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Two different series of nickel Schiff base complexes were prepared as part of a study aimed at discovering new compounds with high affinity and selectivity for quadruplex DNA (qDNA). The new complexes were prepared by modification of a literature method for synthesising N,N-bis-(4-((1-(2-ethyl)piperidine)-oxy)salicylidene)phenylenediaminenickel(ii) (complex (1)). For Series 1 complexes, the phenylenediamine head group of the literature complex was replaced with ethylenediamine, phenanthrenediamine, R,R- and S,S-diaminocyclohexane. These complexes, as well as an asymmetric molecule featuring a naphthalene moiety on one side and a single ethyl piperidinyl salicylidene group on the other, were prepared in order to examine the effect of varying the number and position of aromatic groups on DNA binding. Series 2 complexes were isomers of those in Series 1, in which pendant ethyl piperidine groups were located at different positions. All new complexes were characterised by 1D and 2D NMR spectroscopic methods alongside microanalysis and ESI-MS. In addition, the solid state structures of eight new complexes were determined using single crystal X-ray diffraction methods. N,N-Bis-(4-((1-(2-ethyl)piperidine)oxy)-salicylidine)diaminophenanthrenenickel(ii) (9), was shown by ESI-MS, CD spectroscopy and UV melting studies to exhibit a greater affinity towards, and ability to stabilise, dsDNA than all other complexes in the first series. ESI-MS revealed (9) to have a strong tendency to form a 1:1 complex with the tetramolecular, parallel qDNA molecule Q4, however it exhibited low affinity towards the parallel unimolecular qDNA molecule Q1. The enantiomeric complexes (5) and (7), featuring R,R- and S,S-diaminocyclohexane moieties, respectively, showed similar binding profiles towards all DNA molecules investigated, whereas the asymmetric complex (11), exhibited very low DNA affinity in all cases. Series 2 complexes showed very similar DNA affinity and selectivity to their isomeric c

The solid state structures of two metal complexes of a hexaamine macrobicyclic ligand, in which the metal ion has an exact trigonal prismatic geometry, have been determined. Theoretical calculations showed this is the most stable geometry for d⁰, d¹⁰ and high spin d⁵ metal complexes of the ligand with M–N bond distances >∼2.35 Å.

As part of a program of preparing metal complexes which exhibit unique affinities towards different DNA structures, we have synthesised the novel Schiff base complex N,N'-bis-4-(hydroxysalicylidine)meso-diphenylethylenediaminenickel(ii) (), via the reaction of meso-1,2-diphenylethylenediamine and 2,4-dihydroxybenzaldehyde. This compound was subsequently reacted with 1-(2-chloroethyl)piperidine or 1-(2-chloropropyl)piperidine, to afford the alkylated complexes N,N'-bis-(4-((1-(2-ethyl)piperidine)oxy)salicylidine)meso-1,2-diphenylethylenediaminenickel(ii) () and N,N'-bis-(4-((1-(3-propyl)piperidine)oxy)-salicylidine)meso-1,2-diphenylethylenediaminenickel(ii) (), respectively. These complexes were characterised by microanalysis and X-ray crystallography in the solid state, and in solution by (1)H and (13)C NMR spectroscopy. Electrospray ionisation mass spectrometry (ESI-MS) was used to confirm the identity of () and (). The affinities of () and () towards a discrete 16 mer duplex DNA molecule, and examples of both tetramolecular and unimolecular DNA quadruplexes, was explored using a variety of techniques. In addition, the affinity of two other complexes () and (), towards the same DNA molecules was examined. Complexes () and () were prepared by methods analogous to those which afforded () and (), however 1,2-phenylenediamine was used instead of meso-1,2-diphenylethylenediamine in the initial step of the synthetic procedure. The results of ESI-MS and DNA melting temperature measurements suggest that () and () exhibit a lower affinity than () and () towards the 16 mer duplex DNA molecule, while circular dichroism (CD) spectroscopy suggested that none of the four complexes had a major effect on the conformation of the nucleic acid. In contrast, ESI-MS and CD spectroscopy suggested that both () and () show significant binding to a tetramolecular DNA quadruplex. The results of ESI-MS and Fluorescence Resonance Energy Transfer (FRET) assays indicated that () and () did not

