Structure of Charged Poly(propylene imine) Dendrimers: Theoretical Investigation

A mean‐field model for charged dendrimers has been elaborated and applied to Astramol dendrimers of 5^th generation in salt‐free solution. The free energy of a dendrimer molecule was minimized with respect to the dendrimer size and to the profile of counterion distribution. The model of highly stretched freely jointed chain was used to describe the elasticity of long branches, the dissociated groups were assumed to be localized mostly on the periphery of the molecule, and the electrostatic interactions were described in the Poisson‐Boltzmann approximation. It was found that the osmotic pressure of counterions leads to moderate expansion of dendrimer molecules upon charging, and a significant fraction of counterions is localized within the dendrimer molecule under typical experimental conditions.

The schematic structure of poly(propylene imine) dendrimers for the 4^th generation.     

Deposition of gallium oxide nanodots prepared from metal‐assembling dendrimer molecules isolated by the spacing of the nonmetal‐assembling dendrimer molecules in the two‐dendrimers mixture monolayer

Phenylazomethine dendrimers (DPA) can precisely incorporate metal chlorides onto the imine sites in a stepwise fashion. Such precise dendrimer–metal complexes allow the preparation of size‐controlled subnanometer metal particles. We now propose a novel approach for the fabrication of size‐controlled subnanometer metal oxide dots isolated on a substrate using two different‐type dendrimers. One is a fourth‐generation phenylazomethine dendrimer (DPAG4) and the other is a benzylether dendrimer (BzEG3) with a zinc porphyrin core. Even though the diameter of BzEG3 corresponds to that of DPAG4, BzEG3 has no metal‐complexing site. Upon dip coating on a highly oriented pyrolytic graphite substrate by the mixed solution of the metal chloride‐assembling DPAG4 molecules and BzEG3 molecules, the dendrimer monolayer was immobilized on the substrate. The concentration of the dendrimer mixture was determined in order to separate each DPAG4–metal chloride complex molecule by BzEG3. Monodispersed metaloxide nanodot arrays could be obtained from the dendrimer monolayer in which DPAG4–metal chloride complex molecule is well isolated by the BzEG3 as a spacer after the hydrolysis of metal chlorides followed by the complete removal of dendrimers. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparison of PAMAM-Au and PPI-Au nanocomposites and their catalytic activity for reduction of 4-nitrophenol

Dendrimer-Au nanocomposites are prepared in aqueous solutions using poly(amidoammine)dendrimers (PAMAM) (generation 2, 3, and 5) and poly(propyleneimine)dendrimers (PPI)(generation 2, 3, and 4) by wet chemical NaBH(4) method. The Au nanoparticles thus obtained are 2-4 nm in diameter for both dendrimers and no generation dependence on the particle size is observed, whereas the generations of the dendrimers are increased as stabilization of Au-nanoparticles is achieved with lower dendrimer concentrations. Studies of the reduction reaction of 4-nitrophenol using these nanocomposites show that the rate constants for the PAMAM dendrimers (generations 2 and 3) are higher than those for the PPI dendrimers (generations 2 and 3), while a distinct difference in the rate constants is not seen for the PAMAM dendrimer (generation 5) or the PPI dendrimer (generation 4). In addition, the rate constants for the reduction of 4-nitrophenol involving all the dendrimers decrease with increases in dendrimer concentrations.     

Thermodynamic properties of dendrimers compared with linear polymers: General observations

The pressure‐volume‐temperature and thermal properties of dendrimers based on benzyl ether were measured and compared with literature values for monodisperse, linear polystyrenes. In addition, property measurements are presented for an exact linear analogue to the fifth‐generation dendrimer. The thermodynamic properties' molecular weight behavior for the dendrimers is unique when compared with that of linear polystyrene. All of the evidence presented in this work suggests that some form of structural transition occurs in the bulk at a molecular mass near that for the fourth‐generation dendrimer. No such transition is seen for polystyrene. Dendrimers exhibit an increased packing efficiency as evidenced by a decreased specific volume (increased density) as compared with an exact linear analogue of the fifth‐generation dendrimer analogue, and the dendrimer highlights the entropic differences between the two molecules. In addition, differences in the change in heat capacity with temperature for the two systems further allude to their entropic differences. A crystalline state can be formed for the lower generation dendrimer and linear analogue. This crystalline state is not seen in dendrimers above the third generation. These behaviors compiled with the difference in the glass‐transition temperature for the linear analogue suggest that the dendrimers' microstructure has a significant influence on the bulk thermodynamic state of the material. The Tait equation was fitted to the volume data for comparative purposes; the Tait equation has known limitations but was selected because of its widespread application. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 1766–1777, 2001     

