Use of electron density critical points as chemical function-based reduced representations of pharmacological ligands

In this paper, we propose a reduced representation of molecules of pharmacological interest based on their chemical functions. The proposed representations of the molecules are obtained by a topological analysis of their electron density maps at medium resolution, leading to graphs of critical points. The distribution of the different types of critical points are compared at various levels of resolution for a training set of 22 molecules in order to define the optimal resolution level leading to the best representation of the various chemical functions. The reduced representations can in the future be used for molecular similarity research and pharmacophore proposals.     

Superparamagnetic iron oxide (SPIO) enhancement in the cirrhotic liver: a comparison of two doses of ferumoxides in patients with advanced disease

The aim of this study was to establish whether enhancement of the liver by the MRI contrast agent ferumoxides could be effectively achieved at a reduced dose of 7.5 micromol/kg in patients with advanced liver cirrhosis. Forty-two liver transplant candidates with end-stage cirrhosis underwent SPIO-enhanced MRI at 1.5T, using either 15 micromol/kg or 7.5 micromol/kg ferumoxides. The lower dose of ferumoxides was also used in 21 non-cirrhotic patients with colorectal liver metastases who acted as a control group. The percentage signal intensity loss (PSIL) after SPIO was measured in all patients, and in those patients with tumors the post-SPIO contrast-to-noise ratio (CNR) was measured. The median PSIL after SPIO in the high dose cirrhotic (HDLC), low dose non-cirrhotic (LDNC) and low dose cirrhotic (LDLC) patients was 86.3%, 74.6%, and 64.2% respectively. These differences were significant using the Mann-Whitney U test. Tumors were found in 8 patients in the high dose cirrhotic group, 9 in the low dose cirrhotic group, and all 21 of the control group. No significant differences were found between the CNR values after SPIO in the 3 groups (median values HDLC 15.1, LDNC 23.7, LDLC 19.5). In patients with late-stage cirrhosis the PSIL after SPIO was significantly less at 7.5 micromol/kg than at 15 micromol/kg, but both doses produced a substantial loss of signal. Lesion to liver CNR was not adversely affected by using the lower dose, so when imaging at 1.5T the authors would recommend using 7.5 micromol/kg in patients with liver cirrhosis.     

Angular position of nodes in the superconducting gap of quasi-2D heavy-fermion superconductor CeCoIn5

The thermal conductivity of the heavy-fermion superconductor CeCoIn5 has been studied in a magnetic field rotating within the 2D planes. A clear fourfold symmetry of the thermal conductivity which is characteristic of a superconducting gap with nodes along the ( +/- pi,+/- pi) directions is resolved. The thermal conductivity measurement also reveals a first-order transition at H(c2), indicating a Pauli limited superconducting state. These results indicate that the symmetry most likely belongs to d(x(2)-y(2)), implying that the anisotropic antiferromagnetic fluctuation is relevant to the superconductivity.     

Novel extracellular polymeric substances produced by Cupriavidus necator IPT 027 grown on glucose and crude glycerol originated from biodiesel

The aim of this study was to evaluate the production and properties of novel extracellular polymeric substances (EPS) from glucose (EPS 1) and crude glycerol (CG) from castor beans oil (EPS 2). Cupriavidus necator IPT 027 cultivated with glucose and CG (35 °C, 150 rpm, 72 hr, pH 7, shaker) produced approximately 1.60 ± 0.01 and 2.83 ± 0.02 g l^?1 EPS, respectively, with high‐molecular weight (3.89 × 10⁵ and 1.89 × 10⁷ Da) and constituted of different functional groups such as uronic acid, monosaccharides (glucose, mannose, arabinose, and fucose) and primary amine group. The composition of the fermentable substrate influenced the melting temperature (221.11 and 230.18 °C), crystallinity (34.36% and 37.11%), degradation temperature (255.06 and 296.62 °C) and morphology. EPS showed pseudoplastic non‐Newtonian fluid behavior in the aqueous solutions, presenting potential applicability biotechnological and industrial mainly in food industry as emulsifiers and biosurfactants. This is the first study on the production and characterization of EPS obtained by C. necator IPT 027 in culture with glucose and CG. Copyright © 2016 John Wiley & Sons, Ltd.     

Effect of cyclization of N-terminal glutamine and carbamidomethyl-cysteine (residues) on the chromatographic behavior of peptides in reversed-phase chromatography

N-terminal loss of ammonia is a typical peptide modification chemical artifact observed in bottom-up proteomics experiments. It occurs both in vivo for N-terminal glutamine and in vitro following enzymatic cleavage for both N-terminal glutamine and cysteine alkylated with iodoacetamide. In addition to a mass change of −17.03 Da, modified peptides exhibit increased chromatographic retention in reversed-phase (RP) HPLC systems. The magnitude of this increase varies significantly depending on the peptide sequence and the chromatographic condition used. We have monitored these changes for extensive sets (more than 200 each) of tryptic Gln and Cys N-terminated species. Peptides were separated on 100 Å pore size C18 phases using identical acetonitrile gradient slopes with 3 different eluent compositions: 0.1% trifluoroacetic acid; 0.1% formic acid and 20 mM ammonium formate at pH 10 as ion-pairing modifiers. The observed effect of this modification on RP retention is the product of increased intrinsic hydrophobicity of the modified N-terminal residue, lowering or removing the effect of ion-pairing formation on the hydrophobicity of adjacent residues at acidic pHs; and possibly the increased formation of amphipathic helical structures when the positive charge is removed. Larger retention shifts were observed for Cys terminated peptides compared to Gln, and for smaller peptides. Also the size of the retention increase depends on the eluent conditions: pH 10 ? trifluoroacetic acid < formic acid. Different approaches for incorporation these findings in the peptide retention prediction models are discussed.     

Electro-electrodialysis of HI–I2–H2O mixture using radiation-grafted polymer electrolyte membranes

In the thermochemical water-splitting iodine–sulfur process for hydrogen production, new polymer electrolyte membranes were applied in an electro-membrane process (electro-electrodialysis, EED) to increase the HI molality of HIx solution (HI + I₂ + H₂O mixture) to be over quasi-azeotropic. Radiation grafting of a styrene monomer into a poly(ethylene-co-tetrafluoroethylene) base film and subsequent sulfonation provided electrolyte membranes that had ion exchange capacities (IECs) of 1.1–1.6 mmol/g. With the EED of the HIx solutions using [HI] = [I₂] = 10 mol/kg at 40 °C the transport number of protons, ratio of permeated quantities of water to the protons, and current efficiency all appeared to depend on the IEC of the resulting membranes. When compared to Nafion, the self-made membranes exhibited lower electric cell resistance, and thereby decreasing up to 32% of the overall energy required in the concentration operation.     

A convergent synthesis of the immunosuppressant FTY720 employing aqueous Wittig chemistry

A short, convergent synthesis of the immunosuppressant FTY720 is described involving the use of 4-hydroxymethylbenzaldehyde as a pivotal intermediate. A double Wittig strategy was developed to connect this dual-functional aldehyde with an alkyl-tether and to a readily available TRIS-derivative leading to an efficient synthesis of the target molecule.