Dendrimers In Solution Research Articles

Coarse grained simulations of neutral and charged dendrimers

Dendrimers are macromolecules with a regular-treelike, branched architecture of their skeleton. In terms of the branching number and the number of terminal groups they represent an extreme case among branched polymers. Dendrimers can occur in neutral and various charged states. Due to their highly branched architecture excluded volume effects are of great importance and conformational properties and monomer distribution profiles of dendrimers differ considerably from those of linear polymers. We give an overview of the state-of-the-art knowledge of physical properties of dendrimers as seen from coarse-grained computer simulations. Our main focus is on isolated dendrimers with flexible spacers both in the neutral and in the charged state, as well as complexation of dendrimers with oppositely charged linear polyelectrolytes. We briefly address problems of adsorption and concentration effects in dendrimer solutions and outline recent progress and open questions in this field.

Water-soluble polyelectrolyte complexes of pyridine-containing polyphenylene dendrimers

The sizes of soluble polyelectrolyte complexes formed through mixing of solutions of dimethyl sulfate-alkylated rigid pyridine-containing polyphenylene dendrimers of various generations with the solution of sodium polystyrenesulfonate are measured with the use of dynamic light scattering. Effects of the length of the polyanion chain of the dendrimer, the generation number of the dendrimer, and the charge ratio of polymer components on the sizes of the complexes are examined. The results of this study are in agreement with the theoretical analysis of interaction between the charged dendrimer and the polyelectrolyte of the opposite charge sign and suggest the spontaneous formation of nanosized particles of water-soluble complexes.

Combining metadynamics simulation and experiments to characterize dendrimers in solution

We report a combined theoretical–experimental approach to characterize dendrimers and Polyethylene Glycol (PEG)–dendrimer hybrids in solution. Well-tempered metadynamics simulation allows for an exhaustive sampling of the conformational fluctuations in solution. In contrast to classical molecular dynamics, molecular flexibility can also be captured. Simulations are in agreement with our dynamic light scattering experiments providing a complete picture of these semi-flexible molecules in solution.

Unique Photoluminescence of Diacetylene Containing Dendrimer Self-Assemblies: Application in Positive and Negative Luminescence Patterning

A series of poly(benzyl ether) dendrimers with two benzene-1,3,5-tricarboxamide (BTA) units bridged by diacetylene were synthesized. The formation of hydrogen bonds between BTA units to form the supramolecular self-assembly was confirmed by FT-IR and AFM measurements. When the dendrimers in CH2Cl2 was excited with 280 nm irradiation, the dendrimers exhibited an unexpected strong photoluminescence (PL) around 450 nm in addition to 310 nm fluorescence upon excitation at 280 nm. The PL intensity of each dendrimers has shown generation dependency. With the continuous irradiation of 280 nm UV light, dendrimers exhibited decreased PL emission at both 310 and 450 nm by photopolymerization of diaceytlene units. A poly(vinylidene fluoride) (PVDF) membrane saturated with dendrimer solution were prepared to obtain a patterned PL image. Utilizing a photomask, a negative PL pattern was successfully obtained. When the membrane was annealed to 100 °C, new anomalous PL was generated and opposite type PL-patterned image c...

Interaction between PAMAM‐NH2 G0 dendrimer and dissociated sodium chloride in aqueous solution

The protonation constants of poly(amidoamine) dendrimer (PAMAM-NH2 G0) in an aqueous solution of sodium chloride with an ionic strength of 0.05M were determined by the potentiometric method. The interaction between PAMAM-NH2 and sodium chloride dissociated in water at room temperature was assessed by means of calorimetric and conductometric measurements. Using isothermal calorimetric titration, the number of the moles of dissociated electrolyte combined by a dendrimer mole was estimated. The conductometric measurements indicate a decrease in electrolyte conductivity in the dendrimer solution in relation to the electrolyte solution and confirm that the dendrimer investigated combines electrolyte ions. The results of DFT calculations performed for the protonated structure of PAMAM-NH3+ suggest that the chlorine atom considered is combined with terminal amino groups, which confirms the results of calorimetric and conductometric measurements.