Specific binding structures of dendrimers on lipid bilayer membranes

Dissipative particle dynamics simulations are used to study the specific binding structures of polyamidoamine (PAMAM) dendrimers on amphiphilic membranes and the permeation mechanisms. Mutually consistent coarse-grained (CG) models both for PAMAM dendrimers and for dimyristoylphosphatidylcholine (DMPC) lipid molecules are constructed. The PAMAM CG model describes correctly the conformational behavior of the dendrimers, and the DMPC CG model can properly give the surface tension of the amphiphilic membrane. A series of systematic simulations is performed to investigate the binding structures of the dendrimers on membranes with varied length of the hydrophobic tails of amphiphiles. The permeability of dendrimers across membranes is enhanced upon increasing the dendrimer size (generation). The length of the hydrophobic tails of amphiphiles in turn affects the dendrimer conformation, as well as the binding structure of the dendrimer-membrane complexes. The negative curvature of the membrane formed in the dendrimer-membrane complexes is related to dendrimer concentration. Higher dendrimer concentration together with increased dendrimer generation is observed to enhance the permeability of dendrimers across the amphiphilic membranes.     

Dendritic Molecular Electrochromic Batteries Based on Redox‐Robust Metallocenes

In this Concept article, we summarize and discuss recent reports on dendritic molecular electrochromic batteries. Giant dendrimers containing 3ⁿ⁺² terminal tethers (n=generation number) and terminated by first‐raw late‐transition‐metal metallocenes, permethyl metallocenes and other sandwich complexes were shown to be redox robust. Indeed, they can be oxidized and reduced without decomposition and exist under two stable oxidation states (Fe^III/II, Co^III/II). Thus, a pre‐determined number of electrons (up to 14 000) per dendrimer can be exchanged. Cyclic voltammetry showed a remarkable complete reversibility even up to 14 000 Fe and Co termini in metallodendrimers, indicating fast electron hoping among the redox sites and between dendrimers on a carbon surface covered by arylcarboxylate groups. The dendrimer sizes were measured by dynamic light scattering in solution and by AFM (subsequent to flattening in the condensed state also indicating that these metallodendrimers aggregate to form discrete nanoparticles of dendrimers, as atoms do). The metallodendrimer size varies considerably between the two redox forms due to tether extension of the cationic dendrimers upon oxidation, and a breathing mechanism was shown by atomic and electric force microscopy (AFM and EFM). When the redox potential is very negative, the reduced form is an electron‐reservoir system that can deliver a large number of electrons per dendrimer to various reducible substrates. These systems are thus potential dendritic molecular batteries with two different colors for the two redox forms (electrochromic behavior).     

Self-assembly of ionogenic surfactants during their interaction with poly(propylenimine) dendrimers

The structure of complexes formed by poly(propylenimine) dendrimers of five generations and anionic micelle-forming surfactants is studied by X-ray diffraction. It is shown that, in complexes of lower generation dendrimers, the lamellar packing of surfactants is dominant. In complexes formed by dendrimers of the fourth and fifth generations, packing typical of compact dendrimer molecules prevails. This packing can be attributed to the distorted dense packing of ball-like complex species. Structural models of complexes that allow for penetration of surfactants into the dendrimer molecule and the size ratio of the aliphatic radical of a surfactant and a dendrimer are advanced.     

Facile synthesis of dendrimers combining aza‐Michael addition with Thiol‐yne click chemistry

We report a highly efficient approach to prepare dendrimers by taking advantage of the orthogonal characteristic of aza‐Michael addition and thiol‐yne reactions. A fifth generation dendrimer was synthesized within five steps without protection/activation procedures. The reactions proceed under benign conditions without byproducts, and the target products can be easily purified via extraction or precipitation without chromatography. The structure of each generation dendrimer was characterized using NMR spectroscopy, size exclusion chromatography, and mass spectrometry. The obtained dendrimers can have peripheral amine or alkyne groups. We demonstrated that these groups can be used for selective and specific conjugation with various functional groups. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Self‐assembly of a new class of amphiphilic poly(amidoamine) dendrimers and their electrochemical properties

