Low density lipoprotein undergoes oxidation within lysosomes in cells

The oxidized low density lipoprotein (LDL) hypothesis of atherosclerosis proposes that LDL undergoes oxidation in the interstitial fluid of the arterial wall. We have shown that aggregated (vortexed) nonoxidized LDL was taken up by J774 mouse macrophages and human monocyte-derived macrophages and oxidized intracellularly, as assessed by the microscopic detection of ceroid, an advanced lipid oxidation product. Confocal microscopy showed that the ceroid was located in the lysosomes. To confirm these findings, J774 macrophages were incubated with acetylated LDL, which is internalized rapidly to lysosomes, and then incubated (chase incubation) in the absence of any LDL. The intracellular levels of oxysterols, measured by HPLC, increased during the chase incubation period, showing that LDL must have been oxidized inside the cells. Furthermore, we found that this oxidative modification was inhibited by lipid-soluble antioxidants, an iron chelator taken up by fluid-phase pinocytosis and the lysosomotropic drug chloroquine, which increases the pH of lysosomes. The results indicate that LDL oxidation can occur intracellularly, most probably within lysosomes.

Microwave activation of the electro-oxidation of glucose in alkaline media

The oxidation of glucose is a complex process usually requiring catalytically active electrode surfaces or enzyme-modified electrodes. In this study the effect of high intensity microwave radiation on the oxidation of glucose in alkaline solution at Au, Cu, and Ni electrodes is reported. Calibration experiments with the Fe(CN)63–/4– redox system in aqueous 0.1 M NaOH indicate that strong thermal effects occur at both 50 and 500 µm diameter electrodes with temperatures reaching 380 K. Extreme mass transport effects with mass transport coefficients of kmt > 0.01 m s–1(or kmt > 1.0 cm s–1) are observed at 50 µm diameter electrodes in the presence of microwaves. The electrocatalytic oxidation of glucose at 500 µm diameter Au, Cu, or Ni electrodes immersed in 0.1 M NaOH and in the presence of microwave radiation is shown to be dominated by kinetic control. The magnitude of glucose oxidation currents at Cu electrodes is shown to depend on the thickness of a pre-formed oxide layer. At 50 µm diameter Au, Cu, or Ni electrodes microwave enhanced current densities are generally higher, but only at Au electrodes is a significantly increased rate for the electrocatalytic oxidation of glucose to gluconolactone observed. This rate enhancement appears to be independent of temperature but microwave intensity dependent, and therefore non-thermal in nature. Voltammetric currents observed at Ni electrodes in the presence of microwaves show the best correlation with glucose concentration and are therefore analytically most useful.

Rhodium assisted C-H activation of N-(2 '-hydroxyphenyl)benzaldimines. Synthesis, structure and electrochemical properties of a group of organorhodium complexes

Reaction of a group of N-(2'-hydroxyphenyl)benzaldimines, derived from 2-aminophenol and five para-substituted benzaldehydes (the para substituents are OCH3, CH3, H, Cl and NO2), with [Rh(PPh3)(3)Cl] in refluxing toluene in the presence of a base (NEW afforded a family of organometallic complexes of rhodium(III). The crystal structure of one complex has been determined by X-ray crystallography. In these complexes the benzaldimine ligands are coordinated to the metal center, via dissociation of the phenolic proton and the phenyl proton at the ortho position of the phenyl ring in the imine fragment, as dianionic tridentate C,N,O-donors, and the two PPh3 ligands are trans. The complexes are diamagnetic (low-spin d(6), S = 0) and show intense MLCT transitions in the visible region. Cyclic voltammetry shows a Rh(III)-Rh(IV) oxidation within 0.63-0.93 V vs SCE followed by an oxidation of the coordinated benzaldimine ligand. A reduction of the coordinated benzaldimine is also observed within -0.96 to -1.04 V vs SCE. Potential of the Rh(Ill)-Rh(IV) oxidation is found to be sensitive to the nature of the para-substituent. (c) 2006 Elsevier B.V. All rights reserved.

