Solubilization of Paclitaxel (taxol) by peptoad self-assemblies

A molecular dynamics simulation was carried out involving a paclitaxel molecule, 987 peptoad molecules, and 35 938 water molecules (conditions shown experimentally to effect paclitaxel solubilization in water). The peptoads are shown to form large clumps, the centers of which are dry and thus favorable to hydrogen bonding between paclitaxel and peptoads. Hydrogen-bonding equilibrium among the peptoads themselves in the developing clumps is achieved in 2 ns. The number and position of hydrogen bonds between the paclitaxel and peptoads fluctuate randomly from two to six within a 2-5 ns time frame. Hydrophobic association between the peptoad chains and the apolar paclitaxel groups does not seem to be an important element of the solubilization. Instead, the hydrophobic chains of the peptoads encasing the paclitaxel extend outward into the dry interior of the peptoad clump where other chains in the clump are located. One hopes that studies such as this will ultimately allow rational predictions when designing new and specific drug solubilizers.     

Blends of Aromatic Polyethers Bearing Polar Pyridine Units and Their Evaluation as High Temperature Polymer Electrolytes

Aromatic polyethers containing polar pyridine units in the main chain have been synthesized using different difluoride monomers. Copolymers of 2,5-(4′,4″dihydroxy biphenyl)-pyridine and 3,3′,5,5′-tetramethyl-[1,1′-biphenyl]-4,4′-diol with bis(4-fluorophenyl) sulfone or phenyl phosphine oxide difluoride or decafluorobiphenyl (PTMPySF, PTMPyPO, PTMPyDF) were synthesized. These polymeric structures despite their common structural characteristics, showed totally different behavior in terms of solubility and acid doping ability. Blends of these copolymers have been prepared in order to be evaluated in terms of fuel cell relevant parameters like acid doping ability and conductivity. In most cases flexible membranes were obtained by solution casting. The acid doping ability was controlled based on the blend constituents and composition. The doped membranes exhibited high conductivity values, in the range of 10⁻³ S/cm at room temperature which is increased at 2.5 × 10⁻² S/cm at temperatures up to 180 °C.     

The interaction of water vapors with H3PO4 imbibed electrolyte based on PBI/polysulfone copolymer blends

The interaction of steam with phosphoric acid imbibed electrolyte composed of PBI/PPy(50)coPSF 50/50 polymer blend and its effect on fuel cell performance was studied regarding its permeability through and its chemical interaction with the membrane. It was found that steam is the only gas that permeates the membrane with a permeability coefficient 1.1 × 10⁻¹⁴ mol cm cm⁻² s⁻¹ Pa⁻¹ at 150 °C. This is attributed either to the high solubility of water in phosphoric acid or to the chemical interaction with pyrophosphoric acid_. The latter was demonstrated by carrying out TGA experiments under various water vapor partial pressures. Water reacts with pyrophosphoric acid in order to maintain the equilibrium concentration of phosphoric acid at high level, thus improving proton conductivity and fuel cell performance. In addition it is shown that excess water dissolves in the membrane thus maintaining the “membrane/acid” system at high hydration level. This depends both on temperature and steam partial pressure. Although in the present study it is shown that steam plays a significant role in the performance of the high temperature Polymer electrolyte membrane (PEM) fuel cell, nevertheless its feed with humidified gases is not necessary, due to the back transport of the water produced at the cathode.     

Rod-coil block copolymers incorporating terfluorene segments for stable blue light emission

Spectroscopic studies on a series of rod-coil block copolymers with terfluorene as the rigid segment demonstrate that the main cause of color instability in fluorene oligomers and polymers is aggregate and/or excimer formation and not the presence alone of keto defects (fluorenone formation) along the molecular chain. Keto defects, when present, contribute to the appearance of the undesirable "green" emission band but are not the leading cause of color instability. Thus, the synthesis of materials where aggregation and/or interchain, intersegment interactions are inhibited is the key approach for the production of stable polymeric light-emitting devices (PLED's). The potential of this method is verified by the synthesis of photooxidative stable fluorene/styrene diblock copolymer blue emitters.     

Eine modificirte Quecksilberluftpumpe

Ohne Zusammenfassung     

Equilibrium distributions of dipalmitoyl phosphatidylcholine and dilauroyl phosphatidylcholine in a mixed lipid bilayer: atomistic semigrand canonical ensemble simulations

