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Copper(II) is known to bind in the influenza virus His37 cluster in the homotetrameric M2 proton channel and block the proton current needed for uncoating. Copper complexes based on iminodiacetate also block the M2 proton channel and show reduced cytotoxicity and zebrafish-embryo toxicity. In voltage-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current block showed fast and slow phases, in contrast to the single phase found for amantadine block of wild-type M2. Here, we evaluate the mechanism of block by copper adamantyl iminodiacitate and copper cyclooctyl iminodiacitate complexes and address whether the complexes can coordinate with one or more of the His37 imidazoles. The current traces were fitted to parametrized master equations. The energetics of binding and the rate constants suggest that the first step is copper complex binding within the channel, and the slow step in the current block is the formation of a Cu-histidine coordination complex. Solution-phase isothermal titration calorimetry and density functional theory (DFT) calculations indicate that imidazole binds to the copper complexes. Structural optimization using DFT reveals that the complexes fit inside the channel and project the Cu(II) toward the His37 cluster, allowing one imidazole to form a coordination complex with Cu(II). Electrophysiology and DFT studies also show that the complexes block the G34E amantadine-resistant mutant despite some crowding in the binding site by the glutamates.

Due to their non-toxicity and their ability to be functionalized, magnetite (Fe3O4) nanoparticles (NPs) are good candidates for a variety of biomedical applications. To better implement their applications, it is crucial to well understand the basic structural and magnetic properties of the NPs in correlation with their synthesis method. Here, we show interesting properties of Fe3O4 NPs of various sizes ranging from 5 to 100 nm and the dependence of these properties on particle size and preparation method. One synthetic method based on heating Fe(acac)3 with oleic acid consistently gives 5 ± 1 nm NPs. A second method using the thermal decomposition of Fe(oleate)3 in oleic acid led to larger NPs, greater than 8 nm in size. Increasing the amount of oleic acid caused the average NP size to slightly increase from 8 to 10 nm. Increasing both the reaction temperature and the reaction time caused the NP size to drastically increase from 10 to 100 nm. Powder X-ray diffraction and electron-microscopy imaging show a pure single crystalline Fe3O4 phase for all NPs smaller than 50 nm and spherical in shape. When the NPs get larger than 50 nm, they notably tend to form faceted, FeO core–Fe3O4 shell structures. Magnetometry data collected in various field-cooling conditions show a pure superparamagnetic (SPM) behavior for all NPs smaller than 20 nm. The observed blocking temperature, $T_{B}$ , gradually increases with NP size from about 25–150 K. In addition, the Verwey transition is observed with the emergence of a strong narrow peak at 125 K in the magnetization curves when larger NPs are present. Our data confirm the vanishing of the Verwey transition in smaller NPs. Magnetization loops indicate that the saturating field drastically decreases with NP size. While larger NPs show some coercivity ( $H_{c}$ ) up to 30 mT at 400 K, NPs smaller than 20 nm show no coercivity ( $H_{c} = 0$ ), confirming their pure SPM behavior at high temperature. Upon cooling below $T_{B}$ , some of the SPM NPs gradually show some coercivity, with $H_{c}$ reaching 45 mT at 5 K for the 10 nm NPs, indicating emergent interparticle couplings in the blocked state.

Copper(II) is known to bind in the influenza virus His37 cluster in the homotetrameric M2 proton channel and block the proton current needed for uncoating. Copper complexes based on iminodiacetate also block the M2 proton channel and show reduced cytotoxicity and zebrafish-embryo toxicity. In voltage-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current block showed fast and slow phases in contrast to the single phase found for amantadine block of WT M2. Here we evaluate the mechanism of block by copper adamantyl iminodiacitate (Cu(AMT-IDA)) and copper cyclooctyl iminodiacitate (Cu(CO-IDA)) complexes and address whether the complexes can covalently bind to one or more of the His37 imidazoles. The current traces were fitted to parametrized master equations. The energetics of binding and the rate constants suggest that the first step is copper-complex binding within the channel and the slow step in the current block is the covalent bond formation between copper complex and histidine. Isothermal titration calorimetry (ITC) indicates that a single imidazole binds strongly to the copper complexes. Structural optimization using density functional theory (DFT) reveals that the complexes fit inside the channel and project the Cu(II) towards the His37 cluster allowing one imidazole to form a covalent bond with the Cu(II). Electrophysiology and DFT studies also show that the complexes block the G34E amantadine-resistant mutant in spite of some crowding in the binding site by the glutamates.

Technetium poses an environmental hazard because of its radioactivity and long half-life. It exists in the form of pertechnetate in the environment and can be modeled by the nonradioactive ion perrhenate, since pertechnetate and perrhenate have the same geometry and similar chemical properties. In this research, a new zinc cyclen resorcinarene cavitand (ZCR) column was used in ion chromatography (IC) to efficiently separate perrhenate. Ion chromatography has the advantage of requiring almost no sample preparation for water samples. The ZCR column demonstrated the ability to separate anions: fluoride, chloride, nitrate, sulfate, phosphate, perchlorate, and perrhenate by gradient 2–60 mM NaOH. Unlike other columns, the new column material was selective in retaining perrhenate. The ZCR column also gave a linear range from 2.0 to 1000 mg L−1 for perrhenate with R2 > 0.997. There was a logarithmic relationship between the concentration of perrhenate and its retention time. Excellent perrhenate recovery was achieved on the ZCR column when river water was spiked with perrhenate and perrhenate was preconcentrated. The efficient separations of perrhenate by the ZCR column will potentially assist in pertechnetate separations.

A new sensor for Hg2+ and cysteine detection has been synthesized and tested. The sensor based on cinamaldehyde and pyrimidine absorbs visible light when exposed to Hg2+ and becomes colored. The sensor only changes color due to Hg2+ and does not change when exposed to some other metal ions. Calculations show the change in color is due to lowering of the HOMO-LUMO transition. Titrations show the sensor-Hg2+ complex is composed of two sensor molecules per Hg2+. The limit of detection for Hg2+ is 0.39 μM. The sensor-Hg2+ complex selectively responds to cysteine (Cys), but does not show a color change due to other amino acids. The limit of detection of Cys by the sensor-Hg2+ complex is 0.10 μM.

