Anion-directed template synthesis and hydrolysis of mono-condensed Schiff base of 1,3-pentanediamine and o-hydroxyacetophenone in Ni-II and Cu-II complexes

Bis(o-hydroxyacetophenone)nickel(II) dihydrate, on reaction with 1,3-pentanediamine, yields a bis-chelate complex [NiL2]center dot 2H(2)O (1) of mono-condensed tridentate Schiff base ligand HL {2-[1-(3-aminopentylimino)ethyl]phenol}. The Schiff base has been freed from the complex by precipitating the Nil, as a dimethylglyoximato complex. HL reacts smoothly with Ni(SCN)(2)center dot 4H(2)O furnishing the complex [NiL(NCS)] (2) and with CuCl2 center dot 2H(2)O in the presence of NaN3 or NH4SCN producing [CuL(N-3)](2) (3) or [CuL(NCS)] (4). On the other hand, upon reaction with Cu(ClO4)(2)center dot 6H(2)O and Cu(NO3)(2)center dot 3H(2)O, the Schiff base undergoes hydrolysis to yield ternary complexes [Cu(hap)(pn)(H2O)]ClO4 (5) and [Cu(hap)(pn)(H2O)]NO3 (6), respectively (Hhap = o-hydroxyacetophenone and pn = 1,3-pentanediamine). The ligand HL undergoes hydrolysis also on reaction with Ni(ClO4)(2)center dot 6H(2)O or Ni(NO3)(2)center dot 6H(2)O to yield [Ni(hap)(2)] (7). The structures of the complexes 2, 3, 5, 6, and 7 have been confirmed by single-crystal X-ray analysis. In complex 2, Ni-II possesses square-planar geometry, being coordinated by the tridentate mono-negative Schiff base, L and the isothiocyanate group. The coordination environment around Cu-II in complex 3 is very similar to that in complex 2 but here two units are joined together by end-on, axial-equatorial azide bridges to result in a dimer in which the geometry around Cu-II is square pyramidal. In both 5 and 6, the Cu-II atoms display the square-pyramidal environment; the equatorial sites being coordinated by the two amine groups of 1,3-pentanediamine and two oxygen atoms of o-hydroxyacetophenone. The axial site is coordinated by a water molecule. Complex 7 is a square-planar complex with the Ni atom bonded to four oxygen atoms from two hap moieties. The mononuclear units of 2 and dinuclear units of 3 are linked by strong hydrogen bonds to form a one-dimensional network. The mononuclear units of 5 and 6 are joined together to form a dimer by very strong hydrogen bonds through the coordinated water molecule. These dimers are further involved in hydrogen bonding with the respective counteranions to form 2-D net-like open frameworks. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).

A ferromagnetic linear trinuclear Ni(II)-Schiff base complex supported by phenoxo and cinnamato bridges

A new linear trinuclear nickel(II) complex, [Ni-3(salme)(2)(OCn)(4)] (Hsalme = 2-[(3-methylamino-propylimino)-methyl]-phenol, OCn = cinnamate), showing weak ferromagnetic coupling (J = 1.8(1) cm(-1)) through phenoxo and a novel tridentate bridging mode (1 kappa(OO)-O-2':2 kappa O') of the cinnamate ligand has been synthesized and structurally characterized by X-ray crystallography. (C) 2009 Elsevier B.V. All rights reserved.

