Synthesis of Novel Chiral C 2-symmetric Diaza-18-crown-6 Ether Derivatives and their Enantioselective Recognition of Amino Acid Derivatives

New chiral diaza-18-crown-6 ether derivatives, 5 and 6 were synthesized from (R)-(-)-2-amino-1-bütanol. These chiral artificial receptors exhibit pronounced chiral recognition toward the enantiomers of l- and d- amino acid derivatives. The highest enantioselectivity was observed in the case of Trp-OMe·HCl (K_D/K_L=12.5).     

New polyphenylene‐g‐polystyrene and polyphenylene‐g‐polystyrene/poly(ε‐caprolactone) copolymers by combined controlled polymerization and cross‐coupling processes

1,4‐Dibromo‐2‐(bromomethyl)benzene and 1,3‐dibromo‐5‐(bromomethyl)benzene were used as initiators in the atom transfer radical polymerization of styrene in conjunction with CuBr/2,2′‐bipyridine as a catalyst. The resulting polystyrene (PSt)‐based macromonomers, possessing at one end a 2,5‐dibromophenylene or 3,5‐dibromophenylene moiety, were used in combination with 2,5‐dihexylbenzene‐1,4‐diboronic acid for Suzuki coupling in the presence of Pd(PPh₃)₄ as a catalyst or with the system NiCl₂/2,2′‐bipyridine/triphenylphosphine/Zn for Yamamoto polymerization. Polyphenylenes (PPs) with PSt chains as substitution groups were obtained. The same macromonomers were used in Yamamoto copolycondensation reactions, in combination with a poly(ε‐caprolactone) (PCL) macromonomer, and this resulted in PPs with PSt/PCL side chains. The obtained PPs had good solubility properties in common organic solvents at room temperature similar to those of the starting macromonomers. The new polymers were characterized with ¹H (¹³C) NMR, IR, and gel permeation chromatography. The optical properties of the polymers were monitored with UV and fluorescence spectroscopy. The thermal behaviors of the macromonomers and final PPs were investigated with differential scanning calorimetry and compared. The morphology of PPs containing PSt and PCL blocks was characterized with atomic force microscopy, and a microphase‐separated layered morphology was observed. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 879–896, 2005     

Tuning the surface hydrophobicity of polymer/nanoparticle composite films in the Wenzel regime by composition

Surface hydrophobicity of composite films containing polymer and nanoparticles has been studied as a function of composition. We show that the hydrophobicity can be tuned by adjusting the amount of particles in the two-component system. A sharp transition from a polymer-rich surface to a nanoparticles-rich surface was observed with increasing mass fraction of particles in spin-coated thin films. Water drops on the films did not slide down even at tilt angles of 90 degrees . Contact angle hysteresis increased with the mass fraction of particles indicating that the surface roughness increased as the surfaces remained in the Wenzel regime. Contact angle hysteresis data were quantitatively consistent with predictions of a recent theory.     

Molecular dynamics simulations of DiI-C18(3) in a DPPC lipid bilayer

We performed a 40 ns simulation of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI-C18(3)) in a 1,2-dipalmitoyl-sn-glycero-3-phosphatidyl choline (DPPC) bilayer in order to facilitate interpretation of lipid dynamics and membrane structure from fluorescence lifetime, anisotropy, and fluorescence correlations spectroscopy (FCS). Incorporation of DiI of 1.6 to 3.2 mol% induced negligible changes in area per lipid but detectable increases in bilayer thickness, each of which are indicators of membrane structural perturbation. The DiI chromophore angle was 77 +/- 17 degrees with respect to the bilayer normal, consistent with rotational diffusion inferred from polarization studies. The DiI headgroup was located 0.63 nm below the lipid head group-water interface, a novel result in contrast to some popular cartoon representations of DiI but consistent with DiI's increase in quantum yield when incorporated into lipid bilayers. Importantly, the fast component of rotational anisotropy matched published experimental results demonstrating that sufficient free volume exists at the sub-interfacial region to support fast rotations. Simulations with non-charged DiI head groups exhibited DiI flip-flop, demonstrating that the positively-charged chromophore stabilizes the orientation and location of DiI in a single monolayer. DiI induced detectable changes in interfacial properties of water ordering, electrostatic potential, and changes in P-N vector orientation of DPPC lipids. The diffusion coefficient of DiI (9.7 +/- 0.02 x 10(-8) cm2 s(-1)) was similar to the diffusion of DPPC molecules (10.7 +/- 0.04 x 10(-8) cm2 s(-1)), supporting the conclusion that DiI dynamics reflect lipid dynamics. These results provide the first atomistic level insight into DiI dynamics, results essential in elucidating lipid dynamics through single molecule fluorescence studies.     