Hypochlorite is used as a water disinfectant and it is also produced by biological organisms. Its detection and quantification is important and could lead to its mechanism of reactivity in cells. We have synthesized a new fluorescence sensor for hypochlorite based on bithiophene and furan-carbohydrazide. The sensor shows increased fluorescence as a function of hypochlorite and is selective for hypochlorite. Fluorescence enhancement due to hypochlorite is observed when the sensor is used in aqueous solutions at neutral pH values. Using the sensor, the detection limit for hypochlorite is 4.2 µM, making the sensor practical to determine hypochlorite in water. Applying the sensor to aide in the detection of hypochlorite in zebrafish, showed localization of ClO−/HClO in the air bladders and eyes of zebrafish.

Formation of crystalline hexagonal ZnO prisms from a sol–gel method is presented. The method requires zinc acetate, water, and diethanolamine to create a zinc hydroxide/zinc hydroxide acetate gel, which in the presence of water and upon heating forms hexagonal prisms. Ethanolamines were found to be critical for gel and prism formation, while other bases such NaOH and triethylamine produce nanoparticles. Scanning electron microscope images showed hexagonal prisms with uniform size (approx. 0.5 × 2 µm) and very distinct edges. Transmission electron microscope and electron diffraction images showed that the prisms were highly crystalline with rough surfaces. Transmission electron microscope also showed a change from randomly oriented particles in the gel to ordered crystals after heating. Using an X-ray diffraction high-temperature chamber to characterize the gel, it was determined that it formed ZnO at 100 °C. Along with heating, acetate and water were found to be necessary for prism formation. In a potential application, the prisms efficiently acted as a photocatalyst in the degradation of organic dye.

Monitoring Zn2+ levels in biological environments with fluorescent sensors is important. This paper gives the synthesis and properties of a new Zn2+ sensor based on quinoline and pyridylaminophenol. The sensor is selective for Zn2+ and remains fluorescent when bound to Zn2 even in the presence of other metal ions. Along with fluorescing when bound to Zn2+, the sensor becomes colored when Cu2+ or Co2+ is added to it. These two metal ions result in the sensor becoming yellow. The crystal structure of the Cu–sensor complex shows that all of the sensor's nitrogens are bound to the metal ion. In studies with living cells, the fluorescence intensity of the sensor correlates to the concentration of Zn2+.

The extent of reduction of unsupported iron-based high-temperature water-gas shift catalysts with small (

The synthesis, Zn 2+ binding, crystal structure, and cell imaging studies of a new pyrazole amine quinoline receptor with a flexible binding pocket are described. Upon coordination to Zn 2+ , the absorption of the receptor increases at 364 nm and it fluoresces at 500 nm. The fluorescence response to Zn 2+ is selective for Zn 2+ and does not occur with other metal ions, not even Cd 2+ . In solution, the receptor forms 1:1 complexes with Zn 2+ , but in the solid-state two Zn 2+ ions coordinate to the receptor. The aqueous solubility of the receptor allows for imaging of Zn 2+ in living cells. Cells exposed to receptor and Zn 2+ fluoresce when excited with visible light.

People with chronic kidney disease suffer from uremic toxins which accumulate in their bodies. Detection and quantification of uremic toxins help diagnose kidney problems and start patient care. The aim of this research was to seek a new method to assist this diagnosis by trace level detection and separation of guanidine containing uremic toxins in water and urine. To detect and quantify the uremic toxins, new stationary phases for ion chromatography (IC) columns based on glutamic acid functionalized resorcinarenes bound to divinylbenzene macroporous resin were prepared. The new column packing material afforded separation of the five compounds: guanidinoacetic acid, guanidine, methylguanidine, creatinine, and guanidinobenzoic acid in 30min. Peak resolutions ranged from 7.6 to 1.3. Gradient elutions at ambient temperature with methanesulfonic acid (MSA) solution as eluent resulted in detection levels in water from 10 to 47ppb and in synthetic urine from 28 to 180ppb. Limits of quantification for the analytes using pulsed amperometric detection were 30-160ppb in water and 93-590ppb in urine. Trace levels of creatinine (1ppm) were detected in the urine of a healthy individual using the columns.

A series of novel chloro-complexes of Mn2+, Co2+, Ni2+ and Fe3+ with 2,4,6-tris-(2-pyridyl)-1,3,5-triazine (L1) and thiourea (L2) with the formulae, [Mn(L1)Cl2(EtOH)]L2 (1), [Co(L1)Cl2(H2O)]L2.1/2H2O (2), [Ni(L1)Cl2(H2O)]L2.1/2H2O (3) and [Fe(L1)Cl3]L2 (4) were investigated utilizing convenient methods. Conversely, similar reaction resulted in complex with structure [Mn(L1)(OAc)(H2O)Cl]·H2O (5) in presence of sodium acetate. Pentagonal-bipyramidal geometry around Mn2+ ion is suggested. The solid state ESR spectra of Mn2+, Co2+ and Ni2+ complexes parameters show g|| > g┴ > 2.0023 indicating that the ground state is dx2-y2. Electronic spectra of two Mn2+ and the other complexes and the values of magnetic moments suggest octahedral geometry for complexes while pentagonal-pyramidal for [Mn(L1)Cl2(EtOH)]L2. Biological activity of complexes was tested versus alpathogenic bacteria (E. Coli, S. Aureus and C. Albicans). Further, the cytotoxic activity was screened for in vitro against (HeLa), (MCF-7), (HePG2) and (HeP-2). The role of ionic radii of the metal ion on the biological activity was investigated.

