Electrochemical Synthesis of Benzazoles from Alcohols and o-Substituted Anilines with a Catalytic Amount of Co(II) Salt.

An electrochemical synthesis of benzazoles directly from alcohols and o-substituted anilines has been developed. The reaction conditions have been optimized by varying the composition of the electrolyte and the metal salt used as catalyst. The cyclization proceeds smoothly with a catalytic amount of a cobalt salt under air at room temperature to afford 2-substituted benzimidazoles, benzothiazoles, and benzoxazoles in good to excellent yields with a wide substrate scope.

Electrochemical technique and copper-promoted transformations: selective hydroxylation and amination of arylboronic acids.

An efficient and selective electrosynthesis of phenols and anilines from arylboronic acids in aqueous ammonia is achieved in an undivided cell. By simply changing the concentration of aqueous ammonia and the anode potential, good yields of phenols and anilines can be obtained chemoselectively with high reaction rates. We propose that anodic oxidation could have played an important role in these transformations.

Electrochemical Oxidative C(sp2)-H Amination of Aldehyde Hydrazones with Azoles.

A general and highly efficient method for the electrochemical C(sp2)-H amination of aldehyde hydrazones with azoles has been developed. This reaction proceeds under exogenous metal-, catalyst-, and oxidant-free conditions to provide aminated hydrazone derivatives in good to excellent yields. This strategy applies to both aromatic and aliphatic aldehyde hydrazones and tolerates a broad range of functional groups.

Sensitive Electrochemical Capsaicin Sensor Based on a Screen Printed Electrode Modified with Poly(sodium 4-styrenesulfonate) Functionalized Graphite.

A sensitive capsaicin sensor was constructed based on a poly(sodium 4-styrenesulfonate) functionalized graphite modified screen printed electrode (PSS-Grp/SPE) in this study. The PSS-Grp and poly(diallyldimethylammonium chloride) functionalized graphite (PDDA-Grp) were easily synthesized by interacting Grp with PSS and PDDA through sonication, and resulted in negative and with positive charges on the surface, respectively. The prepared PSS-Grp and PDDA-Grp were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and ultraviolet and visible spectroscopy (UV-vis). The electrochemical performance of PSS-Grp in a 50 µM capsaicin solution presented a current density of 33 µA cm-2, which was much higher than the PDDA-Grp of 1.5 µA cm-2. Our study showed that capsaicin could interact better with strong negative charges on the PSS-Grp/SPE surface to give a higher electrochemical response. The direct electrochemical sensing of capsaicin was achieved at PSS-Grp/SPE using differential pulse stripping voltammetry (DPSV) under the optimized conditions.

Preparation and characterization of aligned carbon nanotube-ruthenium oxide nanocomposites for supercapacitors.

A novel type of ruthenium oxide (RuO(2))-modified multi-walled carbon nanotube (MWNT) nanocomposite electrode (RuO(2)/MWNT) for supercapacitors has been prepared. The nanocomposites were formed by depositing Ru by magnetic-sputtering in an Ar/O(2) atmosphere onto MWNTs, which were synthesized on Ta plates by chemical vapor deposition. Cyclic voltammetry, chronopotentiometry, and electrochemical impedance measurements were applied to investigate the performance of the RuO(2)/MWNT nanocomposite electrodes. The capacitance of the MWNT electrodes in 1.0 M H(2)SO(4) is significantly increased from 0.35 to 16.94 mF cm(-2) by modification with RuO(2). The RuO(2) film on the surface of the nanotubes is composed of small crystal grains with tilted bundle-like microstructures, as observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The results demonstrate a promising route to prepare RuO(2)/MWNT-based double-layer supercapacitors.

Induction of transient ion channel-like pores in a cancer cell by antibiotic peptide.

The anticancer activity of anti-bacterial cecropins makes them potentially useful as peptide anti-cancer drugs. We used the cell-attached patch to study the effect of cecropin B (CB; having one hydrophobic and one amphipathic alpha-helix) and its derivative, cecropin B3 (CB3; having two hydrophobic alpha-helices) on the membrane of Ags cancer cells. Application of 10-60 microM CB onto the membrane of the cancer cell produces short outward currents. Comparative study with CB3, which induces no outward currents, shows that the amphipathic group of CB is necessary for the pore formation. The results provide a rationale to study the cell-killing activity of antimicrobial peptides at the single cancer cell level.

Nanostructured platinum-lipid bilayer composite as biosensor.

The present work describes the preparation of supported bilayer lipid membrane (s-BLM) doped with metal nanoparticles for the design of biosensors. Platinum (Pt) nanoparticles were deposited through s-BLM to build a hybrid device of nanoscale electrode array by potential cycling in 1 mM K(2)PtCl(6) solution containing 0.1 M KCl. The properties of Pt nanoparticle-doped s-BLM composite were then characterized by cyclic voltammetry, electrochemical impedance spectroscopy (EIS) and atomic force microscopy (AFM). Our results showed that Pt nanoparticles grew in voids of the s-BLMs, through which the underlying glassy carbon (GC) electrode was connected, with maximum length extended out of the lipid membrane around 40 nm. Doping of Pt nanoparticles through s-BLM increased the membrane capacitance and decreased the membrane resistance of s-BLM. Pt nanoparticles array in s-BLM electrocatalyzed the reduction of oxygen (O(2)) in phosphate buffer solution (PBS). Practical application of Pt nanoparticle-doped s-BLM for the construction of glucose biosensor was also demonstrated in terms of its dose-response curve, stability and reproducibility. Thus, lipid membrane doped with Pt nanoparticles is a novel electrode system at nanoscale that can penetrate through the insulating membrane to probe molecular recognition and catalytic events at the lipid membrane-solution interface.

