Formal Synthesis of (−)‐Cephalotaxine

A formal synthesis of (?)‐cephalotaxine ( 1 ) by means of a highly stereoselective radical carboazidation process is reported. The synthesis begins with the protected (S)‐cyclopent‐2‐en‐1‐ol derivative 10 and uses the concept of self‐reproduction of a stereogenic center (Schemes 5 and 6). For this purpose, the double bond adjacent to the initial chiral center in 10 is converted into an acetonide after stereoselective dihydroxylation. The initial alcohol function is used to build an exocyclic methylene group suitable for the carboazidation process 8 → 7 (Scheme 7). Finally the protected diol moiety is converted back to an alkene ( 14 → 15 → 6 ) and used for the formation of ring B via a Heck reaction ( 6 →(?)‐ 16 ; Scheme 8).     

Pure short-chain glycerol fatty acid esters and glycerylic cyclocarbonic fatty acid esters as surface active and antimicrobial coagels protecting surfaces by promoting superhydrophilicity

Pure glycerol fatty acid esters and glycerylic cyclocarbonic fatty acid esters have an amphiphilic structure, giving these biomolecules a broad range of physico-chemical and biological properties. Physico-chemical properties depend on chain lengths, odd or even carbon numbers on the chain, and glyceryl or cyclocarbonic polar heads. The spectrum of melting-point values for these molecules is large. Surface-activity is very important and through determination of the critical aggregation concentration (CAC), some fatty-acid esters are considered as solvo-surfactant biomolecules. Coupling these self-aggregation and crystallization properties, superhydrophilic surfaces were obtained. An efficient durable water repellent coating of various metallic and polymeric surfaces was allowed. Moreover, these fatty acid esters promoting superhydrophilicity showed biological activity against Gram positive, Gram negative, and yeast-like micro-organisms. Such surfaces coated by self-assembled fatty acid esters in a stable coagel state present a novel solution to surface-contamination risks from pathogen proliferation.     

Novel Functional Mesoporous Materials Obtained from Nanostructured Diblock Copolymers

Summary: Novel carboxy (COOH)-functionalized mesoporous polystyrene membranes were prepared from polystyrene-block-poly(D,L-lactide) (PS-b-PLA) diblock copolymers through the selective degradation of the PLA block. The combination of atom transfer radical polymerization (ATRP) and ring-opening polymerization (ROP) techniques enabled the synthesis of nanostructured diblock copolymers possessing carboxylic acid functionality at the junction between both blocks. Such copolymers were subjected to shear flow through the use of a channel die to align their nanodomains. Under mild alkaline conditions, the quantitative hydrolysis of the polyester nanodomains afforded mesoporous materials with COOH-coated pore walls. The PS-b-PLA precursors as well as the resulting porous systems were carefully analyzed by size exclusion chromatography (SEC), ¹H NMR, scanning electron microscopy (SEM), and two-dimensional small-angle X-ray scattering (2-D SAXS). Moreover, the specific surface area and pore size distribution were determined by nitrogen sorption porosimetry.     

Kinetic and equilibrium factors affecting saturation of chromium oxide in soda-silicate melts

Factors controlling the rate at which chromium oxide reaches saturation in Na₂O-xSiO₂ liquids have been studied as a function of melt composition and oxygen fugacity. Under an oxidizing atmosphere, liquid Na₂CrO₄ or Cr₂O₃ crystals can be in equilibrium with soda-silicate melts, depending on the concentration of sodium in the studied system. Under reducing conditions, NaCrSi₂O₆ is stabilized in silica-rich melts when T is lower than 1160 °C, while Cr₂O₃ is in equilibrium with the sodium-rich melts when T is above 1160 °C. The chromium oxide (Cr₂O₃) to pyroxene (NaCrSi₂O₆) transformation is described in terms of the time required to reach chemical and textural equilibrium. Na₂CrO₄, NaCrSi₂O₆, and Cr₂O₃ phase stability domains are reported as well as the Na₂O-SiO₂-Cr₂O₃ phase diagram in the studied temperature and fO₂ range.     

An Improved Petal Heuristic for the Vehicle Routeing Problem

Solutions produced by the first generation of heuristics for the vehicle routeing problem are often far from optimal. Recent adaptations of local search improvement heuristics, like tabu search, produce much better solutions but require increased computing time. However there are situations where good solutions must be obtained quickly. The algorithm proposed in this paper yields solutions almost as good as those produced by tabu search adaptations, but at only a small fraction of their computing time. This heuristic can be seen as an improved version of the original petal heuristic. On 14 benchmark test problems, the proposed heuristic yields solutions whose values lie on average within 2.38% of that of the best known solutions.     