Small‐Angle Scattering From Branched Polymers

AbstractThe single‐polymer form factor is determined for branched polymers using a scaling argument in order to recover the low‐Q Porod exponent characteristic of the overall structure. The high‐Q Porod exponent characterizes the local branching structure. An alternative approach based on a high‐Q expansion contains information about functionality, branch length and branch content. The specific case of a starburst dendrimer for which the form factor is known is discussed. The model predictions are compared to small‐angle neutron scattering data from a dilute solution of dendrimer in D2O.magnified image

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

Dendrimers have been widely used as nanostructured carriers for guest species in a variety of applications in medicine, catalysis, and environmental remediation. Theory and simulation methods are an important complement to experimental approaches that are designed to develop a fundamental understanding about how dendrimers interact with guest molecules. This review focuses on computational studies aimed at providing a better understanding of the relevant physicochemical parameters at play in the binding and release mechanisms between polyamidoamine (PAMAM) dendrimers and guest species. We highlight recent contributions that model supramolecular dendrimer-guest complexes over the temporal and spatial scales spanned by simulation methods ranging from all-atom molecular dynamics to statistical field theory. The role of solvent effects on dendrimer-guest interactions and the importance of relating model parameters across multiple scales is discussed.

Synthesis of first- and second-generation imidazole-terminated POSS-core dendrimers and their pH responsive and coordination properties

Imidazole-terminated first- and second-generation poly(amidoamine)-type oligomeric silsesquioxanes (POSS)-core dendrimers (denoted as POSS-Im16 and POSS-Im32, respectively) were synthesized by the ester–amide exchange reaction from first- and second-generation methyl ester-terminated POSS-core dendrimers, respectively. Transmittances of the aqueous POSS-Im32 solution drastically decreased at pH>7.2, but the change was reversible without hysteresis. The results of pH titrations for POSS-Im16 and POSS-Im32 showed well-defined one-step titration curves identical to those of monomeric imidazole compounds, such as 1-methylimidazole. Such simple acid–base behavior caused phase transition in the aqueous dendrimer solution to be highly sensitive to pH changes. The pKa values of 1-methylimidazole, POSS-Im16 and POSS-Im32 were 7.3, 7.0 and 6.7, respectively. Spectrophotometric titrations of the aqueous dendrimer solutions with Cu2+ ions indicated that coordination modes of POSS-Im16 changed from the Cu2+–N2O2 complex to the Cu2+–N4 complex as the concentration of the dendrimers increased; however, only one complexation mode (Cu2+–N4) existed between Cu2+ ions and POSS-Im32.

Internal Dynamics of Dendritic Molecules Probed by Pyrene Excimer Formation

This review exposes the current poor understanding of the internal segmental chain dynamics of dendrimers in solution probed by monitoring the process of excimer formation between pyrene labels covalently attached to the chain ends of dendrimers. The review begins by covering the bases of fluorescence and the kinetics of pyrene excimer formation before describing a procedure based on the Model Free (MF) analysis that is used to analyze quantitatively the fluorescence decays acquired for dendrimers, the ends of which have been fully and covalently labeled with pyrene. Comparison of the various trends obtained by different research groups describing the efficiency of pyrene excimer formation with the generation number of dendrimers illustrates the lack of consensus between the few studies devoted to the topic. One possible reason for this disagreement might reside in the presence of minute amounts of unattached pyrene labels which act as potent fluorescent impurities and affect the analysis of the fluorescence spectra and decays in an uncontrolled manner. The review points out that the MF analysis of the fluorescence decays acquired with pyrene-labeled dendrimers enables one to account for the presence of unattached pyrene and to retrieve information about the internal segmental dynamics of the dendrimer. It provides guidelines that should enable future studies on pyrene-labeled dendrimers to yield results that are more straightforward to interpret.