Zinc sensor molecules containing quinoline have been synthesized, which show fluorescence in the presence of Zn2+. The nitrogen in quinoline is critical to fluorescence and fluorescence enhancement is promoted by deprotonating the sensor’s amide. One of the sensors is highly selective for Zn2+ over Cd2+ and other cations such as Hg2+, Fe2+, Mn2+ and Ca2+. This selectivity can be attributed to the increased absorption of the sensor in the presence of Zn2+ and the strong binding of Zn2+. Structural studies, including X-ray and NMR, show the ability of dipicolylamine (DPA) to bind in facial and meridional manners to Zn2+. Crystal structures of different compounds show Zn2+ coordinating to three, four, and five nitrogens from the compounds. They also indicate that the selectivity of DPA containing compounds towards Zn2+ may originate from Zn2+ being stable in different coordination environments.

A zinc sensor based on quinoline and morpholine has been synthesized. The sensor selectively fluoresces in the presence of Zn2+, while not for other metal ions. Absorbance changes in the 350nm region are observed when Zn2+ binds, which binds in a 1:1 ratio. The sensor fluoresces due to Zn2+ above pH values of 6.0 and in the biological important region. The Zn2+-sensor complex has the unique ability to detect both Hg2+ and HS-. The fluorescence of the Zn2+-sensor complex is quenched when it is exposed to aqueous solutions of Hg2+ with sub-micromolar detection levels for Hg2+. The fluorescence of the Zn2+-sensor complex is also quenched by aqueous solutions of hydrosulfide. The sensor was used to detect Zn2+ and Hg2+ in living cells.

UV-vis and electron paramagnetic resonance (EPR) spectroscopic studies have been carried out on the multinuclear copper(II) complex Cu4BpaRes. The copper atoms are in a tetragonal distorted geometry with nitrogens from bispicolylamine (Bpa) coordinating in the equatorial plane and water molecules or anions completing four coordination sites. The interaction of anions with this polynuclear copper complex in aqueous solution supports the formation of different complex species, which depend on the type and the concentration of the anions. In the presence of excess anions, frozen solution EPR parameters show the formation of species in which the in-plane coordination is characterised by the presence of three nitrogen atoms coming from the ligand and a donor atom from the specific anion. For the bidentate anion ligands and especially for malonate, UV-vis titrations indicate the formation of a 1:4 (Cu4BpaRes:anion) species. EPR experiments support the formation of such a species and indicate that the four copper centres are equivalent and reach penta-coordination via the coordination of both oxygens from the bidentate ligand.

Chemosensors are developed to image zinc ions. Fluorescence enhancement due to Zn2+ binding is an excellent way to detect its presence. A chemosensor for Zn2+ based on dipicolylamine (DPA) groups connected by a pyridyl amide backbone has been synthesized. Addition of 2-chloroacetyl chloride to 2,6-diaminopyridine affords 2,6-bis(chloroethylamido)pyridine, which is converted to the sensor BADPA-P by 2,2′-dipicolylamine displacement of chlorine. This compound along with two others, the mono-DPA, ADPA-P and the benzyl in place of pyridyl, BADPA-B, present three potential Zn2+ sensors. It was found that BADPA-P in the presence of Zn2+ shows a large increase in fluorescence, whether in polar organic or aqueous environments. Its fluorescence in the presence of Cd2+, unlike with Zn2+, is not enhanced when excited at longer wavelengths. Proton NMR measurements, indicate two Zn2+ ions bind to BADPA-P. Also, Zn2+ enhances fluorescence even when other metal ions are present.

Magnetic nanoparticles are increasingly used in nanotechnologies and biomedical applications, such as drug targeting, MRI, bio-separation. Magnetite (Fe3O4) nanoparticles stand to be effective in these roles due to the non-toxic nature of magnetite and its ease of manufacture. To be more effective in these applications, a greater understanding of the magnetic behavior of a collection of magnetite nanoparticles is needed. This research seeks to discover the local magnetic ordering of ensembles of magnetite nanoparticles occurring under various external fields. To complete this study, we use x-ray resonant magnetic scattering (XRMS). Here we discuss the modeling of the magnetic scattering data using a one-dimensional chain of nanoparticles with a mix of ferromagnetic, anti-ferromagnetic, and random orders. By fitting the model to the experimental data, we extracted information about the magnetic correlations in the nanoparticle assembly.

The synthesis and binding properties of a new tetratopic anion receptor are reported. The resorcinarene ligand bearing four cyclen moieties is able to bind four Zn2+ ions and subsequently bind anions. NMR titrations show proton shifts during the binding of the first one or two anions. Isothermal titration calorimetry (ITC) titrations show that two or more anions bind to one tetramer. The tetratopic receptor in methanol has high affinity for dihydrogen phosphate, acetate, and halide ions and weak affinity for nitrate and perchlorate.

In this study, different additives such as cetyltrimethylammonium bromide (CTAB), aluminum nitrate and tri-n-octylphosphine oxide (TOPO) are selected, respectively, to bind zinc acetate in order to investigate its role in the formation of ZnO nanoparticles. Accordingly, the morphology and size of produced ZnO nanoparticles are affected by existence of the additives through XRD analyses and TEM observations. The particle size was found to be 32, 14, 15, and 28 nm for pure zinc acetate, zinc acetate/TOPO, zinc acetate/CTAB, and zinc acetate/aluminum nitrate, respectively. It is observed that the TOPO and CTAB decrease the size of ZnO nanoparticles, while the doping of aluminum to the precursor has no effect on its particle size. The obtained ZnO nanoparticles exhibited the direct optical bandgap of about 3.40–3.45 eV and their photoluminescence spectrum has a UV emission peak at about 363 nm which is slightly blue-shifted due to the smaller particle size of the ZnO nanoparticles in the presence of TOPO and CTAB additives.

Background: We have reported the development of a novel fusion protein (FP) consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase (L-M). The present study compared the effect of this novel FP on the proliferation of human ovarian, skin, breast endometrial and pancreatic cancer cell lines. Methods: The FP, L-M and a mutated FP, with reduced L-M activity, were produced by recombinant methods. The effect of treatment with FP, L-M and mutated FP on the proliferation of the cancer cells was measured in vitro using an MTS assay. Results: The inhibitory effect of the FP was found to be significantly greater than that of L-M alone or the mutated FP. In addition, the FP produced a greater inhibitory effect on an ovarian cancer cell line than on comparable normal, non-cancerous cells. Further, the FP produced a dose-dependent inhibition of the proliferation of pancreatic cancer cell lines. Conclusion: These results suggest that this FP is a potent and selective inhibitor of the proliferation of various cancer cell lines and has potential as a therapeutic agent for the treatment of various methionine-dependent cancers.

