An 8-fold parallel reactor system for combinatorial catalysis research.

Increasing economic globalization and mounting time and cost pressure on the development of new raw materials for the chemical industry as well as materials and environmental engineering constantly raise the demands on technologies to be used. Parallelization, miniaturization, and automation are the main concepts involved in increasing the rate of chemical and biological experimentation.

Oxygen transfer phenomena in 48-well microtiter plates: determination by optical monitoring of sulfite oxidation and verification by real-time measurement during microbial growth.

Oxygen limitation is one of the most frequent problems associated with the application of shaking bioreactors. The gas-liquid oxygen transfer properties of shaken 48-well microtiter plates (MTPs) were analyzed at different filling volumes, shaking diameters, and shaking frequencies. On the one hand, an optical method based on sulfite oxidation was used as a chemical model system to determine the maximum oxygen transfer capacity (OTR(max)). On the other hand, the Respiration Activity Monitoring System (RAMOS) was applied for online measurement of the oxygen transfer rate (OTR) during growth of the methylotropic yeast Hansenula polymorpha. A proportionality constant between the OTR(max) of the biological system and the OTR(max) of the chemical system were indicated from these data, offering the possibility to transform the whole set of chemical data to biologically relevant conditions. The results exposed "out of phase" shaking conditions at a shaking diameter of 1 mm, which were confirmed by theoretical consideration with the phase number (Ph). At larger shaking diameters (2-50 mm) the oxygen transfer rate in MTPs shaken at high frequencies reached values of up to 0.28 mol/L/h, corresponding to a volumetric mass transfer coefficient (k(L)a) of 1,600 1/h. The specific mass transfer area (a) increases exponentially with the shaking frequency up to values of 2,400 1/m. On the contrary, the mass transfer coefficient (k(L)) is constant at a level of about 0.15 m/h over a wide range of shaking frequencies and shaking diameters. However, at high shaking frequencies, when the complete liquid volume forms a thin film on the cylindric wall of the well, the mass transfer coefficient (k(L)) increases linearly to values of up to 0.76 m/h. Essentially, the present investigation demonstrates that the 48-well plate outperforms the 96-well MTP and shake flasks at widely used operating conditions with respect to oxygen supply. The 48-well plates emerge, therefore, as an excellent alternative for microbial cultivation and expression studies combining the advantages of both the high-throughput 96-well MTP and the classical shaken Erlenmeyer flask.

New ligands for a general palladium-catalyzed amination of aryl and heteroaryl chlorides.

The synthesis and application of monodentate N-substituted heteroarylphosphines is described. In general, the ligands are conveniently prepared by selective metallation at the 2-position of the respective N-substituted heterocycle (pyrrole, indole) by using n-butyllithium/tetramethylethylenediamine (TMEDA) followed by quenching with dialkyl- or diarylchlorophosphines. Of the different ligands prepared, the new dialkyl-2-(N-arylindolyl)phosphines (cataCXium P) perform excellently in the palladium-catalyzed amination of aryl and heteroaryl chlorides. Coupling of both activated and deactivated chloroarenes proceeds under mild conditions (room temperature to 60 degrees C). By using optimized conditions remarkable catalyst productivity (total turnover number, TON, up to 8000) and activity (turnover frequency, TOF=14000 h(-1) at 75% conversion) are observed.

Practical synthesis of new and highly efficient ligands for the Suzuki reaction of aryl chlorides.

A practical synthesis of a novel class of phosphine ligands, phosphino substituted N-aryl pyrroles (PAP ligands), has been developed. These ligands are applied in the palladium-catalyzed coupling of a variety of aryl and heteroaryl chlorides with phenylboronic acid showing exceedingly high turnover numbers at mild reaction temperatures and even at room temperature.

Rapid evaluation of oxygen and water permeation through microplate sealing tapes.

Eight commercially available microplate sealing tapes and 10 other suitable materials (transparent wound dressings) are compared qualitatively in terms of their ability to minimize water evaporation from a multiwell plate while maintaining the oxygen supply as high as possible, which is necessary for applications like aerobic growth. The transparency and sterility of the products are considered as well. All evaluated commercially available sealing tapes fall into one of the following two classes: (1) O(2) transfer is comparable to that of an unsealed plate, but water vapor retention is relatively low, or (2) O(2) transfer via the sealing is slower, but the water retention capability is comparably high. All but one of the evaluated wound dressings fall under the second class. That dressing, however, constitutes a compromise by showing both moderate O(2) permeability and medium water retention. But the estimated mass transport in a microtiter plate sealed with this dressing is about 5 times slower than that of an unsealed 96 well plate. The aim of this publication is to enable the reader to choose a microtiter plate sealing from the materials evaluated within this work and to use the rapid methods described herein to easily perform tests of additional sealing materials.

The first highly enantioselective homogeneously catalyzed asymmetric reductive amination: synthesis of alpha-N-benzylamino acids.

High-throughput screening considering a library of 96 chiral P-ligands involved in two types of Rh(I) complexes was used for the identification of homogeneous catalysts for the highly enantioselective reductive amination of alpha-keto acids with benzylamine. After optimization of the reaction conditions and scale-up with a cationic Rh-Deguphos catalyst, a range of chiral alpha-amino acids could be produced by this new reaction in good yield and by up to 98% ee.