Gold(I) complexes are an important tool in the arsenal of established approaches for treating rheumatoid arthritis (RA), while some recent studies have suggested that gold nanoparticles (Au NPs) may also be therapeutically efficacious. These observations prompted the current biological studies involving gold(I) anti-RA agents and Au NPs, which are aimed towards improving our knowledge of how they work. The cytotoxicity of auranofin, aurothiomalate, aurothiosulfate and Au NPs towards RAW264.7 macrophages was evaluated using the MTT assay, with the former compound proving to be the most toxic. The extent of cellular uptake of the various gold agents was determined using graphite furnace atomic absorption spectrometry, while their distribution within macrophages was examined using microprobe synchrotron radiation X-ray fluorescence spectroscopy. The latter technique showed accumulation of gold in discrete regions of the cell, and co-localisation with sulfur in the case of cells treated with aurothiomalate or auranofin. Electrospray ionization mass spectrometry was used to characterize thioredoxin reductase (TrxR) in which the penultimate selenocysteine residue was replaced by cysteine. Mass spectra of solutions of TrxR and aurothiomalate, aurothiosulfate or auranofin showed complexes containing bare gold atoms bound to the protein, or protein adducts containing gold atoms retaining some of their initial ligands. These results support TrxR being an important target of gold(I) drugs used to treat RA, while the finding that Au NPs are incorporated into macrophages, but elicit little toxicity, indicates further exploration of their potential for treatment of RA is warranted.

High power tip sonication was used to prepare dispersions containing multi-walled carbon nanotubes (MWNTs), or multi-walled carbon nanotubes functionalised with carboxylic acid groups (MWNT-COOH) or amine groups (MWNT-NH2). The dispersion of carbon nanotubes was facilitated by the presence of a surfactant (Triton X-100) or various macrocyclic ligands (derivatised porphyrin, phthalocyanine or calixarene) in the solution. Vacuum filtration of the dispersions afforded self-supporting membranes known as buckypapers. Microanalysis provided evidence for retention of the surfactant or macrocyclic ligands in the buckypapers, which were also characterised by measurement of their electrical conductivities (24±16 to 58±11 S/cm), contact angles (28±1° to 55±10°) and mechanical properties (tensile strengths varied between 1.6±0.7 and 13±2 MPa). The surface and internal morphologies of the buckypapers were similar to each other, which correlates with the lack of variation observed in their permeability's towards water. The ability of selected buckypapers to remove trace organic contaminants (TrOCs) was also examined. A buckypaper prepared using Triton X-100 as the dispersant showed more than 80% removal efficiency for 11 out of the 12 TrOCs investigated in this study. On the other hand, a buckypaper prepared from MWNTs and phthalocyaninetetrasulfonic acid exhibited lower removal efficiencies for these TrOCs, possibly due to their smaller specific surface area.

The preparation of free-standing carbon nanotube “buckypaper” (BP) membranes consisting of either single-walled carbon nanotubes (SWNTs) or multi-walled carbon nanotubes (MWNTs), and the antibiotic ciprofloxacin (cipro), is reported. The electrical, mechanical and morphological properties of these membranes have been characterised and are compared to those of the corresponding buckypaper membranes containing the surfactant Triton X-100 (Trix). Analysis of scanning electron microscopic images of the surfaces of SWNT/cipro and SWNT/Trix (Trix = Triton X-100) buckypapers revealed that the diameter of their surface pores was significantly smaller than that of the corresponding materials prepared using MWNTs. Similarly, the average internal pore diameter of both SWNT buckypapers was found to be smaller than that of their MWNT counterparts, after analysis of binding isotherms derived from nitrogen adsorption/desorption measurements performed on the materials. All four buckypaper membranes examined were found to be >99% effective for removing Escherichia coli (E. coli) from aqueous suspensions. However, buckypapers containing ciprofloxacin outperformed their counterparts containing the surfactant. Both MWNT buckypapers were more effective at preventing passage of E. coli than their analogues containing SWNTs, while fluorescence microscopic examination of stained membrane surfaces demonstrated that buckypapers composed of SWNTs had greater bactericidal properties.

The cytotoxicity of the metallointercalators, [Pt(5,6-dimethyl-1,10-phenanthroline)(trans-1R,2Rdiaminocyclohexane)] 2+ ([56MERR]) and [Pt(5,6-dimethyl-1,10-phenanthroline)(trans-1S,2Sdiaminocyclohexane)] 2+ ([56MESS]), towards A549 human lung cancer cells was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC50 value obtained following exposure of A549 cells to [56MESS] for 4 h was approximately three times smaller than that obtained when [56MERR] was administered under the same conditions, indicating that the former complex displayed greater cytotoxicity. Both IC50 values were greater than that obtained after exposure of A549 cells to cisplatin, demonstrating that the latter compound was the most cytotoxic of the three examined. Microprobe synchrotron radiation X-ray fluorescence (SR-XRF) analyses of metallointercalator-treated A549 cells showed that platinum became localised in DNA-rich regions of the nucleus. In contrast, when the same cells were treated with cisplatin the metal became distributed throughout the cell. Determination of the maximum concentration of platinum present inside the cells using graphite furnace atomic absorption spectrophotometry (GFAAS) of platinum-treated cells suggested that there was greater uptake of [56MERR] compared to [56MESS] by the A549 cells, and that platinum uptake did not account for the greater toxicity of [56MESS], as assessed by the MTT assay. Electrospray ionization mass spectrometric (ESI-MS) and circular dichroism (CD) spectroscopic studies of solutions containing either [56MERR] or [56MESS], and a duplex hexadecamer molecule, showed the two metallointercalators displayed very similar affinity towards the nucleic acid. Overall these results indicate that the difference in cytotoxicity of the two platinum metallointercalators is probably the result of variations in their interactions with other cellular components.

