Asymmetric Dendrimers Research Articles

Fluorous Mixture Synthesis of Asymmetric Dendrimers

A divergent fluorous mixture synthesis (FMS) of asymmetric fluorinated dendrimers has been developed. Four generations of fluorinated dendrimers with the same fluorinated moiety were prepared with high efficiency, yield, and purity. Comparison of the physicochemical properties of these dendrimers provided valuable information for their application and future optimization. This strategy has not only provided a practical method for the synthesis and purification of dendrimers, but also established the possibility of utilizing the same fluorinated moiety for FMS.

Molecular Dynamics of Variegated Polyamide Dendrimers

We have used molecular dynamics simulations to study the structures of a range of heterogeneously functionalized (“variegated”) dendrimers and the distributions in space of their caps. By a virtual capping approach, we compare an asymmetric dendrimer (dendritic poly(l-lysine), PLL) and a symmetric polyamide (SPAM) dendrimer. SPAM is larger and more spherical than PLL, and its caps are more evenly distributed throughout the molecule. Protonation of an amine-capped dendrimer causes substantial swelling. The distribution of caps relative to each other is strongly affected by conformational change. Simulation of a SPAM framework with chemically distinct caps shows that whole-dendrimer properties are largely unaffected by the topological arrangement of the caps. Using both modeling approaches, we found that differentiation at the dendrimer’s core produces strongly dipolar dendrimers, while differentiation between branches in the outermost generation produces largely nonpolar dendrimers, with a gradual transiti...

Self-Assembly of Asymmetric Fan-Shaped Dendrimers with Different Generation Numbers at the Air−Water Interface

Monolayer formation of two dendrimers containing a hydrophilic core group (COOH) and hydrophobic peripheral groups (anthracene and aryl ether tail groups), 4-{10-[4-(3,5-bis-benzyloxy)-phenyl]-anthracen-9-yl}-benzoic acid (G1) and 4-(10-{4-[3,5-bis-(3,5-bis-benzyloxy)-benzyloxy]-phenyl}-anthracen-9-yl)-benzoic acid (G2), were studied. To understand the mechanism of the self-assembly of these molecules, we measured the surface pressure-surface area (Pi- A) isotherm and investigated the surface texture of Langmuir-Blodgett monolayers transferred onto hydrophilic silicon wafers. Both dendrimers form circular domains at the onset point of surface pressure as a result of the difference in hydrophobicity between the core group and the peripheral end group. The core group has a functional group at the end of dendrimer and can be anchored on the water surface. Upon further compression, monolayer of G1 shows a domain of molecules whereas a monolayer of G2 is aligned in the direction of compression at 10 mN/m. At higher surface pressure (20 mN/m), G1 molecules have several aggregates of domains, but G2 molecules maintain their ordering. These results were confirmed by the electron density profile of G1 and G2 monolayers transferred to silicon substrates, as measured by X-ray reflectivity.

Lysine dendrimers as vectors for delivery of genetic constructs to eukaryotic cells

Asymmetrical lysine dendrimers are promising as vectors for delivering gene expression constructs into mammalian cells. The condensing, protective, and transfection properties were studied for pentaspherical lysine dendrimer D5 and its analog D5C10, modified with capric acid residues at the outer sphere; in addition, the transfection activity was assayed for complexes DNA-dendrimer-endosomolytic peptide JTS-1. Fatty acid residues incorporated in lysine dendrimers proved to improve their ability to bind DNA, to protect DNA from nuclease degradation, and to ensure its transfer into the nucleus. Peptide JTS-1 introduced in DNA-dendrimer complexes significantly increased their transfection activity. The potentiating effect of JTS-1 was especially high with the DNA-D5C10 complex. An excess of JTS-1 changed the structure of the complexes and reduced their transfection activity. It was assumed that dendrimers D5 and D5C10 are promising vectors for delivering DNA to eukaryotic cells and provide a basis for constructing more refined nonvirus module carriers.

