A cross-linked reverse micelle-encapsulated palladium catalyst

Cross-linked reverse micelle-palladium catalysts are effective and stable cross-coupling catalysts; cross-linking is crucial for stability.     

Solvent effects on the screening of parallel combinatorial libraries for selectors for chiral chromatography

The correlation between the resin-swelling property and the outcome of the crucial equilibration assay used in our parallel library screening method is investigated. It is found that the incorporation of CHCl3 (an effective swelling solvent for both the polystyrene and TentaGel resins) into the equilibration solvent leads to faster equilibration and thus shorter library screening time. The outcome of the equilibration experiment is also found to depend on the chemical nature of the solid base resins. It appears that polystyrene resin, which has a relatively inert surface, provides higher enantioselectivity than the polar TentaGel resin. The importance of a thoroughly swelled resin for the direct assay of functional groups on the resin is demonstrated.     

Thermoreversible,epitaxial fcc<-->bcc transitions in block copolymer solutions

Uncharged block copolymer micelles display thermoreversible transitions between close-packed and bcc lattices for a range of concentration, solvent selectivity, and copolymer composition. Using small-angle x-ray scattering on shear-oriented solutions, highly aligned fcc crystals are seen to transform epitaxially to bcc crystals, with fcc/bcc orientational relationships that are well established in martensitic transformations in metals. The transition is driven by decreasing solvent selectivity with increasing temperature, inducing solvent penetration of the micellar core.     

Incorporating protein flexibility in structure-based drug discovery: using HIV-1 protease as a test case

We have developed a receptor-based pharmacophore method which utilizes a collection of protein structures to account for inherent protein flexibility in structure-based drug design. Several procedures were systematically evaluated to derive the most general protocol for using multiple protein structures. Most notably, incorporating more protein flexibility improved the performance of the method. The pharmacophore models successfully discriminate known inhibitors from drug-like non-inhibitors. Furthermore, the models correctly identify the bound conformations of some ligands. We used unliganded HIV-1 protease to develop and validate this method. Drug design is always initiated with a protein-ligand structure, and such success with unbound protein structures is remarkable - particularly in the case of HIV-1 protease, which has a large conformational change upon binding. This technique holds the promise of successful computer-based drug design before bound crystal structures are even discovered, which can mean a jump-start of 1-3 years in tackling some medically relevant systems with computational methods.     

A ditopic azacryptate proton cage

A tosylated azacryptand readily protonates at the bridgehead amines, becoming a potential ditopic anion receptor. The in-in conformation of the amines facilitates encapsulation of two bromide guests and represents the first structural evidence that a proton cage cryptate can bind two anions internally.     

The role of analogue ions in the ion-pair reversed-phase chromatography of quaternary ammonium compounds

The choice of analogue ion of the mobile phase additive is shown to significantly affect the analysis of quaternary ammonium compounds (QACs) in ion-pair reversed-phase high-performance liquid chromatography. A series of bromide-containing and dodecyl-sulfate-containing mobile phase additives are investigated using two QAC probe analytes. In all instances, the quaternary-ammonium-containing mobile phase additives perform better than the corresponding sodium-containing additives for effective QAC elution. These results indicate that the structure of the analogue ion, not just its formal charge, is important in the reversed-phase ion-pair chromatography of these compounds. The relative elution order of the QAC probe analytes is also influenced by the counter ions of the mobile phase additives, with bromide and dodecyl sulfate offering opposite elution orders.     

Nanotube-vesicle networks with functionalized membranes and interiors

We describe nanotube-vesicle networks with reconstituted membrane protein from cells and with interior activity defined by an injection of microparticles or molecular probes. The functionality of a membrane protein after reconstitution was verified by single-channel ion conductance measurements in excised inside-out patches from the vesicle membranes. The distribution of protein, determined by fluorescence detection, in the network membrane was homogeneous and could diffuse via a nanotube connecting two vesicles. We also show how injecting small unilamellar protein-containing vesicles can differentiate the contents of individual containers in a network. The combination of membrane activity and interior activity was demonstrated by ionophore-assisted accumulation, and internal Calcium Green-mediated detection, of Ca2+ within a single network container. This system can model a variety of biological functions and complex biological multicompartment structures and might serve as a platform for constructing complex sensor and computational devices.