Amphiphilic Dendrimers Research Articles

How stable are amphiphilic dendrimers at the liquid–liquid interface?

By means of molecular dynamics simulations the free energy of adsorption of model dendrimer characterized by monomers of different chemical affinity is predicted as a function of the number and position of the monomers. The results show that modifying the affinity of the only end-monomers with one of the two solvent components (amphiphilic dendrimer) is enough to remarkably increase the stability of the molecule at the interface. The results also indicate that the so called Janus-dendrimer, where only half of the end-monomers are modified, does not show a higher interfacial stability compared with standard amphiphilic one. These findings compare well with simulation results obtained from atomistic simulations performed on polyaminoamide dendrimer at the air–water interface. The free energy profiles have also been compared with those obtained from simpler models which treat the dendrimer molecule as a rigid sphere showing that such simplification is acceptable in poor solvent but not in good solvent where the flexibility of the dendrimer molecule plays a major role in its stability at the interface. These calculations will help in the design of new amphiphilic dendrimers and in predicting their properties at liquid–liquid interface.

Solution Properties of Tadpole-type Cationic Amphiphilic Dendrimers Consisting of an Alkyl Chain, a Quaternary Ammonium, and a Poly(amidoamine) Dendron

Tadpole-type amphiphilic dendrimers consisting of an alkyl chain, a quaternary ammonium bromide (qb) and a poly(amidoamine) dendron (den) (CnqbdenGm, where n represents an alkyl chain with a length of 10,14, or 18 carbons; m is the generation number G of dendron taking the value -0.5, 0.5, or 1.5) were synthesized using N, N-dimethylethylenediamine as a central scaffold. Electrical conductivity, surface tension, pyrene fluorescence, and dynamic light scattering measurements were used to characterize the properties of the dendrimers. In addition, the effect of the alkyl chain length and the generation number of a dendron on these properties was evaluated through a comparison with those of the corresponding previously reported amphiphilic dendrimers with lactobionamide sugar terminal groups (CnqbdenGmLac) and conventional cationic monomeric surfactants (CnTAB). Both critical micelle concentration (cmc) and surface tension (except for C18 series) were lower than those of CnqbdenGmLac and CnTAB with the same alkyl chain length, indicating that the synthesized amphiphilic dendrimers have an excellent micelle-forming ability in solution and high adsorption ability at the air/water interface, in spite of the large bulky dendron structure. When the alkyl chain length and the generation number of the amphiphilic dendrimers were increased, the surface tension became high because of the curved long alkyl chain and the bulky structure of dendron. Further, CnqbdenGm formed micelles with a small size in solution, and the micelles of CnqbdenG(-0.5) had almost a constant size despite the changes in the concentration, while those of CnqbdenG0.5 and CnqbdenG1.5 became smaller with increasing concentration. The difference in the behavior results from the difference in the number of amide groups in the low- and high-generation dendrons.

Irradiation- and thermoinduced synthesis of Ag nanoparticles within amphiphilic carbosilane-thioether dendrimers.

We report on the preparation of new amphiphilic carbosilane-thioether dendrimers by thiol-ene chemistry and their application in the in situ formation of silver nanoparticles (AgNPs) with unusual versatility in approach. In the presence of the dendrimers, AgNPs can be prepared in either water or organic solvents, and by simply using UV irradiation or heat in the reduction step without the need for a chemical reducing agent. Monodisperse size-tunable AgNPs possessing a simple cubic crystal structure were characterized by TEM, SAED, XRD, and other techniques. Susceptibility examination of E. coli indicated strong antibacterial activity of the AgNPs in aqueous solution.

