The ETACS European project for testing the comparability of sensors and analysers

ETACS is the official acronym for the European project "European Testing and Assessment of Comparability of On-line Sensors/Analysers". This project has three main objectives to achieve the comparability of performance data for sensors and analysers in the environmental field. First, to develop a test protocol for validation and comparison of the performance of on-line sensors/analysers. The test protocol is intended to be generic, that is independent of the specific sensors/analysers and the specific parameters to be monitored. Second, the practical testing of this test protocol to assess its applicability and to develop the techniques used. Finally, to achieve widespread acceptance of the test protocol by producer/suppliers, users and relevant authorities to assist its early adoption as an agreed European standard. Laboratory tests for producing the test protocol have been carried out and completed to check the applicability of such a protocol.     

Polarographic determination of chlorpheniramine maleate in pharmaceuticals

The electroreduction of chlorpheniramine maleate has been investigated by a.c. and d.c. polarography, coulometry and cyclic voltammetry. Polarograms recorded from 0.2 M sulphuric acid exhibit a single well-defined 2-electron wave. The current is diffusion-controlled and proportional to the concentration in the entire range 0.3–400 μg ml^?1. A simple and rapid method for the determination of chlorpheniramine maleate in tablets is described.     

A possible mechanism for enantioselectivity in the chiral epoxidation of olefins with

The origin of enantioselectivity in the Jacobsen-Katsuki reaction has been investigated by applying density functional calculations in combination with molecular mechanics methodologies. The calculations suggest that a high enantiomeric excess is connected to three specific features: 1) a chiral diimine bridge, which induces folding of the salen ligand(H2salen = bis(salicylidene)ethylenediamine), and hence the formation of a chiral pocket; 2) bulky groups at the 3,3'-positions of the salen ligand, which cause a preferential approach from the side of the aromatic rings; and 3) pi conjugation of the olefinic double bond, which confers regioselectivity and, consequently, enantioselectivity. In combination with experimental studies, the model also provides a rationale for the decrease in ee values when one of these components is missing.     

Synthesis of 5,6-dihydro-4H-thiopyran-4-ones

The anions of 1,4-diaryl-3-buten-2-ones 1 reacts with arylisothiocyanates, yielding intermediates 4 which can ring close to 5,6-dihydro-4H-thiopyran-4-ones 5 . Under similar reaction conditions ethyl 3-oxo-4-pentenoates 7 gives the 6-spiropyrans 9 . Methylation of 3 gives the S-methylated open form 6 .     

Using model complexes to augment and advance metalloproteinase inhibitor design

The tetrahedral zinc complex [(Tp(Ph,Me))ZnOH] (Tp(Ph,Me) = hydrotris(3,5-phenylmethylpyrazolyl)borate) was combined with 2-thenylmercaptan, ethyl 4,4,4-trifluoroacetoacetate, salicylic acid, salicylamide, thiosalicylic acid, thiosalicylamide, methyl salicylate, methyl thiosalicyliate, and 2-hydroxyacetophenone to form the corresponding [(Tp(Ph,Me))Zn(ZBG)] complexes (ZBG = zinc-binding group). X-ray crystal structures of these complexes were obtained to determine the mode of binding for each ZBG, several of which had been previously studied with SAR by NMR (structure-activity relationship by nuclear magnetic resonance) as potential ligands for use in matrix metalloproteinase inhibitors. The [(Tp(Ph,Me))Zn(ZBG)] complexes show that hydrogen bonding and donor atom acidity have a pronounced effect on the mode of binding for this series of ligands. The results of these studies give valuable insight into how ligand protonation state and intramolecular hydrogen bonds can influence the coordination mode of metal-binding proteinase inhibitors. The findings here suggest that model-based approaches can be used to augment drug discovery methods applied to metalloproteins and can aid second-generation drug design.     

Asymmetric catalytic Mannich reactions catalyzed by urea derivatives: enantioselective synthesis of beta-aryl-beta-amino acids

Highly enantioselective addition reactions between silyl ketene acetals and N-Boc aldimines are catalyzed by the thiourea-based catalyst 1c. Extraordinary scope is observed in this methodology with regard to the imine substrate, with aryl and heteroaromatic derivatives generally affording nearly quantitative yields of beta-amino ester product in up to 98% enantioselectivity.     

Beta-sheet preferences from first principles

The natural amino acids have different preferences of occurring in specific types of secondary protein structure. Simulations are performed on periodic model beta-sheets of 14 different amino acids, at the level of density functional theory, employing the generalized gradient approximation. We find that the statistically observed beta-sheet propensities correlate very well with the calculated binding energies. Analysis of the calculations shows that the beta-sheet propensities are determined by the local flexibility of the individual polypeptide strands.     

Linear programs with an additional reverse convex constraint

A constraintg(x)0 is said to be a reverse convex constraint if the functiong is continuous and strictly quasi-convex. The feasible regions for linear programs with an additional reverse convex constraint are generally non-convex and disconnected. It is shown that the convex hull of the feasible region is a convex polytope and, as a result, there is an optimal solution on an edge of the polytope defined by only the linear constraints. The only possible edges which can contain such an optimal solution are characterized in relation to the best feasible vertex of the polytope defined by only the linear constraints. This characterization then provides a finite algorithm for finding a globally optimal solution.Research supported by NSF Grant ENG76-12250 and ONR Contract N00014-78-C-0428.     

Explorative data analysis of two-dimensional electrophoresis gels

Methods for classification of two-dimensional (2-DE) electrophoresis gels based on multivariate data analysis are demonstrated. Two-dimensional gels of ten wheat varieties are analyzed and it is demonstrated how to classify the wheat varieties in two qualities and a method for initial screening of gels is presented. First, an approach is demonstrated in which no prior knowledge of the separated proteins is used. Alignment of the gels followed by a simple transformation of data makes it possible to analyze the gels in an automated explorative manner by principal component analysis, to determine if the gels should be further analyzed. A more detailed approach is done by analyzing spot volume lists by principal components analysis and partial least square regression. The use of spot volume data offers a mean to investigate the spot pattern and link the classified protein patterns to distinct spots on the gels for further investigation. The explorative approach in analysis of 2-D gels makes it possible, in a fast and convenient way, to screen many gels in order to determine the protein patterns that form clusters and could be selected for further examination.