Multi-element simplex optimization for inductively-coupled plasma/atomic emission spectrometry with a plasma torch having a wide-bore injector tube : Part 1. Conditions for Optimum Detection Limit

An objective function, based on signal-to-background ratio measurements, with a variable step-size simplex procedure is used to optimize conditions for multi-element determinations by inductively-coupled plasma/atomic emission spectrometry. When a typical 10-elements solution was used, the optimization produced small but significant improvements in limits of detection. The ease with which optimal multi-element instrumental conditions were identified is attributed to the compact analytical zone of the plasma produced when a wide-bore (2 mm i.d.) injector tube is used.     

Speciation of silicon and phosphorous using liquid chromatography coupled with sector field high resolution ICP-MS

Sector-field high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) has been used, at R=3000, to resolve spectral interferences caused by N₂⁺ and CO⁺ on ²⁸Si⁺, and NOH⁺ and NO⁺ on ³¹P⁺, thereby facilitating the speciation of these elements. Polydimethylsiloxanes (PDMS), ranging from 162 g mol⁻¹ to 16 500 g mol⁻¹, and their silanol breakdown products, have been separated by size exclusion and reverse phase chromatography, respectively, and detected using HR-ICP-MS. Detection limits (as Si) of between 12–30 ng ml⁻¹ and 0.1–4 ng ml⁻¹ were obtained for the PDMS and silanol compounds, respectively. Quantitative and reproducible methods have been developed for the analysis of four common organophosphorous pesticides in blood plasma, and inorganic phosphates in food, with detection limits of between 0.9–2 ng ml⁻¹ and 1–39 ng ml^−1, respectively.     

Determination of cobalt at picogram levels by high-performance liquid chromatography with chemiluminescence detection

A simple cation-exchange chromatographic system was used to separte cobalt from other metal ions. The cobalt thus separated was detected by the luminol chemiluminescence reaction using a spectrofluorimeter as the detector. A 3σ detection limit of 0.5 ng l^?1 was achieved, without the need for preconcentration, with a 200-μl sample. The system provided a linear analytical working range from 5 ng l^?1 to 10 μg l^?1. The cobalt content of a rice flour certified reference material was determined using the system and gave good agreement with the certificate value.     

Stability of singularly perturbed nonlinear stochastic hybrid systems

The problem of exponential mean-square stability of nonlinear singularly perturbed, stochastic hybrid systems is studied in this article. Two groups of nonlinear systems are considered separately. To obtain the sufficient conditions of stability, two basic approaches of stability analysis for hybrid systems with a given Markovian switching rule and any Markovian switching rule and singularly perturbed non–hybrid systems were combined. The Lyapunov techniques were used in both approaches. The obtained results are illustrated by examples.     

Lacunar derivatives of dibenzotetraaza[14]annulene: synthesis and crystal structure of new receptors produced via bis-alkylation of the macrocyclic precursor

The bis(2-hydroxybenzoyl) derivative of dibenzotetraaza[14]annulene was employed as a substrate for producing new lacunar-type receptors. Alkylation of both phenolic OH groups using aliphatic dibromides and ditosylates efficiently leads to the expected bridged products without recourse to a high dilution procedure. Four new dibenzotetraaza[14]annulene-based lacunar receptors, and one unbridged open-chain bis-octoxy analogue have been synthesized. Synthetic procedures, analytical and spectroscopic characterization are reported. Conformations of the macrocyclic rings in the products as well as non-covalent interactions are discussed on the basis of their crystal structures.     

Synthesis and structures of non-cyclic and cyclic mono- and bisphosphonium salts derived from 1,8-bis(diphenylphosphino)naphthalene

A monoalkylated 1,8-bis(diphenylphosphino)naphthalene (dppn) was prepared by treating diphosphine with 1,8-bis(bromomethyl)naphthalene. Unprecedented cyclizations of monophosphonium salts in polar solvents, such as DMF or acetonitrile were elucidated. The mechanistic pathway of the cyclization reaction was postulated and X-ray crystal structure analyses of the resulting 2,2-diphenyl-2,3-dihydro-1H-2-phosphoniaphenalene bromide was performed. 1,8-Bis(diphenylphosphino)naphthalene and α,α′-dibromo-o-xylene afforded—despite unfavorable steric strain—the first dialkylation product of 1,8-bis(phosphino)naphthalene, namely corresponding cyclic bisphosphonium salt. The use of acetonitrile as the solvent was the key for this synthesis. The bromide anions were exchanged in metathesis reaction with hexafluorophosphate anions and the new compound was fully characterized including single crystal X-ray diffraction. The large distance between phosphorus atoms of 3.974 ? clearly demonstrate a strong proximity effect in this hindered bisphosphonium salt.     

4 + 2]-annulations of chiral organosilanes: Application to the total synthesis of leucascandrolide A

Complete details of an asymmetric synthesis of leucascandrolide A (1) are described. The synthesis highlights the use of two diastereoselective [4 + 2]-annulations for the assembly of the functionalized bispyranyl macrolide 3. An efficient assembly and union of the oxazole-containing side chain 4 with macrolide 3 was carried out using a Mitsunobu reaction. A convergent route to the oxazole side chain was developed using a Sonogashira cross-coupling between 2-trifloyloxazole 16 and alkyne 17, which allowed for the installation of the C9'-C10' (Z)-olefin.     

A chemical approach to the pharmaceutical optimization of an anti-HIV protein

Chemical protein synthesis is important for dissecting the molecular basis of protein function. Here we advance its scope by demonstrating the significant improvement of the multifaceted pharmaceutical profile of small proteins exclusively via a chemical-based approach. The focus of this work centered on CCL-5 (RANTES) derivatives with potent anti-HIV activity. The overall chemical strategy involved a combination of coded and noncoded amino acid mutagenesis, peptide backbone engineering, and site-specific polymer attachment. The ability to alter specific protein residues, as well as precise control of the position and type of polymer attachment, allows for the exploration of specific molecular designs and resulted in novel CCL-5 analogues with significant differences in their respective biochemical and pharmaceutical properties. Using this approach, the complex-interplay of variables contributing to the noncovalent self-association (aggregation) state, CCR-5 specificity, in vivo elimination half-life, and anti-HIV activity of CCL-5-based protein analogues could be empirically evaluated via total chemical synthesis. This work has led to the identification of potent (sub-nanomolar) anti-HIV proteins with significantly improved pharmaceutical profiles, and illustrates the increasing value of protein chemical synthesis in contemporary therapeutic discovery. These antiviral molecules provide a novel mechanism of action for the development of a new generation of anti-HIV therapeutics which are still desperately needed.