Dendrimer Core Research Articles

Probe Mobility in Native Phosphocaseinate Suspensions and in a Concentrated Rennet Gel: Effects of Probe Flexibility and Size

Pulsed field gradient nuclear magnetic resonance and proton nuclear magnetic resonance relaxometry were used to study the self-diffusion coefficients and molecular dynamics of linear (PEGs) and spherical probes (dendrimers) in native phosphocaseinate suspensions and in a concentrated rennet gel. It was shown that both the size and the shape of the diffusing molecules and the matrix topography affected the diffusion and relaxation rates. In suspensions, both translational and rotational diffusion decreased with increasing casein concentrations due to increased restriction in the freedom of motion. Rotational diffusion was, however, less hindered than translational diffusion. After coagulation, translational diffusion increased but rotational diffusion decreased. Analysis of the T₂ relaxation times obtained for probes of different sizes distinguished the free short-chain relaxation formed from a few monomeric units from (i) the relaxation of protons attached to long polymer chains and (ii) the short-chain relaxation attached to a rigid dendrimer core.

DFT study of Raman spectra of phosphorus-containing dendrimers built from thiophosphoryl core

The FT-Raman spectra of the first and second generations of phosphorus-containing dendrimers with terminal benzaldehyde and P–Cl groups have been recorded and analyzed. The structural optimization and normal mode analysis were performed for dendrimers on the basis of the density functional theory (DFT). The calculated geometrical parameters, harmonic vibrational frequencies and Raman scattering activities are predicted in a good agreement with the experimental data. The experimental Raman spectra of dendrimers were interpreted by means of potential energy distribution. Relying on DFT calculations the lines of the core, repeating units and terminal groups of dendrimers were assigned.The influence of the encirclement on the line frequencies and intensities was studied and due to the predictable, controlled and reproducible structure of dendrimers the information, usually inaccessible is obtained. The strong line at 1600cm−1 show marked changes of intensity in dependence of aldehyde (CHO) or azomethyne (CHN) substituents in the aromatic ring. The polarizabilities and lipophilicity of the eleven generations of dendrimers were estimated based on the calculated values of the first generations.

Solubility enhancement of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) using polypolypropylene oxide core PAMAM dendrimers

The aim of the present study was to evaluate the aqueous solubility enhancement properties of polypropylene oxide cored PAMAM (PPO@PAMAM) dendrimers. The solubility of NSAIDs (Ketoprofen, Ibuprofen and Diflunisal) was investigated in the presence of PPO@PAMAM dendrimers at room temperature in buffer solution. The effects of dendrimer concentration, generation and core size on the solubility of NSAIDs have been investigated. The experimental results showed that the solubility of the NSAIDs was approximately proportional to dendrimer concentration and generation. In addition, the effect of core size on the solubility of NSAIDs in constant generation and concentration of PPO@PAMAM dendrimer was Ketoprofen>Diflunisal>Ibuprofen. Under optimized conditions, PPO@PAMAM dendrimers are highly effective solubility enhancer for NSAIDs due to its new polypropylene oxide core.

A New Concept in the Separation of Polyethyleneglycol-Modified PAMAM Dendrons by Liquid Chromatography

In this work, a unique high-performance liquid chromatographic method was developed and applied for monitoring the synthesis of polyethyleneglycol surface modified poly(amidoamine) cystamine core dendrimers (PEG-PAMAMs) and PEG-PAMAM-alkynes with a single alkyne moiety attached to the core of a dendron through a unique sulfhydryl group. The separation of the products was performed on a column with a pentafluorphenylpropyl stationary phase, allowing multiple mechanisms of selectivity. More than 50 peaks were separated in one run, reflecting the degree of dendrimer PEGylation (PEG average molecular mass: 3,000). Moreover, modification of PAMAM with a single alkyne group could be distinguished. The developed method can be used for the general characterization and separation of PAMAM derivatives, in which the degree of modification is critical for final applications.

