Synthesis of ring-oxidized retinoids as substrates of mouse class I alcohol dehydrogenase (ADH1)

Ring-oxidized retinoids have been synthesized stereoselectively using the Stille cross-coupling reaction. Kinetic constants of mouse class I alcohol dehydrogenase (ADH1) with these retinoids were determined.     

Synthesis of 4-amino-5-H-2,3-dihydroisothiazole-1,1-dioxide ring systems on sugar templates via carbanion-mediated sulfonamide intramolecular cyclization reactions (CSIC protocols) of glyco-alpha-sulfonamidonitriles

The carbanion-mediated sulfonate intramolecular cyclizations (CSIC protocols) of glyco-alpha-sulfonamidonitriles derived from readily available monosaccharides have been extensively investigated using potassium carbonate, cesium carbonate, n-BuLi, and LDA as bases. As a result, a series of enantiomerically pure spiro(4-amino-5-H-2,3-dihydroisothiazole-1,1-dioxide) derivatives have been prepared efficiently and isolated in good yield. The synthesis of these new bicyclic systems is key to accessing a novel range of aza analogues of TSAO nucleosides (ATSAOs).     

Tandem RCM-Pauson-Khand reaction for access to tricycles in one step

Starting from conveniently designed dienynes complexed to cobalt, a tandem RCM-intramolecular Pauson-Khand reaction yields tricyclic compounds. The methodology allows the synthesis of 6,5,5 and 7,5,5 systems.     

Variational Evaluation of the HSSH FIR Transitions: The Anomalous K-Doubling

The roto-torsional energy levels of HSSH and DSSD up to J = 20 are evaluated variationally with a Hamiltonian expressed in terms of internal coordinates. The kinetic and potential parameters are derived from ab initio calculations with full optimization of the geometry. The calculated levels are employed for the determination of the centrifugal distortion constants. HSSH is a near-prolate symmetric rotor. The most stable C(2) conformer, calculated with MP4(SDQ)/cc-pVQZ, exhibits a 90.55 degrees dihedral angle. For J = 0, the lowest energies of HSSH and DSSD are 413.4876 cm(-1) (n = 1), 798.0304 cm(-1) (n = 2) and 1151.5773 cm(-1) (n = 3), and 304.3185 cm(-1) (n = 1), 594.2919 cm(-1) (n = 2), and 869.3508 cm(-1) (n = 3), respectively. For J = 60, the ab initio calculations allow the reproduction of the anomalous type-K doubling predicted with perturbation theory. Copyright 2000 Academic Press.     

Quantum cascade laser modulation for correction of matrix-induced background changes in aqueous samples

A robust method for the determination of carbon dioxide in sugar containing solutions using a single distributed feedback quantum cascade laser (QCL) has been developed. By switching the driving current between two selected values, 1.6 and 1 A, emission wavelengths at 2341.4 and 2341.6 cm^-1 could be achieved. The method is based on absorbance measurements in transmission and the calculation of the absorbance differences between both wavenumbers. This allows the elimination of indirect matrix interference produced on carbon dioxide measurements with increasing sugar concentrations. A flow injection setup was employed to produce carbon dioxide standards from a series of bicarbonate solutions (0–3 g/l) by adjusting the pH with a sodium hydroxide/citric acid buffer solution to pH 3.13. Different concentrations (0–90 g/l) of sugar were also mixed on line with the analyte to study their influence on carbon dioxide measurement. As the difference in the two evaluated wavelengths is small compared to the absorption peak of CO₂, the analytical readout of the QCL modulation can be seen as a proportional parameter to the first derivative of FTIR spectra in this spectral region. PACS 42.55.Px; 42.62.Fi     

Effect of pH and ligand charge state on BACE-1 fragment docking performance

In this work we propose a protocol for estimating the effect of pH on the docking performance to BACE-1, which affords the charge state of the inhibitor as well as the protonation state of all ionisable residues in the protein at a given pH value. To the best of our knowledge, this is the first report of a protocol predicting the BACE-1 ligand docking poses not only at the neutral pH at which most crystallographic structures were obtained, but also at the optimal pH of the enzyme (in the acidic range), at which most of the BACE-1 binding affinity assays are performed. We have applied this protocol to a set of 23 fragment-like BACE-1 ligands that span four orders of magnitude in their binding affinities. The pK _a values of the BACE-1 acidic residues deviate substantially from the estimates for model compounds in solution and display a ligand dependent variability, especially in the case of the catalytic Asp dyad residues. This outcome should have a strong bearing on the design of protocols for docking based BACE-1 screening campaigns. Finally, we were able to find an explanation for the poor docking success rate of some fragments based on the availability of anchoring points, a rationale that could help to improve hit rates in BACE-1 screening campaigns.     

Qualitative and quantitative analysis of new alkyl amide arginine surfactants by high-performance liquid chromatography and capillary electrophoresis.

A protocol for the qualitative and quantitative analysis of novel arginine-based cationic surfactants using HPLC and CE was studied and compared. The optimization of the analytical conditions was carried out through a systematic variation of the experimental parameters such as mobile phase, eluent conditions, ion pairing and amount of sample for HPLC, and type of buffer, ion strength, type and amount of organic solvent, sample injection time, applied voltage and column washing and conditioning for CE.