Amphiphilic poly(amidoamine) (PAMAM) dendrimers consisting of a hydrophilic dendrimer core and hydrophobic aromatic dansyl or 1‐(naphthalenyl)‐2‐phenyldiazene (NPD) shells have been synthesized. These amphiphilic dendrimers from the zero generation to the third generation self‐assemble into vesicular aggregates in water. The self‐assembly behavior of these dendrimers strongly depends on their generations. The generation dependence has been further investigated by an exploration of their electrochemical properties. For the PAMAM–NPD aggregates, the photoisomerization process leads to a change in the aggregate size. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5512–5519, 2005     

Photoresponsive nanocarriers based on PAMAM dendrimers with a o‐nitrobenzyl shell

Gn (n = 3, 4, and 5) poly(amidoamine) (PAMAM) dendrimers were synthesized and peripherally modified with photocleavable o‐nitrobenzyl (NB) groups by reacting o‐nitrobenzaldehyde with the terminal amine groups of PAMAM dendrimers, followed by reducing the imine to amine groups with NaBH₄. The NB‐modified dendrimers, Gn‐NB (n = 3, 4, and 5), were characterized by nuclear magnetic resonance and fourier transform infrared spectroscopy. The results showed that the NB groups were successfully attached on the periphery of the dendrimers with near 100% grafting efficiency. Such a photosensitive NB shell could be cut off on irradiation with 365 nm ultraviolet (UV) light. The encapsulation and release of guest molecules, that is, salicylic acid (SA) and adriamycin (ADR), by Gn‐NB were explored. The encapsulation capability of these dendrimers was found to increase as the guest molecular size was decreased and have dependence on the generation of dendrimers as well. For both of SA and ADR, the average encapsulation numbers per dendrimer decreased in the order of G4‐NB > G5‐NB > G3‐NB, indicating that the fourth generation dendrimer was a better container for the guest molecules. The rate of SA release was found to be greater with UV irradiation than that without, suggesting that the NB‐shelled PAMMAM dendrimers could function as a molecular container/box with photoresponsive characteristics. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 551–557, 2010     

Thermosensitive properties of poly(amidoamine) dendrimers with peripheral phenylalanine residues

Dendrimers are unique polymers with globular shapes and well-defined structures. We previously prepared poly(amidoamine) (PAMAM) dendrimers having phenylalanine (Phe) residues at every chain end of the dendrimer as efficient gene carriers. In this study, we found that Phe-derivatized PAMAM dendrimers change their water solubility depending on temperature. The dendrimers were soluble in aqueous solutions at low temperatures, but they became water-insoluble at temperatures above a specific threshold, which is termed the lower critical solution temperature (LCST). Although the LCST of Phe-modified dendrimers decreased with increasing dendrimer generation, these dendrimers exhibited an LCST of 20-30 degrees C under physiological conditions. In addition, the LCST of the dendrimers was controlled by introducing isoleucine (Ile) residues at chain ends of dendrimers at varying ratios with respect to Phe residues. The PAMAM dendrimers are known to encapsulate various drug molecules. For these reasons, temperature-sensitive dendrimers might be useful as efficient drug carriers with controlled size and temperature-responsive properties.     

Syntheses and nickel coordination properties of cyclen substituted with mixed stilbene/poly(ethylene glycol) dendritic arms

We synthesized a series of cyclens substituted with mixed stilbene and poly(ethylene glycol) dendritic arms. All dendrimers terminated with different peripheral groups had good solubility in common organic solvents, and dendrimers terminated with ? CO₂H groups (CO₂H‐dendrimers) were also soluble in alkaline solutions. The nickel coordination properties of these dendrimers were investigated in organic solvents. Dendrimers terminated with ? CN groups (CN‐dendrimers) and the second‐generation CO₂H‐dendrimer [(CO₂H)₈L2] could produce pentacoordinated nickel complexes; the third‐generation CO₂H‐dendrimer [(CO₂H)₁₆L3] could form tetra‐ and pentacoordinated nickel complexes, and the nickel complex of the fourth‐generation CO₂H‐dendrimer [(CO₂H)₃₂L4] could not be obtained. This result was due to the fact that the globular surface of (CO₂H)₁₆L3 formed a hydrogen‐bond network that selectively penetrated cations and inhibited the access of anions to the core. The formation of the hydrogen‐bond network was confirmed by Fourier transform infrared, ¹H NMR, and fluorescence data. The CN‐dendrimers could not form hydrogen bonds on the surface, and the first‐ and second‐generation CO₂H‐dendrimers could not form intramolecular hydrogen‐bond networks. Therefore, they had no selectivity for positive nickel ions and negative chloride ions. (CO₂H)₃₂L4 could not produce a nickel complex because it had a crammed backbone structure that could not penetrate nickel and chloride ions. Therefore, it was possible to control the ion access of cations and anions with the hydrogen‐bond network of (CO₂H)₁₆L3. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5414–5428, 2005     