The role of Ti3+ interstitials in TiO2(110) reduction and oxidation

Here we describe results which teach us much about the mechanism of the reduction and oxidation of TiO2(110) by the application of scanning tunnelling microscopy imaging at high temperatures. Titania reduces at high temperature by thermal oxygen loss to leave localized (i.e. Ti3+) and delocalized electrons on the lattice Ti, and a reduced titania interstitial that diffuses into the bulk of the crystal. The interstitial titania can be recalled to the surface by treatment in very low pressures of oxygen, occurring at a significant rate even at 573 K. This re-oxidation occurs by re-growth of titania layers in a Volmer-Weber manner, by a repeating sequence in which in-growth of extra titania within the cross-linked (1 x 2) structure completes the (1 x 1) bulk termination. The next layer then initiates with the nucleation of points and strings which extend to form islands of cross-linked (1 x 2), which once again grow and fill in to reform the (1 x 1). This process continues in a cyclical manner to form many new layers of well-ordered titania. The details of the mechanism and kinetics of the process are considered.

Tris-(1,3-diaryltriazenide) complexes of rhodium: synthesis, structure and, spectral and electrochemical properties

Reaction of 1,3-diaryltriazenes (abbreviated in general as HL-R, where R stands for the para-substituent in the aryl fragment and H stands for the dissociable hydrogen atom, R = OCH3, CH3, H, Cl, NO2) with [Rh(PPh3)(2)(CO)Cl] in ethanol in the presence of NEt3 produces a series of tris-diaryltriazenide complexes of rhodium of type [Rh(L-R)(3)], where the triazenes are coordinated to rhodium as monoanionic, bidentate N,N-donors. Structure of the [Rh(L-OCH3)(3)] complex has been determined by X-ray crystallography. The complexes are diamagnetic, and show characteristic H-1 NMR signals and intense MLCT transitions in the visible region. They also fluoresce in the visible region under ambient condition while excited at around 400 nm. Cyclic voltammetry on these complexes shows a Rh(III)-Rh(IV) oxidation (within 0.84-1.67 V vs SCE), followed by an oxidation of the coordinated tri- and azene ligand (except the R = NO2 complex). An irreversible reduction of the coordinated triazene is also observed for all the complexes below -1.03 V vs SCE.

Synthesis, structure, and electrochemical properties of a family of 2-(arylazo)phenolate complexes of ruthenium with unusual C-C coupling and N=Ncleavage

Reaction of 2-(4'-R-phenylazo)-4-methylphenols (R = OCH3, CH3, H, Cl, and NO2) with [Ru(dmso)(4)Cl-2] affords a family of five ruthenium(III) complexes, containing a 2-(arylazo)phenolate ligand forming a six-membered chelate ring and a tetradentate ligand formed from two 2-(arylazo) phenols via an unusual C-C coupling linki.ng the two ortho carbons of the phenyl rings in the arylazo fragment. A similar reaction with 2-(2'-methylphenylazo)-4-methylphenol with [Ru(dmso)(4)Cl-2] has afforded a similar complex, in which one 2-(2'-methylphenylazo)-4-methylphenolate ligand is coordinated forming a six-membered chelate ring, and the other two ligands have undergone the C-C coupling reaction, and the coupled species is coordinated as a tetradentate ligand forming a five-membered N,O-chelate ring, a nine-membered N,N-chelate ring, and another five-membered chelate ring. Reaction of 2-(2',6'-dimethylphenylazo)-4-methylphenol with [Ru(dmso)(4)Cl-2] has afforded a complex in which two 2-(2',6'-dimethylphenylazo)-4-methylphenols are coordinated as bidentate N,O-donors forming five- and six-membered chelate rings, while the third one has undergone cleavage across the N=N bond, and the phenolate fragment, thus generated, remains coordinated to the metal center in the iminosemiquinonate form. Structures of four selected complexes have been determined by X-ray crystallography. The first six complexes are one-electron paramagnetic and show rhombic ESR spectra. The last complex is diamagnetic and shows characteristic H-1 NMR signals. All the complexes show intense charge-transfer transitions in the visible region and a Ru(III)-Ru(IV) oxidation on the positive side of SCE and a Ru(III)-Ru(II) reduction on the negative side.