Electrophoresis Poly(Dimethylsiloxane)/Glass Chips with Integrated Active Cooling for Quantification of Amino Acids

Abstract

The objective of this work was to develop and characterize a poly(dimethylsiloxane) device with an integrated active cooling function able to carry out capillary electrophoresis separations. Polymer-based microdevices are indispensable to recent advances in biomedical analysis. In particular, they have been applied to many microfluidic platforms owing to their low cost, ease of fabrication, and versatility in preparing complex microstructures. However, when applied to capillary electrophoresis separations, polymer microfluidic structures present an inherent disadvantage compared to glass and Si structures; they have a lower thermal conductivity than glass and Si. Although miniaturized devices allow operation at high electric fields, they face separation efficiency limitations due to Joule heating. There is, therefore, a strong need of developing capillary electrophoresis microfluidic structures with active cooling in order to operate at a higher electric field and potentially increase separation efficiency in these microdevices. A poly(dimethylsiloxane)/glass hybrid microfluidic capillary electrophoresis system is presented, where Joule heating was minimized by using an integrated active cooling function. Two poly(dimethylsiloxane) slabs with embedded microfluidic structures were irreversibly sealed on both sides of a thin glass slide. The top poly(dimethylsiloxane) slab was used to carry out capillary electrophoresis separations, whereas the bottom poly(dimethylsiloxane) slab was employed to cool down the buffer solution used during the capillary electrophoresis separation. As demonstrated on current versus voltage plots and on capillary electrophoresis electropherograms, capillary electrophoresis separation was able to be operated at a higher electric field when using the cooling function. The cooling rate was adjustable by varying the flow rate and the initial temperature of the liquid flowing in the cooling microfluidic structure.     

Simple equilibrium dialysis-high-performance liquid chromatographic method for the in vitro assessment of 5-methoxypsoralen bound to human albumin

Increasingly used in therapeutics, 5-methoxypsoralen (5-MOP), a linear furocoumarin, associated with UVA irradiation (PUVA), is now an established treatment for skin diseases such as vitiligo, mycosis funcoides and particularly psoriasis. Successful PUVA therapy depends on a sufficiently high peak 5-MOP plasma concentration coinciding with the UVA irradiation. However, as with most drugs, only the free plasma fraction is able to enter the target cells and has a pharmacological effect. In this work, the binding of 5-MOP to human albumin was studied in vitro, using a dialysis chamber. Bound and free 5-MOP fractions were quantified by a modification of Stolk's high-performance liquid chromatographic method. Dialysis was performed at 37 degrees C and pH 7.4 for 2 h, against a 4% albumin solution in phosphate buffer. The 5-MOP concentrations used were from 5 x 10(-5) to 5 x 10(-2) g/l in 1 x 10(-1) g/l steps. The 5-MOP bound strongly to human albumin in an unsaturable way. The mean 5-MOP binding to albumin was 95.3%. These results are in accordance with those published by Artuc et al. and not with those of Veronese et al., who found a lower saturable fixation (91%). These two research groups used tritiated 5-MOP. The technique used in this work is simple and inexpensive. It can be employed easily in vivo, e.g., for the assessment of 5-MOP free fractions in different therapeutic conditions.     

Gentle cell trapping and release on a microfluidic chip by in situ alginate hydrogel formation

Microfluidic devices are increasingly used to perform biological experiments on a single-cell basis. However, long-term stability of cell positions is still an issue. A novel biocompatible method for cell entrapment and release on a microchip is presented. It is based on the controlled formation of an alginate hydrogel by bringing two laminar flows of alginate and calcium ions in the range of 2 mM to 40 mM into contact. The resulting growth of a gel bar is used to enclose and immobilize yeast cells. Adding ethylenediaminetetraacetic acid (EDTA) to the alginate solution allows for control of the hydrogel growth, and by varying the ratio of Ca(2+) to EDTA concentrations gel growth or gel shrinkage can be induced at will. Trapped cells are released during shrinkage of the gel. The trapping efficiency for different cell speeds is investigated and the properties of gel growth are discussed using a diffusion model. Precise positioning of a single cell is demonstrated. The technique presented allows not only the reversible immobilization of cells under gentle conditions but also offers the potential of long-term cell cultures as shown by on-chip incubation of yeast cells. The procedure may provide a simple and fully biocompatible technique for a multitude of innovative experiments on cells in microsystems.     

Cell immersion and cell dipping in microfluidic devices

Combining deflective dielectrophoretic barriers with controlled pressure driven liquid flows in microfluidic devices allows accurate handling of particles such as biological cells in suspensions. Working towards cell-based lab-on-a-chip applications, a platform permitting rapid testing of devices having different dielectrophoretic and fluidic subunits was developed. The performance of such a system is shown in the cases of (A) flooding a small number of immobilised cells with a dye and (B) transient buffer swapping of a large number of cells in flow. The transition times for moving cells from one reagent to the other are below 0.5 s in the case of flow-through cell dipping.