New carriers have been prepared based on the aza-18-crown-6 structure to facilitate membrane transport of ions. One of these incorporates four aza-18-crown-6 molecules bonded to a resorcinarene ring. The other, aza-18-crown-6 bonded to an undecyl chain, was studied as a monomeric analog. These carriers have been included in dichloromethane bulk liquid membranes (BLMs) to assess cation influence on competitive transport among anions (ReO 4 − , NO 3 − , ClO 4 − ). ReO 4 − was investigated as a non-radioactive analog of the pertechnetate anion, which is of interest in nuclear waste separations. The permeability values and selectivity for ReO 4 − and ClO 4 − were the greatest when neutral source and receiving phases were used with K + as the co-transported cation. The carriers also showed selectivity for ReO 4 − and ClO 4 − over NO 3 − with K + and Na + as the co-transported cations using neutral and basic aqueous phase solutions. It was also found that some cations inhibit anion transport.

A series of unsymmetrical bi- and tetrathiophenes have been synthesized with bipyridine and phosphonic acid functional groups. To do this, phosphonic esters were bonded to thiophenes and the thiophenes coupled to bipyridine. After synthesis of the thienylbipyridines, bis(bipyridine) ruthenium was coordinated to them through the bipyridines. The thienylbipyridines absorb visible light and fluoresce; however, on attachment to ruthenium, both their fluorescence and that of ruthenium are quenched. An additional effect of coordinating ruthenium to the thiophenes is a new absorption band around 470 nm. Variation in oligothiophene length and bipyridine substitution position allowed comparison of the effect of these variables on electronic properties. The longer oligothiophenes display lower-energy absorptions and emissions than that of the shorter thiophenes. In contrast, the position of the bipyridine attachment does not have a large effect on the absorbance or emission wavelength, or on the fluorescence quantum yield.

Trace levels of pharmaceuticals have been detected in surface water and may pose a health risk to humans and other organisms. New chromatographic materials will help identify and quantify these contaminants. We introduce a new ion chromatographic (IC) material designed to separate cationic pharmaceuticals and report its ability to separate a group of guanidine compounds. Guanidine moieties are strongly basic and protonated under acid conditions, and therefore can potentially be separated on the newly designed stationary phase and detected by ion exchange chromatography. The new column packing material is based on glutamic acids bonded to resorcinarene moieties that in turn are bound to divinylbenzene macroporous resin. Detection limits in the range of 5-30 μg L(-1) were achieved using integrated pulsed amperometric detection (IPAD) for guanidine (G), methylguanidine (MG), 1,1-dimethylbiguanide (DMG), agmatine (AGM), guanidinobenzoic acid (GBA) and cimetidine (CIM). Suppressed conductivity (CD) and UV-vis detection resulted in limits of detection similar to IPAD, in the range of 2-66 μg L(-1), but were not able to detect all of the analytes. Three water sources, river, lake, and marsh, were analyzed and despite matrix effects, sensitivity for guanidine compounds was in the 100 μg L(-1) range and apparent recoveries were 80-96%. The peak area precision was 0.01-2.89% for IPAD, CD and UV-vis detection.

Azotobacter vinelandii flavodoxin hydroquinone (FldHQ) is a physiological reductant to nitrogenase supporting catalysis that is twice as energy efficient (ATP/2e – = 2) as dithionite (ATP/2e – = 4). This catalytic efficiency results from reduction of Fe protein from A. vinelandii (Av2) to the all-ferrous oxidation state ([Fe 4 S 4 ] 0 ), in contrast to dithionite, which only reduces Av2 to the [Fe 4 S 4 ] 1+ state. Like FldHQ, Ti(III) citrate yields ATP/2e – = 2, and Ti(III)-reduced [Fe 4 S 4 ] 0 Av2 has a S = 4 spin state and characteristic Mossbauer spectrum, a parallel mode g = 16.4 EPR signal, and a shoulder at 520 nm in its UV-vis spectrum, each of which distinguish the S = 4 [Fe 4 S 4 ] 0 Av2 from other states. In this study, we demonstrate that FldHQ makes [Fe 4 S 4 ] 0 Av2, which is sufficiently characterized to demonstrate unique physical properties that distinguish it from the previously characterized Ti(III)-reduced [Fe 4 S 4 ] 0 Av2. In particular, Evans NMR magnetic susceptibility and EPR measurements indicate that FldHQ-reduced [Fe 4 S 4 ] 0 Av2 has an S = 0 spin state (like [Fe 4 S 4 ] 2+ Av2). There is no g = 16.4 EPR signal and no shoulder at 520 nm in its absorbance spectrum, which resembles that of [Fe 4 S 4 ] 1+ Av2. That the physiological reductant to Av2 is capable of forming [Fe 4 S 4 ] 0 Av2 has important implications for in vivo nitrogenase activity.

Indium-doped CdSe nanoparticles have been synthesized and characterized. Their light absorption, photoluminescence, and structure are similar to undoped CdSe nanoparticles. The greater part of the In associated with the nanoparticles is removed when the nanoparticles undergo ligand exchange by pyridine. As observed with undoped nanoparticles, a ZnS capping layer on the indium-doped nanoparticles results in enhanced nanocrystal photoluminescence. Also, the ZnS cap enhances the retention of In by the nanoparticles. Elemental analysis shows ligand exchange causes CdSe to be lost and capping with ZnS results in the loss of Se. We conclude that In-doped nanoparticles have most of the In on their surface, capping helps the nanoparticles retain the In, and they do not have altered electronic properties.