A novel bioelectrode system has been prepared in which an enzyme and a conducting polymerhydrogel are combined in a nanostructured scaffold. The latter consists of fibres of carbonNanoWeb, grown by chemical vapour deposition onto reticulated vitreous carbon (RVC). Thecatalytic currents produced by this new bioelectrode system are significantly larger than those obtained using conventional electrodes.

Single crystal X-ray studies are recorded for five copper(II) complexes of macrobicyclic ligands. In both [Cu(sar)][ZnCl 4] (295, 170 K) determinations ('sar' = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) and [Cu(NH 3) 2sar]Cl 4•6H 2O (295 K), the lig

The bicyclic hexaamine "cage" ligand Me 8tricosaneN6 (1,5,5,9,13,13,20,20-octamethyl-3,7,11,15,18, 22-hexaazabicyclo[7.7.7]tricosane) is capable of encapsulating octahedral metal ions, yet its expanded cavity allows the complexed metal to adopt a variety

Polypyrrole (PPy) films doped with acid-treated multi-walled carbon nanotubes (CNTs) were prepared by galvanostatic polymerisation of pyrrole (Py) dissolved in aqueous dispersions of CNTs, which served as the background electrolyte. Morphological characterization of PPy(CNT) films showed a random deposition of the polymer on the surface of the support material, with the former creating a porous, interconnecting three-dimensional network structure. The porous nature of PPy(CNT) films favours movement of large amounts of water in and out of the films during redox cycling, which also causes extensive volume changes. Raman spectroscopy, the electrochemical quartz crystal microbalance method and scanning electron microscopy were used to explore the properties of PPy(CNT) films. In addition, the factors influencing the electrochemically controlled transport of metal ions across composite membranes composed of polypyrrole doped with acid-treated multi-walled carbon nanotubes (PPy(CNT)) were studied. The factors examined were: The polymerization conditions (current density and time), the type of support material on which the polypyrrole films were deposited, and the use of single layer or bilayer type polypyrrole films. The flux of metal ions across the composite membranes was able to be electrochemically controlled when NucleoporeR track-etched membranes were used as the support material, while the flux was controlled by the concentration gradient present when polyvinylidene difluoride (PVDF) was used as the support material for PPy(CNT) films. However, electrochemically controlled movement of metal ions across PVDF-supported membranes was achieved when a bilayer type PPy film (PPy(pTS)/PPy(CNT)) was used (pTS = toluene-4-sulfonic acid). Increasing the thickness of the PPy(CNT) layer in the composite membrane was found to enhance the membranes permeability towards K+. Copyright 2011 Elsevier B.V. All rights reserved.

"Single crystal X-ray studies are recorded for five copper(II) complexes of macrobicyclic ligands. In both [Cu(sar)][ZnCl(4)] (295, 170 K) determinations (sar = 3,6, 10,13,16,19-hexaazabicyclo[6.6.6]icosane) and [Cu(NH(3))(2) sar]Cl(4)center dot 6H(2)O (295 K), the ligand encapsulates the copper atom by coordinating through all six nitrogen atoms, though distortions of the primary coordination sphere from an octahedral array are both marked and quite different in the two cases. [Cu(sar)](2+) undergoes a relatively facile detachment of one ligand strand in acid solution, giving a species with a different bound-N configuration to that of the reactant and which may be crystallised in various forms. In the solid of composition Cu(ClO(4))(2)center dot 2HClO(4)center dot 1/2HCl center dot H(2)O center dot sar(295 K) the complex present is binuclear [(sarH)CuClCu(sarH(2))](ClO(4))(6)center dot 2H(2)O, with the linear CuClCu array comprising the apical bonds of a pair of square-pyramidal ClCuN(4) components. In mononuclear [Cu(sarH(2))(O-NO(2))](NO(3))(3)center dot 3H(2)O (295 K) two of the ligand strings coordinate in a quasi-square-planar array, with an approach of an anionic oxygen atom to one of the remaining opposed axial coordination sites. In the crystalline complex formed between copper(II) triflate (Cu(tfs)(2); tfs = F(3)CSO(3)(-)) and the expanded macrobicycle Me(5)tricosaneN(6) (Me(5)tricosaneN(6) fac-1,5,9,13,20-pentamethyl-3,7,11,15,18,22-hexaazabicyclo[7.7.7]tricosane), the ligand, despite the lack of any protonation, is found (295, 150 K) to be bound in a quinquedentate form, with one triflate-O occupying the sixth coordination site about the metal, in the mononuclear complex [Cu(Me(5)tricosaneN(6))(O-tfs)](tfs). This contrasts with the perchlorate counterpart wherein all nitrogen atoms are coordinated within an encapsulating cage."