Free radicals, metals and antioxidants in oxidative stress-induced cancer

Oxygen-free radicals, more generally known as reactive oxygen species (ROS) along with reactive nitrogen species (RNS) are well recognised for playing a dual role as both deleterious and beneficial species. The "two-faced" character of ROS is substantiated by growing body of evidence that ROS within cells act as secondary messengers in intracellular signalling cascades, which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. The cumulative production of ROS/RNS through either endogenous or exogenous insults is termed oxidative stress and is common for many types of cancer cell that are linked with altered redox regulation of cellular signalling pathways. Oxidative stress induces a cellular redox imbalance which has been found to be present in various cancer cells compared with normal cells; the redox imbalance thus may be related to oncogenic stimulation. DNA mutation is a critical step in carcinogenesis and elevated levels of oxidative DNA lesions (8-OH-G) have been noted in various tumours, strongly implicating such damage in the etiology of cancer. It appears that the DNA damage is predominantly linked with the initiation process. This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process. Attention is focused on structural, chemical and biochemical aspects of free radicals, the endogenous and exogenous sources of their generation, the metal (iron, copper, chromium, cobalt, vanadium, cadmium, arsenic, nickel)-mediated formation of free radicals (e.g. Fenton chemistry), the DNA damage (both mitochondrial and nuclear), the damage to lipids and proteins by free radicals, the phenomenon of oxidative stress, cancer and the redox environment of a cell, the mechanisms of carcinogenesis and the role of signalling cascades by ROS; in particular. ROS activation of AP-1 (activator protein) and NF-kappa B (nuclear factor kappa B) signal transduction pathways, which, in turn lead to the transcription of genes involved in cell growth regulatory pathways. The role of enzymatic (superoxide dismutase (Cu. Zn-SOD. Mn-SOD), catalase, glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E, carotenoids, thiol antioxidants (glutathione, thioredoxin and lipoic acid), flavonoids, selenium and others) in the process of careinogenesis as well as the antioxidant interactions with various regulatory factors, including Ref-1, NF-kappa B, AP-1 are also reviewed. 2006 Elsevier Ireland Ltd. All rights reserved.

Oxidation of polycrystalline Ni studied by spectromicroscopy: Phase separation in the early stages of crystallite growth

Low-energy and photoemission electron microscopy enables the determination of facet planes of polycrystalline surfaces and the study of their chemical composition at the sub-m scale. Using these techniques the early oxidation stages of nickel were studied. After exposing the surface to 20 L of oxygen at 373 K a uniform layer of chemisorbed oxygen was found on all facets. After oxygen exposure at 473–673 K, small NiO crystallites are formed on all facets but not in the vicinity of all grain boundaries. The crystallites are separated by areas of bare Ni without significant oxygen coverage.

Thermal decomposition of potassium hexanitronickelate(II) hydrate

The thermal decomposition of the complex K-4[Ni(NO2)6]center dot H2O has been investigated over the temperature range 25-600 degrees C by a combination of infrared spectroscopy, powder X-ray diffraction, FAB-mass spectrometry and elemental analysis. The first stage of reaction is loss of water and isomerisation of one of the coordinated nitro groups to form the complex K-4 [Ni(NO2)(4) (ONO)]center dot NO2. At temperatures around 200 degrees C the remaining nitro groups within the complex isomerise to the chelating nitrite form and this process acts as a precursor to the loss of NO2 gas at temperatures above 270 degrees C. The product, which is stable up to 600 degrees C, is the complex K-4[Ni(ONO)(4)]center dot NO2, where the nickel atom is formally in the +1 oxidation state. (c) 2005 Elsevier B.V. All rights reserved.

Using pH abnormalities in diseased skin to trigger and target topical therapy

Abstract Purpose: The pH discrepancy between healthy and atopic dermatitis skin was identified as a site specific trigger for delivering hydrocortisone from microcapsules. Methods: Using Eudragit L100, a pH-responsive polymer which dissolves at pH 6, hydrocortisone-loaded microparticles were produced by oil-in-oil microencapsulation or spray drying. Release and permeation of hydrocortisone from microparticles alone or in gels was assessed and preliminary stability data was determined. Results: Drug release from microparticles was pH-dependent though the particles produced by spray drying also gave significant non-pH dependent burst release, resulting from their porous nature or from drug enrichment on the surface of these particles. This pH-responsive release was maintained upon incorporation of the oil-in-oil microparticles into Carbopol- and HPMC-based gel formulations. In-vitro studies showed 4 to 5-fold higher drug permeation through porcine skin from the gels at pH 7 compared to pH 5. Conclusions: Permeation studies showed that the oil-in-oil generated particles deliver essentially no drug at normal (intact) skin pH (5.0 – 5.5) but that delivery can be triggered and targeted to atopic dermatitis skin where the pH is elevated. The incorporation of these microparticles into Carbopol- and HPMC-based aqueous gel formulations demonstrated good stability and pH-responsive permeation into porcine skin.

