Stable Crystalline Salts of Haloperidol: A Highly Water-Soluble Mesylate Salt

Haloperidol, an antipsychotic drug, was screened for new solid crystalline phases using high throughput crystallization in pursuit of solubility improvement. Due to the highly basic nature of the API, all the solid forms with acids were obtained in the form of salts. Eleven crystalline salts in the form of oxalate (1:1), benzoate (1:1), salicylate (1:1 and 1:2), 4-hydroxybenzoate (1:1), 4-hydroxybenzoate ethyl acetate solvate (1:1:1), 3,4-dihydroxybenzoate (1:1), 3,5-dihydroxybenzoate (1:1), mesylate (1:1), besylate (1:1), and tosylate (1:1) salt were achieved. There is an insertion of carboxylate or sulfonate anion into the hydrogen bonding pattern of haloperidol. The salts with the aliphatic carboxylic acids were found to be more prone to form salt hydrates compared with aromatic carboxylate salts. All the salts were subjected to solubility measurement in water at neutral pH. There was no direct correlation observed between the solubility of the salt and its coformer. All the salts are stable at room temperature as well as after 24 h slurry experiment except the oxalate salt, which showed an unusual phase transformation from its hydrated form to the anhydrous form. A structureproperty relationship was examined to analyze the solubility behavior of the solid forms.

Immunogen design for HIV-1 and influenza

Vaccines provide the most cost effective defense against pathogens. Although vaccines have been designed for a number of viral diseases, a vaccine against HIV-1 still remains elusive. In contrast while there are excellent influenza vaccines, these need to be changed every few years because of antigenic drift and shift The recent discovery of a large number of broadly neutralizing antibodies (bNAbs) and structural characterization of the conserved epitopes targeted by them presents an opportunity for structure based HIV-1 and influenza A vaccine design. We discuss strategies to design immunogens either targeting a particular antigenic region or focusing on native structure stabilization. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. (C) 2014 Elsevier B.V. All rights reserved.

Optical and structural properties of highly porous shell structured Fe doped TiO2 thin films

TiO2 thin films with 0.2 wt%, 0.4 wt%, 0.6 wt%, and 0.8 wt% Fe were prepared on glass and silicon substrates using sol-gel spin coating technique. The optical cut-off points are increasingly red-shifted and the absorption edge is shifted over the higher wavelength region with Fe content increasing. As Fe content increases, the optical band gap decreases from 3.03 to 2.48 eV whereas the tail width increases from 0.26 to 1.43 eV. The X-ray diffraction (XRD) patterns for doped films at 0.2 wt% and 0.8 wt% Fe reveal no characteristic peaks, indicating that the film is amorphous whereas undoped TiO2 exhibits (101) orientation with anatase phase. Thin films of higher Fe content exhibit a homogeneous, uniform, and nano-structured highly porous shell morphology.

Highly compressible behavior of polymer mediated three-dimensional network of graphene foam

The compressive behavior of graphene foam (GF) and its polymer (polydimethyl siloxane) (PDMS) infiltrated structure are presented. While GF showed an irreversible compressibility, the GF/PDMS structure revealed a highly reversible mechanical behavior up to many cycles of compression and also possesses a six times higher compressive strength. In addition, the strain rate demonstrated a negligible effect on both the maximum achieved stress and energy absorption in the GF/PDMS structure. The mechanical responses of both GF and GF/PDMS structure are compared with carbon nanotubes based cellular structure and its composite with PDMS, where GF/PDMS presented a dominant mechanical characteristic among other carbon based micro foam structures. Therefore, the improved mechanical properties of GF/PDMS suggest its potential for dampers, cushions, packaging, etc.

Hybrid and Rogue Kinases Encoded in the Genomes of Model Eukaryotes

The highly modular nature of protein kinases generates diverse functional roles mediated by evolutionary events such as domain recombination, insertion and deletion of domains. Usually domain architecture of a kinase is related to the subfamily to which the kinase catalytic domain belongs. However outlier kinases with unusual domain architectures serve in the expansion of the functional space of the protein kinase family. For example, Src kinases are made-up of SH2 and SH3 domains in addition to the kinase catalytic domain. A kinase which lacks these two domains but retains sequence characteristics within the kinase catalytic domain is an outlier that is likely to have modes of regulation different from classical src kinases. This study defines two types of outlier kinases: hybrids and rogues depending on the nature of domain recombination. Hybrid kinases are those where the catalytic kinase domain belongs to a kinase subfamily but the domain architecture is typical of another kinase subfamily. Rogue kinases are those with kinase catalytic domain characteristic of a kinase subfamily but the domain architecture is typical of neither that subfamily nor any other kinase subfamily. This report provides a consolidated set of such hybrid and rogue kinases gleaned from six eukaryotic genomes-S. cerevisiae, D. melanogaster, C. elegans, M. musculus, T. rubripes and H. sapiens-and discusses their functions. The presence of such kinases necessitates a revisiting of the classification scheme of the protein kinase family using full length sequences apart from classical classification using solely the sequences of kinase catalytic domains. The study of these kinases provides a good insight in engineering signalling pathways for a desired output. Lastly, identification of hybrids and rogues in pathogenic protozoa such as P. falciparum sheds light on possible strategies in host-pathogen interactions.