Shape‐Persistent and Adaptive Multivalency: Rigid Transgeden (TGD) and Flexible PAMAM Dendrimers for Heparin Binding

This study investigates transgeden (TGD) dendrimers (polyamidoamine (PAMAM)‐type dendrimers modified with rigid polyphenylenevinylene (PPV) cores) and compares their heparin‐binding ability with commercially available PAMAM dendrimers. Although the peripheral ligands are near‐identical between the two dendrimer families, their heparin binding is very different. At low generation (G1), TGD outperforms PAMAM, but at higher generation (G2 and G3), the PAMAMs are better. Heparin binding also depends strongly on the dendrimer/heparin ratio. We explain these effects using multiscale modelling. TGD dendrimers exhibit “shape‐persistent multivalency”; the rigidity means that small clusters of surface amines are locally well optimised for target binding, but it prevents the overall nanoscale structure from rearranging to maximise its contacts with a single heparin chain. Conversely, PAMAM dendrimers exhibit “adaptive multivalency”; the flexibility means individual surface ligands are not so well optimised locally to bind heparin chains, but the nanostructure can adapt more easily and maximise its binding contacts. As such, this study exemplifies important new paradigms in multivalent biomolecular recognition.     

Poly(propylene imine) dendrimers as plasticizers for polyvinyl chloride

Fourth and fifth generation poly(propylene imine) dendrimers and methyl and benzyl functionalized copolymers of these dendrimers are solution blended with poly(vinyl chloride) (PVC). The methyl‐derivative copolymer is observed to be dispersed in PVC as judged by optical and dynamic scanning calorimetry measurements. This dispersion leads to a substantial reduction in the glass transition temperature and a commensurate plasticization effect, demonstrating that functionalized dendrimer copolymers can successfully plasticize semicrystalline polymers. This plasticization is thought to occur as a result of additional free volume from the highly branched structure of the dendrimer. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1970–1975, 2007     

Light-harvesting in carbonyl-terminated phenylacetylene dendrimers: The role of delocalized excited States and the scaling of light-harvesting efficiency with dendrimer size

The photophysics of a family of conjugated phenylacetylene (PA) light-harvesting dendrimers are studied using steady-state and time-resolved optical spectroscopy. The dendrimers consist of a substituted PA core surrounded by meta-branched PA arms. The total number of PA moieties ranges from 3 (first generation) to 63 (fifth generation). By using an alcohol/ketone substituent at the dendrimer core, we avoid through-space Forster transfer from the peripheral PA donors to the core acceptor (in this case, the carbonyl group), which simplifies the analysis of these molecules relative to the perylene-terminated molecules studied previously. The delocalized excited states previously identified in smaller dendrons are seen in these larger dendrimers as well, and their influence on the intersite electronic energy transfer (EET) is analyzed in terms of a point-dipole Forster model. We find that these new delocalized states can both enhance EET (by decreasing the spatial separation between donor and acceptor) and degrade it (by lowering the emission cross section and shifting the energy, resulting in poorer spectral overlap between donor and acceptor). The combination of these two effects leads to a calculated intersite transfer time of 6 ps, in reasonable agreement with the 5-17 ps range obtained from experiment. In addition to characterizing the electronic states and intersite energy transfer times, we also examine how the overall light-harvesting efficiency scales with dendrimer size. After taking the size dependence of other nonradiative processes, such as excimer formation, into account, the overall dendrimer quenching rate k(Q) is found to decrease exponentially with dendrimer size over the first four generations. This exponential decrease is predicted by simple theoretical considerations and by kinetic models, but the dependence on generation is steeper than expected based on those models, probably due to increased disorder in the larger dendrimers. We discuss the implications of these results for dendrimeric light-harvesting structures based on PA and other chemical motifs.     

Extraction of Au nanoparticles having narrow size distributions from within dendrimer templates

Here, we show that Au nanoparticles having diameters of less than 2.2 nm can be extracted from within the interior of PAMAM dendrimers using n-alkanethiol extractants. Extraction proceeds quickly, regardless of the size of the nanoparticle, the dendrimer generation, or the peripheral functionalization of the dendrimer. The extraction rate is fastest for the lowest generation dendrimers, the smallest nanoparticles, and the shortest chain-length n-alkanethiols. Other important results of this study include the following. First, within the accuracy of absorbance spectroscopy, the extraction yield is quantitative. Second, NMR and FT-IR spectroscopy indicate that after extraction the dendrimer remains in the aqueous phase and can be used to template additional metal particles. Third, the size and optical characteristics of the extracted nanoparticles are the same as the precursor dendrimer-encapsulated nanoparticles (DENs). Fourth, a 100-fold excess of n-alkanethiol molecules is required to prevent aggregation of DENs during extraction.     