Cluster and reentrant anomalies of nearly Gaussian core particles

We study through integral equation theory and numerical simulations the structure and dynamics of fluids composed of ultrasoft, nearly Gaussian particles. Namely, we explore the fluid phase diagram of a model in which particles interact via the generalized exponential potential u(r) = εexp[−(r/σ)n], with a softness exponent n slightly larger than 2. In addition to the well-known anomaly associated with reentrant melting, the structure and dynamics of the fluid display two additional anomalies, which are visible in the isothermal variation of the structure factor and diffusivity. These features are correlated with the appearance of dimers in the fluid phase and with the subsequent modification of the cluster structure upon compression. We corroborate these results through an analysis of the local minima of the potential energy surface, in which clusters appear as much tighter conglomerates of particles. We find that reentrant melting and clustering coexist for softness exponents ranging from 2+ up to values relevant for the description of amphiphilic dendrimers, i.e., n = 3.

Synthesis and physical behavior of amphiphilic dendrimers with layered organization of hydrophilic and hydrophobic blocks

Amphiphilic carbosilane dendrimers with novel architectural layout have been synthesized. These dendrimers contain peripheral groups consisting of covalently bound promesogenic fragments and hydrophilic (oligoethyleneglycolic) linkages which are connected to a carbosilane core in two distinct ways: as spacer or as tail arrangement. Such molecules have a block structure where the hydrophilic and hydrophobic blocks are distributed within the dendrimer forming layers of different polarity. The hydrophilic layer is either enclosed between two hydrophobic parts of the molecule or is situated on the periphery. The synthetic strategy for achieving these structures is described. The interfacial properties of the dendrimers were studied and the influence of the dendritic structure’s organization on the Langmuir film formation process is assessed.

Dilational Properties of Novel Amphiphilic Dendrimers at Water–Air and Water–Heptane Interfaces

In this work, a series of novel amphiphilic dendrimers taking polyamidoamine dendrimer as the core with different hydrophobic tails QPAMC(m) were synthesized and the dilational properties were studied as monolayers by dilational rheological measurements at the water-air and water-n-heptane interfaces to explore the nature of adsorption behaviors. The results showed that the maximum values of the dilational modulus seemed to have no obvious variation in a wide change of hydrophobic chain length at the surface. However, there was considerable variability in the tendency of the influence of bulk concentration on the dilational modulus at the two different interfaces. It was interestingly found that the diffusion-exchange process slowed down with the increase of alkyl chain length leading to more elastic nature of adsorption film, which was contrary to the tendencies of conventional single chain and gemini surfactants. It is reasonable to consider that, in the case of the molecule having short chain length such as QPAMC(8), the alkyl chains are too short to overlap across the headgroup, enable the intermolecular hydrophobic interaction to be predominant with increasing of surface concentration, which enhances the elasticity and shows the slowest diffusion-exchange process. Whereas, when the chain length increases to 12 or 16, the alkyl chains are long enough to act intramolecularly to form intracohesion conformation, which results in enhancing the diffusion-exchange process. In conclusion, the interfacial behaviors are dictated by the size ratio between the tail and headgroup. A reasonable model with respect to the molecular interaction was proposed on the basis of experimental data. The results of interfacial tension relaxation and dynamic light scattering (DLS) experiments, in accord with the proposed mechanism, also present the unusual tendency comparing to the traditional single or gemini surfactants.

Efficient energy transfer between amphiphilic dendrimers with oligo(p-phenylenevinylene) core branches and oligo(ethylene oxide) termini in micelles

The efficient fluorescence resonance energy transfer (FRET) between amphiphilic dendrimers with oligo(p-phenylenevinylene) core branches and oligo(ethylene oxide) termini have been observed in micelles. All dendrimers show the critical micelle concentration and lower critical solution temperature as well as fluorescent emission. Tailoring electronic structures of the conjugated amphiphiles for FRET have been conveniently achieved by varying the branch number and/or the conjugated core structure. The Stern-Volmer constants (KSV) for FRET were found to be 4.51 × 10−5 and 8.78 × 10−5 M for Den 30–40 and Den 50–40, respectively. The effects external stimuli such as solvent and temperature on FRET have been also investigated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

Nanofiltration Membranes with Modified Active Layer Using Aromatic Polyamide Dendrimers