Highly Sensitive Carbon Nanotubes Coated Etched Fiber Bragg Grating Sensor for Humidity Sensing

The sensing of relative humidity (RH) at room temperature has potential applications in several areas ranging from biomedical to horticulture, paper, and textile industries. In this paper, a highly sensitive humidity sensor based on carbon nanotubes (CNTs) coated on the surface of an etched fiber Bragg grating (EFBG) sensor has been demonstrated, for detecting RH over a wide range of 20%-90% at room temperature. When water molecules interact with the CNT coated EFBG, the effective refractive index of the fiber core changes, resulting in a shift in the Bragg wavelength. It has been possible to achieve a high sensitivity of similar to 31 pm/% RH, which is the highest compared with many of the existing FBG-based humidity sensors. The limit of detection in the CNT coated EFBG has been found to be similar to 0.03 RH. The experimental data shows a linear response of Bragg wavelength shift with increase in humidity. This novel method of incorporating CNTs on to the FBG sensor for humidity sensing has not been reported before.

Highly efficient WO3-ZnO mixed oxides for photocatalysis

Monoclinic nanocuboid WO3 enhanced the photocatalyst efficiency of quasi nanobelt zinc oxide for dye degradation in the presence of visible light radiation. Combustion synthesized ZnO resulted in a belt-like morphology through in situ cluster formation of near spherical particles but homogenously disperses and strongly adheres to nanocuboid WO3 during physical mixing. Cationic methylene blue (MB) and anionic orange G (OG) undergo degradation through a charge transfer mechanism in the presence of WO3-ZnO (1 : 9 weight percentage ratio) mixture. The photocatalytic reaction was enhanced due to the reduction in the recombination of photogenerated electron-holes. The high degree of 90% degradation of both dyes is due to the activity of the mixed oxides, which is much higher than that obtained either with WO3 or ZnO individually.

Highly efficient WO3-ZnO mixed oxides for photocatalysis

Monoclinic nanocuboid WO3 enhanced the photocatalyst efficiency of quasi nanobelt zinc oxide for dye degradation in the presence of visible light radiation. Combustion synthesized ZnO resulted in a belt-like morphology through in situ cluster formation of near spherical particles but homogenously disperses and strongly adheres to nanocuboid WO3 during physical mixing. Cationic methylene blue (MB) and anionic orange G (OG) undergo degradation through a charge transfer mechanism in the presence of WO3-ZnO (1 : 9 weight percentage ratio) mixture. The photocatalytic reaction was enhanced due to the reduction in the recombination of photogenerated electron-holes. The high degree of 90% degradation of both dyes is due to the activity of the mixed oxides, which is much higher than that obtained either with WO3 or ZnO individually.

Designing Elastic Organic Crystals: Highly Flexible Polyhalogenated N-Benzylideneanilines

The intermolecular interactions and structural features in crystals of seven halogenated N-benzylideneanilines (Schiff bases), all of which exhibit remarkable flexibility, were examined to identify the common packing features that are the raison d'etre for the observed elasticity. The following two features, in part related, were identified as essential to obtain elastic organic crystals: 1)A multitude of weak and dispersive interactions, including halogen bonds, which may act as structural buffers for deformation through easy rupture and reformation during bending; and 2)corrugated packing patterns that would get interlocked and, in the process, prevent long-range sliding of molecular planes.

