C11 Alkyl Chain Research Articles

Chemical Conformation Induced Transport Carrier Switching in Molecular Junction based on Carboxylic-Terminated Thiol Molecules

The paper demonstrates the effect of the chemical conformation of the -COOH group on the transport characteristic including conductance, rectification, and length effect in molecular junctions (MJs) formed by self-assembled monolayers of carboxylic-terminated thiol molecules. For an alkyl chain shorter than C11, the transport mechanism was attributed to a direct off-resonant tunneling of a hole carrier, located at the Au-S interface, whereas a hopping mechanism was assigned to the alkyl chain longer than the C11 chain located at the -COOH group. The hopping mechanism may be operated by electron transport associated with the breaking of the -OH bonding likely driven by a voltage. Importantly, at the C11 alkyl chain, we observed that the transport carrier operating in MJs could change from a hole carrier into an electron carrier. The result strongly proves that the chemical conformation should be considered in analyzing molecular electronics and provides a basis for the rational design of molecular electronic devices.

Controlled Self-Assembly of Multiple-Responsive Superamphiphilc Polymers Based on Host-Guest Inclusions of a Modified PEG with β-Cyclodextrin.

Superamphiphilic polymers (SAPs) constructed by host-guest inclusion can self-assemble into various nanostructures in solution, which can find applications in many fields such as nanodevices, drug delivery, and template synthesis. Herein, we report the controlled self-assembly of multiple-responsive SAP based on a selective host-guest inclusion of β-cyclodextrin (β-CD) with a modified poly(ethylene glycol) (PEG) (FcC11AzoPEG) consisting of a ferrocene (Fc) end group, a C11 alkyl chain, an azobenzene (Azo) block, and a poly(ethylene glycol)methyl ether (PEG) chain. These SAPs can self-assemble into interesting nanostructures in water upon exposure to different stimuli because β-CD can be selectively included with different guests, such as Fc, Azo, and C11 alkyl chain, under different stimuli. The inclusion complex of Fc with β-CD (Fc@β-CD SAP) can form nanowire micelles in aqueous solution. The nanowire micelles can be transformed into spindle micelles with the addition of oxidant because the majority of β-CDs dissociated from the complex Fc@β-CD SAP due to a conversion of Fc to Fc+ and will preferentially include with Azo group to form another dominant inclusion complex (Azo@β-CD SAP). After UV irradiation, the spindle micelles can be further transformed into spherical micelles because most of β-CDs are excluded from the complex Azo@β-CD SAP due to a trans- to cis-Azo conversion and then form a dominant inclusion complex with C11 alkyl chains (C11@β-CD SAP). This work not only demonstrates the selective host-guest inclusion of stimuli-responsive groups modified PEG with β-CD but also provides a useful approach for construction of diverse morphologies.

Crystal structure of 5-{3-[2,6-dimethyl-4-(5-methyl-1,2,4-oxa-diazol-3-yl)phen-oxy]prop-yl}-N-(11-hy-droxy-undec-yl)isoxazole-3-carboxamide hemihydrate.

The title compound, C29H42N4O5·0.5H2O, comprises four structural units. A flexible prop-yloxy unit in a gauche conformation, with a -C(H2)-C(H2)-C(H2)-O- torsion angle of -64.32 (18)°, connects an isoxazole ring and an approximately planar phenyl-oxa-diazole ring system [with a maxixmum devation of 0.061 (2) Å], which are oriented almost parallel to one another with a dihedral angle of 10.75 (7)°. Furthermore, a C11-alkyl chain with a terminal hy-droxy group links to the 3-position of the isoxazole ring via an amide bond. In the crystal, a half-occupancy solvent water mol-ecule connects to a neighbouring mol-ecule via an inter-molecular O-H⋯O(water) hydrogen bond to the C11-alkyl chain hy-droxy group.

Synthesis of Janus-like gold nanoparticles with hydrophilic/hydrophobic faces by surface ligand exchange and their self-assemblies in water.

