Intermediates involved in serotonin oxidation catalyzed by Cu bound Aβ peptides

The degradation of neurotransmitters is a hallmark feature of Alzheimer''s disease (AD). Copper bound Aβ peptides, invoked to be involved in the pathology of AD, are found to catalyze the oxidation of serotonin (5-HT) by H₂O₂. A combination of EPR and resonance Raman spectroscopy reveals the formation of a Cu(ii)–OOH species and a dimeric, EPR silent, Cu₂O₂ bis-μ-oxo species under the reaction conditions. The Cu(ii)–OOH species, which can be selectively formed in the presence of excess H₂O₂, is the reactive intermediate responsible for 5-HT oxidation. H₂O₂ produced by the reaction of O₂ with reduced Cu(i)–Aβ species can also oxidize 5-HT. Both these pathways are physiologically relevant and may be involved in the observed decay of neurotransmitters as observed in AD patients.

The mononuclear copper hydroperoxo species (Cu(ii)–OOH) of Cu–Aβ is the active oxidant responsible for serotonin oxidation by Cu–Aβ in the presence of physiologically relevant oxidants like O₂ and H₂O₂, which can potentially cause oxidative degradation of neurotransmitters, a marker of Alzheimer''s disease.     

Influence of chemical composition and sequence length on the transport properties of proton exchange membranes

One of the integral parts of the fuel cell is the proton exchange membrane. Our research group has been engaged in the past few years in the synthesis of several sulfonated poly(arylene ether) random copolymers. The copolymers were varied in both the bisphenol structure as well as in the functional groups in the backbone such as sulfone and ketones. To compare the effect of sequence length, multiblock copolymers based on poly(arylene ether sulfone)s were synthesized. This paper aims to describe our investigation of the effect of chemical composition, morphology, and ion exchange capacity (IEC) on the transport properties of proton conducting membranes. The key properties examined were proton conductivity, methanol permeability, and water self diffusion coefficient in the membranes. It was observed that under fully hydrated conditions, proton conductivity for both random and block copolymers was a function of IEC and water uptake. However, under partially hydrated conditions, the block copolymers showed improved proton conductivity over the random copolymers. The proton conductivity for the block copolymer series was found to increase with increasing block lengths under partially hydrated conditions. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2226–2239, 2006     

New poly(p‐phenylene vinylene) derivatives with two oxadiazole rings per repeat unit: Synthesis,photophysical properties,electroluminescence, and metal ion recognition

Two new poly(p‐phenylene vinylene) derivatives OX1‐PPV and OX2‐PPV bearing two 1,3,4‐oxadiazole rings per repeat unit and a fully conjugated backbone with solubilizing dodecyloxy side groups were synthesized and investigated. The amorphous conjugated polymers had glass‐transition temperature values of 60–75 °C and emitted intense blue or greenish‐blue light in solution with photoluminescence (PL) emission maxima at 379–492 nm and PL quantum yields of 0.41–0.52. In the solid state they emitted yellowish‐green light with PL emission maxima at 533–555 nm. Cyclic voltammetry showed that both conjugated polymers had reversible reduction and irreversible oxidation, making them n‐type materials. The electron affinity of OX2‐PPV was estimated as 2.85 eV whereas that of OX1‐PPV was 2.75 eV. Yellow electroluminescence (EL) was achieved from single‐layer light‐emitting diodes of OX2‐PPV with an EL emission maximum at 555 nm and a brightness of 70 cd/m². Polymer OX2‐PPV, which was functionalized with 2,6‐bis(1,3,4‐oxadiazole‐2‐yl)pyridine, demonstrated sensitivity to various metal ions as a fluorescence‐mode chemosensor. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2112–2123, 2004     

Multiblock copolymers of poly(2,5‐benzophenone) and disulfonated poly(arylene ether sulfone) for proton‐exchange membranes. I. Synthesis and characterization