Over the past 2 decades there has been increasing interest in metal complexes that bind non-covalently to DNA, driven in part by a host of potential applications for molecules that can accomplish this task with high affinity and selectivity. As a result many workers have used a wide variety of experimental techniques, several of which are discussed in other chapters of this book, to unravel the details of the precise intermolecular interactions involved. Here we discuss one of the most recent additions to the armory of techniques used by chemists to interrogate metal complex/ DNA interactions. For the majority of its existence mass spectrometry (MS) has proven to be of enormous advantage to chemists by virtue of its ability to provide the molecular weights of compounds as well as structural information via fragmentation patterns. However, the high energies associated with many earlier MS techniques which result in fragmentation of covalent bonds, prevent its application for studying weaker intermolecular interactions. The advent of soft ionisation methods such as matrix assisted laser desorption ionisation (MALDI) and electrospray ionisation (ESI) has revolutionised mass spectrometric analysis of biomolecules, by allowing these normally fragile molecules to be introduced into the gas phase for analysis with minimal, if any, fragmentation. It was then recognised that ESI–MS, in particular, might be suitable for investigating non-covalent interactions between small molecules and either proteins or nucleic acids. This was confirmed by a number of early studies involving organic intercalators and minor groove binding ligands, prompting our interest in evaluating ESI–MS as a tool for studying non-covalent interactions between metal complexes and DNA. This chapter contains a discussion of the basic principles behind ESI–MS that enable it to introduce representative samples of solutions containing metal complexes and DNA into the gas phase for analysis. This will be follow

A mechanism for the macroscopic charge balance during the transport of anions and cations across polypyrrole based composite membranes is proposed. For the mechanism to be studied, anions and cations were monitored simultaneously across PPy based composite membranes, which are known to have cation exchange (PPy(PSS)), anion exchange (PPy(ClO 4)) and mixed ion exchange properties (PPy(pTS)). Even though none of the membranes were found to be completely permselective, the flux of cations was higher than that of anions across the PPy(PSS) composite membrane, while the flux of anions was higher than that of cations across the PPy(ClO 4) composite membrane. Distinct changes in pH of the receiving solution were also observed. These were a decrease in pH when a predominantly anion exchanging polypyrrole composite membrane was used, and an increase in pH when a membrane that maintains charge balance principally by cation exchange was used. When membranes which display approximately equal permeability towards anions and cations were used the pH of the receiving solution was ca. 6-8. There was only a negligible flux of Ca 2+ across the PPy(PSS) membrane in the transport experiments carried out with the source solution consisting of either Ca(NO 3) 2 or an equimolar mixture of KNO 3 and Ca(NO 3) 2. The PPy(PSS) composite membrane was impermeable towards NO 3 - ions when the source solution was Ca(NO 3) 2 but permeability towards NO 3 - was observed when the source solution was either KNO 3 or an equimolar mixture of KNO 3 and Ca(NO 3) 2. Copyright 2011 Elsevier Ltd. All rights reserved.

