Gold(I) NHC catalysts immobilized to amphiphilic block copolymers: a versatile approach to micellar gold catalysis in water

Fifteen gold(I)-NHC-functionalized amphiphilic block copolymers that differ in the type of linker (ethyl, pentyl, octyl and benzyl) that attaches the gold(I) NHC catalyst to the block copolymer backbone, as well as, the substitution pattern of the NHC ligand (i. e. mesityl, methyl, 2,6-diisopropylphenyl and n-hexyl) were synthesized by a reversible addition and fragmentation transfer (RAFT) polymerization process. Micelle formation of the gold(I) NHC polymers was analyzed by electron microscopy and dynamic light scattering and revealed spherical and rod-like particles from 12 to 96 nm. In the micellar, gold(I) catalyzed cycloisomerization of an allene to the corresponding dihydrofuran, linker flexibility and substitution pattern of the NHC-ligand showed a strong effect on the catalytic activity. Best results were obtained were obtained for gold(I) NHC catalysts bound to the polymer backbone by pentyl linker whereas the rather stiff benzyl linker gave lowest catalyst conversion. Moreover, the polymer catalyst could be recycled in four consecutive runs and gave activities from 35 to 84 % in the fourth run and underscores the importance of fine tuning structural parameters to achieve high conversion under micellar reaction conditions

Efficient synthesis of macromolecular DO3A@Gn derivatives for potential application in MRI diagnostics: from polymer conjugates to polymer nanoparticles

Herein, the synthesis of three different macromolecular DO3A@Gn conjugates based on poly(2-oxazoline)s is presented. Therefore, poly(2-methyl-2-oxazoline) is synthesized by a ring-opening, cationic polymerization and the polymerization is terminated with DO3A(tBu)3. The best results are obtained after 48 h at 120 °C with degree of termination of 86%. After deprotection of the DO3A ligand and complexation with Gn3+, relaxivity as measured with a magnetic field strength of 9.4 T (400 MHz) reveals values for r1 of up to 2.32 mm−1 s−1. The concept is extended to a block copolymer based on 2-heptyl-2-oxazoline and 2-methyl-2-oxazoline that is again terminated with DO3A(tBu)3 to form micelles with a size of 12.6 ± 0.7 nm after DO3A(tBu)3 termination and deprotection of the 1,4,7,10-tetraazacyclododecane-N,N,N,N-tetraacetic acid ligand. After complexation with Gn3+, relaxivity r1 is 10.1 mm−1 s−1 as determined from the slope of the plot of 1/T1 against the gadolinium(III) concentration at 9.4 T. Finally, crosslinked nanoparticles are prepared from amphiphilic macro-monomers that form micelles in water and are crosslinked throughout the core in the presence of azoisobutyronitrile (AIBN). The nanoparticle is 32.9 ± 7.8 nm in size after Gn3+ complexation and reveals a relaxivity r1 of 6.77 mm−1 s−1

Combining SNLP-like Planning and Dependency-Maintenance

Real world planning tasks like manufacturing process planning often don't allow to formalize all of the relevant knowledge. Especially, preferences between alternatives are hard to acquire but have high influence on the efficiency of the planning process and the quality of the solution. We describe the essential features of the CAPlan planning architecture that supports cooperative problem solving to narrow the gap caused by absent preference and control knowledge. The architecture combines an SNLP-like base planner with mechanisms for explict representation and maintenance of dependencies between planning decisions. The flexible control interface of CAPlan allows a combination of autonomous and interactive planning in which a user can participate in the problem solving process. Especially, the rejection of arbitrary decisions by a user or dependency-directed backtracking mechanisms are supported by CAPlan

Identification of an expanded set of translationally active methionine analogues in Escherichia coli