A pulse radiolysis study of free radicals formed by one-electron oxidation of the antimalarial drug pyronaridine

Free radicals from one-electron oxidation of the antimalarial drug pyronaridine have been studied by pulse radiolysis. The results show that pyronaridine is readily oxidised to an intermediate semi-iminoquine radical by inorganic and organic free radicals, including those derived from tryptophan and acetaminophen. The pyronaridine radical is rapidly reduced by both ascorbate and caffeic acid. The results indicate that the one-electron reduction potential of the pyronaridine radical at neutral pH lies between those of acetaminophen (707 mV) and caffeic acid (534 mV). The pyronaridine radical decays to produce the iminoquinone, detected by electrospray mass spectrometry, in a second-order process that density functional theory (DFT) calculations (UB3LYP/6-31+G*) suggest is a disproportionation reaction. Important calculated dimensions of pyronaridine, its phenoxyl and aminyl radical, as well as the iminoquinone, are presented.

An electrochemical study of 4-aminothiophenol/pt nanoparticle multilayers on gold electrodes

Quartz crystal microbalance (QCM) measurements of the formation of a 4-aminothiophenol (4-ATP)self-assembled monolayer (SAM) at a gold electrode showed that a surface coverage of 118 ng cm(-2) was obtained after a 3 h exposure period, indicating that good surface coverage was achieved. Cyclic voltammetry of the ferricyanide redox couple across this SAM modified surface produced similar results to those of a bare electrode; however, the electroreduction of oxygen was found to be impaired. The 4-ATP SAM layer was not stable to repeated electrochemical oxidation and reduction; it is believed that the 4-ATP SAM layer was first converted to a 4'-mercapto-N-phenylquinone diimine (NPQD) layer followed by subsequent formation of a 4'-mercapto-N-phenylquinone monoimine (NPQM) layer. We also report a quartz crystal microbalance study of the attachment of platinum nanoparticles to such SAM modified electrodes. We show that five times the amount of platinum nanoparticles can be attached to a 4-ATP modified electrode surface (observed frequency change - 187 Hz) compared with an NPQD modified electrode surface (observed frequency change -35 Hz). The presence of the platinum particles was confirmed electrochemically by their surface electrochemical properties, which were different from those of the underlying gold electrode. It is believed that this is the first time that such direct evidence of electrochemical communication between platinum nanoparticles and a SAM modified electrode surface has been obtained. It was also shown to be possible to build up multilayer SAM/nanoparticle modified surfaces while maintaining efficient electrochemical communication. Up to three SAM/nanoparticle sandwich layers were constructed.

DNA cleavage and antitumour activity of platinum(II) and copper(II) compounds derived from 4-methyl-2-N-(2-pyridylmethyl)aminophenol: spectroscopic, electrochemical and biological investigation

The reaction of the redox-active ligand, Hpyramol (4-methyl-2-N-(2-pyridylmethyl)aminophenol) with K2PtCl4 yields monofunctional square-planar [Pt(pyrimol)Cl], PtL-Cl, which was structurally characterised by single-crystal X-ray diffraction and NMR spectroscopy. This compound unexpectedly cleaves supercoiled double-stranded DNA stoichiometrically and oxidatively, in a non-specific manner without any external reductant added, under physiological conditions. Spectro-electrochemical investigations of PtL-Cl were carried out in comparison with the analogue CuL-Cl as a reference compound. The results support a phenolate oxidation, generating a phenoxyl radical responsible for the ligand-based DNA cleavage property of the title compounds. Time-dependent in vitro cytotoxicity assays were performed with both PtL-Cl and CuL-Cl in various cancer cell lines. The compound CuL-Cl overcomes cisplatin-resistance in ovarian carcinoma and mouse leukaemia cell lines, with additional activity in some other cells. The platinum analogue, PtL-Cl also inhibits cell-proliferation selectively. Additionally, cellular-uptake studies performed for both compounds in ovarian carcinoma cell lines showed that significant amounts of Pt and Cu were accumulated in the A2780 and A2780R cancer cells. The conformational and structural changes induced by PtL-Cl and CuL-Cl on calf thymus DNA and phi X174 supercoiled phage DNA at ambient conditions were followed by electrophoretic mobility assay and circular dichroism spectroscopy. The compounds induce extensive DNA degradation and unwinding, along with formation of a monoadduct at the DNA minor groove. Thus, hybrid effects of metal-centre variation, multiple DNA-binding modes and ligand-based redox activity towards cancer cell-growth inhibition have been demonstrated. Finally, reactions of PtL-Cl with DNA model bases (9-Ethylguanine and 5'-GMP) followed by NMR and MS showed slow binding at Guanine-N7 and for the double stranded self complimentary oligonucleotide d(GTCGAC)(2) in the minor groove.