AbstractThe modification of a commercial nanofiltration (NF) membrane (TFC‐S) with shape‐persistent dendritic molecules is reported. Amphiphilic aromatic polyamide dendrimers (G1–G3) are synthesized via a divergent approach and used for membrane active layer modification by direct percolation. The permeate samples collected from the percolation experiments are analyzed by UV‐visible spectroscopy to monitor the influence of dendrimer generations on percolation behavior and active layer modification. Further characterization of modified membranes by Rutherford backscattering spectrometry and atomic force microscopy techniques reveals a relatively low‐level accumulation of dendrimers inside the original TFC‐S NF membrane active layer and subsequent formation of a coating of pure aramide dendrimers on top of the active layer. A PES‐PVA ultrafiltration membrane is used as a control membrane support (without an NF active layer) showing that structural compatibility between the dendrimers and support plays an important role in the membrane modification process. The performance of the modified TFC‐S membrane is evaluated on the basis of the rejection abilities for a variety of water contaminants having a range of molecular size and chemistry. As the water flux is inversely proportional to the thickness of the active layer, the amount of dendrimers deposited for specific contaminants are optimized to improve the solute rejection while maintaining high water flux.

Glycine-Terminated Dendritic Amphiphiles for Nonviral Gene Delivery

Development of nonviral vectors for the successful application of gene therapy through siRNA/DNA transfection of cells is still a great challenge in current research. (1, 2) In the present study, we have developed multivalent polyglycerol dendron based amphiphiles with well-defined molecular structures that express controlled glycine arrays on their surfaces. The structure-activity relationships with respect to the siRNA complexation, toxicity, and transfection profiles were studied with synthesized amphiphilic polycations. Our findings revealed that a second-generation amphiphilic dendrimer (G2-octaamine, 4) that has eight amine groups on its surface and a hydrophobic C-18 alkyl chain at the core of the dendron, acts as an efficient vector to deliver siRNA and achieve potent gene silencing by investigating the knockdown of luciferase and GAPDH gene activity in HeLa cells. Interestingly, the amphiphilic vector is nontoxic even at higher ratio of N/P 100. To the best of our knowledge this is the first example of successful in vitro siRNA transfection using dendritic amphiphiles. We believe that this supramolecular complex may serve as a new promising alternative for nonviral siRNA delivery systems and will be investigated for in vivo siRNA delivery in the future.

An Amphiphilic Dendrimer for Effective Delivery of Small Interfering RNA and Gene Silencing In Vitro and In Vivo

An amphiphilic dendrimer bearing a hydrophobic alkyl chain and hydrophilic poly(amidoamine) dendrons is able to combine the advantageous features of lipid and dendrimer vectors to deliver a heat shock protein 27 siRNA and produce potent gene silencing and anticancer activity in vitro and in vivo in a prostate cancer model. This dendrimer can be used alternatively for treating various diseases.

An Amphiphilic Dendrimer for Effective Delivery of Small Interfering RNA and Gene Silencing In Vitro and In Vivo

An Amphiphilic Dendrimer for Effective Delivery of Small Interfering RNA and Gene Silencing In Vitro and In Vivo

Structural properties of dendrimer–colloid mixtures

We consider binary mixtures of colloidal particles and amphiphilic dendrimers of the second generation by means of Monte Carlo simulations. By using the effective interactions between monomer-resolved dendrimers and colloids, we compare the results of simulations of mixtures stemming from a full monomer-resolved description with the effective two-component description at different densities, composition ratios, colloid diameters and interaction strengths. Additionally, we map the two-component system onto an effective one-component model for the colloids in the presence of the dendrimers. Simulations based on the resulting depletion potentials allow us to extend the comparison to yet another level of coarse graining and to examine under which conditions this two-step approach is valid. In addition, a preliminary outlook into the phase behavior of this system is given.

