Transfer printing of DNA by "click" chemistry

This paper describes a straightforward procedure to immobilize oligonucleotides on glass substrates in well-defined micropatterns by microcontact printing with a dendrimer-modified stamp. The oligonucleotides are efficiently immobilized by "click" chemistry induced by microcontact printing. Acetylene-modified oligonucleotides were treated with an azide-terminated glass slide under the confinement of the dendrimer-modified stamp, without the use of a Cu(I) catalyst. The immobilization is an irreversible, covalent, and one-step reaction that results in stable attachment of the oligonucleotides. Oligonucleotides with the acetylene-modification at the 5' terminus hybridize selectively with full-length, complementary targets. Strands with more than one acetylene linker do not hybridize with complementary strands.     

Self-Organized Growth of Sodium Borate-Rich Droplets in a Phase-Separated Sodium Borosilicate Glass

A glass with the composition 60 SiO_2, 37 B₂O_3, and 3 Na₂O was casted and subsequently cooled to room temperature. During subsequent heat treatment at temperatures in the range from 520 to 680°C, the glass shows phase separation and SiO₂-rich droplets in a B₂O₃-rich matrix are formed. The droplet size strongly depends on the temperature and duration of heat treatment. In the dilatometric curves of the phase-separated glasses, two glass transition temperatures are observed. At high annealing temperatures, the transition temperatures vary according to the decomposition cupola. At lower temperatures, the phase formation is restricted by the kinetics. Particle sizes and growth rates are not governed by Ostwald ripening and deviate from the expected rate law d ~ t^1/3. The exponent in the rate law is much smaller than one-third, and hence, the coarsening of the droplet structured is hindered. In analogy to crystal growth models reported in the literature, this growth hindrance is explained by the formation of a highly viscous shell around growing particles.     

Why Does Industry Not Use Immobilized Transition Metal Complexes as Catalysts?

Much effort has gone into the immobilization of homogeneous catalysts based on the idea that in this way the catalysts could be not only separated more easily from the product but also reused several times, thus reducing the cost of the catalyst use. So far none of these immobilized catalysts have been used by industry. In this article we critically review the use of immobilized homogeneous catalysts from the point of view of process development for the pharmaceutical and fine chemical industry. The first and foremost question that needs to be answered is: will immobilizing a homogeneous catalyst really lead to lower costs? The answer is thus far always no. This is caused mostly by the fact that homogeneous catalysts are not stable and thus there is little point in immobilizing them. The second reason is the extra added cost that is incurred in immobilizing the catalysts. Other problems are lower rates, sometimes lower selectivities and metal leaching. Three different areas are discussed. The research on immobilized metathesis catalysts is analyzed in detail; in general the immobilized catalysts do not achieve sufficient turnovers to be interesting for industrial use. Very many publications have appeared on immobilized palladium catalysts that were used for C C bond‐forming reactions, such as Suzuki, Heck or Sonogashira reactions. These catalysts are invariably converted to nanoparticles after the first run. Although these catalysts can be reused, there is no reason to use an expensive support based on immobilized ligands. This also does not protect the product from palladium contamination. Even more effort has gone into the immobilization of homogeneous hydrogenation catalysts. Most of these catalysts suffer from the same problems as the other immobilized catalysts: catalyst deactivation, low turnover numbers, and leaching of the metal. In addition, the heterogenization adds complexity to the system, increasing risk and prolonging process development.

     

Asymmetric Transfer Hydrogenation of Ketones with Modified Grubbs Metathesis Catalysts: On the Way to a Tandem Process

Herein, we report the successful transformation of a 1^st generation Grubbs metathesis catalyst into an asymmetric transfer hydrogenation (ATH) catalyst. Upon addition of a chiral amine ligand, an alcohol and a base, the 1^st generation Hoveyda–Grubbs catalyst ( HG‐I ) was found to promote the enantioselective reduction of acetophenone to 1‐phenylethanol. After optimizing the order of addition and the reaction conditions, the substrate scope was assessed leading to enantiomeric excesses up to 97% ee. NMR experiments were run in order to get information about the in situ‐generated ATH catalyst. Furthermore, the possibility to perform olefin metathesis and ketone transfer hydrogenation sequentially in one pot was demonstrated, and the first tandem olefin metathesis–ketone asymmetric transfer hydrogenation was carried out.

