pH triggered self-assembly of core cross-linked star polymers possessing thermoresponsive cores

Core cross-linked star polymers possessing responsiveness to pH and temperature stimuli have been prepared, and we demonstrate how changes to pH and temperature can be used to trigger the release and uptake of a hydrophobic dye.     

Determination of inorganic anions in environmental waters with a hydroxide-selective column

US Environmental Protection Agency Method 300.0 specifies the use of an IonPac AS4A anion-exchange column with a carbonate-hydrogencarbonate eluent and suppressed conductivity detection for the determination of inorganic anions in environmental waters by ion chromatography. Hydroxide eluents have not typically been used for the routine analysis of common inorganic anions due to the lack of an appropriate hydroxide selective column and the difficulty in preparing contaminant free hydroxide eluents. The use of ion chromatography with a hydroxide-selective IonPac AS17 column, automated eluent generation and potassium hydroxide gradient represents a new approach to the routine determination of inorganic anions in environmental waters. This new approach, which is a modification of Method 300.0, allows equivalent method performance with improved linearity, precision, and method detection limits. The AS17 column provides superior retention of fluoride from the column void volume and improved resolution from small organic acids, such as formate and acetate, compared to the AS4A column. Quantitative recoveries were obtained for all the common inorganic anions spiked into typical environmental waters using this new approach, and the Performance Based Measurement System Tier 1 method validation quality control acceptance criteria are well within the acceptable ranges defined by Method 300.0. In addition, the EG40 eluent generator eliminates the need to manually prepare eluents, increasing the level of automation and ease-of-use of the ion chromatography system.     

ReverseScreen3D: a structure-based ligand matching method to identify protein targets

Ligand promiscuity, which is now recognized as an extremely common phenomenon, is a major underlying cause of drug toxicity. We have developed a new reverse virtual screening (VS) method called ReverseScreen3D, which can be used to predict the potential protein targets of a query compound of interest. The method uses a 2D fingerprint-based method to select a ligand template from each unique binding site of each protein within a target database. The target database contains only the structurally determined bioactive conformations of known ligands. The 2D comparison is followed by a 3D structural comparison to the selected query ligand using a geometric matching method, in order to prioritize each target binding site in the database. We have evaluated the performance of the ReverseScreen2D and 3D methods using a diverse set of small molecule protein inhibitors known to have multiple targets, and have shown that they are able to provide a highly significant enrichment of true targets in the database. Furthermore, we have shown that the 3D structural comparison improves early enrichment when compared with the 2D method alone, and that the 3D method performs well even in the absence of 2D similarity to the template ligands. By carrying out further experimental screening on the prioritized list of targets, it may be possible to determine the potential targets of a new compound or determine the off-targets of an existing drug. The ReverseScreen3D method has been incorporated into a Web server, which is freely available at http://www.modelling.leeds.ac.uk/ReverseScreen3D .     

Synthesis,separation, and assignment of the seven geometric isomers of [Co(dien)(ibn)Cl]2+

All seven possible geometric isomers (four mer and three facial) for the [Co(dien)(ibn)Cl](2+) system have been synthesized (dien = diethylenetriamine, ibn = 1,2-diamino-2-methylpropane). Their structures in dimethyl sulfoxide solution have been uniquely determined by two-dimensional NMR spectroscopy (DQCOSY and NOESY).     

Analysis of perfluorinated carboxylic acids in soils: detection and quantitation issues at low concentrations

Methods were developed for the extraction from soil, identification, confirmation and quantitation by LC/MS/MS of trace levels of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA). Whereas PFOA, PFNA and PFDA all can be quantitated using the method of standard additions, PFOA also can be quantitated less laboriously using 13C4-PFOA as a matrix internal standard. The impact of extract matrices on signal varied between soils and temporally during analytical runs rendering 13C4-PFOA unsuitable as a matrix internal standard for quantitating perfluorinated carboxylic acids (PFCAs) other than PFOA, which co-elutes with 13C4-PFOA. In fact, for soil extracts, quantitation of PFCAs based on external calibrations proved about as accurate as use of matrix internal standards for target analytes that do not co-elute with the matrix internal standard. Also, 13C4-PFOA should be used carefully as a matrix internal standard for trace levels of PFOA because some 13C4-PFOA standards contain trace impurities of unlabelled PFOA. When the presence of PFCAs in soil extracts is being determined by LC/MS/MS, detection limits are best defined by statistical methods that quantify the significance of contrast between analytical signal and background noise using multiple analyses. Further, when developing a calibration of low concentrations using weighted regression, the central tendency of the calibration line is best fitted using graphical depictions of error. As the MDL for the transition-product quantitation ion is approached in LC/MS/MS, relatively weak signals of transition-product confirmation ions can be used as a rejection criterion by looking for anomalously high values of the ratio of the confirmation to the quantitation ion.     

Structure–Activity Studies of Cysteine‐Rich α‐Conotoxins that Inhibit High‐Voltage‐Activated Calcium Channels via GABAB Receptor Activation Reveal a Minimal Functional Motif

α‐Conotoxins are disulfide‐rich peptides that target nicotinic acetylcholine receptors. Recently we identified several α‐conotoxins that also modulate voltage‐gated calcium channels by acting as G protein‐coupled GABA_B receptor (GABA_BR) agonists. These α‐conotoxins are promising drug leads for the treatment of chronic pain. To elucidate the diversity of α‐conotoxins that act through this mechanism, we synthesized and characterized a set of peptides with homology to α‐conotoxins known to inhibit high voltage‐activated calcium channels via GABA_BR activation. Remarkably, all disulfide isomers of the active α‐conotoxins Pu1.2 and Pn1.2, and the previously studied Vc1.1 showed similar levels of biological activity. Structure determination by NMR spectroscopy helped us identify a simplified biologically active eight residue peptide motif containing a single disulfide bond that is an excellent lead molecule for developing a new generation of analgesic peptide drugs.