion of one ligand and one pyridine-2-carboxamido end of the other. The hexacoordination of each Ni²⁺ ion is achieved by a water molecule. The complexes obtained with the deprotonated form of the ligand imply the coordination through the nitrogen atoms of the amidic groups.     

Synthesis, crystal structures, and molecular hyperpolarizabilities of a new Schiff base ligand, and its copper(II), nickel(II), and cobalt(II) metal complexes

A new ligand (HL) obtained from the Schiff base condensation of 4-(diethylamino)salicylaldehyde with 4-nitroaniline is reported, with its nickel(II), copper(II), and cobalt(II) complexes. The crystal structures are reported for the four derivatives. While, Ni^IIL₂ and Cu^IIL₂ are centrosymmetric molecules, Co^IIL₂ exhibits a pseudo-tetrahedral molecular structure. The quadratic hyperpolarizabilities (β) of HL and Co^IIL₂, measured by electric field induced second harmonic (EFISH) technique, are equal to 66 and 110 × 10⁻³⁰ cm⁵ esu⁻¹, respectively. Beside a geometric effect (pseudo-T_d symmetry), the coordination of the metal center provides an intrinsic enhancement of the NLO response. In addition, an enhancement of the thermal stability of about 60° is found upon metal complexation.     

Azo-containing pyridine amide ligand. A six-coordinate nickel(II) complex and its one-electron oxidized species: Structure and properties

A new potentially tridentate ligand HL¹¹ consisting of 2-pyridinecarboxamide unit and azo functionality has been used, in its deprotonated form, to prepare a nickel(II) complex which has been structurally characterized. The ligand L¹¹(−) affords a bis-complex [Ni^II(L¹¹)₂] (1). In 1, the two L¹¹(−) ligands bind to the Ni^II center in a mer configuration. The relative orientations within the pairs of pyridyl-N, deprotonated amido-N, and azo-N atoms are cis, trans, and cis, respectively. The Ni^IIN₂(pyridyl)N′₂(amide)N″₂(azo) coordination environment is severely distorted from ideal octahedral geometry. The Ni-N_am (am = amide) bond lengths are the shortest and the Ni-N_azo bond lengths are the longest. Complex 1 exhibits a quasireversible Ni^III/Ni^II redox process. Moreover, the complex displays two ligand-centered (azo group) quasireversible redox processes. Spectroscopic (absorption and EPR) properties have been studied on coulometrically-generated nickel(III) species. To understand the nature of metal-ligand bonding interactions Density Functional Theory (DFT) calculations have been performed on 1 at the B3LYP level of theory. Calculations have also been done for closely related nickel(II) complexes of deprotonated pyridine amide ligands and comparative discussion has been made using observed results.     

Structure and magnetic properties of a trinuclear nickel(II) complex with benzenetricarboxylate bridge

Novel trinuclear Ni(II) complex [Ni₃(pmdien)₃(btc)(H₂O)₃](ClO₄)₃ · 4H₂O, 1 where pmdien = N,N,N′,N′,N″-pentamethyldiethylenetriamine, H₃btc = 1,3,5-benzenetricarboxylic (trimesic) acid, has been prepared and structurally characterized. Three nickel atoms are bridged by btc trianion and their coordination sphere is completed by three N atoms of pmdien and O atom of the water molecule. The three nickel(II) magnetic centers are equivalent and their coordination spheres are completed to deformed octahedrons. Magnetic susceptibility was measured over the temperature range 1.8–300 K and zJ′ = ?0.19 cm^?1, D = 3.79 cm^?1, g = 2.18 parameters were calculated.     