Tautomeric forms of PPI dendrimers functionalized with 4-(4′-ethoxybenzoyloxy)salicylaldehyde chromophores

Bonding of the promesogenic unit derived from 4-(4′-ethoxybenzoyloxy)salicylaldehyde to the amino terminated PPI dendrimer chains results in formation of the salicylidenimine chromophore groups. Absorption and fluorescence investigations of the dendrimer solutions supported by the quantum chemistry calculations revealed that the chromophore groups may exist in enol and keto tautomeric forms with relative concentrations depending on the dendrimer generation and solvent. The dendrimer fluorescence is attributed to nπ∗ states of keto tautomers which may also be formed from excited enol tautomers.

Influence of pH on dendritic structure of strongly fluorescent persulfate-treated poly(amidoamine) dendrimer

The influence of pH on the dendritic structure of strongly fluorescent ammonium persulfate (APS)-treated poly(amidoamine) (PAMAM) dendrimers was examined. The APS-treated PAMAM dendrimers were prepared by aging of 0.2 mM aqueous solutions of a hydroxyl groups-terminated, generation-five PAMAM (G5OH) dendrimer together with 200 μl of 0.1 M APS solutions. The G5OH dendrimer showed an absorbance at 280 nm, which was red-shifted to 360 nm after APS treatment. The APS-treated G5OH dendrimer solutions emitted much stronger fluorescence than the pristine G5OH dendrimer solutions when irradiated at 360 nm. The pH of the G5OH dendrimer solution is 7.6 while that of the APS-treated G5OH dendrimer solution is 5.2. The pore surface of both pristine and fluorescent G5OH dendrimers was altered more significantly under acidic than basic conditions. The tertiary amine groups of the pore surface of the fluorescent G5OH dendrimers were protonated by APS treatment as well as under the acidic condition; therefore, the pore surface of the G5OH dendrimer was filled with tertiary ammonium cations, which were, however, further deprotonated under basic conditions. The sulfur anions (VI and II) were generated during the hydrolysis of APS, which were interacted with the G5OH dendrimers under both acidic and basic conditions.

Mechanisms of molecular polarization of bithiophenesilane dendrimers in solutions

A number of consecutive generations of bithiophenesilane dendrimers and their precursors are studied by the methods of the equilibrium electro-optical Kerr effect, dielectric polarization, and absorption spectroscopy in dilute toluene solutions. It is shown that the molecules of hybrid dendrimers containing bithiophene fragments covalently linked via silicon atoms are not kinetically rigid and feature the small-scale mechanism of interaction with external electric fields. A tris(bithiophene)methylsilane fragment is found to be the subunit responsible for the electro-optical and optical spectral properties of the above hybrid dendrimers. It is revealed that the polarization of bithiophensilane dendrimers predominantly shows the deformation pattern.

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.

Synthesis and Properties of Dendritic Emitters with a Fluorinated Starburst Oxadiazole Core and Twisted Carbazole Dendrons

Three generations of novel dendrimers (G1, G2, and G3) with an electron-deficient fluorinated starburst oxadiazole core and twisted carbazoles as dendrons were synthesized via aromatic nucleophilic substitution reaction at ambient temperature by the weak base potassium fluoride with a high selectivity in a nearly quantitative yield, which was attributed to the high reactivity of the para fluorine atom activated by oxadiazole and multiple fluorine atoms. 1H NMR, 19F NMR, elemental analysis, and MALDI-TOF MS results confirmed the designed chemical structures. Varying the generation to gradually modify the dendrons could gradiently modulate the HOMO−LUMO energy band gaps of Gn, which was verified by cyclic voltammetry results. Photoluminescent spectra showed the dual fluorescence emission of the dendrimers in solutions, which indicated that twist intramolecular charge transfer occurred between oxadiazole and carbazole separated by nonconjugated bonds. The Gn-based devices with the configuration of ITO/PEDOT:PSS/Gn/TPBI/AlQ/LiF/Al displayed a stable green emission in their electroluminescent spectra with a gradual increase in external quantum efficiency and current efficiency for higher-generation dendrimers, owing to gradually improved charge transport. The device with G3 possessed the lowest turn-on voltage along with the highest external quantum efficiency of 1.49%, maximum current efficiency of 4.6 cd/A, and a high luminance of 4882 cd/m2, indicating that it had the best carrier balance.