New polymer inclusion membrane (PIM) carriers to facilitate membrane transport of anions have been prepared consisting of bis(pyridylmethyl)amine compounds coordinated to transition metal ions (Fe3+, Cu2+, Zn2+). One of the carriers is based on a resorcinarene bonded to four bis(pyridylmethyl)amines. These carriers have been included in cellulose triacetate (CTA) based PIMs to study competitive transport among halides (F−, Cl−, Br−, I−) and oxoanions (SO42−, SeO42−, NO3− and ReO4−). Several compounds, tris(2-butoxyethyl) phosphate, dibutyl phthalate and ethylbenzoate, ethyl phthalyl ethyl glycolate and benzoic acid 2-ethoxyethyl ester, were used as plasticizers in the membranes to provide solubility of the metal carrier complexes. Separations were performed with and without antiport anions. Permeabilities of oxoanions increased with the use of 0.05 M KCl as an antiport solution. In some cases, Cl− was selectively transported over F−, Br− and I− in contradiction to the usual Hoffmeister-based selectivities. Excellent ReO4− transport over NO3−, SO42− and SeO42− was observed for certain systems. Permselectivity for ReO4−/NO3− was 312 for a PIM using ethyl phthalyl ethyl glycolate as plasticizer, zinc complex as carrier and an antiport solution of 0.05 M KCl.

Anion binding has been achieved with a resorcinarene substituted with four 2,2'-dipicolylamine moieties on the upper rim. The four dipicolylamine groups reside in proximity on one rim of the cavitand. The dipicolylamine groups were protonated with triflic acid to provide the cationic ammonium sites for anion binding. This anion receptor binds strongly to anions of different geometries, such as H(2)PO(4)(-), Cl(-), F(-), CH(3)CO(2)(-), HSO(4)(-), and NO(3)(-). The association constants for binding these anions are large, on the order of log K = 5 in CD(3)CN, a solvent of intermediate dielectric constant. These values represent significant binding compared to other cavitands with nitrogen pendant groups. Evidence suggests that the cavitand provides two identical receptor sites formed by two dipicolylamine groups, facilitating the simultaneous binding of two anions. Intramolecular binding of anions between two protonated dipicolylamine groups is indicated on the basis of the comparison to a structurally similar monomeric analogue and by semiempirical PM3 molecular modeling. Titrations with the analogue result in much weaker anion association, even at high concentrations, indicating the importance of proximity and preorganization of sites on the cavitand upper rim.

Reaction of 1-phenyl 5-(aminophenyl) 9-(2-pyridyl) benzimidazole derivatives (2) with cis-Ru(bpy)2Cl2 in MeCN results in the formation of N-(aryl) imidazo[1,5a] pyridine derivatives (4) and cis-[Ru(bpy)2(MeCN)2]2+(5). Crystal structures of N-(4-chlorophenyl) imidazo[1,5a] pyridine (4b) and cis-[Ru(bpy)2(MeCN)2](ClO4)2(5) are also reported.

Two new porous materials have been formed by allowing cobalt-assembled cages to self-assemble in the presence of potassium and cobalt ions. In both materials, the cages act as structural units that are linked by barium ions. During the assembly process, voids are created between the cages. In the case of the potassium material, K4Ba2Co412 (1=octaiminodiacetate resorcinarene), potassium ions either bind to the cages or are disordered in the channels of the material. For the cobalt material, Co2Ba2Co412, the cobalt counter cations are coordinated to water and carboxylate oxygens of 1 and reside within the voids. These materials have different structures than previously reported materials formed with cages and Group II cations. The channels in the K4Ba2Co412 material are 14×12 A and run in two directions through the material. The channels in the Co2Ba2Co412 material are smaller (11×9 A) and run in only one direction. In both materials the channels are surrounded by waters and methyl groups. These materials show how a single building unit, in this case a metal-assembled cage, can be used to construct various materials, even materials with transition and alkali metal ions in their channels.

The amidate function participates in the coordination chemistry of iron containing biomolecules such as the anti-tumor drug bleomycin and the enzyme nitrile hydratase. Our interest in amidate coordination prompted an investigation of the iron complexes of the potentially tetradentate ligand N-(bis(2-pyridyl)methyl)pyridine-2-carboxamide (HL). A number of complexes have been isolated and structurally characterized, including [FeII(L)2] (1), [FeIII(LOCH3)Br2(CH3OH)] (3), [FeIII 2(μ-OH)2(LOCH3)2Br2] (4), and [FeIII 4(μ-OCH3)2(LO)2Br6] (5). In these complexes L acts as a meridional tridentate ligand, as previously observed for the corresponding [Cu(L)Cl(CH3OH)] complex (Inorg. Chem. 39 (2000) 5326). In the cases of 3 and 4, the hydrogen of the tertiary carbon has been replaced by a methoxy group in the course of complex synthesis. In the case of 5, the tertiary hydrogen is replaced by hydroxide, and this oxygen and the dangling pyridine act as a bidentate ligand to a second iron ion. When the reaction of FeBr3 and HL was carried out in acetonitrile in the presence of base but in the absence of air, the ligand was cleaved into two pieces, affording [FeIIBr2(pyridine-2-carboxamide)(di-2-pyridylketone)] (6). It is proposed that the coordination of the amide nitrogen of HL to an iron(III) center as an amidate activates the α-CH bond and results in the oxidation of the α-CNamide bond to an imine.

Two novel polysiloxanes containing the metal complex, Co(TACN)(3+)2 (TACN= 1,4,7-triazacyclononane) were used as coatings for capillary electrophoresis (CE) and capillary electrochromatography (CEC). Through crosslinking and covalent bonding, the positively charged polymers were bonded to silica supports. In both CE and CEC, these coatings exhibited strong, pH-independent, and anodic electroosmotic flow (EOF), and had excellent long-term stability. Successful separations of aromatic acids were achieved in CE. In CEC, separation of alkylbenzenes (7 min) and basic compounds (20 min) was achieved with higher resolving power than conventional octadecyl silica packings. These polymers represent a new class of coatings for CE and CEC that generate pH-independent EOF.