Spectroscopic, cytotoxic and DFT studies of a luminescent palladium(II) complex of a hydrazone ligand that induces apoptosis in human prostate cancer cells

A luminescent palladium(II) complex [Pd(L)Cl], 1a was synthesized with the acyclic tridentate quinoline-2-carboxaldehyde-2-pyridylhydrazone ligand, HL, 1. The ligand, 1 showed a selective chromogenic behavior towards Pd²⁺ by changing the color of the solution from yellow to blue-violet, which can easily be detected by the naked-eye. DFT and TDDFT calculations were performed to determine the geometry optimized structures of the ligand 1 and the complex 1a as well as to correlate the electronic transitions. The complex 1a exhibits strong interaction towards DNA as revealed from K_b (intrinsic binding constant) and K_sq (Stern Volmer quenching constant) values, which are 1.47 × 10⁵ M⁻¹ and 5.67, respectively. The cytotoxicity of 1a has been examined with human prostate cancer cells (PC-3) and the sub-lethal dose (8 μM) determined by dose-dependence studies. The relative degree of apoptotic and necrotic cell death using a sub-lethal dose were measured by flow cytometry. The cell cycle analysis shows that the complex 1a exhibits effective cell growth inhibition by triggering G2/M phase arrest and apoptosis in cancer cells. Moreover, its treatment triggers the mitochondrial pathway resulting in cytochrome c release and caspase-3 activation.     

Synthesis, structure, and magnetism of a binuclear Co(II) complex of a potentially bis-tridentate verdazyl radical ligand

The synthesis, structure, and magnetic properties of a dinuclear Co(II) complex of a tridentate verdazyl radical are presented. The reaction of a tetrazane containing a 4,6-bis(2-pyridyl)-pyrimid-2-yl substituent with cobalt chloride hexahydrate in aerated solution leads to in situ oxidation of the tetrazane to a verdazyl radical which is coordinated to Co(II) in a tridentate manner. The second tridentate coordination site of the verdazyl remains vacant. The crystal structure reveals the complex to be dimeric, with the cobalt ions linked by two bridging chlorides. The structure of Co₂Cl₂ core is highly asymmetric, with two short (2.3317 Å) and two long (2.744 Å) Co-Cl bonds. There are relatively short intermolecular contacts between coordinated verdazyl radicals in the solid state. Magnetic susceptibility data from 2 to 300 K suggest intramolecular ferromagnetic interactions, and modeling of the high-temperature data produced a best fit with J_Co-verdazyl of +20 cm⁻¹.     

A trigonal-prismatic Ag(I) complex and an octahedral Cu(II) complex incorporating with oxamide Ni(II) complex ligand: Syntheses, crystal structures and oxidative nuclease activities

A mononuclear macrocyclic complex Ni^IIL^3a (L^3a = dianion of 2,3-dioxo-5,6:13,14-dibenzo-9,10-cyclohexyl-7,12-bis(methoxycarbonyl)-1,4,8,11-tetraazacyclotetradeca-7,11-diene), which shows high DNA cleavage activity in the presence of H₂O₂, was reported in our previous work. Considering that many systems for natural enzyme-mediated DNA cleavage contain two or more metal active sites, two new trinuclear complexes [Cu(NiL^3a)₂(dca)₂]·2CH₃OH (abbreviated as Cu(NiL^3a)₂) and [Ag(NiL^3a)₂(NO₃)]·2CH₃OH·0.5H₂O (abbreviated as Ag(NiL^3a)₂) were synthesized in this work, where dca is the dicyanamide. The complexes were structurally characterized by single crystal X-ray analysis. The central Cu(II) or Ag(I) atom is linked to two [NiL^3a] ligands by oxamido bridges forming a trinuclear structure. In Cu(NiL^3a)₂, the central Cu(II) ion is in an octahedral coordination geometry. Whereas in Ag(NiL^3a)₂, the central Ag(I) ion is in a rarely reported trigonal-prismatic coordination geometry. The DNA cleavage behavior of the complexes in the presence of H₂O₂ was studied in detail. Comparing with the NiL^3a, the trinuclear complex Ag(NiL^3a)₂ nearly has no ability to cleave DNA, whereas Cu(NiL^3a)₂ is a much better DNA cleavage agent. Cu(NiL^3a)₂ can efficiently convert supercoiled DNA to nicked DNA with a rate constant of 0.074 ± 0.002 min⁻¹ when 40 μM Cu(NiL^3a)₂ and 0.6 mM H₂O₂ are used. The cleavage mechanism between the complex Cu(NiL^3a)₂ and plasmid DNA is likely to involve singlet oxygen as reactive oxygen species. Circular dichroism (CD) and fluorescence spectroscopy indicate that both Cu(NiL^3a)₂ and NiL^3a bind to DNA by a groove binding mode, and the binding between Cu(NiL^3a)₂ and DNA is much stronger than that between NiL^3a and DNA. The present results may provide some information for the design of efficient multinuclear artificial nucleases.     