Chitosan-based mucoadhesive tablets for oral delivery of ibuprofen

Chitosan and its half-acetylated derivative have been compared as excipients in mucoadhesive tablets containing ibuprofen. Initially the powder formulations containing the polymers and the drug were prepared by either co-spray drying or physical co-grinding. Polymer–drug interactions and the degree of drug crystallinity in these formulations were assessed by infrared spectroscopy and differential scanning calorimetry. Tablets were prepared and their swelling and dissolution properties were studied in media of various pHs. Mucoadhesive properties of ibuprofen-loaded and drug-free tablets were evaluated by analysing their detachment from pig gastric mucosa over a range of pHs. Greater polymer–drug interactions were seen for spray-dried particles compared to co-ground samples and drug loading into chitosan-based microparticles (41%) was greater than the corresponding half-acetylated samples (32%). Swelling and drug release was greater with the half-acetylated chitosan tablets than tablets containing the parent polymer and both tablets were mucoadhesive, the extent of which was dependent on substrate pH. The results illustrate the potential sustained drug delivery benefits of both chitosan and its half-acetylated derivative as mucoadhesive tablet excipients.

Synthesis, crystal structure, and catecholase activity of three trinuclear heterometallic NiII2-MnII complexes derived from a salen-type Schiff base ligand

Three new trinuclear heterometallic nickel(II)manganese(II) complexes, [(NiL)2Mn(NCS)2] (1), [(NiL)2Mn(NCO)2] (2), and [{NiL(EtOH)}2Mn(NO2)2]center dot 2EtOH (3), have been synthesized by using [NiL] as the so-called ligand complex [where H2L = N,N'-bis(salicylidene)-1,3-propanediamine] and have been structurally characterized. Crystal structure analyses revealed that complexes 1 and 2 are angular trinuclear species, in which two terminal four-coordinate square planar [NiL] moieties are coordinated to a central MnII through double phenoxido bridges. The MnII is in a six-coordinate distorted octahedral environment that is bonded additionally to two mutually cis nitrogen atoms of terminal thiocyanate (in 1) and cyanate (in 2). In complex 3, in addition to the double phenoxo bridge, the two terminal NiII ions are linked to the central MnII by means of a nitrite bridge (1?N:2?O) that, together with a coordinated ethanol molecule, gives rise to an octahedral environment around the NiII ions and consequently the structure becomes linear. Catecholase activity of these three complexes was examined by using 3,5-di-tert-butylcatechol (3,5-DTBC) as the substrate. All three complexes mimic catecholase activity and the rate of catechol oxidation follows saturation kinetics with respect to the substrate and first-order kinetics with respect to the catalyst. The EPR spectra of the complexes exhibit characteristic six line spectra, which indicate the presence of high-spin octahedral MnII species in solution state. The ESI-MS positive spectrum of 1 in the presence of 3,5-DTBC has been recorded to investigate possible complexsubstrate intermediates.

Complexes of NiX2 (X=Cl− and NO3−) with a NNO donor Schiff base: anion dependent structural variations and spectroscopic behaviour

Two new nickel(11) complexes, [NiLL'(H2O)(2)Cl] (1) and [{NiLL'(H2O)](2)(mu-H)]NO3·H2O(2), have been synthesized using a tridentate Schiff base ligand, HL, 2-[(2-dimethylamino-ethylimino)-methyl]-phenol, along with Cl- or NO3(-) as an anionic co-ligand or counter anion (where L'H = salicylaldehyde). Both complexes have been characterized by X-ray crystallography. The structural analyses reveal that complex 1 is mononuclear whereas 2 is a hydrogen-bridged dinuclear complex. The Ni(II) ions possess a distorted octahedral geometry in both structures. Both complexes show negative solvatochromic behaviour with increasing donor number (DN) of the solvent. In more coordinating solvents, like DMSO or methanol, the colour of the solutions is green, whereas in less coordinating solvents, like dichloromethane (DCM) or acetonitrile, it is red.