Importance of size-to-charge ratio in construction of stable and uniform nanoscale RNA/dendrimer complexes

Formation of RNA/dendrimer complexes between various RNA molecules and PAMAM dendrimers was studied using atomic force microscopy. Our results demonstrate that effective construction of stable nanoscale and uniform RNA/dendrimer complexes depends critically on the size of the RNA molecule, the dendrimer generation and the charge ratio between the dendrimer and the RNA. Larger RNA molecules, higher generations of dendrimers and larger dendrimer-to-RNA charge ratios lead to the formation of stable, uniform nanoscale RNA/dendrimer complexes. These findings provide new insights in developing dendrimer systems for RNA delivery.     

Interfacial regions governing internal cavities of dendrimers. Studies of poly(alkyl aryl ether) dendrimers constituted with linkers of varying alkyl chain length

This report deals with a study of the properties of internal cavities of dendritic macromolecules that are capable of encapsulating and mediating photoreactions of guest molecules. The internal cavity structures of dendrimers are determined by the interfacial regions between the aqueous exterior and hydrocarbon like interior constituted by the linkers that connect symmetrically sited branch points constituting the dendrimer and head groups that cap the dendrimers. Phloroglucinol-based poly(alkyl aryl ether) dendrimers constituted with a homologous series of alkyl linkers were undertaken for the current study. Twelve dendrimers within first, second, and third generations, having ethyl, n-propyl, n-butyl, and n-pentyl groups as the linkers and hydroxyl groups at peripheries in each generation, were synthesized. Encapsulation of pyrene and coumarins by aqueous basic solutions of dendrimers were monitored by UV-vis and fluorescence spectroscopies, which showed that a lower generation dendrimer with an optimal alkyl linker presented better encapsulation abilities than a higher generation dendrimer. Norrish type I photoreaction of dibenzyl ketone was carried out within the above series of dendrimers to probe their abilities to hold guests and reactive intermediate radical pairs within themselves. The extent of cage effect from the series of third generation dendrimers was observed to be higher with dendrimers having an n-pentyl group as the linker.     

Oligosaccharide-modified poly(propyleneimine) dendrimers: synthesis, structure determination, and Cu(II) complexation

The multiple application of reductive amination on primary amino groups of first and second generation poly(propyleneimine) dendrimers is used as a one-pot approach to introduce twice the amount of the oligosaccharide units as surface groups, compared to initially present amino groups in the first and second generation dendrimers. This was proven by (1)H NMR, MALDI-TOF-MS, and LILBID-MS analysis. The size of these dendrimers was determined by the hydrodynamic radius using pulsed field gradient NMR and dynamic light scattering. Molecular modeling confirmed the presence of dense-shell dendrimers. These dendrimers exhibit a generation dependent Cu(II)/dendrimer ratio in an aqueous environment, highlighting these materials as possible metal-carrier systems with a well-defined oligosaccharide protection shell for application in a biological environment.     

Synthesis of poly(propylene imine) dendrimers via homogeneous reduction process using lithium aluminium hydride: Bioconjugation with folic acid and doxorubicin release kinetics

The heterogeneous reduction process for synthesis of poly(propylene imine) (PPI) dendrimer has been replaced by a novel and homogeneous process. Accordingly, to prepare half generations, acrylonitrile was added to amine groups via Michael addition reaction. Then, nitrile groups were reduced via homogeneous hydrogenation using lithium aluminium hydride to synthesize fifth‐generation PPI dendrimers with ethylenediamine core. Also, peripheral primary amine groups were conjugated with folic acid (FA). Fourier transform infrared and ¹³C NMR spectroscopies and gel permeation chromatograph y were used to prove the synthesis of the various structures. Finally fifth‐generation and FA‐conjugated fifth‐generation PPI dendrimers were loaded with doxorubicin and exposed to environments with different pH values to examine the release properties of the structures. Also, drug release kinetics was investigated by fitting experimental data with various release models. The synthesized dendritic structures showed Higuchi model release behaviour due to better solubility of drug in release media with respect to dendrimer cavities.