Influence of H+ and calcium ions on surface functional groups of Synechococcus PCC 7942 cells

The chemistry of the surface functional groups of picocyanobacteria Synechococcus PCC 7942 cells was examined as a function of H+ and calcium concentrations. Titration experiments, infrared spectroscopy, biosorption experiments, and chemical modeling were used to gain insight into the mechanisms of biosorption. The pKa and concentration of active sites on the cell wall were clarified with the aid of potentiometric titration. Modeling calculations and infrared spectra are consistent with pKa's values of 4.3, 5.2, 6.9, 9.1, and 10.0 and a total concentration of 7.8 x 10(-4) mol g(-1). Spectral analysis of an aqueous cellular suspension revealed a presence of carboxyl, amide, phosphate, hydroxyl, and carbohydrate moieties. Correspondence between spectral data and potentiometric titration curves supported the hypothesis that carboxylate groups and phosphodiester groups mediate calcium adsorption to bacterial cells. This process is strongly pH dependent. In the second part of the experimental work, Synechococcus cells were suspended in the presence of different calcium concentrations. Mechanistic modeling demonstrated that the calcium adsorption phenomenon can be described taking into account only two mechanisms: ion exchange and complexation.     

Total synthesis and NMR investigations of cylindramide

Cylindramide (1) was built up from three components: a hydroxyornithine derivative 7, a tetrazolylsulfone 8, and a substituted pentalene subunit 9. Derivative 7 was prepared in a six-step reaction sequence involving the Wittig reaction and a Sharpless asymmetric dihydroxylation starting from N-Boc-3-aminopropanal (12). Tetrazolylsulfone 8 was accessible in four steps from dioxinone 22. The synthesis of the pentalene fragment 9 started from cycloocta-1,5-diene 26, that was converted into enantiopure bicyclo[3.3.0]octanedione 29. The latter was functionalized to give derivative 9. The total synthesis was accomplished by inducing C-C bond formation by Sonogashira coupling of derivatives 9 and 7 followed by olefination with tetrazolylsulfone 8 under Julia-Kocienski conditions, macrocyclization, and subsequent Lacey-Dieckmann condensation to form the tetramic acid unit. As indicated by extensive 1H and 13C NMR spectroscopic investigations (DQF-COSY, ROESY spectra), the stereochemistry of synthetic cylindramide (1) corresponds with that of the naturally occurring product. ROE data were used for molecular modeling of the lowest-energy structures for cylindramide.     

Topology Optimization of 3D Elastic Structures Using Boundary Elements

A numerical approach for the topological optimization of 3D linear elastic problems using boundary elements and the topological derivative is presented in this work. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Patchy worm-like micelles: solution structure studied by small-angle neutron scattering

Triblock terpolymers exhibit a rich self-organization behavior including the formation of fascinating cylindrical core-shell structures with a phase separated corona. After crystallization-induced self-assembly of polystyrene-block-polyethylene-block-poly(methyl methacrylate) triblock terpolymers (abbreviated as SEMs = Styrene-Ethylene-Methacrylates) from solution, worm-like core-shell micelles with a patchy corona of polystyrene and poly(methyl methacrylate) were observed by transmission electron microscopy. However, the solution structure is still a matter of debate. Here, we present a method to distinguish in situ between a Janus-type (two faced) and a patchy (multiple compartments) configuration of the corona. To discriminate between both models the scattering intensity must be determined mainly by one corona compartment. Contrast variation in small-angle neutron scattering enables us to focus on one compartment of the worm-like micelles. The results validate the existence of the patchy structure also in solution.     

Bi- to tetravalent glycoclusters: synthesis, structure-activity profiles as lectin inhibitors and impact of combining both valency and headgroup tailoring on selectivity

The emerging functional versatility of cellular glycans makes research on the design of synthetic inhibitors a timely topic. In detail, the combination of ligand (or headgroup or contact site) structure with spatial parameters that depend on topological and geometrical factors underlies the physiological selectivity of glycan-protein (lectin) recognition. We herein tested a panel of bi-, tri- and tetravalent compounds against two plant agglutinins and adhesion/growth-regulatory lectins (galectins). In addition, we examined the impact of headgroup tailoring (converting lactose to 2'-fucosyllactose) in combination with valency increase in two assay types of increasing biorelevance (from solid-phase binding to cell binding). Compounds were prepared using copper-catalysed azide alkyne cycloaddition from peracetylated lactosyl or 2'-fucosyllactosyl azides. Significant inhibition was achieved for the plant toxin with a tetravalent compound. Different levels of sensitivity were noted for the three groups of the galectin family. The headgroup extension to 2'-fucosyllactose led to a selectivity gain, especially for the chimera-type galectin-3. Valency increase established discrimination against the homodimeric proteins, whereas the combination of valency with the headgroup extension led to discrimination against the tandem-repeat-type galectin-8 for chicken galectins but not human galectins-3 and -4. Thus, detailed structure-activity profiling of glycoclusters combined with suitably modifying the contact site for the targeted lectin will help minimize cross-reactivity among this class of closely related proteins.     