     

Design considerations for the absolute testing approach of aspherics using combined diffractive optical elements

Aspheric optical surfaces are often tested using diffractive optics as null elements. For precise measurements, the errors caused by the diffractive optical element must be calibrated. Recently, we reported first experimental results of a three position quasi-absolute test for rotationally invariant aspherics by using combined-diffractive optical elements (combo-DOEs). Here we investigate the effects of the DOE substrate errors on the proposed calibration procedure and present a set of criteria for designing an optimized combo-DOE. It is demonstrated that this optimized design enhances the overall consistency of the procedure. Furthermore, the rotationally varying part of the surface deviations is compared with the rotationally varying deviations obtained by an N-position averaging procedure and is found to be in good agreement.     

Real-time single-molecule imaging of oxidation catalysis at a liquid-solid interface

Many chemical reactions are catalysed by metal complexes, and insight into their mechanisms is essential for the design of future catalysts. A variety of conventional spectroscopic techniques are available for the study of reaction mechanisms at the ensemble level, and, only recently, fluorescence microscopy techniques have been applied to monitor single chemical reactions carried out on crystal faces and by enzymes. With scanning tunnelling microscopy (STM) it has become possible to obtain, during chemical reactions, spatial information at the atomic level. The majority of these STM studies have been carried out under ultrahigh vacuum, far removed from conditions encountered in laboratory processes. Here we report the single-molecule imaging of oxidation catalysis by monitoring, with STM, individual manganese porphyrin catalysts, in real time, at a liquid-solid interface. It is found that the oxygen atoms from an O2 molecule are bound to adjacent porphyrin catalysts on the surface before their incorporation into an alkene substrate.     

On the classification of prostate carcinoma with methods from spatial statistics.

Gleason grading is a common method used by pathologists to determine the aggressivity of prostate cancer on the basis of histological slide preparations. The advantage of this grading system is a good correlation with the biological behavior of the tumor, while its drawback is the subjectivity underlying the judgements of pathologists. Therefore, an automation of Gleason grading would be desirable. In this paper, we examined 780 digitized grayscale images of 78 different cases, which were split into a training and a test set. We developed two methods based on combinations of morphological characteristics like area fraction, line length, and Euler number to classify into the categories "Gleason score < 7" and "Gleason score > or = 7." In particular, the distinction between these two classes has great impact on the prognosis of patients. The agreement of each method with visual diagnosis was 87.18% and 92.31% within the training set and 66.67% and 64.10% within the test set, respectively.     

IR-MALDI-MS analysis of HPTLC-separated phospholipid mixtures directly from the TLC plate

The application of a recently developed direct coupling of high-performance thin-layer chromatography (HPTLC) and infrared matrix-assisted laser desorption/ionization orthogonal extracting time-of-flight mass spectrometry (Dreisewerd, K.; Müthing, J.; Rohlfing, A.; Meisen, I.; Vukelic, Z.; Peter-Katalinic, J.; Hillenkamp, F.; Berkenkamp, S. Anal. Chem. 2005, 77, 4098-4107) to the analysis of phospholipid mixtures is demonstrated. Mixtures of six phospholipid types were exemplarily analyzed. The sensitivity was found to be in the range between about 10 and 150 pmol of material spotted for HPTLC, depending on phospholipid acidity, Rf value, and ion polarity. The lateral resolution of the analysis is on the order of the laser focus diameter of about 220 x 300 microm2, allowing differentiation between phospholipid species of different acyl chain composition within one single HPTLC band, which were undistiguishable by a mere visual assessment. Analyte diffusion due to the addition of glycerol to the HPTLC plate was found to be-if at all notable-of only minor importance.