The bicyclic hexaamine "cage" ligand Me 8tricosaneN 6 (1,5,5,9,13,13,20,20-octamethyl-3,7,11,15,18, 22-hexaazabicyclo[7.7.7]tricosane) is capable of encapsulating octahedral metal ions, yet its expanded cavity allows the complexed metal to adopt a variety of geometries comprising either hexadentate or pentadentate coordination of the ligand. When complexed to Cu II the lability of the metal results in a dynamic equilibrium in solution between hexadentate- and pentadentate- coordinated complexes of Me 8tricosaneN 6. Both [Cu(Me 8tricosaneN 6)](ClO 4) 2 (6-coordinate) and [Cu(Me 8tricosaneN 6)](S 2O 6) (5-coordinate) have been characterized structurally. In weak acid (pH 1) a singly protonated complex [Cu(HMe 8tricosaneN 6)] 3+ has been isolated that finds the ligand binding as a pentadentate with the uncoordinated amine being protonated. vis-NIR and electron paramagnetic resonance (EPR) spectroscopy show that the predominant solution structure of [Cu(Me 8tricosaneN 6)] 2+ at neutral pH comprises a five-coordinate, square pyramidal complex. Cyclic voltammetry of the square pyramidal [Cu(Me 8tricosaneN 6)] 2+ complex reveals a reversible Cu II/I couple. All of these structural, spectroscopic, and electrochemical features contrast with the smaller cavity and well studied "sarcophagine" (sar, 3,6,10,13,16,19-hexaazabicyclo[6.6. 6]eicosane) Cu II complexes which are invariably hexadentate coordinated in neutral solution and cannot stabilize a Cu I form. 2011 American Chemical Society.

The conducting polymer polypyrrole, PPy, was used as the active component of a cation exchange membrane for transferring a range of metal ions between two solutions by electrical modulation of the polymer between its conducting and non-conducting states. The cation exchange membranes consisted of platinum sputter-coated polyvinylidene difluoride (PVDF) which had been coated with polypyrrole doped with sulfonated calix[6]arene (PPy(C6S)). It was shown that applying a constant potential in the range 0.4 to +0.6 V did not result in any metal ion flux across the PVDF/Pt-PPy(C6S) membrane. However, a gradual but steady increase in metal ion concentration was detected in the receiving cell when -0.8 V was applied to the membrane. To investigate the effect of film thickness on the permeability of metal ions, transport experiments were performed with composite membranes containing 2.0, 3.3, and 5.6 mu m thick PPy(C6S) films. The permeability of the metals across the membrane increased as the PPy(C6S) film thickness decreased and was found to decrease in the following order: Ca2+ > K+ > Mn2+ >> Co2+, when the receiving cell contained deionised water. The PVDF/Pt-PPy(C6S) composite membrane showed significant permeability towards metal ions such as Ca2+, K+ and Mn2+, with the flux for Ca2+ higher than that seen for this metal ion with any previously studied PPy films containing other complexing dopants. (C) 2010 Elsevier B.V. All rights reserved.

This paper describes the results of spectroelectrochemical studies performed using thin films composed of polypyrrole (PPy) doped with either para-toluenesulfonate (pTS) or poly-2-methoxyaniline-5-sulfonic acid (PMAS). Both films displayed changes in their absorption spectra consistent with reduction of the oxidised form of polypyrrole (PPy), when subjected to negative potentials after immersion in acetonitrile solutions containing tetrabutylammonium perchlorate (TBAP). Surprisingly, at even more negative potentials, both films showed a further set of spectral changes including the reappearance of a free carrier tail at wavelengths beyond 600 nm. These spectral changes suggest that the conductivity of the films was increasing at very negative potentials, a conclusion supported by in situ resistometry experiments performed using PPy/pTS films. These additional spectral changes were not observed during spectroelectrochemistry experiments performed using PPy films immersed in aqueous solutions, or organic solvents that had previously been de-aerated. These observations, as well as other evidence, suggest that molecular oxygen plays an important role in the occurrence of the additional spectral changes observed at very negative potentials. (C) 2009 Elsevier B.V. All rights reserved.

The electrochemical quartz crystal microbalance technique was used to examine the ion exchange behaviour and charge compensation mechanism of polypyrrole (PPy) doped with polystyrene sulfonate (PSS) immersed in electrolytes containing singly, doubly and triply charged metal ions. New insights were obtained concerning the mechanism of charge compensation and ion exchange behaviour of PPy/PSS films in electrolytes with triply and doubly charged transition metal ions. Understanding the ion exchange behaviour of conducting polymers immersed in these types of aqueous media could play a pivotal part in the development of methods for removing toxic metals from water supplies. Charge compensation occurred predominantly by means of cation movement for PPy/PSS films when the electrolyte was KNO3, Ca(NO3)(2), Mn(NO3)(2) or Co(NO3)(2). After prolonged redox cycling the electroactivity, of the polymer decreases slightly, and the charge compensation mechanism becomes complex owing to movement of ions and neutral species in opposite directions. The charge compensation mechanism for PPy/PSS films immersed in aqueous Cr(NO3)(3) and Al(NO3)(3) solutions was also complex, with the ion exchange behaviour shifting towards anion movement to and from the polymer. (C) 2009 Elsevier B.V. All rights reserved.