Bladder cancer has a 60%-70% recurrence rate most likely due to any residual tumour left behind after a transurethral resection (TUR). Failure to completely resect the cancer can lead to recurrence and progression into higher grade tumours with metastatic potential. We present here a novel therapy to treat superficial tumours with the potential to decrease recurrence. The therapy is a heat-based approach in which bladder tumour specific single-walled carbon nanotubes (SWCNTs) are delivered intravesically at a very low dose (0.1 mg SWCNT per kg body weight) followed 24 h later by a short 30 s treatment with a 360° near-infrared light that heats only the bound nanotubes. The energy density of the treatment was 50 J cm-2, and the power density that this treatment corresponds to is 1.7 W cm-2, which is relatively low. Nanotubes are specifically targeted to the tumour via the interaction of annexin V (AV) and phosphatidylserine, which is normally internalised on healthy tissue but externalised on tumours and the tumour vasculature. SWCNTs are conjugated to AV, which binds specifically to bladder cancer cells as confirmed in vitro and in vivo. Due to this specific localisation, NIR light can be used to heat the tumour while conserving the healthy bladder wall. In a short-term efficacy study in mice with orthotopic MB49 murine bladder tumours treated with the SWCNT-AV conjugate and NIR light, no tumours were visible on the bladder wall 24 h after NIR light treatment, and there was no damage to the bladder. In a separate survival study in mice with the same type of orthotopic tumours, there was a 50% cure rate at 116 days when the study was ended. At 116 days, no treatment toxicity was observed, and no nanotubes were detected in the clearance organs or bladder.

Porous materials resembling zeolites that are composed of organic and inorganic building units were synthesized and characterized. Control of pore and channel size was achieved by using different-sized cations. The metal-assembled, anionic cage molecule, Co(4)1(2)(8-), with a hydrophobic cavity and four carboxylate rich arms, was used as a structural unit for the formation of materials with pores and channels. When assembled into a solid material with dications (Mg(2+), Ca(2+), Sr(2+), and Ba(2+)), Co(4)1(2)(8-) arranges into sheets of cages linked together by cations. The series of materials based on Co(4)1(2)(8-) and containing alkaline earth cations was characterized using X-ray crystallography. The magnesium material packs with cages close together, has small channels, and has cation-carboxylate linkages in three dimensions. The calcium material has cages packed with voids between them and has 5 x 10 A channels and 10 x 21 A pores. The strontium and barium materials also pack with voids between the cages and similarly to each other. They have 11 x 13 A and 11 x 11 A channels and 10 x 27 A and 9 x 27 A pores, respectively. Each of these materials has many (20-50) solvent water molecules associated with each cage. The associated water can be removed from and adsorbed by the materials. The heat of water binding has been measured to be -52 kJ/mol (Mg(4)Co(4)1(2)); -47 kJ/mol (Ca(4)Co(4)1(2)); -48 kJ/mol (Sr(4)Co(4)1(2)); -49 kJ/mol (Ba(4)Co(4)1(2)).

The air-stable complex [Fe(6-Me3-TPA) (O2CAr)]+ [1; 6-Me3-TPA = tris(6-methyl-2-pyridylmethyl)amine] has been synthesized as a model for the iron(II) site of lipoxygenase. This iron(II) complex reacts with 0.5 equiv ROOH to form a yellow species, which has been formulated as [FeIII(OH)(6-Me3-TPA) (O2CAr)]+ (2) by electrospray mass spectrometry. Addition of more ROOH converts 2 into a purple species, which is characterized by electrospray ionization mass spectrometry and resonance Raman spectroscopy as [FeIII(OOR)(6-Me3-TPA)(O2CAr)]+. The purple species is metastable and decomposes via Fe-O bond homolysis to regenerate the starting iron(II) complex. These metal-centered transformations parallel the changes observed for lipoxygenase in its reaction with its product hydroperoxide.

A new 7,16-bis(quinolin-8-ylmethyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane ligand, L, has been prepared and its crystal structure reported. In addition, the structure of the protonated ligand H2L has been determined. H2L is of interest because of interatomic interactions between the ligand and perchlorate ions. The mononuclear Ba(II) (BaL), and dinuclear Cu(II) (Cu2L) complexes of L have been prepared and their crystal structures determined. Stability constants and other thermodynamic data valid in methanol at 23 or 25° for these and several other complexes of L have been obtained. Among the metal ions studied, L forms the most stable complex with Ba2+. In addition, L selectively binds Cu2+ over Ni2+ by about 3 orders of magnitude. Some of the complexes have been studied using nmr and uv-vis spectroscopic techniques. Crystal data are given for L, space group, P21c, a = 8.8325(14) A, b = 13.808(3) A, c = 13.310(3) A; β = 94.72(2)° Z=2, R = 0.0727; for H2L, space group, P21/c, a = 14.685(3) A, b = 15.035(6) A, c = 17.369(4) A, β = 90.366(12)°, Z = 4, R = 0.0781; for BaL, space group, Pbcn, a = 17.314(3) A, b = 9.539(2) A, c = 22.081(3) A, Z = 4, R = 0.0354; and for Cu2L, space group, Cc, a = 19.762(2) A, b = 14.413(2) A, c = 14.935(2) A, β = 98.753(12)°, Z = 4, R = 0.0564. Cu2+ forms a hydroxo-bridged dinuclear complex with L while Ba2+ forms a mononuclear complex with L in which its two side arms are not involved in complexation.

Current research efforts focus on using metal ions to bring organic molecules together and in so doing form structures that resemble large common materials, such as boxes, cages, grids, and channels. These metal-organic supramolecular structures are at the interface between molecular and macromolecular chemistry. As a contribution to this field of chemistry, we have focused on binding metal ions to cupped-shaped template molecules, which can be appended with functional groups. These resorcinarene-based molecules have four phenyl groups linked together into a ring and various functional groups attached to their upper rim. Some of the functional groups, bispyridylmethylamine (bpa) and iminodiacetic acid, are able to coordinate to metal ions. In the case of the bispyridylmethylamine resorcinarene, 2, a tetranuclear metal complex is formed when it is allowed to coordinate to copper(II). The copper centers surround the resorcinarene cavity and are not electronically coupled. In contrast to the Cu428+ ...