Cyclic dominance in adaptive networks

The Rock-Paper-Scissors (RPS) game is a paradigmatic model for cyclic dominance in biological systems. Here we consider this game in the social context of competition between opinions in a networked society. In our model, every agent has an opinion which is drawn from the three choices: rock, paper or scissors. In every timestep a link is selected randomly and the game is played between the nodes connected by the link. The loser either adopts the opinion of the winner or rewires the link. These rules define an adaptive network on which the agents’ opinions coevolve with the network topology of social contacts. We show analytically and numerically that nonequilibrium phase transitions occur as a function of the rewiring strength. The transitions separate four distinct phases which differ in the observed dynamics of opinions and topology. In particular, there is one phase where the population settles to an arbitrary consensus opinion. We present a detailed analysis of the corresponding transitions revealing an apparently paradoxical behavior. The system approaches consensus states where they are unstable, whereas other dynamics prevail when the consensus states are stable.     

Synthesis and characterization of a new semi-interpenetrating polymer network hydrogel obtained by gamma radiations

A new polyacrylic acid/polyhydroxybutyrate semi-interpenetrating polymer network hydrogel, the s-IPN/PAA-PHB, was prepared by a gamma radiation-induced polymerization. Thermal behavior was studied by thermogravimetric analysis (TG) and Differential scanning calorimetry (DSC), while the s-IPNs composition, FTIR spectra, and swelling kinetics were also determined. It was found that the DSC curve showed a melting point which is attributed to polyhydroxybutyrate. The TG curves showed various stages of degradation which are in correspondence of the presence of crosslinked polyacrylic acid and confirmed the higher thermal stability of the polymer network. The s-IPN/PAA-PHB composition was 10% of PHB and 90% of PAA. Moreover, the network reached approximately 600% of swelling in water, so it behaves like a superabsorbent hydrogel.     

Inclusion complexes of ketoconazole with beta-cyclodextrin: physicochemical characterization and in vitro dissolution behaviour of its vaginal suppositories

Ketoconazole (KZ) is an imidazole antifungal agent which is administered topically and also orally. KZ is practically insoluble in water. Vaginal candidiasis is a common condition and up to 75% of all women have at least one episode of this infection during their lifetime. The aim of study was to prepare KZ/β-cyclodextrin (β-CD) complex to improve the physicochemical properties of KZ and to investigate the possibility of preparing vaginal suppositories with the complexes. A linear increase in KZ solubility as a function of β-CD concentration was verified using the phase-solubility diagram. The resulting diagram was classified as A_L-type, is generally related to the formation of a soluble complex. Complexes were prepared in a 1:1 molar ratio by different methods, namely freeze-drying, spray-drying, co-evaporation and kneading. Characterization of the complexes prepared was performed by practical yield %, aqueous solubility, active agent amount analyses, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD) and ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy. Characterization studies provided additional evidences of complexation. The paddle method defined in USP31 was used in in vitro dissolution experiments on the prepared vaginal suppositories. It was found that solubility enhancement by preparing KZ/β-CD complexes depends on the type of the preparation method. Dissolution of KZ from complexes was found to be faster than the active agent and the commercial suppositories. This result may be attributed to the interactions between β-CD and active agent, high energetic amorphous state and decrease in the interfacial tension between insoluble active agent and dissolution media.     

Inclusion complexes of fluconazole with β-cyclodextrin: physicochemical characterization and in vitro evaluation of its formulation

Fluconazole (FZ) is a triazole antifungal drug administered orally or intravenously. It is employed for the treatment of mycotic infections. However, the efficacy of FZ is limited with its poor aqueous solubility and low dissolution rate. One of the important pharmaceutical advantages of cyclodextrins is to improve pharmacological efficacy of drugs due to increasing their aqueous solubility. The aim of present study was to prepare an inclusion complex of FZ and β-cyclodextrin (β-CD) to improve the physicochemical and biopharmaceutical properties of FZ. The effects of β-CD on the solubility of FZ were investigated according to the phase solubility technique. Complexes were prepared with 1:1 M ratio by different methods namely, freeze-drying, spray-drying, co-evaporation and kneading. For the characterization of FZ/β-CD complex, FZ amount, practical yield %, thermal, aqueous solubility, XRD, FT-IR and NMR (¹H and ¹³C) analysis were performed. In vitro dissolution from hard cellulose capsules containing FZ/β-CD complexes was compared to pure FZ and its commercial capsules and evaluated by f₁ (difference) and f₂ (similarity) factors. Paddle method defined in USP 31 together with high pressure liquid chromatographic method were used in in vitro dissolution experiments. It was found that solubility enhancement by FZ/β-CD complexes depends on the type of the preparation method. High release of active agent from hard cellulose capsules prepared with β-CD complexes compared to commercial capsules was attributed to the interactions between β-CD and active agent, high energetic amorphous state and inclusion complex formation.     

Pd(II) complexes of novel phosphine ligands: Synthesis,characterization, and catalytic activities on Heck reaction

Novel phosphine oxides, (((3-methylpyridin-2-yl)amino)methyl)diphenylphosphine oxide (1) and diphenyl((pyrazin-2-ylamino)methyl)phosphine oxide (2), were synthesized and characterized. Phosphines ligands (3 and 4) were obtained by the reduction of 1 and 2 with AlH₃, monitored by ³¹P NMR spectroscopy. Pd(II) complexes of 3 and 4 were synthesized and characterized (5 and 6). The catalytic activity of 5 and 6 was tested on the reaction of styrene with both activated and deactivated aryl bromides in air. The results of the catalytic experiments were discussed through DFT calculations.