Chemical details on nucleolipid supramolecular architecture: molecular modeling and physicochemical studies

Nucleolipids are currently under investigation as vectors for oligonucleotides (ON) delivery thanks to their supramolecular organization properties and their ability to develop specific interactions (i.e., stacking and potential Watson and Crick hydrogen bonds) for lipoplexes formation. To investigate the factors that govern the interaction events at a molecular level and optimize nucleolipid chemical structures, physicochemical experiments (tensiometry, AFM, BAM, and ellipsometry) combined with molecular dynamics simulation were performed on a series of zwitterionic nucleolipids (PUPC, DPUPC, PAPC) featuring a phosphocholine chain (PC). After construction and initial equilibration, simulations of pure nucleolipid bilayers were run for 100 ns at constant temperature and pressure, and their properties were compared to experimental data and to natural dipalmitoylphosphatidylcholine (DPPC) bilayers. Nucleolipid-based membranes are significantly more ordered and compact than DPPC bilayers mainly due to the presence of many intermolecular interactions between nucleoside polar heads. The hydrophilic phosphocholine moieties connected to the 5' hydroxyls are located above the bilayers, penalizing nucleic bases accessibility for further interactions with ON. Hence, a neutral nucleolipid (PUOH) without hydrophilic phosphocholine was inserted in the membranes. Simulations and experimental analysis of nucleolipid membranes in interaction with a single strand RNA structure indicate that PUOH interacts with ON in the subphase. This study demonstrates that molecular modeling can be used to determine the interactions between oligonucleotide and nucleolipids.     

Self-assembly of model amphiphilic Janus particles

We apply molecular dynamics simulations to investigate the structure formation of amphiphilic Janus particles in the bulk phase. The Janus particles are modeled as (soft) spheres composed of a hydrophilic and hydrophobic part. Their orientation is described by a vector representing an internal degree of freedom. Investigating energy fluctuations and cluster size distributions, we determine the aggregation line in a temperature-density-diagram, where the reduced temperature is an inverse measure for the anisotropic coupling. Below this aggregation line clusters of various sizes depending on density and reduced temperature are found. For low densities in the range ρ? ≤ 0.3, the cluster size distribution has a broad maximum, indicating simultaneous existence of various cluster sizes between 5 and 10. We find no hint of a condensation transition of these clustered systems. In the case of higher densities (ρ? = 0.5 and 0.6), the cluster size distribution shows an extremely narrow peak at clusters of size 13. In these icosahedrons, the particles are arranged in a closed-packed manner, thereby maximizing the number of bonds. Analyzing the translational mean-square displacement we also observe indications of hindered diffusion due to aggregation.     

Eine Rinde erobert die Welt

The quinine‐containing bark of Cinchona trees was probably the most valuable drug the Americas gave to the world. For centuries it was the only remedy against malaria and still is heavily used for that purpose. The isolation, structure determination and total synthesis of quinine are all chemical masterpieces. Today, Cinchona alkaloids are not only used for the treatment of various diseases but also are very powerful catalysts and auxiliary compounds in the synthesis of pure enantiomers in chemical and pharmaceutical industry. Last but not least, a pinch of quinine bestows tonic water and several classical cocktails that little extra that we enjoy. So Cheers to all drinks containing this wonderful alkaloid, no matter whether stirred or shaken.     

Competition between ligands for Al2O3 in aqueous solution

The adsorption of two classes of carboxylic ligands (i.e., aliphatic and aromatic small molecules), onto α-alumina nanoparticles was investigated. A new methodology was used whereby two molecules were simultaneously equilibrated with the inorganic material. A two-dimensional representation of the adsorption of the two complexing molecules enables us to differentiate between pairs of ligands with (i) independent adsorption on different sites of the alumina particles, (ii) competing adsorption on the same sites, or (iii) a mix thereof. Both the highest affinity ligands (tetracarboxylic acid, citric acid, and tiron), and the way they compete with lower affinity ligands have been identified. The combination of carbon skeleton and complexing groups required to produce the ligand of highest affinity at pH 5 has been recognized. In particular, the role of the OH in the α position of a carboxylic group and the role of the distance between two carboxylic groups are emphasized.