Conventional molecular dynamics (MD) simulations are seriously limited by the slow rate of diffusive mixing in their ability to predict lateral distributions of different lipid types within mixed-lipid bilayers using atomistic models. A method to overcome this limitation, using configuration-bias Monte Carlo (MC) "mutation" moves to transform lipids from one type to another in dynamic equilibrium, is demonstrated in binary fluid-phase mixtures of lipids whose tails differ in length by four carbons. The hybrid MC-MD method operates within a semigrand canonical ensemble, so that an equilibrium composition of the mixture is determined by a constant difference in chemical potential (Delta(mu)) chosen for the components. Within several nanoseconds, bilayer structures initiated as pure dipalmitoyl phosphatidylcholine (DPPC) or pure dilauroyl phosphatidylcholine (DLPC) converge to a common composition and structure in independent simulations conducted at the same Delta(mu). Trends in bilayer thickness, area per lipid, density distributions across the bilayer, and order parameters have been investigated at three mixture compositions and compared with results from the pure bilayers at 323 K. The mixtures showed a moderate increase in DPPC acyl tail sites crossing the bilayer midplane relative to pure DPPC. Correlations between lateral positions of the two lipid types within or across the bilayer were found to be weak or absent. While the lateral distribution is consistent with nearly ideal mixing, the dependence of composition on Delta(mu) indicates a positive excess free energy of mixing.     

Fully automated flexible docking of ligands into flexible synthetic receptors using forward and inverse docking strategies

The prediction of the structure of host-guest complexes is one of the most challenging problems in supramolecular chemistry. Usual procedures for docking of ligands into receptors do not take full conformational freedom of the host molecule into account. We describe and apply a new docking approach which performs a conformational sampling of the host and then sequentially docks the ligand into all receptor conformers using the incremental construction technique of the FlexX software platform. The applicability of this approach is validated on a set of host-guest complexes with known crystal structure. Moreover, we demonstrate that due to the interchangeability of the roles of host and guest, the docking process can be inverted. In this inverse docking mode, the receptor molecule is docked around its ligand. For all investigated test cases, the predicted structures are in good agreement with the experiment for both normal (forward) and inverse docking. Since the ligand is often smaller than the receptor and, thus, its conformational space is more restricted, the inverse docking approach leads in most cases to considerable speed-up. By having the choice between two alternative docking directions, the application range of the method is significantly extended. Finally, an important result of this study is the suitability of the simple energy function used here for structure prediction of complexes in organic media.     

Comparative study of electrostatic binding vs. complexation of Cu2+ ions with water‐soluble polymers containing styrene sulphonic acid and/or maleic acid units or their sodium salt forms

The interaction of Cu²⁺ ions with the homopolymer poly(styrene sulfonic acid) (PSSH), as well as with the copolymers of maleic acid (MAc) with styrene sulfonic acid (SSH) or vinyl acetate (VAc), was investigated in dilute aqueous solution through turbidimetry, potentiometry, viscometry, and spectrophotometry in the visible region. Cu²⁺ ions were introduced either through neutralization with Cu(OH)₂ of the acid form of the (co)polymers (PSSH, P(SSH‐co‐MAc) and P(VAc‐co‐MAc)) or through mixing of the sodium salt form of the (co)polymers (PSSNa, P(SSNa‐co‐MANa) and P(VAc‐co‐MANa)) with CuSO₄. Turbidimetry, potentiometry, and spectrophotometry revealed that the first carboxylic group of MAc or both carboxylate groups of MANa are involved in the complexation with Cu²⁺ ions when neutralization with Cu(OH)₂ or mixing with CuSO₄ are applied, respectively. The increased values of the reduced viscosity observed mainly at the first stages of neutralization of P(VAc‐co‐MAc) with Cu(OH)₂ indicate that interchain polymer‐Cu²⁺ complexation takes possibly place. Finally, the spectrophotometric behavior observed upon neutralization of P(SSH‐co‐MAc) with Cu(OH)₂ or mixing of P(SSNa‐co‐MANa) with CuSO₄ revealed that the strength of counterion binding by the sulfonate groups is, in fact, comparable with the complexation of Cu²⁺ ions with the carboxylate groups of MAc. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1149–1158, 2008     

Synthesis of alternating polystyrene/poly(ethyleneoxide) branched polymacromonomers

Newly designed PS/PEO alternating branched polymacromonomers have been obtained by polycondensation of alpha-dicarboxy-functionalized polystyrene and alpha-dihydroxy-functionalized polyethyleneoxide. 4-[3,5-Bis(methoxycarbonyl)phenoxymethyl]benzyl bromide was used as atom-transfer radical polymerization (ATRP) initiator for the synthesis of alpha-dicarboxy functionalized polystyrenes. These macromonomers possess low polydispersities and molecular weights in the range of 7000 to 100,000, as proved by gel permeation chromatography (GPC) and 1H NMR. Alpha-dihydroxy functionalized polyethyleneoxide (PEO) was synthesized by treatment of monofunctionalized PEO with 3,5-bis(benzyloxy)benzoyl chloride. Polycondensation of the alpha-dicarboxy PS with the alpha-dihydroxy PEO in solution or in bulk resulted in alternating PS/PEO polymacromonomers, which were effectively purified from the unreacted macromonomers and characterized by using 1H NMR, GPC, thermal analysis, and optical microscopy. Light-scattering measurements in organic solvents like THF or dioxane have shown that these polymacromonomers form stable micelles.