Interaction between PAMAM-NH2 G4 dendrimer and 5-fluorouracil in aqueous solution

The formation equilibrium of poly(amidoamine) dendrimer (PAMAM-NH2 G4) complex with an oncologic drug such as 5-fluorouracil (5-FU) in water at room temperature was examined. Using the results of the drug solubility in dendrimer solutions and the method of equilibrium dialysis, the maximal number of drug molecules in the dendrimer–drug complex and its equilibrium constant were evaluated. Solubility results show that PAMAM-NH2 G4 dendrimer can transfer tens 5-fluorouracil molecules in aqueous solution. The number of active sites in a dendrimer macromolecule being capable of combining the drug, determined by the separation method, amounts to n=30±4. The calculated equilibrium constant of the 5-FU-active site bonding is equal to K=(400±120).

Solubility of aceclofenac in polyamidoamine dendrimer solutions

In the present study we investigated the effect of polyamidoamine (PAMAM) dendrimers on the aqueous solubility of aceclofenac. The aqueous solubility of aceclofenac was measured in the presence of dendrimers in distilled water. The effect of variables, such as pH condition, concentration, temperature and generation (molecule size) of dendrimer, has been investigated. Results showed that the solubility of aceclofenac in the dendrimer solutions was proportional to dendrimer concentration. The order in which the dendrimers increased the solubility at a constant pH condition was G3 > G0. The influence of dendrimer solution pH on the solubility enhancement of aceclofenac suggests that it involves an electrostatic interaction between the carboxyl group of the aceclofenac molecule and the amine groups of the dendrimer molecule. The solubility of aceclofenac was inversely proportional to the temperature of dendrimer solution.Different generation (G0 and G3) PAMAM dendrimers have the potential to significantly enhance the solubility of poor water-soluble drugs.

Unsurpassed cage effect for the photolysis of dibenzyl ketones in water-soluble dendrimers

Amphiphilic water-soluble poly(alkyl aryl ether) dendrimers Gn (n = 1-3) with charge-neutral tetraethylene glycol monomethyl ethers at their periphery were synthesized as microreactors to control the photochemical reactions of dibenzyl ketone derivatives in aqueous solutions. Photophysical studies demonstrated that Gn can encapsulate organic molecules and provide a hydrophobic microenvironment. The product distribution of photolysis of dibenzyl ketone derivatives can be successfully controlled by encapsulating the substrates within dendrimers, and an unsurpassed cage effect of 1.00 is reached in high generation dendrimers, revealing that a thick and compact "shell" was formed at the periphery of the dendrimers. The cage effect is also significantly influenced by the substituent at the para-position of the guest molecules. The higher generation dendrimers exhibit a better confined microenvironment and the aggregates possess more compact cavities to "lock" the guests than the corresponding unimolecular dendrimers. After photolysis, the separation of products can be easily achieved by extracting from the dendrimer solutions and the dendrimers are simply recovered and reused.