Organic/Metallic Nanohybrids Based on Amphiphilic Dumbbell-Shaped Dendrimers

In this study, we synthesized a series of amphiphilic dumbbell-shaped dendrimers through the addition reactions of a hydrophilic poly(oxyalkylene) with hydrophobic dendrons based on 4-isocyanate-4'-(3,3-dimethyl-2,4-dioxo-azetidine)diphenylmethane with different numbers of branching generations. The addition reaction of azetidine-2,4-diones of dendrons to amines of poly(oxyalkylene) was proceeded by stirring the reactants in dry tetrahydrofuran (THF) under nitrogen at 60 °C. In aqueous media, the dumbbell-shaped dendrimers self-assembled into micelles with their hydrophobic dendrons in the core and their hydrophilic poly(oxyalkylene) segments forming loops in the corona shell. Employing the unique self-assembled micelle structures as templates for subsequent chemical reduction of the Ag(+) ions, we generated new types of organic/metallic [silver nanoparticle (AgNP)] nanohybrid clusters. The long poly(oxyalkylene) loops that extended into the aqueous phase complexed with the Ag(+) ions, providing the suspension with steric stabilization to prevent the AgNPs from collision and flocculation. After reduction, the AgNPs were present in a homogeneous distribution in the round dendrimer micelle-stabilized nanoclusters. The diameter of each AgNP was less than 10 nm; the diameter of each round nanocluster was in the range of 50-200 nm. The encapsulation efficiency of the AgNPs in micelles was about 54-69% for the dumbbell-shaped dendrimer based organic/AgNP nanohybrid.

Design and synthesis of novel amphiphilic Janus dendrimers for bone-targeted drug delivery

In this paper, we synthesized a range of amphiphilic Janus dendrimers, which consisted of acidic amino acid and naproxen molecules as the peripheral groups, as novel potential bone-targeting dendritic drug delivery. These dendrimers take advantage of a dendritic display to carry multiple drug molecules and targeting moieties simultaneously. All of the dendrimers exhibited more than 80% binding rates to hydroxyapatite (HAP), especially the [G2]-dendrimers (2a and 2b) showed dramatic binding rates (>95%). Moreover, the solubility of naproxen was remarkably enhanced by the dendritic drug delivery system, especially the naproxen concentration of 2b achieved 5.37mg/ml, which is more than 28-fold over that of native drug. Furthermore, cell viability studies showed that all the dendrimers exhibited no significant cytotoxicity against HEK293 cells. These results provided an effective entry to the development of new bone-targeting drugs.

Large clusters and hollow microfibers by multicomponent self-assembly of citrate stabilized gold nanoparticles with temperature-responsive amphiphilic dendrimers

Gold clusters with controlled sizes have been prepared by controlled self-assembly of citrate stabilized gold nanoparticles (AuNPs) with temperature-responsive luminescent amphiphilic dendrimers (Den 40) of oligo(p-phenylene vinylene) core branches and oligo(ethylene oxide) terminal chains. The shape and size of the resultant gold clusters depend strongly on the molar ratio of Den 40 to AuNPs. These gold clusters can further assemble into hollow microfibers decorated with AuNPs, which can be used as a promising substrate for surface enhanced Raman spectroscopy (SERS). The formation of spherical gold clusters and hollow microfibers simply by self-assembly of AuNPs and luminescent amphiphilic dendrimers (Den 40) could not only provide some useful insights for producing multifunctional materials via multicomponent self-assembly but also offer promise for potential applications of the self-assemblies in many systems, such as SERS and stimuli-responsive sensors.

Accessing lipophilic ligands in dendrimer-based amphiphilic supramolecular assemblies for protein-induced disassembly.

Supramolecular nanoassemblies that respond to the presence of proteins are of great interest, as aberrations in protein concentrations represent the primary imbalances found in a diseased state. We present here a molecular design, syntheses, and study of facially amphiphilic dendrimers that respond to the presence of the protein, immunoglobulin G. It is of particular interest that the ligand functionality, utilized for causing the binding-induced disassembly, be lipophilic. Demonstration of binding with lipophilic ligands greatly expands the repertoire of binding-induced disassembly, since this covers a rather large class of ligand moieties designed for proteins and these provide specific insights into the mechanistic pathways that are available for the binding-induced disassembly process. Here, we describe the details of the binding induced disassembly, including the change in size of the assembly in response to proteins, concurrent release of noncovalently encapsulated guest molecules, and the specificity of the disassembly process.

