Polyoxometalate Clusters Integrated into Peptide Chains and as Inorganic Amino Acids: Solution‐ and Solid‐Phase Approaches

General synthetic methods for the grafting of peptide chains onto polyoxometalate clusters by the use of general activated precursors have been developed. Using a solution‐phase approach, pre‐synthesized peptides can be grafted to a metal oxide cluster to produce hybrids of unprecedented scale (up to 30 residues). An adapted solid‐phase method allows the incorporation of these clusters, which may be regarded as novel hybrid unnatural amino acids, during the peptide synthesis itself. These methods may open the way for the automated synthesis of peptides and perhaps even proteins that contain “inorganic” amino acids.     

3D Printed High‐Throughput Hydrothermal Reactionware for Discovery,Optimization, and Scale‐Up

3D printing techniques allow the laboratory‐scale design and production of reactionware tailored to specific experimental requirements. To increase the range and versatility of reactionware devices, sealed, monolithic reactors suitable for use in hydrothermal synthesis have been digitally designed and realized. The fabrication process allows the introduction of reaction mixtures directly into the reactors during the production, and also enables the manufacture of devices of varying scales and geometries unavailable in traditional equipment. The utility of these devices is shown by the use of 3D printed, high‐throughput array reactors to discover two new coordination polymers, optimize the synthesis of one of these, and scale‐up its synthesis using larger reactors produced on the same 3D printer. Reactors were also used to produce phase‐pure samples of coordination polymers MIL‐96 and HKUST‐1, in yields comparable to synthesis in traditional apparatus.     

Implementation of a Gaussian Beam Laser and Aspheric Optics for High Spatial Resolution MALDI Imaging MS

We have investigated the use of a Gaussian beam laser for MALDI Imaging Mass Spectrometry to provide a precisely defined laser spot of 5 μm diameter on target using a commercial MALDI TOF instrument originally designed to produce a 20 μm diameter laser beam spot at its smallest setting. A Gaussian beam laser was installed in the instrument in combination with an aspheric focusing lens. This ion source produced sharp ion images at 5 μm spatial resolution with signals of high intensity as shown for images from thin tissue sections of mouse brain.

Alternatively linking fullerene and conjugated polymers

The stereo‐electronic control over bisadditions of conjugated polymers to fullerene (C₆₀) is explored in the formation of alternating copolymers. The chemistry, resulting configuration, and properties of poly(3‐hexylthiophene)‐alt‐C₆₀ copolymers prepared by either classic pyrrolidine ring formation or an atom transfer radical addition are compared. Both routes result in controlled additions of polymers to C₆₀. Extensive macromolecular modeling through PM6 methods indicate that there is no conjugation between P3HT and C₆₀ in the systems studied. This along with 2D‐NMR, AFM, and photovoltaic characterizations of the materials indicate the importance of the structure of the modified C₆₀ and the nature of the linking group between C₆₀ and P3HT segments in determining the morphology of the copolymers in the solid state. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2304–2317, 2009     

Fast generic-gradient reversed-phase high-performance liquid chromatography using short narrow-bore columns packed with small nonporous silica particles for the analysis of combinatorial libraries.

The extremely large number of samples generated for the quality control analysis of combinatorial libraries that are developed in the pharmaceutical research for drug discovery requires fast generic methods such as rapid-gradient reversed-phase high-performance liquid chromatography (HPLC). These methods are necessary as standard procedures to produce up to several hundreds of analytical results per day and should be optimized in order to be applied to library products of widely differing polarities. This work presents an optimized generic method using a narrow-bore column packed with 1.5-microm nonporous particles and a completely automated HPLC workstation configured for the best efficiency, throughput, and robustness with this column. A test mix of 12 compounds with a wide polarity range is separated within 1.5 min with a cycle time of 3.5 min. The throughput is further enhanced using a Gilson 233XL dual-injection sampler to feed two parallel HPLC systems in order to perform 34 analyses per hour.