Quinacrine enhances vesicular stomatitis virus inactivation and diminishes hemolysis of dimethylmethylene blue-phototreated red cells

Several photodynamic methods for virus inactivation in red blood cell (RBC) suspensions have resulted in unwanted hemolysis during extended 1-6 degrees C storage. To explore the possibility that hemolysis may be mediated by a membrane-bound dye, a molecule similar in structure to yet different in light absorption properties from the photosensitizer was used as an inhibitor for RBC membrane binding in virus photoinactivation and photohemolysis studies. The addition of 500 pM quinacrine to oxygenated RBC before treatment with 3.6 microM dimethylmethylene blue (DMMB) and 219 mJ/cm2 red light resulted in an increased extracellular concentration of the sensitizer, increased extracelluar viral inactivation kinetics, and decreased hemolysis during 1-6 degrees C storage without alteration of quinacrine absorption properties. These results collectively suggest that despite its recognized affinity for viral nucleic acid, DMMB also binds to RBC membranes and that the bound dye is, in part, responsible for photoinduced hemolysis.     

TMV microarrays: hybridization-based assembly of DNA-programmed viral nanotemplates

The intrinsic ability of biological molecules to self-organize into complex structures has the potential to revolutionize methods for the assembly of nanomaterials and devices. In this work, nucleic acid hybridization was used to simultaneously assemble different Tobacco mosaic virus (TMV) nanotemplates onto a glass substrate patterned with address specific capture DNAs. To accomplish this, TMV-based nanotemplates were programmed with linker DNAs containing sequence specific addresses and hybridized directly to the capture DNAs. This assembly process proved to be a reliable, selective, and controllable means to assemble multiple TMV nanotemplates.     

Toward the synthesis of norzoanthamine: complete fragment assembly

The complex marine alkaloid norzoanthamine (2) was envisioned to be assembled from three key building blocks: the C1-C5 fragment A, the C6-C10 fragment B, and the C11-C24 fragment C. The synthesis of fragment A was achieved in 14 steps and 33% overall yield from (R)-gamma-hydroxymethyl-gamma-butyrolactone. Fragment B was made in two steps from PMB-protected 4-pentynol in 76% yield. The C11-C24 fragment C was made from (S)-carvone via (R)-isocarvone in 18 steps (6% overall yield). The convergent stereoselective synthesis of the entire carbon framework (C1-C24) of the target molecule was achieved via the following assemblage. Alkenyl iodide 20 derived from the C11-C24 fragment C was coupled to fragment B (C6-C10) through a high-yielding Stille coupling reaction of these two sterically very demanding coupling partners, affording the key Diels-Alder precursor 24. The intramolecular Diels-Alder reaction proceeded smoothly in excellent yield and diastereoselectivity, generating the tricyclic trans-anti-trans perhydrophenanthrene motif of norzoanthamine (C6-C24). The final fragment coupling between lithiated fragment A (C1-C5) and aldehyde 40 (C6-C24) has also been successfully accomplished affording the entire carbon framework of the natural product.     

Thioglycuronides: synthesis and application in the assembly of acidic oligosaccharides

[reaction: see text] Partially protected thioglycuronic acids are prepared efficiently by chemo- and regioselective oxidation of the corresponding thioglycosides using the TEMPO/BAIB reagent combination. After esterification, the thioglycuronic acids proved to be useful as both donor and acceptor in sulfonium-mediated condensations toward acidic di- and trisaccharides.     

