Synthesis and biological activity of novel epothilone aziridines

[reaction: see text]. A series of 12alpha,13alpha-aziridinyl epothilone derivatives were synthesized in an efficient manner from epothilone A. The final semisynthetic route involves a formal double-inversion of stereochemistry at both the C12 and C13 positions. All aziridine analogues were tested for effects on tubulin binding polymerization and cytotoxicity. The results indicate that the aziridine moiety is a viable isosteric replacement for the epoxide in the case of epothilones.     

Equivalence of vacuum Yang-Mills gravitation and vacuum Einstein gravitation

In the Yang-Mills formulation of gravitational dynamics based uponSL(2,C) spin transformations acting on Dirac spinors, the vacuum field equations are R +C R = 0 and and . HereR is the Ricci curvature andC is the Weyl conformal curvature; is a coupling constant. We show the equivalence between solutions of these equations and the vacuum Einstein equationsR = 0. The proof uses the Newman-Penrose formalism.Supported by a NATO fellowship.Supported by a SRC fellowship.     

Characterization and kinetic performance of 2.1 × 100 mm production columns packed with new 1.6 μm superficially porous particles

The overall kinetic performance of three production columns (2.1 mm × 100 mm format) packed with 1.6 μm superficially porous CORTECS‐C₁₈+ particles was assessed on a low‐dispersive I‐class ACQUITY instrument. The values of their minimum intrinsic reduced plate heights (h_min = 1.42, 1.57, and 1.75) were measured at room temperature (295 K) for a small molecule (naphthalene) with an acetonitrile/water eluent mixture (75:25, v/v). These narrow‐bore columns provide an average intrinsic efficiency of 395 000 plates per meter. The gradient separation of 14 small molecules shows that these columns have a peak capacity about 25% larger than similar ones packed with fully porous BEH‐C₁₈ particles (1.7 μm) or shorter (50 mm) columns packed with smaller core–shell particles (1.3 μm) operated under very high pressure (>1000 bar) for steep gradient elution (analysis time 80 s). In contrast, because their permeabilities are lower than those of columns packed with larger core–shell particles, their peak capacities are 25% smaller than those of narrow‐bore columns packed with standard 2.7 μm core–shell particles.     

Os(VIII)-catalysed oxidation of sulfides by sodium salt of N-chlorobenzenesulfonamide

Catalytic activity of Os(VIII) in the oxidation of some twenty organic sulfides with sodium salt of N-chlorobenzenesulfonamide (CAB) has been investigated in alkaline (pH8.7) t-butanol–water (1:1 v/v) medium. Significant retarding influence of [OH⁻] on the reactivity is exhibited. The catalysed reaction is strongly accelerated in the presence of Hg(II). Imperfections are observed in the linear Hammett relationship in the case of –NO₂ substituents.     

Two-dimensional liquid chromatography/mass spectrometry/mass spectrometry separation of water-soluble metabolites

Off-line two-dimensional liquid chromatography with tandem mass spectrometry detection (2D-LC/MS-MS) was used to separate a set of metabolomic species. Water-soluble metabolites were extracted from Escherichia coli and Saccharomyces cerevisae cultures and were immediately analyzed using strong cation exchange (SCX)-hydrophilic interaction chromatography (HILIC). Metabolite mixtures are well-suited for multidimensional chromatography as the range of components varies widely with respect to polarity and chemical makeup. Some currently used methods employ two different separations for the detection of positively and negatively ionized metabolites by mass spectrometry. Here we developed a single set of chromatographic conditions for both ionization modes and were able to detect a total of 141 extracted metabolite species, with an overall peak capacity of ca. 2500. We show that a single two-dimensional separation method is sufficient and practical when a pair or more of unidimensional separations are used in metabolomics.     

Raman spectroscopic investigation on the microenvironment of the liver tissues of Zebrafish (Danio rerio) due to titanium dioxide exposure

Nano titanium dioxide (nTiO₂), generally considered to be toxicologically inert, is manufactured in large quantities and extensively applied in consumer products. The small size and large surface area endow them with an active group or intrinsic toxicity. Advances in instrumentation are making Raman spectroscopy the tool of choice for an increasing number of (bio) chemical applications. One of the great advantages of this technique is its ability to provide information on the concentration, structure and interaction of biochemical molecules in their microenvironments within intact cells and tissues, non-destructively. Zebrafish (Danio rerio), one of the most important vertebrate model organisms used in developmental biology, are increasingly used in biomedical research, particularly as a model of human disease. In the present work, an attempt is made to study the effect of titanium dioxide, both nano and bulk, on the microenvironment of the liver tissues of Zebrafish using FT-Raman spectroscopy. The results of the present study suggest that TiO₂ exposure demonstrate a marked influence on the microenvironments of the liver tissues of Zebrafish. A shift to a higher wavenumber and an increase in the intensity of the band at ∼1087 cm⁻¹ in the TiO₂ exposed tissues suggest that some of the conformational changes resulting from the alkali recovery process takes place due to TiO₂ exposure. The decreased intensity ratio (I₃₂₂₀/I₃₄₀₀) observed in the titanium-exposed tissues suggests a decreased water domain size, which could be interpreted in terms of weaker hydrogen-bonded molecular species of water in the TiO₂ exposed tissues. The observed shift of COO⁻ bands to higher frequencies shows the disruption of salt bridges as a result of a change in the oppositely charged partners and due to the enhanced random coil conformation. The variation in the intensity ratio of the tyrosyl doublet (I₈₅₈/I₈₂₅) indicates variation in the hydrogen bonding of the phenolic hydroxyl group due to TiO₂ exposure. The results further suggest that the microenvironments are greatly altered due to titanium nano exposure when compared to titanium bulk. In conclusion, the results indicate that FT-Raman spectroscopy might be a useful tool for rapid assessment of nano particle biological interactions.     

Retention mechanism divergence of a mixed mode stationary phase for high performance liquid chromatography

Mixed mode stationary phases utilize secondary retention mechanisms to add a dimensionality to the surface of high performance liquid chromatography (HPLC) adsorbents. This approach was used by several authors to improve the separation performance of single dimension separations. We explored the magnitude of these secondary interactions by performing an off-line two-dimensional (2D)-HPLC separation with a Scherzo SM-C18 column of a β-lactoglobulin tryptic digest with a mobile phase pH of 7 in the first dimension and 2 in the second. Mechanism divergence was determined using the peak capacity and a geometric approach to factor analysis, to measure the correlation. This separation was repeated with a C18 stationary phase as a control. It was found that the C18 column had a correlation coefficient of 0.784, smaller than the mixed mode column, 0.884. This indicated that the retention mechanisms of the C18 column were more divergent under these two pH environments than the mixed mode column. However, the SM-C18 still provided alternative selectivity of the peptides to that of the C18 and could be considered as a good alternative for further 2D-HPLC separations.