Four iron(II) ions help assemble a container molecule (1), by bringing together two hemispherical resorc[4]arenes. The resorc[4]arene ligands are appended with four iminodiacetate moieties which act as ligands for the iron atoms. X-ray crystallographic analysis of 1 shows that the iron atoms are coordinated in an N,N-cis-fac manner and exhibit a trigonal prismatic geometry. When 1 is formed in water, six water molecules, hydrogen bonded together, occupy its cavity. However, when 1 is formed with bromobenzene present in the water solution, bromobenzene is trapped in the cavity. Multinuclear NMR experiments (1H, 2H, and 19F) demonstrate the pH-dependent encapsulation of various organic guest molecules by 1, e.g., substituted benzenes, alkanes, ethers, and chlorocarbons. Complex 1 is the first iron(II)-containing cage complex that is formed by assembly of resorcinarene molecules and that binds neutral organic molecules.

Calix[4]resorcinarenes serve as host molecules for small guest molecules. Recently calixarenes have been appended to chiral molecules in an attempt to promote chiral recognition. To take advantage of both cavity host and chiral substituent properties the position of the chiral moiety is important. We report the synthesis and structural characterization of two calix[4]resorcinarene based molecules that have helical chirality in the solid state. The calix[4]resorcinarene 1 has chiral l-proline ethyl ester substituents positioned perpendicular to the cavity whereas the calix[4]resorcinarene 2 has morpholines positioned parallel to the cavity which extend the depth of the cavity. Compound 1 is one of the first compounds to show the position of chiral centers with respect to the calixarene cavity. 1H and 13C NMR spectroscopy indicate that the helical chirality of 2 is retained at low temperature in nonpolar solvents.

A fusion protein was genetically engineered that contains an antimicrobial peptide, designated P2, at its carboxy terminus and bovine prochymosin at its amino terminus. Bovine prochymosin was chosen as the fusion partner because of its complete insolubility in Escherichia coli, a property utilized to protect the cells from the toxic effects of the antimicrobial peptide. This fusion protein was purified by centrifugation as an insoluble inclusion body. A methionine linker between prochymosin and the P2 peptide enabled P2 to be released by digestion with cyanogen bromide. Cation exchange HPLC followed by reversed-phase HPLC were used to purify the P2 peptide. The recombinant P2 peptide's molecular mass was confirmed by mass spectrometry to within 0.1% of the theoretical value (2480.9 Da), and the antimicrobial activity of the purified recombinant P2 against E. coli D31 was determined to be identical to that of the chemically synthesized peptide (minimal inhibitory concentration of 5 mg/mL). Although the yield of the fusion protein after expression by the cells was high (16% of the total cell protein), the percentage recovery of the P2 peptide in the inclusion bodies was relatively low, which appears to be due to losses in the cyanogen bromide digestion step.

The synthesis, spectroscopic characterisation, conformational switching and fluorescence quenching efficiency of a resorcinarene-based cavitand containing Zn-salen (Zn-Cav) are reported. Synthesis of Zn-Cav was accomplished by the condensation of a quinoxaline derivatised with Zn-salen and a resorcinarene-based cavitand containing three quinoxalines. 1H NMR spectroscopy confirmed that in DMSO, chloroform and acetone Zn-Cav resides in the vase conformation. The molecular geometry of Zn-Cav selectively changes from vase to kite under acidic conditions. Detection by fluorescence quenching of nitro-containing molecules, such as 4-nitrotoluene, 2,4-dinitrotoluene and 2,3-dimethyl-2,3-dinitrobutane was explored by spectrofluorimetry. It was found that the fluorescence of Zn-Cav is efficiently quenched by nitroaromatic compounds.

The hydroxylation of cyclohexane by t-butyl hydroperoxide using [Fe2O(TPA)2(H2O)2]4+ (1, TPA = tris(2-pyridylmethyl)amine) as the catalyst has been investigated with the use of a syringe pump to control the concentration of the alkyl hydroperoxide. Unlike an alkoxy radical-based radical chain autoxidation mechanism, the reaction observed produces only alcohol (no ketone) with a deuterium kinetic isotope effect of 10, similar to heme-catalyzed hydroxylations. An alkylperoxoiron(III) intermediate can be trapped at −40°C and characterized by a number of spectroscopic methods. A mechanistic scheme is proposed involving this intermediate which either serves as the precursor to the metal-based oxidant or oxidizes the substrate directly.

A new metal ion sensor that contains quinoline and pyridylaminophenol has been synthesized. In acetonitrile and in the presence of Zn(2+), the sensor fluoresces. In contrast, in aqueous solutions the sensor fluoresces in the presence of Cd(2+). The fluorescence of the molecule is selective for Zn(2+) or Cd(2+) and shows no fluorescence with other metal ions. The crystal structure of the Cd(2+) complex shows coordination through the amide and phenol oxygens, as well as the amine nitrogen of the sensor. The sensor also acts as a colorimetric sensor for Co(2+) by changing color from colorless to yellow. The color change is selective for Co(2+) and is not observed with other metal ions. The unique combination of pyridine and phenol groups with quinoline results in the properties of this sensor.

Resorcinarene-based deep cavitands alanine methyl resorcinarene acid (AMA), alanine undecyl resorcinarene acid (AUA) and glycine undecyl resorcinarene acid (GUA), which contain chiral amino acids, have been synthesized. The upper rim of the resorcinarene host is elongated with four identical substituents topped with alanine and glycine groups. The structures of the new resorcinarenes were elucidated by nuclear magnetic resonance (NMR), mass spectrometry (MS) and the sustained off-resonance irradiation collision induced dissociation (SORI-CID) technique in FTICR-MS. These studies revealed that eight water molecules associate to the cavitand, two for each alanine group. The alanine substituent groups are proposed to form a kite-like structure around the resorcinarene scaffold. The binding of AMA, AUA, and GUA with chiral R- and S-methyl benzyl amines was studied by (1)H NMR titration, and compared to that of a binary L-tartaric acid and the monoacid phthalyl alanine (PA). The results show that these compounds interact with amine guests; however, with four carboxylic acid groups, they bind several amine molecules strongly while the binary L-tartaric acid only binds one amine guest strongly. The simple compound PA, which contains one carboxylic group, shows weak binding to the amines. The (1)H NMR titration of AUA with primary, secondary, and tertiary chiral amines showed that it can discriminate between these three types of amines and showed chiral discrimination for chiral secondary amines.