This study aims at the synthesis of Janus gold nanoparticles (Janus GNPs) with hydrophilic/hydrophobic faces by a simple ligand exchange reaction in an homogeneous system and at the elucidation of the self-assembled structures of the Janus GNPs in water. As hydrophilic surface ligands, we synthesized hexaethylene glycol (E6)-terminated thiolate ligands with C3, C7, or C11 alkyl chains, referred to as E6C3, E6C7, and E6C11, respectively. As a hydrophobic ligand, a butyl-headed thiolate ligand C4-E6C11, in which a C4 alkyl was introduced on the E6C11 terminus, was synthesized. The degree of segregation between the two ligands on the GNPs (5 nm in diameter) was examined by matrix-assisted laser desorption/ionization time-of fright mass spectrometry (MALDI-TOF MS) analysis. We found that the choice of immobilization methods, one-step or two-step addition of the two ligands to the GNP solution, crucially affects the degree of segregation. The two-step addition of a hydrophilic ligand (E6C3) followed by a hydrophobic ligand (C4-E6C11) produced a large degree of segregation on the GNPs, providing Janus-like GNPs. When dispersed in water, these Janus-like GNPs formed assemblies of ∼160 nm in diameter, whereas Domain GNPs, in which the two ligands formed partial domains on the surface, were precipitated even when the molar ratio of the hydrophilic ligand and the hydrophobic ligand on the surface of the NPs was almost 1:1. The assembled structure of the Janus-like GNPs in water was directly observed by pulsed coherent X-ray solution scattering using an X-ray free-electron laser, revealing irregular spherical structures with uneven surfaces.

Myristoylated Derivatives of 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine) bi-Functional Prodrugs with Potent Anti-HIV-1 Activity and Low Cytotoxicity

To improve in vitro antiviral activity and selectivity of stavudine (d4T), a range of its bi-functional prodrugs, 5'-O-myristoylated derivatives, have been synthesized. Stavudine 5'-O-myristoylated esters were synthesized using modified Parang's procedure. The cytotoxicity and anti-HIV activity was evaluated in the established MT-4 cell line. The level of p24 protein in culture medium was assayed, and EC50 and EC90 values were determined. Excellent anti-HIV activity was obtained for stavudine derivatives 2',3'-didehydro-2',3'-dideoxy-5'-O-(11-thioethylundecanoyl) thymidine, 2',3'-didehydro-2',3'-dideoxy-5'-O-(12-thioethyldodecanoyl) thymidine and 5'-O-(12-azidododecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine with C10 and C11 alkyl chains bearing thioethyl- and azido- substituents. These prodrugs were more potent than the parent stavudine, as is clear from their EC50 values: 2',3'-didehydro-2',3'-dideoxy-5'-O-(11-thioethylundecanoyl) thymidine (R=CO(CH2)10SC2H5, EC50 0.06 μM), 2',3'-didehydro-2',3'-dideoxy-5'-O-(12-thioethyldodecanoyl) thymidine (R=CO(CH2)11SC2H5, EC50 0.09 μM) and 5'-O-(12-azidododecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine (R=CO(CH2)11N3, EC50 0.06 μM), while 50% cytotoxic concentration was >16.65 μM, >7.5 μM and >18.53 μM, respectively. Overall data demonstrate that compounds 2',3'-didehydro-2',3'-dideoxy-5'-O-(11-thioethylundecanoyl) thymidine, 2',3'-didehydro-2',3'-dideoxy-5'-O-(12-thioethyldodecanoyl) thymidine and 5'-O-(12-azidododecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine are very potent and selective anti-HIV agents and could be useful in treatment of HIV infections of the central nervous system.

Synthesis and Biological Evaluation of Novel N‐Alkyl Tetra‐ and Decahydroisoquinolines: Novel Antifungals that Target Ergosterol Biosynthesis

A series of N-alkyl trans-decahydroisoquinoline, 1,2,3,4-tetrahydroisoquinoline, and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized starting from the respective secondary amines by N-alkylation with alkyl bromides. The compounds with C11-alkyl chains showed antifungal potency comparable to clotrimazole, and inhibit enzymes of the ergosterol biosynthesis (Δ14-reductase and Δ8,7-isomerase), depending on the heterocyclic scaffold and the investigated species.

Meso‐Substituted Liquid Porphyrins

Meso-substituted A(4)-porphyrins bearing 3,4,5-trialkoxyphenyl substituents are efficiently synthesized and characterized. Porphyrins bearing twelve C10 and C11 alkyl chains turned out to be liquid at room temperature. The remaining porphyrins, bearing C8, C9, C12, and C18 alkyl chains, have low melting points and high solubility in nonpolar solvents. Their differential scanning calorimetry distinctly shows, in most cases, only one phase transition.

Core chirality based tailoring of the liquid crystalline properties of supermolecular tetrapedes

A series of novel supermolecular star-shaped tetrapede chiral liquid crystals (LCs), incorporating carbohydrates, methyl α-D-glucopyranoside or methyl α-D-mannopyranoside, as chiral cores surrounded by four cyanobiphenyl mesogenic groups linked by either C6 or C11 alkyl chain spacers, have been synthesised. These non-conventional thermotropic carbohydrate-based chiral liquid crystals exhibit chiral nematic and smectic A mesophases over broad temperature ranges. The mesomorphic properties were characterized by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). The effect of the flexible spacer length in addition to the stereogenic and conformational properties of the chiral cores is discussed.