Highly sensitive and rapid detection of acetylcholine using an ITO plate modified with platinum-graphene nanoparticles

Determining the concentrations of acetylcholine (ACh) and choline (Ch) is clinically important. ACh is a neurotransmitter that acts as a key link in the communication between neurons in the spinal cord and in nerve skeletal junctions in vertebrates, and plays an important role in transmitting signals in the brain. A bienzymatic sensor for the detection of ACh was prepared by co-immobilizing choline oxidase (ChO) and acetylcholinesterase (AChE) on graphene matrix/platinum nanoparticles, and then electrodepositing them on an ITO-coated glass plate. Graphene nanoparticles were decorated with platinum nanoparticles and were electrodeposited on a modified ITO-coated glass plate to form a modified electrode. The modified electrode was characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) studies. The optimum response of the enzyme electrode was obtained at pH 7.0 and 35 degrees C. The response time of this ACh-sensing system was shown to be 4 s. The linear range of responses to ACh was 0.005-700 mu M. This biosensor exhibits excellent anti-interferential abilities and good stability, retaining 50% of its original current even after 4 months. It has been applied for the detection of ACh levels in human serum samples.

Highly Dense ZnO Nanowires Grown on Graphene Foam for Ultraviolet Photodetection

Growth of highly dense ZnO nanowires (ZnO NWs) is demonstrated on three-dimensional graphene foam (GF) using resistive thermal evaporation technique. Photoresponse of the as-grown hybrid structure of ZnO NWs on GF (ZnO NWs/GF) is evaluated for ultraviolet (UV) detection. Excellent photoresponse with fast response and recovery times of 9.5 and 38 s with external quantum efficiency of 2490.8% is demonstrated at low illumination power density of 1.3 mW/cm(2). In addition, due to excellent charge carrier transport, mobility of graphene reduces the recombination rate of photogenerated charge carriers, hence the lifetime of photogenerated free charge carriers enhances in the photodetectors.

Achieving Highly Efficient, Selective, and Stable CO2 Reduction on Nitrogen-Doped Carbon Nanotubes

The challenge in the electrosynthesis of fuels from CO2 is to achieve durable and active performance with cost-effective catalysts. Here, we report that carbon nanotubes (CNTs), doped with nitrogen to form resident electron-rich defects, can act as highly efficient and, more importantly, stable catalysts for the conversion of CO2 to CO. The unprecedented overpotential (-0.18 V) and selectivity (80%) observed on nitrogen-doped CNTs (NCNTs) are attributed to their unique features to facilitate the reaction, including (i) high electrical conductivity, (ii) preferable catalytic sites (pyridinic N defects), and (iii) low free energy for CO2 activation and high barrier for hydrogen evolution. Indeed, DFT calculations show a low free energy barrier for the potential-limiting step to form key intermediate COOH as well as strong binding energy of adsorbed CON and weak binding energy for the adsorbed CO. The highest selective site toward CO production is pyridinic N, and the NCNT-based electrodes exhibit no degradation over 10 h of continuous operation, suggesting the structural stability of the electrode.

Simultaneous Determination of Catecholamines in Presence of Uric Acid and Ascorbic Acid at a Highly Sensitive Electrochemically Activated Carbon Paste Electrode

A simple yet remarkable, electrochemically activated carbon paste electrode (EACPE) was prepared by successive potential cycling of carbon paste in a 0.1 M NaOH solution and was effectively used for the simultaneous determination of catecholamines such as dopamine (DA), epinephrine (E) and Norepinephrine (NE) in presence of uric acid (UA) and ascorbic acid (AA). Taking DA as the ideal catecholamine, the electrochemical behaviors of DA, UA and AA such as scan rate and pH variation was studied by cyclic voltammetry (CV) in phosphate buffer solution (PBS, pH 7.1). This electrochemical sensor exhibited strong electrocatalytic activity towards the oxidation of a mixture of catecholamines, UA and AA with apparent reduction of overpotentials. Crider optimum conditions, limit of detection (S/N = 3) of DA, E, NE, UA and AA was found to be 0.08, 0.08, 0.07, 0.1 and 6.0 mu M, respectively by differential pulse voltammetry (DPV). The analytical performance of this modified electrode as a biosensor was also demonstrated for the determination of DA, UA and AA in dopamine injection, human urine and vitamin C tablets, respectively, in presence of other interfering substances. (C) 2015 The Electrochemical Society. All-rights reserved.

GRMHD formulation of highly super-Chandrasekhar magnetized white dwarfs: stable configurations of non-spherical white dwarfs

The topic of magnetized super-Chandrasekhar white dwarfs is in the limelight, particularly in the last few years, since our proposal of their existence. By full-scale general relativistic magnetohydrodynamic (GRMHD) numerical analysis, we confirm in this work the existence of stable, highly magnetized, significantly super-Chandrasekhar white dwarfs with mass more than 3 solar mass. While a poloidal field geometry renders the white dwarfs oblate, a toroidal field makes them prolate retaining an overall quasi-spherical shape, as speculated in our earlier work. These white dwarfs are expected to serve as the progenitors of over-luminous type Ia supernovae.