PH Responsiveness of polyelectrolyte dendrimers: a dynamical perspective

A combined quasi-elastic neutron scattering (QENS) and high-resolution solution NMR spectroscopy study was conducted to investigate the internal dynamics of aqueous (D2O) G5 PAMAM dendrimer solutions as a function of molecular protonation at room temperature. Localized motion of the dendrimer segments was clearly exhibited in the QENS data analysis while the global, center-of-mass translational diffusion was measured by NMR. Our results unambiguously demonstrate an increased rapidity in local scale (∼ 3 A) motion upon increasing the molecular protonation. This is contrary to an intuitive picture that increased charge stiffens the dendrimer segments thereby inhibiting local motion. These charge-induced changes may be a result of interactions with the surrounding counterions and water molecules as the segments explore additional intra-dendrimer volume made available by slight electrostatic swelling and redistribution of mass in the dendrimer interior. This observation is relevant to development of a microscopic picture of dendrimer-based packages as guest-molecule delivery vehicles because reorganization of the confining dendrimer segments must be a precursor to guest-molecule release.

A Fluorinated Dendrimer-Based Nanotechnology Platform

We aimed to develop a directly detected magnetic resonance imaging (MRI) contrast agent for use with high fields based on a nanoscale fluorinated dendrimer-based platform for F MRI and overcome some of the problems with F MRI. The dendrimers were prepared in a convergent manner by making the appropriate dendron, followed by coupling to a central core. The dendrons were prepared by attaching 3 equivalents of the fluorinated amino acid to the 3 carboxylic acids of the repeat branch unit followed by deprotection of the amine branch point, and either coupling to another repeat branch unit (increasing the generation G) or used directly allowing the precise growth of the dendrimer. The size of the dendrimers was determined by diffusion nuclear magnetic resonance (NMR) spectroscopy. The toxicity of the dendrimers was measured using the MTT assay. Fluorine longitudinal relaxation time measurements were performed on a Bruker ACP-500 NMR using a saturation recovery experiment at 470.59 MHz frequency. Healthy 150 g Sprague-Dawley female rats were imaged using a dendrimer solution. The size of the dendrimers is generally less than 3 nm, 2 orders of magnitude smaller than the size of the perfluorocarbon nanoparticles (about 200 nm). The longitudinal relaxation time, T1, decreases with increasing dendrimer generation. A significant improvement in relaxation rate and signal-to-noise ratio can be achieved by either the chemical modification of the dendrimer with a gadolinium-chelate or by the physical addition of exogenous contrast agent. Although the dendrimers with fluorine in the surface layer are toxic, this toxicity is easily reduced by burying the fluorine further into the dendrimer interior. (19)F MR images of the rat using the dendrimer solution were rapidly obtained at 7 Tesla, the strong contrast in the heart generated by the dendrimer can be seen. A novel fluorinated dendrimer-based nanotechnology platform in (19)F MRI and a new bifunctional DOTA chelate were prepared and characterized. We introduce 2 methods for reducing the (19)F longitudinal relaxation time: (a) Increasing the generation; (b) covalent and noncovalent introduction of Gd(III)-chelates. A new bifunctional Gd(III)-chelate is presented. The investigations of imaging on rats suggest potential importance of the dendrimers in (19)F MRI application.

Formation of soluble complexes of cationic polypyridylphenylene dendrimers with DNA

The complexation of DNA with a dendrimer with the successive addition of the dendrimer solution to the solution of DNA leads to the appearance and accumulation of compact particles with a diameter of Dh = 100 ± 10 nm that coexist with particles whose dimensions coincide with those of free DNA molecules (Dh = 450 ± 50 nm). The fraction of large particles decreases regularly; moreover, when the equimolar ratio of charged groups of interacting components is achieved, these particles disappear. The coexistence of practically free DNA molecules and a compact soluble negatively charged complex is confirmed by a sedimentation assay. Further addition of the dendrimer up to a certain ratio of charged groups of the components, much higher than unity, brings about phase separation, while at a large excess of charge groups of the dendrimer (above fivefold), the system turns out to be fully single-phase and composed of compact (110 ± 10 nm) cationic soluble complexes. Owing to the positive charge and small size of complex particles no greater than a critical value of 150 nm, the particles possess an important ability to interact with a positively charged cell membrane and to enter a living cell via endocytosis.