A dual biosensor for 2‐alkyl‐4‐quinolone quorum‐sensing signal molecules

Pseudomonas, Burkholderia and Alteromonas species produce diverse 2-alkyl-4-quinolones (AHQs) which inhibit the growth of bacteria, algae and phytoplankton, chelate iron, modulate mammalian host immune defences and act as quorum-sensing (QS) signal molecules. To facilitate the detection, identification and quantification of the major Pseudomonas aeruginosa AHQs 2-heptyl-3-hydroxy-4-quinolone (PQS) and 2-heptyl-4-quinolone (HHQ) we developed two different AHQ biosensors. These were constructed by introducing either a lecA::luxCDABE or a pqsA::luxCDABE reporter gene fusion into a P. aeruginosa pqsA mutant which cannot synthesize AHQs. While both biosensors responded similarly to PQS (EC(50) 18 +/- 4 microM), the pqsA::luxCDABE biosensor was most sensitively activated by HHQ (EC(50) 0.44 +/- 0.1 microM). This biosensor was also activated albeit less sensitively by (i) PQS analogues with alkyl chains varying from C1 to C11, (ii) HHQ analogues with C9 and C11 alkyl chains and (iii) 2-heptyl-4-hydroxyquinoline-N-oxide (HHQNO). The AHQ biosensor also responded differentially to the AHQs present in cell free culture supernatants prepared from PAO1 and isogenic strains carrying mutations in genes (pqsA, pqsH, lasR, lasI, rhlR, rhlI) known to influence AHQ production. The AHQ profiles of P. aeruginosa strains was also evaluated by overlaying thin layer chromatogram (TLC) plates with the pqsA::luxCDABE biosensor. In PAO1, three major bioluminescent spots were observed which correspond to PQS, HHQ and a mixture of 2 nonyl-4-quinolone and HHQNO. We also noted that on TLC plates the biosensor not only produced bioluminescence in response to AHQs but also the green pigment, pyocyanin which offers an alternative visual indicator for AHQ production.

Structure of the Smectic B Phase Formed by Linear and Branched Perfluoroalkyl-Alkanes

The structure of the smectic B phase formed by perfluorodecylalkanes has been analyzed through the synthesis of three molecules and a careful investigation of their mesophases. Molecules with C8, C10 and a branched C11 alkyl chain were considered. The structure factor analysis of 001 reflexions is consistent with the picture of alternating electron rich and electron poor sublayers. A structural model with segregated perfluoroalkyl chains in the middle of the layer and disordered alkyl chains on each sides is proposed. This model is discussed in terms of space filling arguments: chain lengths, cross section compatibility in the layer and compactness. Infrared dichroic ratios of the CH2 and CF2 stretching modes confirm that perfluoroalkyl subunits are perpendicular to the SB layer while alkyl ones, in a quasi molten state, fill the remaining layer space.

The 2.46 .ANG. Resolution Structure of the Pancreatic Lipase-Colipase Complex Inhibited by a C11 Alkyl Phosphonate

Pancreatic lipase belongs to the serine esterase family and can therefore be inhibited by classical serine reagents such as diisopropyl fluoride or E600. In an attempt to further characterize the active site and catalytic mechanism, we synthesized a C11 alkyl phosphonate compound. This compound is an effective inhibitor of pancreatic lipase. The crystal structure of the pancreatic lipase-colipase complex inhibited by this compound was determined at a resolution of 2.46 A and refined to a final R-factor of 18.3%. As was observed in the case of the structure of the ternary pancreatic lipase-colipase-phospholipid complex, the binding of the ligand induces rearrangements of two surface loops in comparison with the closed structure of the enzyme (van Tilbeurgh et al., 1993b). The inhibitor, which could be clearly observed in the active site, was covalently bound to the active site serine Ser152. A racemic mixture of the inhibitor was used in the crystallization, and there exists evidence that both enantiomers are bound at the active site. The C11 alkyl chain of the first enantiomer fits into a hydrophobic groove and is though to thus mimic the interaction between the leaving fatty acid of a triglyceride substrate and the protein. The alkyl chain of the second enantiomer also has an elongated conformation and interacts with hydrophobic patches on the surface of the open amphipathic lid. This may indicate the location of a second alkyl chain of a triglyceride substrate. Some of the detergent molecules, needed for the crystallization, were also observed in the crystal. Some of them were located at the entrance of the active site, bound to the hydrophobic part of the lid. On the basis of this crystallographic study, a hypothesis about the binding mode of real substrates and the organization of the active site is proposed.