Anion-directed template synthesis and hydrolysis of mono-condensed Schiff base of 1,3-pentanediamine ando-hydroxyacetophenone in NiII and CuII Complexes

Bis(o-hydroxyacetophenone)nickel(II) dihydrate, on reaction with 1,3-pentanediamine, yields a bis-chelate complex [NiL2]·2H2O (1) of mono-condensed tridentate Schiff baseligand HL {2-[1-(3-aminopentylimino)ethyl]phenol}. The Schiff base has been freed from the complex by precipitating the NiII as a dimethylglyoximato complex. HL reacts smoothly with Ni(SCN)2·4H2O furnishing the complex [NiL(NCS)] (2) and with CuCl2·2H2O in the presence of NaN3 or NH4SCN producing [CuL(N3)]2 (3) or [CuL(NCS)] (4). On the other hand, upon reaction with Cu(ClO4)2·6H2O and Cu(NO3)2·3H2O, the Schiff base undergoes hydrolysis to yield ternary complexes [Cu(hap)(pn)(H2O)]ClO4 (5) and [Cu(hap)(pn)(H2O)]NO3 (6), respectively (Hhap = o-hydroxyacetophenone and pn = 1,3-pentanediamine). The ligand HL undergoes hydrolysis also on reaction with Ni(ClO4)2·6H2O or Ni(NO3)2·6H2O to yield [Ni(hap)2] (7). The structures of the complexes 2, 3, 5, 6, and 7 have been confirmed by single-crystal X-ray analysis. In complex 2, NiII possesses square-planar geometry, being coordinated by the tridentate mono-negative Schiff base, L and the isothiocyanate group. The coordination environment around CuII in complex 3 is very similar to that in complex 2 but here two units are joined together by end-on, axial-equatorial azide bridges to result in a dimer in which the geometry around CuII is square pyramidal. In both 5 and 6, the CuII atoms display the square-pyramidal environment; the equatorial sites being coordinated by the two amine groups of 1,3-pentanediamine and two oxygen atoms of o-hydroxyacetophenone. The axial site is coordinated by a water molecule. Complex 7 is a square-planar complex with the Ni atom bonded to four oxygen atoms from two hap moieties. The mononuclear units of 2 and dinuclear units of 3 are linked by strong hydrogen bonds to form a one-dimensional network. The mononuclear units of 5 and 6 are joined together to form a dimer by very strong hydrogen bonds through the coordinated water molecule. These dimers are further involved in hydrogen bonding with the respective counteranions to form 2-D net-like open frameworks.

Fish oil supplementation alters numbers of circulating endothelial progenitor cells and micro particles independent of eNOS genotype

Background Emerging cellular markers of endothelial damage and repair include endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) respectively. Effects of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and influence of genetic background on these markers are not known. Objective This study investigated the effects of fish oil supplementation on both classical and novel markers of endothelial function in subjects prospectively genotyped for the Asp298 eNOS polymorphism and at moderate risk of CVD. Design 84 subjects with moderate risk of CVD (n=40 GG and n=44 GT/TT) completed a randomized, double-blind, placebo-controlled, 8-week cross-over trial of fish oil supplementation providing 1.5 g/d LC n-3 PUFA. Effects of genotype and fish oil supplementation on the blood lipid profile, inflammatory markers, vascular function (EndoPAT) and numbers of circulating EPCs and EMP (flow cytometry) were assessed. Results There was no significant effect of fish oil supplementation on blood pressure, plasma lipids or plasma glucose, although there was a trend (P = 0.069) towards a decrease in plasma TG concentration after FO supplementation compared to placebo. GT/TT subjects tended to have higher levels of total cholesterol and LDL-cholesterol, but vascular function was not affected by either treatment or eNOS genotype. Biochemical markers of endothelial function were also unaffected by treatment and eNOS genotype. In contrast, there was a significant effect of fish oil supplementation on cellular markers of endothelial function. Fish oil supplementation increased numbers of EPCs and reduced numbers of EMPs relative to the placebo, potentially favouring maintenance of endothelial integrity. There was no influence of genotype for any of the cellular markers of endothelial function, indicating that the effects of fish oil supplementation were independent of eNOS genotype. Conclusions Emerging cellular markers of endothelial damage, integrity and repair appear to be sensitive to potentially beneficial modification by dietary n-3 PUFA.