Nanophase‐separated, hydrophilic–hydrophobic multiblock copolymers are promising proton‐exchange‐membrane materials because of their ability to form various morphological structures that enhance transport. A series of poly(2,5‐benzophenone)‐activated, telechelic aryl fluoride oligomers with different block molecular weights were successfully synthesized by the Ni(0)‐catalyzed coupling of 2,5‐dichlorobenzophenone and the end‐capping agent 4‐chloro‐4′‐fluorobenzophenone. These telechelic oligomers (hydrophobic) were then copolymerized with phenoxide‐terminated, disulfonated poly(arylene ether sulfone)s (hydrophilic) by nucleophilic, aromatic substitution to form hydrophilic–hydrophobic multiblock copolymers. High‐molecular‐weight multiblock copolymers with number‐average block lengths ranging from 3000 to 10,000 g/mol were successfully synthesized. Two separate glass‐transition temperatures were observed via differential scanning calorimetry in the transparent multiblock copolymer films when each block length was longer than 6000 g/mol. Tapping‐mode atomic force microscopy also showed clear nanophase separation between the hydrophilic and hydrophobic domains and the influence of the block length as it increased from 6000 to 10,000 g/mol. Transparent and creasable films were solvent‐cast and exhibited moderate proton conductivity and low water uptake. These copolymers are promising candidates for high‐temperature proton‐exchange membranes in fuel cells, which will be reported separately in part II of this series. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 284–294, 2007     

Role of PVA in synthesis of nano Co3O4‐decorated graphene oxide

Polymeric materials have been found to be ideal candidates for the synthesis of organic–inorganic nanomaterials. We have obtained Co₃O₄‐decorated graphene oxide (GO) nanocomposites by a simple polymer combustion method. Polyvinyl alcohol (PVA) of two different molecular weights, 14,000 and 125,000, was used for the synthesis. The pristine sample was annealed at 300, 500, and 800°C. PVA has played an important role in the formation of GO and Co₃O₄ nanoparticles. Synthesized Co₃O₄–GO nanocomposites were characterized by X‐ray diffraction, Fourier transform infrared, Raman, electron paramagnetic resonance, transmission electron microscopy, and vibrating sample magnetometry. Reflection peaks at 12° and 37° in an X‐ray study confirm the formation of Co₃O₄–GO. Raman study validates the presence of GO in nanocomposites of Co₃O₄–GO. Room temperature ferromagnetism was observed in all annealed samples. The highest coercivity of 462 G was observed for 300°C annealed samples as compared with bulk Co₃O₄. On the basis of the results obtained, a mechanism of formation is proposed. Copyright © 2015 John Wiley & Sons, Ltd.     

S K-edge XAS and DFT calculations on SAM dependent pyruvate formate-lyase activating enzyme: nature of interaction between the Fe4S4 cluster and SAM and its role in reactivity

S K-edge X-ray absorption spectroscopy on the resting oxidized and the S-adenosyl-l-methionine (SAM) bound forms of pyruvate formate-lyase activating enzyme are reported. The data show an increase in pre-edge intensity, which is due to additional contributions from sulfide and thiolate of the Fe(4)S(4) cluster into the C-S σ* orbital. This experimentally demonstrates that there is a backbonding interaction between the Fe(4)S(4) cluster and C-S σ* orbitals of SAM in this inner sphere complex. DFT calculations that reproduce the data indicate that this backbonding is enhanced in the reduced form and that this configurational interaction between the donor and acceptor orbitals facilitates the electron transfer from the cluster to the SAM, which otherwise has a large outer sphere electron transfer barrier. The energy of the reductive cleavage of the C-S bond is sensitive to the dielectric of the protein in the immediate vicinity of the site as a high dielectric stabilizes the more charge separated reactant increasing the reaction barrier. This may provide a mechanism for generation of the 5'-deoxyadenosyl radical upon substrate binding.     