Hydrogen-bonding-mediated vesicular assembly of functionalized naphthalene-diimide-based bolaamphiphile and guest-induced gelation in water

This paper describes the spontaneous vesicular assembly of a naphthalene-diimide (NDI)-based non-ionic bolaamphiphile in aqueous medium by using the synergistic effects of π-stacking and hydrogen bonding. Site isolation of the hydrogen-bonding functionality (hydrazide), a strategy that has been adopted so elegantly in nature, has been executed in this system to protect these moieties from the bulk water so that the distinct role of hydrogen bonding in the self-assembly of hydrazide-functionalized NDI building blocks could be realized, even in aqueous solution. Furthermore, the electron-deficient NDI-based bolaamphiphile could engage in donor-acceptor (D-A) charge-transfer (CT) interactions with a water-insoluble electron-rich pyrene donor by virtue of intercalation of the latter chromophore in between two NDI building blocks. Remarkably, even when pyrene was located between two NDI blocks, intermolecular hydrogen-bonding networks between the NDI-linked hydrazide groups could be retained. However, time-dependent AFM studies revealed that the radius of curvature of the alternately stacked D-A assembly increased significantly, thereby leading to intervesicular fusion, which eventually resulted in rupturing of the membrane to form 1D fibers. Such 2D-to-1D morphological transition produced CT-mediated hydrogels at relatively higher concentrations. Instead of pyrene, when a water-soluble carboxylate-functionalized pyrene derivative was used as the intercalator, non-covalent tunable in-situ surface-functionalization could be achieved, as evidenced by the zeta-potential measurements.     

Membrane processing of oily streams. Wastewater treatment and waste reduction

The use of membranes to treat oil–water emulsions is increasing, especially in applications where the value of the recovered materials is high, e.g., recycling aqueous cleaners and machining coolants. For separation of oil emulsions as an end-of-pipe treatment, membranes are more likely where process volumes are less than 50 000 gal (190 m³) per day. Membranes could also be useful in a hybrid system when it is combined with conventional chemical treatment systems to concentrate sludges. This review describes several case studies of these applications, and discusses the possible pitfalls and potential of in applying membranes to the treatment of oily wastes.     

Bio-directed synthesis and assembly of nanomaterials

This tutorial review provides an overview of bio-directed synthesis of nanomaterials, starting with the foundation of biomineralization research--how organisms are able to biomineralize materials in vivo--and progressing to studies of biomineralization in vitro. This research is of interest to biologists, chemists and materials scientists alike, especially in light of efforts to find 'greener' methods of inorganic material synthesis. Examples of applications of nanomaterials synthesized by these methods are provided to demonstrate the end goals of biomineralization research.     

Chemical synthesis of intentionally misfolded homogeneous glycoprotein: a unique approach for the study of glycoprotein quality control

Biosynthesis of glycoproteins in the endoplasmic reticulum employs a quality control system, which discriminates and excludes misfolded malfunctional glycoproteins from a correctly folded one. As chemical tools to study the glycoprotein quality control system, we systematically synthesized misfolded homogeneous glycoproteins bearing a high-mannose type oligosaccharide via oxidative misfolding of a chemically synthesized homogeneous glycopeptide. The endoplasmic reticulum folding sensor enzyme, UDP-glucose:glycoprotein glucosyltransferase (UGGT), recognizes a specific folding intermediate, which exhibits a molten globule-like hydrophobic nature.     

Para-acyl-calix[9]arenes: synthesis and interfacial assembly

The synthesis of a series of five para-acyl-calix[9]arenes has been achieved with total substitution as shown by MALDI-TOF mass spectrometry. All compounds form stable monolayers at the air–water interface, with apparent molecular areas between 200 and 330 Å².     

Peptide inhibitors of viral assembly: a novel route to broad-spectrum antivirals

We investigated the potential of small peptide segments to function as broad-spectrum antiviral drug leads. We extracted the α-helical peptide segments that share common secondary-structure environments in the capsid protein-protein interfaces of three unrelated virus classes (PRD1-like, HK97-like, and BTV-like) that encompass different levels of pathogenicity to humans, animals, and plants. The potential for the binding of these peptides to the individual capsid proteins was then investigated using blind docking simulations. Most of the extracted α-helical peptides were found to interact favorably with one or more of the protein-protein interfaces within the capsid in all three classes of virus. Moreover, binding of these peptides to the interface regions was found to block one or more of the putative "hot spot" regions on the protein interface, thereby providing the potential to disrupt virus capsid assembly via competitive interaction with other capsid proteins. In particular, binding of the GDFNALSN peptide was found to block interface "hot spot" regions in most of the viruses, providing a potential lead for broad-spectrum antiviral drug therapy.     