Observing the in situ chiral modification of Ni nanoparticles using scanning transmission X-ray microspectroscopy

Enantioselective heterogeneous hydrogenation of Cdouble bond; length as m-dashO bonds is of great potential importance in the synthesis of chirally pure products for the pharmaceutical and fine chemical industries. One of the most widely studied examples of such a reaction is the hydrogenation of β-ketoesters and β-diketoesters over Ni-based catalysts in the presence of a chiral modifier. Here we use scanning transmission X-ray microscopy combined with near-edge X-ray absorption fine structure spectroscopy (STXM/NEXAFS) to investigate the adsorption of the chiral modifier, namely (R,R)-tartaric acid, onto individual nickel nanoparticles. The C K-edge spectra strongly suggest that tartaric acid deposited onto the nanoparticle surfaces from aqueous solutions undergoes a keto-enol tautomerisation. Furthermore, we are able to interrogate the Ni L2,3-edge resonances of individual metal nanoparticles which, combined with X-ray diffraction (XRD) patterns showed them to consist of a pure nickel phase rather than the more thermodynamically stable bulk nickel oxide. Importantly, there appears to be no “particle size effect” on the adsorption mode of the tartaric acid in the particle size range ~ 90–~ 300 nm.

State-resolved gas-surface reactivity of methane in the symmetric C-H stretch vibration on Ni(100)

The state-resolved reactivity of CH4 in its totally symmetric C-H stretch vibration (�1) has been measured on a Ni(100) surface. Methane molecules were accelerated to kinetic energies of 49 and 63:5 kJ=mol in a molecular beam and vibrationally excited to �1 by stimulated Raman pumping before surface impact at normal incidence. The reactivity of the symmetric-stretch excited CH4 is about an order of magnitude higher than that of methane excited to the antisymmetric stretch (�3) reported by Juurlink et al. [Phys. Rev. Lett. 83, 868 (1999)] and is similar to that we have previously observed for the excitation of the first overtone (2�3). The difference between the state-resolved reactivity for �1 and �3 is consistent with predictions of a vibrationally adiabatic model of the methane reaction dynamics and indicates that statistical models cannot correctly describe the chemisorption of CH4 on nickel.

Mode-specificity and transition state-specific energy redistribution in the chemisorption of CH4 on Ni{100}

We have investigated methane (CH4) dissociative chemisorption on the Ni{100} surface by first-principles molecular dynamics (MD) simulations. Our results show that this reaction is mode-specific, with the n1 state being the most strongly coupled to efficient energy flow into the reaction coordinate when the molecule reaches the transition state. By performing MD simulations for two different transition state (TS) structures we provide evidence of TS structure-specific energy redistribution in methane chemisorption. Our results are compared with recently reported state-resolved measurement of methane adsorption probability on nickel surfaces, and we find that a strong correlation exists between the highest vibrational efficacy measured on Ni{100} for the n1 state and the calculated highest fractional vibrational energy content in this mode.

Bond-selective energy redistribution in the chemisorption of CH3D and CD3H on Pt{1 1 0}-(1 2): a first-principles molecular dynamics study

We have investigated the chemisorption of CH3D and CD3H on Pt{11 0}-(1 2) by performing first-principles molecular dynamics simulations of the recombinative desorption of CH3D (from adsorbed methyl and deuterium) and of CD3H (from adsorbed trideuteromethyl and hydrogen). Vibrational analysis of the symmetry adapted internal coordinates of the desorbing molecules shows that excitation of the single C– D (C–H) bond in the parent molecule is strongly correlated with energy excess in the reaction coordinate. The results of the molecular dynamics simulations are consistent with observed mode- and bond-specific reactivity measurements for chemisorption of methane and its isotopomers on platinum and nickel surfaces.