202. Effect of Modification with Lipophilic Fragments and Inclusion of Endosomolytic Peptide on Transfection Efficiency Mediated by Lysine Dendrimers

Development of effective non-viral DNA carriers is considered to be a perspective approach for DNA delivery into eucaryotic cells with gene therapy aims. Our research was devoted to group of asymmetric lysine dendrimers. We studied fifth generation dendrimer D5 and its analog D5C10 which was modified by capric acid residues in external sphere. All vehicles were investigated for their capacity to bind DNA (using gel-retardation and ethidium bromide exclusion assay) and to provide protection plasmid DNA from nuclease degradation (using DNAse I protection test). Transfectional capacity of dendrimers were tested according to the efficiency of beta- galactosidase gene expression in HeLa cells. Modification of dendrimers by capric residues resulted in increase of ability to bind and to protect DNA from enzymatic degradation. Besides, D5C10 provides 10-fold more effective DNA delivery into cells, compared to D5. Addition of endosomolytic peptide JTS-1 to DNA/dendrimer complexes resulted in significant increase of gene delivery with dendrimers, especially with D5C10. The transfection effectiveness for DNA/D5C10/JTS-1 reached 16%. Thus we demonstrate that D5 and D5C10 carriers are perspective vehicles for DNA delivery into cells and can be basis for the development of more effective modular non-viral systems.

The synthesis and properties of solution processable red-emitting phosphorescent dendrimers

We report methodology for the preparation of symmetric and asymmetric solution processable phosphorescent dendrimers that are comprised of 2-ethylhexyloxy surface groups, biphenyl based dendrons, and iridium(III) complex cores. The symmetric dendrimer has three dendritic 2-benzo[b]thiophene-2′-ylpyridyl (BTP) ligands with the dendritic ligands responsible for red emission. The asymmetric dendrimer has two dendritic 2-phenylpyridyl ligands and one unsubstituted BTP ligand. Iridium(III) complexes comprised of 2-phenylpyridyl ligands are normally associated with green emission whereas those containing BTP ligands emit red light. Red emission is observed from the asymmetric dendrimer demonstrating that emission occurs primarily from the metal-to-ligand charge transfer state associated with the ligand with the lowest HOMO–LUMO energy gap. The photoluminescence quantum yields (PLQYs) of the symmetric and asymmetric dendrimers were strongly dependent on the dendrimer structure. In solution the PLQYs of the asymmetric and symmetric dendrimers were 47 ± 5% and 29 ± 3% respectively. The photoluminescence lifetime of the emissive state of both dendrimers in solution was 7.3 ± 0.1 µs. In the solid state the comparative PLQYs were reversed with the symmetric dendrimer having a PLQY of 10 ± 1% and the asymmetric dendrimer a PLQY of 7 ± 1%. The comparatively larger decrease in PLQY for the asymmetric dendrimer in the solid state is attributed to increased core–core interactions. The intermolecular interactions are greater in the asymmetric dendrimer because there is no dendron on the BTP ligand. Electrochemical analysis shows that charge is injected directly into the cores of the dendrimers.

Surface alignment and control of a dendritic liquid crystal in ultrathin films

Surface alignment and control of hexagonal molecular cylinders from an asymmetric supramolecular liquid crystal was established. Transmission electron microscopy images show that the cylinders are strongly affected by the substrate and film thickness. The cylinders align perpendicular to a hydrophobic substrate, while planar alignment takes place on hydrophilic surfaces. Different morphologies are encountered depending on the film thickness. Thick films of such a material exhibit a highly ordered hexagonal structure where the cylinders are oriented either parallel or perpendicular depending on the substrate. For thin films whose thickness is 10 nm < t < 20 nm, they spontaneously form holes with straight edges aligned with hexagonal symmetry of the (10) orientation of the underlying molecular lattice. Thinner films lead to a liquid-like disordered in-plane structure. Unlike the behaviour of thin films of a typical block copolymer, where the natural period of the block copolymer is manifested through the formation of hole, the hole structures from these types of asymmetric dendrimers can be attributed to the low surface energy planes, revealed by the faceting of discontinuous films.

Surface Order in Thin Films of Self-Assembled Columnar Liquid Crystals

The way in which alignment of hexagonal columnar mesophases depends on molecular structure, film thickness, and surface interactions is investigated. Homeotropic orientation of tapered nonpolymeric and polymeric amphiphilic columnar molecules occurs most readily on carbon substrates. The planar alignment of asymmetric dendrimers is favored on a water surface but is not possible for a symmetric dendrimer. For the polymeric material, film thickness has a significant influence on the morphology. Thick films align homeotropically, but films that are only a few column diameters in thickness are planar, and their thickness is quantized. Because they must contain an integral number of layers of cylinders, the resulting morphology is terraced.