Hydrothermal synthesis and characterization of a two-dimensional nickel(II) complex containing benzenehexacarboxylic acid (mellitic acid)

The hydrothermal synthesis, single crystal X-ray structure and magnetic properties of a two-dimensional (2-D) coordination polymer, [Ni₄(C₆(COO)₆)(OH)₂(H₂O)₆] (1), is described. Complex 1 consists of dimer motifs of pseudo octahedral NiO₆ linked through μ3-OH to generate one-dimensional (1-D) chains which are further bridged by the mellitate ligands to form non interpenetrated undulating sheet structure. The sheets are further connected by hydrogen bonding interaction to yield a three-dimensional (3-D) structure. The temperature dependence of magnetic susceptibilities revealed the presence of antiferromagnetic interaction between nickel centers.     

Interaction of copper(II) and nickel(II) with a bis-amide ligand functionalized with pyridine moieties: Thermodynamic and spectroscopic studies in aqueous solution

We synthesized a new bis-amide ligand derived from the l(+)-tartaric acid. We then determined its protonation constants and the stability constants of the copper(II) and nickel(II) chelates by potentiometry as well as ESI-MS and UV-Vis spectroscopy. We found that both metal ions are able to induce the deprotonation and the coordination of an amide nitrogen donor atom. In the case of copper complexes, the data show the formation of two major species: Cu₂(L₂H₋₃)⁺ and Cu₂(LH₋₄). EPR and XAS experiments led us to precise the relative structure of these compounds. In Cu₂(L₂H₋₃)⁺, each metal center is coordinated by pyridinic and amidic nitrogen atoms of one ligand and by nitrogen and oxygen atoms from pyridine and hydroxyl moieties from the other one. In Cu₂(LH₋₄), the copper centers are coordinated by pyridinic and amidic nitrogen atoms, as well as a deprotonated hydroxyl group of the ligand. In this latter complex, the lower value of the Cu-Cu distance determined from EXAFS experiments and compared to the one of the solid species likely involve the formation of an exogeneous hydroxyl bridge between the two copper centers. With Ni(II) ions, the only one major species is the mononuclear Ni(LH₋₂) complex, in which Ni(II) is held in an octahedral environment with the metal center chelated by the two pyridinic and the two amidic nitrogen atoms, and two oxygen atoms from water molecules.     

Molecular structures of nickel(II) monochelates of a racemic tridentate ligand and co-ligand induced structural variations

Using a racemic mixture of the tridentate ligand, (((2-pyridyl)ethylamine)methyl)phenolate ion (L⁻) and , NCS⁻, (NC)₂N⁻, OAc⁻ as coligands, complexes having the formula [Ni(L)(N₃)] (1), [Ni(L)(NCS)]₂ (2), [Ni₂(L)₂(OAc)(N(CN)₂)]_n (3) were prepared and structurally characterized. In 1, Ni(II) has a square planar geometry and phenolate oxygen is involved in dipolar ?N^δ+ interaction with electrophilic central nitrogen atom of coordinated azide ion. Complex 2 is dimeric in nature and nickel(II) is penta-coordinated. Compounds 1 and 2 exist as centrosymmetric dimers made up of a pair of R and S enantiomers of L. In 3, an acetate and phenoxo bridged dinickel complex is present which is further linked to a zig-zag coordination polymer by the dicyanamide ion. In a given chain of 3, both L have same enantiomeric form and either RR or SS dimers are repeated along the chain. The magnetic properties are described.