Biomimetic postcapillary expansions for enhancing rare blood cell separation on a microfluidic chip

Blood cells naturally auto-segregate in postcapillary venules, with the erythrocytes (red blood cells, RBCs) aggregating near the axis of flow and the nucleated cells (NCs)--which include leukocytes, progenitor cells and, in cancer patients, circulating tumor cells--marginating toward the vessel wall. We have used this principle to design a microfluidic device that extracts nucleated cells (NCs) from whole blood. Fabricated using polydimethylsiloxane (PDMS) soft lithography, the biomimetic cell extraction device consists of rectangular microchannels that are 20-400 μm wide, 11 μm deep and up to 2 cm long. The key design feature is the use of repeated expansions/contractions of triangular geometry mimicking postcapillary venules, which enhance margination and optimize the extraction. The device operates on unprocessed whole blood and is able to extract 94 ± 4.5% of NCs with 45.75 ± 2.5-fold enrichment in concentration at a rate of 5 nl s(-1). The device eliminates the need to preprocess blood via centrifugation or RBC lysis, and is ready to be implemented as the initial stage of lab-on-a-chip devices that require enriched nucleated cells. The potential downstream applications are numerous, encompassing all preclinical and clinical assays that operate on enriched NC populations and include on-chip flow cytometry (A. Y. Fu et al., Anal. Chem., 2002, 74, 2451-2457; A. Y. Fu et al., Nat. Biotechnol., 1999, 17, 1109-1111), genetic analyses (M. M. Wang et al., Nat. Biotechnol., 2005, 23, 83-87; L. C. Waters et al., Anal. Chem., 1998, 70, 5172-5176) and circulating tumor cell extraction (S. Nagrath et al., Nature, 2007, 450, 1235-1241; S. L. Stott et al., Proc. Natl. Acad. Sci. U. S. A., 2010, 18392-18397; H. K. Lin et al., Clin. Cancer Res., 2010, 16, 5011-5018).     

Noble metals in polyoxometalate chemistry: palladium-containing derivatives of the monolacunary Keggin and Wells-Dawson tungstophosphates

We have prepared the three novel Pd(II)-containing tungstophosphates [Pd(2)(α-PW(11)O(39)H(0.5))(2)](9-) and two structural isomers of [Pd(2)(α(2)-P(2)W(17)O(61)H(n))(2)]((16-2n)-) via simple synthetic procedures and characterized their potassium salts by single-crystal X-ray diffraction, elemental analysis, and IR and multinuclear ((31)P and (183)W) NMR spectroscopy. This study sheds light on the long-standing question about the nature and structure of the actual products formed in the reaction of Pd(II) ions with monolacunary Keggin-type [α-XW(11)O(39)](n-) and Wells-Dawson-type [α(2)-P(2)W(17)O(61)](10-) heteropolytungstates.     

2,7-Diaminofluorene-based organic dyes for dye-sensitized solar cells: effect of auxiliary donor on optical and electrochemical properties

New organic dyes containing a diarylaminofluorene unit as an electron donor and cyanoacrylic acid as acceptor and anchoring group in a donor-π-donor-π-acceptor architecture have been synthesized and characterized as sensitizers for nanocrystalline TiO(2)-based dye-sensitized solar cells. They have shown three major electronic absorptions originating from the π-π* and charge-transfer transitions covering the broad visible range (250-550 nm) in solution. The charge-transfer transition of the dyes exhibited negative solvatochromism, suggesting a polarized ground state. They have also displayed acidochromism in solution owing to the presence of a protonation-deprotonation equilibrium. On comparison with the triphenylamine and carbazole-based parent dyes (E)-2-cyano-3-(4-(diphenylamino)phenyl)acrylic acid and (E)-2-cyano-3-(9-ethyl-9H-carbazol-3-yl)acrylic acid they exhibited longer wavelength absorptions and facile oxidation, indicating the stronger electron-donating ability of the auxiliary chromophores. In addition, they exhibited nearly two times larger light-to-electron conversion efficiency under simulated AM 1.5 G irradiation (100 mW cm(-2)) with an aperture mask when compared to the parent dyes. Among the new dyes, the one containing the naphthylphenylamine segment showed better device characteristics attributable to the higher HOMO energy level which probably facilitates the regeneration of the dye and effective suppression of the back reaction of the injected electrons with the I(3)(-) in the electrolyte. The optical properties of the dyes were modeled using TDDFT simulations employing different theoretical models (B3LYP, CAM-B3LYP, and MPW1K), and the best correlations with the observed parameters have been found for CAM-B3LYP and MPW1K calculations. The electron lifetimes extracted from the electrochemical impedance measurements of the dye-sensitized solar cells were used to interpret the solar cell efficiency alternations.