Hypoxic condition-selective upconversion via triplet–triplet annihilation based on POSS-core dendrimer complexes

The influence on the efficiencies of the triplet–triplet annihilation (TTA)-supported upconversion by oxygen under biomimetic conditions was investigated. From the solution containing the dendrimer complexes based on polyhedral oligomeric silsesquioxane (POSS)-core dendrimer with the Pt complex of octaethylporphyrin (PtOEP) and anthracene in PBS, the fluorescence emission of anthracene depending on the dissolved oxygen (DO) concentrations via the TTA-supported upconversion was obtained with the excitation light at 540nm. In particular, we observed strong emission only under hypoxic conditions. In addition, it was found that the emission intensity via TTA-supported upconversion can be reversibly regulated by the DO concentrations in the solution.

ChemInform Abstract: Homogeneous Dihydroxylation of Olefins Catalyzed by OsO42‐ Immobilized on a Dendritic Backbone with a Tertiary Nitrogen at Its Core Position.

AbstractA novel bis(ammonium osmate) core dendrimer efficiently catalyzes the homogeneous dihydroxylation of olefins with a low level of osmium leaching.

Claw Amphiphiles with a Dendrimer Core: Nanoparticle Stability and Drug Encapsulation Are Directly Proportional to the Number of Digits

There are numerous pharmaceutical, food, and consumer product applications requiring the incorporation of hydrophobic solutes within aqueous media. Often amphiphiles and/or polymers are used to produce encapsulating nanostructures. Because the encapsulation efficiencies of these nanostructures directly impact on the process or product, it is often desirable to optimize this parameter. To produce these advanced functional materials, we hypothesized that an amphiphile with a claw shape would favor polymer aggregation into nanoparticles and hydrophobic compound encapsulation. Claw amphiphiles were prepared by attaching one end of comb-shaped chitosan amphiphile chains [N,N,N-trimethyl, N,N-dimethyl, N-monomethyl, N-palmitoyl, N-acetyl, 6-O-glycol chitosan (GCPQA)] to a central dendrimer core [generation 3 diaminobutane poly(propylenimine) dendrimer (DAB)] to give DAB-GCPQA. The linear chitosan amphiphile (GCPQA) forms the digits of the claw. These claw amphiphiles were very stable and had a high encapsulating efficiency. DAB-GCPQAs (Mn = 30 and 70 kDa) had extremely low critical micelle concentrations [CMCs = 0.43 μg mL(-1) (13 nM) and 0.093 μg mL(-1) (0.9 nM), respectively], and their CMCs were lower than that of linear GCPQA [Mn = 14 kDa, CMC = 0.77 μg mL(-1) (38 nM)]. The claw amphiphile CMCs decreased linearly with the number of digits (r(2) = 0.98), and drug encapsulation (hydrophobic drug propofol) in 4 mg mL(-1) dispersions of the amphiphiles increased linearly (r(2) = 0.94) with the number of digits. DAB-GCPQA70 (4 mg mL(-1), 0.058 mM) encapsulated propofol (7.3 mg mL(-1), 40 mM). Finally, despite their stability, claw amphiphile nanoparticles are able to release the encapsulated drug in vivo, as shown with the claw amphiphile-propofol formulations in a murine loss of righting reflex model.

Dendritic upconverting nanoparticles enable in vivo multiphoton microscopy with low-power continuous wave sources.

