Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies.

The chemical synthesis of molecular probes to identify and study membrane proteins involved in the biological pathway of protein glycosylation is described. Two short-chain glycolipid analogs that mimic the naturally occurring substrate mannosyl phosphoryl dolichol exhibit either photoreactive and clickable properties or allow the use of a fluorescence readout. Both probes consist of a hydrophilic mannose headgroup that is linked to a citronellol derivative via a phosphodiester bridge. Moreover, a novel phosphoramidite chemistry-based method offers a straightforward approach for the non-enzymatic incorporation of the saccharide moiety in an anomerically pure form.

Supramolecular Organization of Dye Molecules in Zeolite L Channels: Synthesis, Properties, and Composite Materials.

Sequential insertion of different dyes into the 1D channels of zeolite L (ZL) leads to supramolecular sandwich structures and allows the formation of sophisticated antenna composites for light harvesting, transport, and trapping. The synthesis and properties of dye molecules, host materials, composites, and composites embedded in polymer matrices, including two- and three-color antenna systems, are described. Perylene diimide (PDI) dyes are an important class of chromophores and are of great interest for the synthesis of artificial antenna systems. They are especially well suited to advancing our understanding of the structure-transport relationship in ZL because their core fits tightly through the 12-ring channel opening. The substituents at both ends of the PDIs can be varied to a large extent without influencing their electronic absorption and fluorescence spectra. The intercalation/insertion of 17 PDIs, 2 terrylenes, and 1 quaterrylene into ZL are compared and their interactions with the inner surface of the ZL nanochannels discussed. ZL crystals of about 500 nm in size have been used because they meet the criteria that must be respected for the preparation of antenna composites for light harvesting, transport, and trapping. The photostability of dyes is considerably improved by inserting them into the ZL channels because the guests are protected by being confined. Plugging the channel entrances, so that the guests cannot escape into the environment is a prerequisite for achieving long-term stability of composites embedded in an organic matrix. Successful methods to achieve this goal are described. Finally, the embedding of dye-ZL composites in polymer matrices, while maintaining optical transparency, is reported. These results facilitate the rational design of advanced dye-zeolite composite materials and provide powerful tools for further developing and understanding artificial antenna systems, which are among the most fascinating subjects of current photochemistry and photophysics.

Hydrodynamic and Thermophoretic Effects on the Supramolecular Chirality of Pyrene-Derived Nanosheets.

Chiroptical properties of two-dimensional (2D) supramolecular assemblies (nanosheets) of achiral, charged pyrene trimers (Py3 ) are rendered chiral by asymmetric physical perturbations. Chiral stimuli in a cuvette can originate either from controlled temperature gradients or by very gentle stirring. The chiroptical activity strongly depends on the degree of supramolecular order of the nanosheets, which is easily controlled by the method of preparation. The high degree of structural order ensures strong cooperative effects within the aggregates, rendering them more susceptible to external stimuli. The samples prepared by using slow thermal annealing protocols are both CD and LD active (in stagnant and stirred solutions), whereas for isothermally aged samples chiroptical activity was in all cases undetectable. In the case of temperature gradients, the optical activity of 2D assemblies could be recorded for a stagnant solution due to migration of the aggregates from the hottest to the coldest regions of the system. However, a considerably stronger exciton coupling, coinciding with the J-band of the interacting pyrenes, is developed upon subtle vortexing (0.5 Hz, 30 rpm) of the aqueous solution of the nanosheets. The sign of the exciton coupling is inverted upon switching between clockwise and counter-clockwise rotation. The supramolecular chirality is evidenced by the appearance of CD activity. To exclude artefacts from proper CD spectra, the contribution from LD to the observed CD was determined. The data suggest that the aggregates experience asymmetrical deformation and alignment effects because of the presence of chiral flows.

Influence of perylenediimide-pyrene supramolecular interactions on the stability of DNA-based hybrids: Importance of electrostatic complementarity.

Aromatic π-π stacking interactions are ubiquitous in nature, medicinal chemistry and materials sciences. They play a crucial role in the stacking of nucleobases, thus stabilising the DNA double helix. The following paper describes a series of chimeric DNA-polycyclic aromatic hydrocarbon (PAH) hybrids. The PAH building blocks are electron-rich pyrene and electron-poor perylenediimide (PDI), and were incorporated into complementary DNA strands. The hybrids contain different numbers of pyrene-PDI interactions that were found to directly influence duplex stability. As the pyrene-PDI ratio approaches 1:1, the stability of the duplexes increases with an average value of 7.5 °C per pyrene-PDI supramolecular interaction indicating the importance of electrostatic complementarity for aromatic π-π stacking interactions.

Three-component, one-pot sequential synthesis of functionalized cyclazines: 3H-1,2a1,3-triazaacenaphthylenes.

An efficient tandem route to the synthesis of 3H-1,2a(1),3-triazaacenaphthylene derivatives of the cyclazine family has been developed. Target compounds were obtained in moderate to good yields by a Yb(OTf)(3)/Ag(2)CO(3)-catalyzed, three-component domino reaction. This in turn will set the stage for a wide application of this useful reaction for the synthesis of structurally diverse polyheterocyclic skeletons containing the imidazo[1,2-a]pyridine privileged structure.

Design, synthesis and evaluation of monovalent ligands for the asialoglycoprotein receptor (ASGP-R).

A series of novel aryl-substituted triazolyl D-galactosamine derivatives was synthesized as ligands for the carbohydrate recognition domain of the major subunit H1 (H1-CRD) of the human asialoglycoprotein receptor (ASGP-R). The compounds were biologically evaluated with a newly developed competitive binding assay, surface plasmon resonance and by a competitive NMR binding experiment. With compound 1b, a new ligand with a twofold improved affinity to the best so far known D-GalNAc was identified. This small, drug-like ligand can be used as targeting device for drug delivery to hepatocytes.

Trivalent, Gal/GalNAc-containing ligands designed for the asialoglycoprotein receptor.

A series of novel, fluorescent ligands designed to bind with high affinity and specificity to the asialoglycoprotein receptor (ASGP-R) has been synthesized and tested on human liver cells. The compounds bear three non-reducing, beta-linked Gal or GalNAc moieties linked to flexible spacers for an optimal spatial interaction with the binding site of the ASGP-R. The final constructs were selectively endocytosed by HepG2 cells derived from parenchymal liver cells-the major human liver cell type-in a process that was visualized with the aid of fluorescence microscopy. Furthermore, the internalization was analyzed with flow cytometry, which showed the process to be receptor-mediated and selective. The compounds described in this work could serve as valuable tools for studying hepatic endocytosis, and are suited as carriers for site-specific drug delivery to the liver.