Novel supramolecular network in tri- and mono-nuclear oxovanadium(V)-salicyl-hydroximate: Synthesis, structure and catalytic oxidation of hydrocarbons using H2O2 as terminal oxidant

oxovanadium(V) salicylhydroximate complexes, [VO(SHA)(H2O)]center dot 1.58H(2)O (1) and [V3O3(CSHA)(3) (H2O)(3)]center dot 3CH(3)COCH(3) (2) have been synthesized by reaction of VO43- with N-salicyl hydroxamic acid (SHAHS) and N-(5-chlorosalicyl) hydroxamic acid (CSHAH(3)), respectively, in methanol medium. Compound 1 on reaction with pyridine 2,6-dicarboxylic acid (PyDCH2) yields mononuclear complex [VO(SHAH(2))(PyDC)] (3). Treatment of compound 3 with hydrogen peroxide at low pH (2-3) and low temperature (0-5 degrees C) yields a stable oxoperoxovanadium(V) complex H[VO(O-2)(PyDC)(H2O)]center dot 2.5H(2)O (4). All four complexes (1-4) have been characterized by spectroscopic (IR, UV-Vis, V-51 NMR) and single crystal X-ray analyses. Intermolecular hydrogen bonds link complex 1 into hexanuclear clusters consisting of six {VNO5} octahedra surrounded by twelve {VNO5} octahedra to form an annular ring. While the molecular packing in 2 generates a two-dimensional framework hydrogen bonds involving the solvent acetone molecules, the mononuclear complexes 3 and 4 exhibit three-dimensional supramolecular architecture. The compounds 1 and 2 behave as good catalysts for oxygenation of benzylic, aromatic, carbocyclic and aliphatic hydrocarbons to their corresponding hydroxylated and oxygenated products using H2O2 as terminal oxidant; the process affords very good yield and turnover number. The catalysis work shows that cyclohexane is a very easily oxidizable substrate giving the highest turnover number (TON) while n-hexane and n-heptane show limited yield, longer time involvement and lesser TON than other hydrocarbons. (C) 2008 Elsevier Ltd. All rights reserved.

Strongly nucleophilic RhI centre in square-planar complexes with terdentate (κ3) 2,2′:6′,2′′-terpyridine ligands: crystallographic, electrochemical and density functional theoretical studies

Rh-I-terpyridine complexes have been unambiguously formed for the first time. The 2,21:6',2"-terpyridine (tpy), 4'-chloro-2,2':6',2"-terpyridine (4'-Cl-tpy) and 4'-(tert-butyldimethylsilyl-ortho-carboranyl)-2,2':6',2"-terpyridine (carboranyl-tpy) ligands were used for successful syntheses and characterisation of the corresponding Rh-I complexes with halide coligands, [Rh(X)(4'-Y-terpyridine)] (X = Cl, Y = H, Cl, carboranyl; X = Br, Y = H). All four neutral Rh-tpy complexes are square planar, with Rh-X bonds in the plane of the 4'-Y-terpyridine ligands. Full characterisation of these dark blue, highly air-sensitive compounds was hampered by their poor solubility in various organic solvents. This is mainly due to the formation of pi-stacked aggregates, as evidenced by the crystal structure of [Rh(Cl)(tpy)]; in addition, [Rh(Cl)(carboranyl-tpy)] merely forms discrete dimers. The (bonding) properties of the novel Rh-I-terpyridine complexes have been studied with single-crystal X-ray diffraction, (time-dependent) density functional theoretical (DFT) calculations, far-infrared spectroscopy, electronic absorption spectroscopy and cyclic voltammetry. From DFT calculations, the HOMO of the studied Rh-I-terpyridine complexes involves predominantly the metal centre, while the LUMO resides on the terpyridine ligand. Absorption bands of the studied complexes in the visible region (400-900 nm) can be assigned to MLCT and MLCT/XLCT transitions. The relatively low oxidation potentials of [Rh(X)(tpy)] (X = Cl, Br) point to a high electron density on the metal centre. This makes the Rh-I-terpyridine complexes strongly nucleophilic and (potentially) highly reactive towards various (small) substrate molecules containing carbon-halide bonds.

