A method for treating the passage of a charged hard sphere ion as it passes through a sharp dielectric boundary

In the implicit solvent models of electrolytes (such as the primitive model (PM)), the ions are modeled as point charges in the centers of spheres (hard spheres in the case of the PM). The surfaces of the spheres are not polarizable which makes these models appropriate to use in computer simulations of electrolyte systems where these ions do not leave their host dielectrics. The same assumption makes them inappropriate in simulations where these ions cross dielectric boundaries because the interaction energy of the point charge with the polarization charge induced on the dielectric boundary diverges. In this paper, we propose a procedure to treat the passage of such ions through dielectric interfaces with an interpolation method. Inspired by the "bubble ion" model (in which the ion's surface is polarizable), we define a space-dependent effective dielectric coefficient, ε(eff)(r), for the ion that overlaps with the dielectric boundary. Then, we replace the "bubble ion" with a point charge that has an effective charge q/ε(eff)(r) and remove the portion of the dielectric boundary where the ion overlaps with it. We implement the interpolation procedure using the induced charge computation method [D. Boda, D. Gillespie, W. Nonner, D. Henderson, and B. Eisenberg, Phys. Rev. E 69, 046702 (2004)]. We analyze the various energy terms using a spherical ion passing through an infinite flat dielectric boundary as an example.     

Synthesen und ungewöhnliche Mesophasensequenzen von Kohlenwasserstoffen eines neuartigen Typs nicht-calamitischer Flüssigkristalle

Abstract

Mehrere Vertreter einer neuen Familie thermotroper, nicht-calamitischer Flüssigkristalle, die p-substituierten, biaxialen und zentrosymmetrischen 1,2,3,5,6,7-Hexakis(phenylethinyl)naphthaline 3a-f, wurden in einer Pd-kataly-sierten CC-Kupplungsreaktion aus dem entsprechenden Hexabromnaphthalin und verschiedenartig monosubstituiertem Acetylen (2a-f) synthetisiert. Diese Synthesemethode stellt ein vielversprechendes, ‘Lego-artiges’ Aufbauprinzip für Mesogene mit flächendeckenden, hoch ungesättigten und konjugierten π-Systemen als neuen Typ von ‘Super-disc-Kernen’ dar. Die stabilen Mesophasenbereiche von 3a-f reichen von c. 42 bis 180 K. Mit einer Ausnahme (3a) zeigen alle neuen Verbindungen eine stabile, fluide N_D-Phase. Während ein Kohlenwasserstoff dieser Serie (3e) sowie der Hexaether 3f nur eine Mesophase ausbilden, zeigen die vier Kohlenwasserstoffe 3a-d Multimesomorphismus mit einer inversen Phasen-sequenz (C → N_D → 2 D → I) bei den mittleren Homologen 3b-d. Beim schnellen Heizen der N_D-Phase des Kohlenwasserstoffs 3d ist kurzfristig eine instabile reentrant-isotrope Phase zu beobachten, die sich in eine columnare Mesophase umwandelt. der Vergleich der Kohlenwasserstoffe 3a-e mit dem Hexaether 3f läßt erstmals bei nicht-calamitischen Flüssigkristallen schlüssig einen elektronischen Effekt von Sauerstoffatomen, den Bindegliedern zwischen den leicht polarisierbaren ‘Super-disc-Kernen’ und den Lateralfunktionen, auf die Stabilität ihrer N_D-Phasen nachweisen. Sauerstoffatome in diesen Positionen stabilisieren die N_D-Phase, oder, mit anderen Worten, destabilisieren columnare Mesophasen.     

Unusual Formation of a β-linked Disaccharide in a Nis Glycosylation

Abstract

The N-halosuccinimide glycosylation is a highly selective reaction that leads to trans-configured 1-alkoxy-2-halo-glycosides (halo = bromo, iodo).²³ As an exception to the generally observed exclusive formation of α-linked glycosides in such reactions,² we obtained a 3 / 1 mixture of α- and β-disaccharide 6 and 7, when we treated the silylated glycal 4 with NIS (N-iodosuccinimide) and the glycoside 5.⁴ The similarly protected arabino glycal 9, on the other hand, gave exclusively the expected α-linked saccharide 11, when treated with NIS and the alcohol component 10.⁵ Silylated glycals 4 and 9 were obtained from L-digitoxal 1 ⁶ and L-rhamnal 8 ⁷ by treatment with tert-butyldiphenylchlorosilane⁸ and tert-butyldimethylchlorosilane,⁹ respectively. In both cases the 3-O-silylated derivatives formed in high yields. Only in case of the ribo-configuration minor amounts of a 4-O-silylated product 3 were identified.     