Ferrocene encapsulated within symmetric dendrimers: a deeper understanding of dendritic effects on redox potential.

Ferrocene has been encapsulated within a symmetric ether-amide dendritic shell and its redox potential monitored in a variety of solvents. The dendritic effect generated by the branched shell is different in different solvents. In less polar, non hydrogen bond donor solvents, attachment of the branched shell to ferrocene increases its E(1/2), indicating that oxidation to ferrocenium (charge buildup) becomes thermodynamically hindered by the dendrimer, a result explained by the dendrimer providing a less polar medium than that of the surrounding electrolyte solution. The effect of electrolyte concentration on redox potential was also investigated, and it was shown that the concentration of "innocent" electrolyte has a significant effect on the redox potential by increasing the overall polarity of the surrounding medium. Dendritic destabilization of charge buildup is in agreement with the majority of reported dendritic effects. A notable exception to this is provided by the asymmetric ferrocene dendrimers previously reported by Kaifer and co-workers, in which the branching facilitated oxidation, and it is proposed that in this case the dendritic effect is generated by a different mechanism. Interestingly, in methanol, the new symmetric ferrocene dendrimer exhibited almost no dendritic effect, a result explained by the ability of methanol to interact extensively with the branched shell, generating a more open superstructure. By comparison of all the new data with other reports, this study provides a key insight into the structure-activity relationships which control redox processes in dendrimers and also an insight into the electrochemical process itself.

DNA transfection and transfected cell viability using amphipathic asymmetric dendrimers

Amphipathic asymmetric dendrimers have been investigated for use in delivery of genes into cells, with the objective of optimising transfection efficiency and maintaining cell viability. We have synthesised amphipathic asymmetric dendrimers by solid phase methods. The ability of two of these to transfect BHK cells in culture with β-galactosidase gene was determined by X-gal staining. Cell viability was measured by the MTT assay for BHK cells, and by spectroscopy for lysis of erythrocytes. Interactions between dendrimer and DNA were investigated by agarose gel electrophoresis. BHK cells were optimally transfected at 5:1 +/− charge ratio yielding 20% cells receiving at least one copy of the plasmid. Cell viability decreased when the dendrimer to DNA ratio exceeded 5:1. Raising the pH significantly affected the electrophoretic mobility of complexes of dendrimer and DNA. We conclude that amphipathic asymmetric dendrimers enable efficient plasmid DNA uptake into BHK cells. Cell viability is maintained at high concentrations of dendrimer when complexed with DNA at a 5:1 +/− charge ratio. Efficiency of transfection and cell viability suggest the system may be suitable for gene delivery in vivo.

Isomerism of asymmetric dendrimers and stereoisomerism of alkanes

Two extremes of isomerism in constructing acyclic chemical networks are considered. On the one hand, building blocks without symmetry generate dendrimers. On the other, tetradentate building blocks of full symmetry give stereoisomerism of alkanes. Dissimilarity characteristic theorem is applicable to both situations in generating and enumerating isomers. A new category of graph-theoretical trees, ones with finite color-coded links, is modeled for dendrimers and analyzed using the Cayley scheme. Bidentate, tridentate and tetradentate dendrimers are enumerated. A homologous series of polyol-type molecules is also enumerated. Concepts of chirotopicity and stereogenicity are found embodied within the counting scheme. This scheme indicates that irregular carbon nodes orderly dispose molecular chirality and are genuine ‘elements’ of chirality, even though this idea was once unpopular.

On the scent of asymmetrical dandelion dendrimers: Part I. Starting materials from the regiospecific aminolysis of N 3P 3Cl 6 by amino-alcohols

Starting materials for the design of asymmetrical dandelion dendrimers were synthesized upon the preliminary fixation of suitable amino-alcohols on hexachlorocyclotriphosphazene, N 3P 3Cl 6, as “blockers”. Further linkage of diamines on solid supports leads to the expected asymmetrical moieties.