Membrane receptor probes: solid-phase synthesis of biotin-Asp-PEG-arvanil derivatives

[structure: see text] A modular, flexible solid-phase synthetic route for the preparation of biotinylated cross-linking probes of membrane receptors is described. The route utilizes an orthogonal protection strategy employing a Pd[0] cleavable allyl linker attached to the probe via an aspartate residue. The versatility of the method is illustrated through the synthesis of a number of arvanil-derived cannabinoid receptor ligands displaying either a photoaffinity or a chemical cross-linking group.     

Total synthesis of laulimalide: assembly of the fragments and completion of the synthesis of the natural product and a potent analogue

Herein, we present a full account of our efforts to couple the northern and the southern building blocks, the synthesis of which were described in the preceding paper, along with the modifications required to ultimately lead to a successful synthesis of laulimalide. Key highlights include an exceptionally efficient and atom-economical intramolecular ruthenium-catalyzed alkene-alkyne coupling to build the macrocycle, followed by a highly stereoselective 1,3-allylic isomerization promoted by a rhenium complex. Interestingly, the designed synthetic route also allowed us to prepare an analogue of the natural product that possesses significant cytotoxic activity. We also report a second generation route that provides a more concise synthesis of the natural product.     

Monodisperse nanocrystals: general synthesis, assembly, and their applications

This article summarizes the recent advances in the synthesis, assembly and applications of monodisperse nanocrystals, which may be suggestive for the designed synthesis and assemblies of target nanocrystals according to practical requirements.     

One-pot synthesis and characterization of a chromophore--donor--acceptor assembly

The acid-functionalized tris-heteroleptic chromophore--donor--acceptor assembly [RuII(bpyCOOH)(bpyCH2PTZ)(bpyCH2MV2+)](PF6)4]4+ (1) (bpyCOOH = 4'-methyl-2,2'-bipyridine-4-carboxylic acid; bpyCH2PTZ = 10-((4'-methyl-2,2'-bipyridin-4-yl)methyl)phenothiazine; bpyCH2MV2+ = 1-((4'-methyl-2,2'-bipyridin-4-yl)methyl)-1'-methyl- 4,4'-bipyridinediium) was synthesized in a one-pot reaction by careful selection of the order of ligand addition to RuCl2(DMSO)4 (DMSO = dimethyl sulfoxide). The success of this method was based upon separation and isolation of 1 from mixtures containing ligand-scrambled products by cation exchange chromatography. Metal-to-ligand charge-transfer (MLCT) excitation in acetonitrile at 464 nm was followed by intramolecular electron transfer to give a redox-separated state [RuII(bpyCOOH)(bpyCH2PTZ.+)(bpyCH2MV.+)]4+ with an efficiency of eta RS = 0.35 +/- 0.05.     

Towards the total synthesis of FD-838: modular enantioselective assembly of the core

A rapid assembly of the tetracyclic core of FD-838, featuring a catalytic asymmetric Stetter reaction, is described.     

Iterative molecular assembly based on the cation-pool method. Convergent synthesis of dendritic molecules

An iterative method for molecular assembly has been developed based on the cation-pool method using (trimethylsilyl)diphenylmethane as a building block. The silyl group works as both an activating group of the benzene ring in the Friedel-Crafts type reaction and an electroauxiliary in the subsequent low temperature anodic oxidation to generate dendritic diarylcarbenium ions, which were well characterized by low-temperature NMR spectroscopy. The convergent synthesis of dendritic molecules has been achieved by repeating the sequence.