Predicting the Size and Properties of Dendrimersomes from the Lamellar Structure of Their Amphiphilic Janus Dendrimers

Dendrimersomes are stable, monodisperse unilamellar vesicles self-assembled in water from amphiphilic Janus dendrimers. Their size, stability, and membrane structure are determined by the chemical structure of Janus dendrimer and the method of self-assembly. Comparative analysis of the periodic arrays in bulk and dendrimersomes assembled by ethanol injection in water of 11 libraries containing 108 Janus dendrimers is reported. Analysis in bulk and in water was performed by differential scanning calorimetry, X-ray diffraction, dynamic light scattering, and cryo-TEM. An inverse proportionality between size, stability, mechanical properties of dendrimersomes, and thickness of their membrane was discovered. This dependence was explained by the tendency of alkyl chains forming the hydrophobic part of the dendrimersome to produce the same local packing density regardless of the branching pattern from the hydrophobic part of the dendrimer. For the same hydrophobic alkyl chain length, the largest, toughest, and most stable dendrimersomes are those with the thinnest membrane that results from the interdigitation of the alkyl groups of the Janus dendrimer. A simplified spherical-shell model of the dendrimersome was used to demonstrate the direct correlation between the concentration of Janus dendrimer in water, c, and the size of self-assembled dendrimersome. This concentration-size dependence demonstrates that the mass of the vesicle membrane is proportional with c. A methodology to predict the size of the dendrimersome based on this correlation was developed. This methodology explains the inverse proportionality between the size of dendrimersome and its membrane thickness, and provides a good agreement between the experimental and predicted size of dendrimersome.

Stability of Amphiphilic Dendrimers at the Water/Air Interface

By means of atomistic molecular dynamics simulations, we investigate the structure and stability of alkyl-modified polyamido-amide (PAMAM) dendrimers at the air/water interface as a function of the number and the relative position of the modified end groups. We find that the PAMAM dendrimer with all terminal groups functionalized is more stable at the interface than the Janus dendrimer where only half the amine groups are modified. This result is explained in terms of softness of the dendrimer molecule which adapts its conformation to maximize the favorable amide-water contacts segregating the alkyl chains and increasing the structural order of the "hydrophilic core". We interpret the stability of the molecule at the interface also in terms of particle wettability and energy components. We verify that the atomistic model follows the prediction of the thermodynamic analytical theory adopting an oblate or prolate shape and orientating its longest axis parallel to the normal to the interface. These results indicate that monolayers of fully functionalized molecules could be as stable as (or more stable than) those self-assembled from proper Janus molecules.

Guest-release control in enzyme-sensitive, amphiphilic-dendrimer-based nanoparticles through photochemical crosslinking.

Stimuli sensitive, facially amphiphilic dendrimers have been synthesized and their enzyme-responsive nature has been determined with dual fluorescence responses of both covalently conjugated and non-covalently bound reporter units. These dual responses are correlated to ascertain the effect of enzymatic action on micellar aggregates and the consequential guest release. The release of the guest molecule is conveniently tuned by stabilizing the micellar aggregates through photochemical crosslinking of hydrophobic coumarin units. This photo-crosslinking is also utilized as a tool to investigate the mode of enzyme-substrate interaction in the context of aggregate-monomer equilibrium.

Self-organization of amphiphilic liquid-crystalline dendrimers in bulk and at the interface

A comparative analysis of the structure and phase behavior of synthesized carbosilane amphiphilic LC dendrimers of the third generation containing mesogenic phenyl and oligo(ethylene glycol) fragments is performed. When phenol groups are replaced with oligo(ethylene glycol) moieties, the temperature interval of the existence of the LC phase in the mesogen-containing dendrimers decreases. The chemical nature of hydrophilic terminal groups is found to control the organization of dendrimers in the smectic mesophase. Structural models for their packing are proposed. Amphiphilic dendrimers are shown to form stable Langmuir films at the water/air interface. Surface-pressure-surface area-isotherms are constructed. The effect of the chemical nature of hydrophilic groups on the formation of a monolayer at the interface and on the packing density of dendrimer molecules in the monolayer is discussed.