Assembly of Melleolide Antibiotics Involves a Polyketide Synthase with Cross-Coupling Activity

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Photo-attaching functional polymers to cellulose fibers for the design of chemically modified paper

We introduce a novel approach for preparing polymer-modified and chemically microstructured paper substrates by a photo-chemical attachment of functional polymers to cellulose microfibers inside model filter papers. Poly(methyl methacrylate), PMMA copolymers, which carry a defined amount of photo-reactive benzophenone functional groups, are adsorbed to paper substrates from solution by a simple dip coating process, followed by covalent attachment of the physisorbed polymers through UV-light irradiation. Non-bound macromolecules can be removed from paper sheets by simple solvent extraction, and the resulting polymer-modified substrates were analysed with respect to chemical identity, attached polymer mass, and homogeneity of the polymer attachment. The amount of paper-attached polymers can be conveniently controlled in a wide range from a few mg/g cellulose fiber up to several tenth of mg/g cellulose fiber, by adjusting the polymer concentration in the coating solution. Polymers are being attached by photo-chemical means, and chemical micro patterns on paper can be designed by lithographical means. In first proof-of-concept studies, millimeter-scale channels were prepared that can be used to control fluid penetration by capillary actions. Because of the modularity in the design of photo-reactive polymers, a number of different chemically microstructured papers can be envisioned which may become potentially interesting in lab-on-paper devices.     

Synthesis and Reactions of Anhydro-Azido-thio-D-lyxofuranosides 1

2,5-anhydro-3-azido-2-thio-D-lyxofuranosides and 3,5-anhydro-2-azido-3-thio-D-lyxofuranosides were prepared from methyl D-xylofuranoside or methyl D-ribofuranoside via corresponding 2,3-epoxysugars or the 5-O-trityl derivative. The sulfur was introduced into molecules by use of the thio-Mitsunobu reaction. Bicyclic azido-thiosugars were transformed into nucleoside analogues, oxidized to sulfoxides and sulfones, and reduced to bicyclic amino-thiosugars. Structures and configurations of products were determined by NMR spectroscopy or X-ray structure analyses.     

On the Nature of Interactions between Ionic Liquids and Small Amino‐Acid‐Based Biomolecules

During the last decade, ionic liquids (ILs) have revealed promising properties and applications in many research fields, including biotechnology and biological sciences. The focus of this contribution is to give a critical review of the phenomena observed and current knowledge of the interactions occurring on a molecular basis. As opposed to the huge advances made in understanding the properties of proteins in ILs, complementary investigations dealing with interactions between ILs and peptides or oligopeptides are underrepresented and are mostly only of phenomenological nature. However, the field has received more attention in the last few years. This Review features a meta‐analysis of the available data and findings and should, therefore, provide a basis for a scientifically profound understanding of the nature and mechanisms of interactions between ILs and structured or nonstructured peptides. Fundamental aspects of the interactions between different peptides/oligopeptides and ILs are complemented by sections on the experimental (spectroscopy, structural biology) and theoretical (computational chemistry) possibilities to explain the phenomena reported so far in the literature. In effect, this should lead to the development of novel applications and support the understanding of IL–solute interactions in general.     

Natural products as DNA methyltransferase inhibitors: a computer-aided discovery approach

DNA methyltransferases (DNMTs) represent promising targets for the development of unique anticancer drugs. However, all DNMT inhibitors currently in clinical use are nonselective cytosine analogs with significant cytotoxic side-effects. Several natural products, covering diverse chemical classes, have indicated DNMT inhibitory activity, but these effects have yet to be systematically evaluated. In this study, we provide experimental data suggesting that two of the most prominent natural products associated with DNA methylation inhibition, (−)-epigallocathechin-3-gallate (EGCG) and curcumin, have little or no pharmacologically relevant inhibitory activity. We therefore conducted a virtual screen of a large database of natural products with a validated homology model of the catalytic domain of DNMT1. The virtual screening focused on a lead-like subset of the natural products docked with DNMT1, using three docking programs, following a multistep docking approach. Prior to docking, the lead-like subset was characterized in terms of chemical space coverage and scaffold content. Consensus hits with high predicted docking affinity for DNMT1 by all three docking programs were identified. One hit showed DNMT1 inhibitory activity in a previous study. The virtual screening hits were located within the biological-relevant chemical space of drugs, and represent potential unique DNMT inhibitors of natural origin. Validation of these virtual screening hits is warranted.     

Mechanism-based inactivation by aromatization of the transaminase BioA involved in biotin biosynthesis in Mycobaterium tuberculosis

BioA catalyzes the second step of biotin biosynthesis, and this enzyme represents a potential target to develop new antitubercular agents. Herein we report the design, synthesis, and biochemical characterization of a mechanism-based inhibitor (1) featuring a 3,6-dihydropyrid-2-one heterocycle that covalently modifies the pyridoxal 5'-phosphate (PLP) cofactor of BioA through aromatization. The structure of the PLP adduct was confirmed by MS/MS and X-ray crystallography at 1.94 ? resolution. Inactivation of BioA by 1 was time- and concentration-dependent and protected by substrate. We used a conditional knock-down mutant of M. tuberculosis to demonstrate the antitubercular activity of 1 correlated with BioA expression, and these results provide support for the designed mechanism of action.