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.     

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.     

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.     

Approaches to comprehensive multidimensional liquid chromatography systems

This work compares the performance of the three different schemes implementing two-dimensional liquid chromatography (2D-LC) in terms of the peak capacity that they can generate and of the time that they need to complete a two-dimensional analysis. We discuss in detail how time is spent in these two-dimensional liquid chromatography×liquid$\text{chromatography}\times \text{liquid}$ chromatography (LC×LC$\text{LC}\times \text{LC}$) schemes and how to compare them. Keeping constant the characteristics of the first-dimension separation, we systematically varied those of the second-dimension separation and of its coupling to the first-dimension. In the process, five systems were created, based on the principles of the three known implementations of comprehensive 2D-LC. This work demonstrates an original method for the selection of the best comprehensive 2D-LC approach, depending on the desired peak capacity and on time constraints. The decision to use a 2D-LC method arises from the need to achieve a given resolution (i.e., a target peak capacity) within as short a time as possible or to reach the highest possible resolution in a given analysis time. Using the most appropriate schemes, we suggest how it is realistically possible to generate peak capacities ranging from 266 in just over 20 min or about 2800 in 2.3 h. When the time available for a two-dimensional separation is very short and the desired peak capacity cannot be achieved in 1D-LC, an on-line 2D-LC approach is unquestionably best. However, if a longer analysis time is acceptable, a 10-fold increase in the peak capacity can be obtained at the cost of a mere 7-fold increase in total analysis time.