Redox-active polymers based on nonbridged metal−metal bonds. Electrochemical formation of [Os(bpy)(CO)(L)]n(bpy = 2,2‘-bipyridine; L = CO, MeCN) and of their reduced forms: a spectroelectrochemical study

IR, UV-vis, and EPR spectroelectrochemistry at variable temperatures and in different solvents were applied to investigate in situ the formation of electroactive molecular chains with a nonbridged Os-Os backbone, in particular, the polymer [Os-0(bpy)(CO)(2)](n), (bpy = 2,2'-bipyridine), from a mononuclear Os(II) carbonyl precursor, [Os-II(bpy)(CO)(2)Cl-2]. The one-electron-reduced form, [Os-II(bpy(.-))(CO)(2)Cl-2](-), has been characterized spectroscopically at low temperatures. This radical anion is the key intermediate in the electrochemical propagation process responsible for the metal-metal bond formation. Unambiguous spectroscopic evidence has been gained also for the formation of [{Os-0(bpy(.-))(CO)(2)}(-)](n), the electron-rich electrocatalyst of CO2 reduction. The polymer species are fairly well soluble in butyronitrile, which is important for their potential utilization in nanoscience, for example, as conducting molecular wires. We have also shown that complete solubility is accomplished for the monocarbonyl-acetonitrile derivative of the polymer, [Os-0(bpy)(CO)(MeCN)(2)Cl](n).

Rigid ferrocenophane and its metal complexes with transition and alkaline-earth metal ions

The rigid [6]ferrocenophane, L-1, was synthesised by condensation of 1,1'-ferrocene dicarbaldehyde with trans-1,2-diaminocyclohexane in high dilution at r.t. followed by reduction. When other experimental conditions were employed, the [6,6,6]ferrocenephane (L-2) was also obtained. Both compounds were characterised by single crystal X-ray crystallography. The protonation of L-1 and its metal complexation were evaluated by the effect on the electron-transfer process of the ferrocene (fc) unit of L-1 using cyclic voltammetry (CV) and square wave voltammetry (SWV) in anhydrous CH3CN solution and in 0.1 M (Bu4NPF6)-Bu-n as the supporting electrolyte. The electrochemical process of L-1 between 300 and 900 mV is complicated by amine oxidation. On the other hand, an anodic shift from the fc/fc(+) wave of L-1 of 249, 225, 81 and 61 mV was observed by formation of Zn2+, Ni2+, Pd2+ and Cu2+ complexes, respectively. Whereas Mg2+ and Ca2+ only have with L-1 weak interactions and they promote the acid-base equilibrium of L-1. This reveals that L-1 is an interesting molecular redox sensor for detection of Zn2+ and Ni2+, although the kinetics of the Zn2+ complex formation is much faster than that of the Ni2+ one. The X-ray crystal structure of [(PdLCl2)-Cl-1] was determined and showed a square-planar environment with Pd(II) and Fe(II) centres separated by 3.781(1) angstrom. The experimental anodic shifts were elucidated by DFT calculations on the [(MLCl2)-Cl-1] series and they are related to the nature of the HOMO of these complexes and a four-electron, two-orbital interaction.