Amino acid incorporation into proteins in vivo is controlled most stringently by the aminoacyl-tRNA synthetases. Here we report the incorporation of several new methionine analogues into protein by increasing the rate of their activation by the methionyl-tRNA synthetase (MetRS) of Escherichia coli. cis-Crotylglycine (4), 2-aminoheptanoic acid (7), norvaline (8), 2-butynylglycine (11), and allylglycine (12) will each support protein synthesis in methionine-depleted cultures of E. coli when MetRS is overexpressed and the medium is supplemented with the analogue at millimolar concentrations. These investigations suggest important opportunities for protein engineering, as expansion of the translational apparatus toward other amino acid analogues by similar strategies should also be possible

Synthesis of redox-responsive core–shell nanoparticles: insights into core-crosslinking efficiency

Core-crosslinked micelles have become an important class of materials for biomedical applications. However, there has been little work attempting to quantify the efficiency of the core crosslinking reaction, instead residual polymers are usually removed by dialysis. In this work we have prepared core crosslinked micelles based on poly(2-ethyl-2-oxazoline)-block-poly(n-butyl acrylate-co-D,L-homocysteine thiolactone acrylamide). Core crosslinking was examined by the addition of six different di- and triamines and nucleophilic ring-opening of the thiolactone ring. By using size exclusion chromatography (SEC) we were able to quantify the amount of crosslinked micelle and free block copolymer and were able to optimize the crosslinking conditions in terms of temperature, reaction time and crosslinker equivalents to obtain up to 80% core-crosslinked micelles. Subsequently, micelles that were crosslinked with cystamine were degraded in the presence of dithiothreitol (DTT) and resulted in degradation times of 1.5 h to 5 h and depended strongly on the composition of the hydrophobic core as shown by dynamic light scattering (DLS) and size exclusion chromatography (SEC). Cytotoxicity assays of the core-crosslinked micelles and block copolymer precursors were performed with COS7 cells and revealed high cell viabilities up to 0.1 mg mL−1

Synthesis and characterization of cationic hydrogels from thiolated copolymers for independent manipulation of mechanical and chemical properties of cell substrates

Cells sense both mechanical and chemical properties in their environment and respond to these inputs with altered phenotypes. Precise and selective experimental manipulations of these environmental cues require biocompatible synthetic materials, for which multiple properties can be fine-tuned independently from each other. For example, cells typically show critical thresholds for cell adhesion as a function of substrate parameters such as stiffness and the degree of functionalization. However, the choice of tailor-made, defined materials to produce such cell adhesion substrates is still very limited. Here, a platform of synthetic hydrogels based on well-defined thiolated copolymers is presented. Therefore, four disulfide crosslinked hydrogels of different composition by free radical polymerization are prepared. After cleavage with dithiothreitol, four soluble copolymers P1–P4 with 0–96% cationic monomer content are obtained. P1 and P4 are then combined with PEGDA3500 as a crosslinker, to fabricate 12 hydrogels with variable elasticity, ranging from 8.1 to 26.3 kPa and cationic group concentrations of up to 350 µmol cm−3. Systematic analysis using COS7 cells shows that all of these hydrogels are nontoxic. However, successful cell adhesion requires both a minimal elasticity and a minimal cationic group concentration

Towards DNA-encoded micellar chemistry: DNA-micelle association and environment sensitivity of catalysis

The development of DNA-compatible reaction methodologies is a central theme to advance DNA-encoded screening library technology. Recently, we were able to show that sulfonic acid-functionalized block copolymer micelles facilitated Brønsted acid-promoted reactions such as the Povarov reaction on DNA-coupled starting materials with minimal DNA degradation. Here, the impact of polymer composition on micelle shape, and reaction conversion was investigated. A dozen sulfonic acid-functionalized block copolymers of different molar mass and composition were prepared by RAFT polymerization and were tested in the Povarov reaction, removal of the Boc protective group, and the Biginelli reaction. The results showed trends in the polymer structure-micellar catalytic activity relationship. For instance, micelles composed of block copolymers with shorter acrylate ester chains formed smaller particles and tended to provide faster reaction kinetics. Moreover, fluorescence quenching experiments as well as circular dichroism spectroscopy showed that DNA-oligomer-conjugates, although highly water-soluble, accumulated very effectively in the micellar compartments, which is a prerequisite for carrying out a DNA-encoded reaction in the presence of polymer micelles