Modification of carbon nanotubes with redox hydrogel: improvement of amperometric sensing sensitivity for redox enzymes.

This study demonstrated that redox hydrogel-modified carbon nanotube (CNT) electrodes can be developed as an amperometric sensor that are sensitive, specific and fast and do not require auxiliary enzymes. A redox polymer, poly(vinylimidazole) complexed with Os(4,4'-dimethylbpy)(2)Cl (PVI-dmeOs) was electrodeposited on Ta-supported multi-walled CNTs. The resulted PVI-dmeOs thin film did not change the surface morphology of the CNTs, but turned the CNT surface from hydrophobic to hydrophilic, as studied by scanning electron microscopy (SEM) and static water contact angle measurements. Cyclic voltammetry measurements in a Fe(CN)(6)(3-) solution and electrochemical impedance measurements in an equimolar Fe(CN)(6)(3-/4-) solution demonstrated that the PVI-dmeOs hydrogel thin film was electronic conductive with a resistance of about 15Omega. The PVI-dmeOs/CNT electrodes sensed rapidly, sensitively and specifically to model redox enzymes (glucose oxidase (GOD) and lactate oxidase (LOD)) in amperometric experiments in electrolyte solutions containing the substrates of the measured redox enzymes. Both the CNT substrate and the thin PVI-dmeOs film enhanced the sensing sensitivities. Exploration of the mechanisms suggests that the PVI-dmeOs film may enhance the sensing sensitivities by wiring the enzyme molecules through the redox centers tethered on the mobile redox polymer backbones to the CNT electrodes.

Selective and sensitive electrochemical detection of glucose in neutral solution using platinum-lead alloy nanoparticle/carbon nanotube nanocomposites.

Electrodeposition of Pt-Pb nanoparticles (PtPbNPs) to multi-walled carbon nanotubes (MWCNTs) resulted in a stable PtPbNP/MWCNT nanocomposite with high electrocatalytic activity to glucose oxidation in either neutral or alkaline medium. More importantly, the nanocomposite electrode with a slight modification exhibited high sensitivity, high selectivity, and low detection limit in amperometric glucose sensing at physiological neutral pH (poised at a negative potential). At +0.30 V in neutral solution, the nanocomposite electrode exhibited linearity up to 11 mM of glucose with a sensitivity of 17.8 microA cm(-2) mM(-1) and a detection limit of 1.8 microM (S/N=3). Electroactive ascorbic acid (0.1 mM), uric acid (0.1 mM) and fructose (0.3 mM) invoked only 23%, 14% and 9%, respectively, of the current response obtained for 3 mM glucose. At -0.15 V in neutral solution, the electrode responded linearly to glucose up to 5 mM with a detection limit of 0.16 mM (S/N=3) and detection sensitivity of approximately 18 microA cm(-2) mM(-1). At this negative potential, ascorbic acid, uric acid, and fructose were not electroactive, therefore, not interfering with glucose sensing. Modification of the nanocomposite electrode with Nafion coating followed by electrodeposition of a second layer of PtPbNPs on the Nafion coated PtPbNP/MWCNT nanocomposite produced a glucose sensor (poised at -0.15 V) with a lower detection limit (7.0 microM at S/N=3) and comparable sensitivity, selectivity and linearity compared to the PtPbNP/MWCNT nanocomposite. The Nafion coating lowered the detection limit by reducing the background noise, while the second layer of PtPbNPs restored the sensitivity to the level before Nafion coating.

Differential mechanisms underlying the modulation of delayed-rectifier K+ channel in mouse neocortical neurons by nitric oxide.

The modulatory effects of nitric oxide (NO) on voltage-dependent K+ channels are intricate. In our present study, the augmentation and reduction of K+ currents by NO donor S-nitro-N-acetylpenicillamine (SNAP) and pure dissolved NO was observed in dissociated neurons from mice neocortex with both whole cell and cell-attached patch clamp. By using a specific electrochemical sensor, the critical concentrations of NO that increased or reduced the channel activities were accurately quantified. Low concentrations of SNAP (20 microM) or NO solution (0.1 microM) enhanced whole cell delayed rectifier K+ -current (IK) and left the fast inactivating A current (IA) unchanged. However, high concentrations of SNAP (100 microM) and NO (0.5 microM) reduced both IK and IA currents. In cell-attached experiments, a significant increase in channel open probability (NP0) was observed when using low concentrations of SNAP or NO. High concentrations of SNAP or NO dramatically decreased NP0. The increase in channel activities by low concentrations of SNAP was abolished in the presence of either inhibitors of soluble guaylate cyclase or inhibitors of cGMP-dependent protein kinase G, suggesting a link to the NO-cGMP signaling cascade. The reduction of channel activities by high concentrations of SNAP was reversed by the reducing agent dithiothreitol, implying a redox reaction mechanism. Thus both NO-cGMP signaling and a redox mechanism are involved in the modulation of IK channel activity for neuron excitability.