We report a group of optical imaging probes, comprising upconverting lanthanide nanoparticles (UCNPs) and polyanionic dendrimers. Dendrimers with rigid cores and multiple carboxylate groups at the periphery are able to tightly bind to surfaces of UCNPs pretreated with NOBF(4), yielding stable, water-soluble, biocompatible nanomaterials. Unlike conventional linear polymers, dendrimers adhere to UCNPs by donating only a fraction of their peripheral groups to the UCNP-surface interactions. The remaining termini make up an interface between the nanoparticle and the aqueous phase, enhancing solubility and offering multiple possibilities for subsequent modification. Using optical probes as dendrimer cores makes it possible to couple the UCNPs signal to analyte-sensitive detection via UCNP-to-chromophore excitation energy transfer (EET). As an example, we demonstrate that UCNPs modified with porphyrin-dendrimers can operate as upconverting ratiometric pH nanosensors. Dendritic UCNPs possess excellent photostability, solubility, and biocompatibility, which make them directly suitable for in vivo imaging. Polyglutamic dendritic UCNPs injected in the blood of a mouse allowed mapping of the cortical vasculature down to 400 μm under the tissue surface, thus demonstrating feasibility of in vivo high-resolution two-photon microscopy with continuous wave (CW) excitation sources. Dendrimerization as a method of solubilization of UCNPs opens up numerous possibilities for use of these unique agents in biological imaging and sensing.

Interest of designed cyclodextrin-tools in gene delivery

Cyclodextrins (CyDs) currently displays even today the image of a natural macrocyclic compound largely dominant in the formation of inclusion complexes with small hydrophobic molecules. During the past 10 years, advances in this field allowed to achieve more and more sophisticated CyDs derivatives opening a simple access in scale-up quantities to original and better CyD-based gene delivery systems. In addition, possibility to combine covalent and supramolecular approaches offers new venues for the design of tailor-made CyD-based nanovehicles to improve their transfection ability and gene transfer in cells. In this account, we describe our recent progress in the construction of a novel CyD-based G0 (generation number) core dendrimer, scalable to CyD oligomers by a strategy using protonable guanidine tethers and whose concept can be generalized for the assembly of CyD pre-coated dendrimers. The synthetic strategy based on an original Staudinger-Aza-Wittig tandem coupling reaction. We present an outline of the different analytical strategies to characterize CyD-ODN (cyclodextrin-oligodeoxynucleotide) complexes. Among them, Capillary electrophoresis (CE) was used to perfectly characterize our CyD-siRNA and CyD-DNA complexes and shown to be a very attractive method with advantages of low sample consumption, rapid analysis speed, and high efficiency that make this technology a major tool for association constant measurement. Finally, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model bis-guanidinium-tetrakis-β-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA in eukaryotic cells.

Construction of Snowflake-Shaped Dendritic Covalent Assemblies with Rigid Conjugated Networks

A convergent method for the construction of shape-persistent nanoscale assemblies with conjugated backbones was developed. The copper-free Sonogashira coupling reaction was successfully applied to the formation of multiple covalent connections between conjugated terminals (iodide substituted aryl groups) of AB(2)-type outer components and four conjugated terminals (acetylenic bonds) of an inner A(4)-type core dendrimer. The conjugated networks in the starting components are expanded during the assembly process to afford nanoscale dendritic conjugated networks of the type A(4)(AB(2))(4), which have a porphyrin core, and longer (3.9 or 4.5 nm) and shorter (1.6 nm) conjugated chains. Fluorescence measurements revealed that singlet energy is effectively transferred in the assemblies from peripheral benzyl ether units and conjugated chains to the free base porphyrin core.

Conjugated Polyelectrolyte Dendrimers: Aggregation, Photophysics, and Amplified Quenching