The selectivity and separation of transition metal ions on two columns packed with cyclen-based macrocycles adsorbed onto 55% cross-linked styrene–divinylbenzene resin are presented. The N-cyclen and cyclen–resorcinarene stationary phases were made by adsorbing hydrophobically substituted N-cyclen or a cyclen–resorcinarene derivative (cyclenbowl) on the resin, respectively. The stability constants of cyclen with transition metal ions demonstrate that cyclen has selectivity for Cu2+ over other transition metal ions. Mn2+, Co2+, Ni2+, Cd2+, and Zn2+ ions were separated from Cu2+ using HNO3 eluent with the cyclenbowl column. The preconcentration of Cu2+ in parts per billion level from a high concentration matrix of Mn2+, Co2+, Ni2+, Cd2+, and Zn2+ ions was achieved in the cyclenbowl column using a nitric acid eluent gradient. Recovery of Cu2+ at >98% was obtained based on direct interaction of metal ion and cyclen. Although Mn2+, Co2+, Ni2+, Cd2+, and Zn2+ were not separated by HNO3 eluent, addition of oxalic acid yielded a very good separation. A retention mechanism is proposed for the latter system in which the protonated cyclen units attract negatively charged HC2O4− ions that cooperate with cyclen sites in retaining transition metal ions.

A new 7,16-bis(quinolin-8-ylmethyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane ligand, L, has been prepared and its crystal structure reported. In addition, the structure of the protonated ligand H2L has been determined. H2L is of interest because of interatomic interactions between the ligand and perchlorate ions. The mononuclear Ba(II) (BaL), and dinuclear Cu(II) (Cu2L) complexes of L have been prepared and their crystal structures determined. Stability constants and other thermodynamic data valid in methanol at 23 or 25° for these and several other complexes of L have been obtained. Among the metal ions studied, L forms the most stable complex with Ba2+. In addition, L selectively binds Cu2+ over Ni2+ by about 3 orders of magnitude. Some of the complexes have been studied using nmr and uv-vis spectroscopic techniques. Crystal data are given for L, space group, P21c, a = 8.8325(14) A, b = 13.808(3) A, c = 13.310(3) A; β = 94.72(2)° Z=2, R = 0.0727; for H2L, space group, P21/c, a = 14.685(3) A, b = 15.035(6) A, c = 17.369(4) A, β = 90.366(12)°, Z = 4, R = 0.0781; for BaL, space group, Pbcn, a = 17.314(3) A, b = 9.539(2) A, c = 22.081(3) A, Z = 4, R = 0.0354; and for Cu2L, space group, Cc, a = 19.762(2) A, b = 14.413(2) A, c = 14.935(2) A, β = 98.753(12)°, Z = 4, R = 0.0564. Cu2+ forms a hydroxo-bridged dinuclear complex with L while Ba2+ forms a mononuclear complex with L in which its two side arms are not involved in complexation.

Current research efforts focus on using metal ions to bring organic molecules together and in so doing form structures that resemble large common materials, such as boxes, cages, grids, and channels. These metal-organic supramolecular structures are at the interface between molecular and macromolecular chemistry. As a contribution to this field of chemistry, we have focused on binding metal ions to cupped-shaped template molecules, which can be appended with functional groups. These resorcinarene-based molecules have four phenyl groups linked together into a ring and various functional groups attached to their upper rim. Some of the functional groups, bispyridylmethylamine (bpa) and iminodiacetic acid, are able to coordinate to metal ions. In the case of the bispyridylmethylamine resorcinarene, 2, a tetranuclear metal complex is formed when it is allowed to coordinate to copper(II). The copper centers surround the resorcinarene cavity and are not electronically coupled. In contrast to the Cu428+ ...

N-undecyl cyclen and a resorcinarene bowl bearing four cyclen arms have been applied as anion exchangers in ion chromatography by strong adsorption to a reversed-phase column. The column loaded with the resorcinarene bowl cyclen tetramer exhibited significantly better performance in anion separation than that with N-undecyl cyclen monomer in isocratic elution mode. Both columns were tested for polarizable anion preconcentration or removal. By changing the eluent type from sodium bicarbonate to sodium hydroxide, the degree of protonation of the cyclen molecules could be modified, and the column capacity for anion retention adjusted thereby. Capacity gradient elution was successfully applied to removing sample matrix ions in the preconcentration of perchlorate and perrhenate ions as example analytes.

This project explores a novel treatment of breast cancer that uses single-walled carbon nanotubes (SWNTs) in photodynamic therapy, in which the SWNTs are targeted to the endothelial cells that line the tumor vasculature. The purpose of this project is to evaluate this treatment concept using human endothelial cells in vitro. Recombinant annexin V has been produced in good purity and high yield, and it has been shown to bind strongly to plastic-immobilized phosphatidylserine (PS), with a dissociation constant (Kd ) of 5.1 nM. A new method was developed for conjugating amino groups of annexin V to single-walled carbon nanotubes (SWNTs) that retains the strong absorbance of the SWNTs at 980 nm. This method uses the linker fluorenylmethoxycarbonyl (Fmoc)-amine-PEG-succinimidyl carboxy methyl ester. The loading of annexin V on the SWNTs was high (7.7 mg protein/mg SWNTs). Human endothelial cells grown in vitro could be killed almost completely when SWNT-Fmoc-PEG-annexin V was bound to the cells and with laser light at 980 nm and an energy density of 195 J/cm2. By contract, there was no harm to cells with SWNT-Fmoc-PEG-annexin V bound and no laser treatment, and there was no harm to cells with no SWNT-Fmoc-PEG-annexin V bound receiving laser treatment.