Microelectrode array biochip: tool for in vitro drug screening based on the detection of a drug effect on dopamine release from PC12 cells.

Novel, yet simple detection techniques of drug effect, including the effect of a vesicular monoamine transporter inhibitor (reserpine), a dopamine precursor (L-dopa), and a dopamine transporter inhibitor (nomifensine), on dopamine release from dopaminergic PC12 cells were developed based on a microelectrode array (MEA) biochip. Upon multi-injections of KCl solution into the culture of PC12 cells attached on a MEA biochip, the K+-stimulated dopamine release was temporally and amperometrically recorded by biochip microelectrodes. Two parameters in the recorded amperometric spectra were defined in this study: the peak current of the first KCl injection (Max1), and the steady current after the fourth KCl injection (St4). Statistically significant effects of L-dopa and reserpine were demonstrated by comparing both Max1 and St4 of the second detections in drugs with those of the control without drug treatment. The values of both Max1 and St4 in the first detections were normalized as 1. In contrast, the statistically significant effect of nomifensine was detected by comparing the ratios of St4 to Max1 in the first detections in drug with those of the control. The reason for using different analytical methods for measurements between L-dopa/reserpine and nomifensine lies in the different mechanisms of action on PC12 cells among these drugs. The novel analytical methods developed use the same detection setup and parameters, and the data analysis for the effect of drugs becomes simple. The methods hence may provide a high-throughput in vitro drug screening approach for dopamine-related psychiatric disorders.

Augmentation of hypoxia-induced nitric oxide generation in the rat carotid body adapted to chronic hypoxia: an involvement of constitutive and inducible nitric oxide synthases.

Acute hypoxia increases the endogenous release of nitric oxide (NO) in rat carotid body and the expression of nitric oxide synthases is modulated by chronic hypoxia. The aim of the study was to examine hypoxia-induced NO generation in rat carotid body adapted to chronic hypoxia with inspired oxygen at 10% for 4 weeks. The concentration of NO was measured electrochemically with a Pt/Nafion/Pd-IrOx/POAP modified electrode inserted into the isolated carotid body superfused with bicarbonate-buffer saline at 35 degrees C. Acute hypoxia increased the concentration of NO by 471.3+/-71.4 nM in the carotid body of chronically hypoxic (CH) rats. The amount of NO release induced by hypoxia was significantly augmented when compared with that of the normoxic control (87.6+/-15.9 nM). The hypoxia-induced NO generation was markedly attenuated by pretreatment with L- NG-nitroarginine methylester (L-NAME; 500 microM), a non-selective nitric oxide synthase (NOS) inhibitor and also by removal of extracellular calcium with the calcium chelator EGTA (5 mM). Additionally, NO generation during hypoxia was reduced by 30% in the CH carotid body treated with S-methylisothiourea (SMT; 50 microM), a specific blocker of inducible NOS (iNOS). Immunohistochemical study revealed that positive iNOS protein immunoreactivity was detected in clusters of glomus cells in the carotid bodies of CH rats, but not in the normoxic group. Thus, chronic hypoxia enhances hypoxia-induced NO generation mediated by calcium-dependent NOSs and iNOS in the carotid body. Extracellular recording of sinus nerve activity of CH carotid bodies showed that L-NAME treatment enhanced the afferent discharge in response to hypoxia, confirming that the generation of NO suppresses the activities of carotid chemoreceptors. Taken together, our results suggest that hypoxia-induced NO production increases in the rat carotid body adapted to chronic hypoxia and that constitutive and inducible NOSs are involved in the NO generation. The enhancement of NO generation may play a physiological role in blunting the hypoxic chemosensitivity during chronic hypoxia.

Biosensing properties of diamond and carbon nanotubes.

The biochemical properties of boron-doped diamond (BDD), carbon nanofiber, fullerene, and multiwalled carbon nanotube (MWCNT) electrodes have been investigated comparatively. Physiochemical factors which affect the biosensing properties such as surface hydrophobicities, effective surface area, and intrinsic material properties are studied. Voltammetric responses of the as-grown thin film electrode and surface-modified electrode to biomolecules such as L-ascorbic acid (L-AA), dopamine (DA), and uric acid are examined. As-grown MWCNT electrodes exhibit selective voltammetric responses to the different biomolecules and faster electron-transfer kinetics compared to BDD. The selective response is due to the considerably lower anodic potential of L-AA on MWCNT (-48 mVvs Ag/AgCl compared to 575 mV on BDD). This electrocatalytic response can be replicated on a nonselective carbon nanofiber electrode by coating it with gold nanoparticles. BDD has no intrinsic selective response to L-AA, and surface modification by anodic polarization is necessary for resolving L-AA and DA.