Conjugated polyelectrolyte dendrimers (CPDs) are monodisperse macromolecules that feature a fully π-conjugated dendrimer core surrounded on the periphery by ionic solubilizing groups. CPDs are soluble in water and polar organic solvents, and they exhibit photophysics characteristic of the π-conjugated chromophores comprising the dendrimer core. Here we describe the synthesis and photophysical characterization of series of three generations of CPDs based on a phenylene ethynylene repeat unit structure that is surrounded by an array of anionic sodium carboxylate groups. Molecular dynamics simulations indicate that the first-generation CPD is flat while the second- and third-generation CPDs adopt oblate structures. Photophysical studies, including absorption, fluorescence spectroscopy, and lifetimes, show that the ester protected precursor dendrimers exhibit highly efficient blue fluorescence in THF solution emanating from the phenylene ethynylene chromophore that is in the dendrimer core. By contrast, the water-soluble CPDs have much lower fluorescence quantum yields and the absorption and fluorescence spectra exhibit features of strong chromophore-chromophore interactions. The results are interpreted as suggesting that the CPDs exist as dimer or multimer aggregates, even in very dilute solution. Fluorescence quenching of the anionic CPDs with the dication electron acceptor N,N'-dimethylviologen (MV(2+)) is very efficient, with Stern-Volmer quenching constants (K(SV)) increasing with generation number. The third-generation CPD exhibits highly efficient amplified quenching, with K(SV) ∼ 5 × 10(6) M(-1).

"Light Switch" Effect Upon Binding of Ru-dppz to Water-Soluble Conjugated Polyelectrolyte Dendrimers.

We report the "light switch" effect of [Ru(bpy)2(dppz)](2+) (where bpy = 2,2'-bipyridine and dppz = dipyrido[3,2-a:2',3'-c] phenazine, Ru-dppz) in the presence of anionic conjugated polyelectrolyte dendrimers (CPDs). The metal-to-ligand charge-transfer luminescence from Ru-dppz is efficient in the presence of CPD because the complex is shielded from water by binding to the hydrophobic dendrimer core.

Effects of salt on the size and internal structure of PAMAM dendrimers at different pH

G4 and G5 polyamidoamine dendrimers solvated with explicit water, counterions and NaCl ions (0.15, 1 M) were simulated at two levels of protonation, which mimic their electrostatic charges at pH 5 and 7. We used the previously parametrised coarse-grained dendrimer model which had predicted the experimentally measured and theoretically calculated size and internal structure of the dendrimer at different pH values. In this study, addition of ≤ 1 M NaCl does not significantly modulate the dendrimer size, in agreement with experiments and other theoretical studies. In particular, added salt ions do not change the dense-shell and dense-core structures of dendrimers without salt, respectively, at pH 5 and 7. Besides counterions, only a few excess ions penetrate and occupy the dendrimer interior, leading to unchanged volume of the inner cavity in the dendrimer core. These results indicate that addition of ≤ 1 M NaCl does not modulate the efficiency of encapsulating hydrophobic drugs or compounds.

Synthesis and characterization of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles

With the aim to develop a novel water-soluble modified chitosan nanoparticle with tuned size and improved antibacterial activity, quaternized carboxymethyl chitosan/poly(amidoamine) dendrimers (CM-HTCC/PAMAM) were synthesized. Firstly low-generation amino-terminated poly(amidoamine) (PAMAM) dendrimers were prepared via repetitive reactions between Michael addition and amidation, which were then employed for modifying quaternized carboxymethyl chitosan (CM-HTCC). Prior to the reaction of CM-HTCC with PAMAM, carboxylic groups in CM-HTCC were activated with EDC/NHS in order to enhance the reaction efficiency. FT-IR, 1H NMR, elemental analysis and XRD were performed to characterize CM-HTCC/PAMAM dendrimers. Turbidity measurements showed that CM-HTCC/PAMAM dendrimers had good water-solubility. TEM images indicated that CM-HTCC/PAMAM dendrimers existed as smooth and spherical nanoparticles in aqueous solution. The results of antibacterial activity explored that CM-HTCC/PAMAM dendrimer nanoparticles displayed higher antibacterial activity against Gram-negative bacteria Escherichia coli (E. coli), whereas they showed much less efficiency against Gram-positive bacteria Staphylococcus aureus (S. aureus) compared to quaternized chitosan (HTCC).

Evaluation of Jeffamine®‐cored PAMAM dendrimers as an efficient in vitro gene delivery system

In this study, we investigated gene delivery properties of Jeffamine-cored polyamidoamine (PAMAM) dendrimers (JCPDs). The effects of dendrimer concentration, generation, and core size on the gene delivery have been analyzed. The experimental results showed that the JCPD effectively delivered plasmid DNA inside the HeLa cells, and the transfection efficiency improved considerably as the number of generation increased. The cytotoxicity of JCPD in different concentration was tested for HeLa cell line. JCPD was complexed with a lacZ gene carrying plasmid and tested for transfection efficiency using quantitative β-galactosidase expression assay. Additionally, confocal microscopy results revealed that JCPD effectively delivered green fluorescent protein-expressing plasmid into HeLa cells and produced fluorescent signal with satisfactory efficiency. The highest transfection efficiency was obtained from JCPDs G4 and G5, which mixed with expression plasmid vectors at a 10/1 weight ratio. These results indicated that under optimized conditions, JCPD can be considered as an efficient transfection reagent and can be effectively used for gene delivery applications.

Synthesis of Dendrimer‐Encapsulated Silver Nanoparticles and Its Catalytic Activity on the Reduction of 4‐Nitrophenol

AbstractA new type of water soluble PEG core dendrimer having hydroxyl groups at the periphery was synthesized and used to prepare silver nanoparticles. The dendrimer and the dendrimer encapsulated nanoparticles (DENs) were characterized by spectroscopic techniques. The kinetics of catalytic activity of the prepared silver nanoparticle on the reduction of 4‐nitrophenol to 4‐aminophenol by NaBH4 as a reductant was studied using UV‐Visible spectrophotometer.

Novel Peptide‐Shelled Dendrimer with Dramatically Changeable Thermo‐Responsive Character

The preparation of a novel peptide/dendrimer hybrid is reported in which an elastin-like oligopeptide is successfully assembled onto a poly(amidoamine) dendrimer surface (G4-ELP), and its unique thermo-responsive behavior is discussed. As a result, the G4-ELP is found to exhibit LCST behavior in the pH range 3-10 including physiological temperature range under neutral-pH conditions. Moreover, cooperative interplay between the folding state of the ELP shell and the ionization state of the dendrimer core enables the G4-ELP to control its LCST widely by pH variation. This achievement provides a new insight for the design of dual-responsive materials with a potential in biological applications.

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.

DAB-Am-4 based colorimetric receptors for fluoride and pyrophosphate anions

Flexible four armed polypropylenimine tetraamine dendrimer (DAB-Am-4) core linked through urea moieties to a chromophore (aza group) gave rise to the colorimetric sensor 1 for fluoride ions, and a fluorophore (naphthyl group) attached to a similar assembly resulted in 2 which showed an excellent association constant with pyrophosphate anions.

Star polypeptides by NCA polymerisation from dendritic initiators: synthesis and enzyme controlled payload release

Well-defined star polypeptides were successfully synthesised by initiation of γ-benzyl-L-glutamate N-carboxyanhydride (NCA) from polypropylene imine (PPI) dendrimers. The dendrimer generation and the dendrimer to NCA ratio were systematically varied to afford a range of star shaped architectures with a maximum of 8 to 64 poly(γ-benzyl-L-glutamate) (PBLG) arms. High molar masses up to 500 000 g mol−1 were achieved that were otherwise unobtainable for the analogous linear polypeptides in the absence of the dendrimer core. By deprotection the PBLG star polypeptides were converted into poly(L-glutamic acid) (PGA) star polypeptides. Various concentrations of rhodamine B could be loaded into the polypeptide star architectures dependent on the number of PGA arms and the length of the grafted polypeptide chain produced. Furthermore, the polypeptidic nature of PGA-grafted dendrimers ensures their responsiveness, through controlled degradation, to the target enzyme thermolysin. An enzyme-responsive release mechanism was devised and demonstrated in which rhodamine B payload was released upon incubation with thermolysin but not the control enzyme chymotrypsin. The rate and extent of rhodamine B release was dependent on the composition of the hybrid material, which can be readily tuned to provide highly specific temporal and spatial controlled release.