Small Dendrimers Research Articles

From IHF protein to design and synthesis of a sequence-specific DNA bending peptide.

The design and synthesis of a small peptide that mimics the integration host factor (IHF), a major nucleoid-associated protein, is reported. IHF induces DNA compaction by sequence-specific binding that leads to significant bending of the DNA double strand. In a modular approach a small L-lysine dendrimer responsible for nonspecific charge-charge interactions was linked to a cyclopeptide. The latter was designed for specific DNA recognition in the minor groove followed by bending of the double strand.

Poly(amidoamine) dendrimers as nanoscale diffusion probes in sol-gel films investigated by total internal reflection fluorescence spectroscopy.

Three generations of poly(amidoamine) dendrimers were dye-labeled and chemically modified to have terminal carboxyl groups and used as variably sized probes to study diffusion in thin sol-gel films. Total internal reflection fluorescence spectroscopy experiments, both correlation and concentration-jump measurements, were employed to measure the relative populations and effective diffusion coefficients of dendrimers in the films. For films prepared from small (27-nm) silica particles, larger dendrimers could be completely excluded from penetrating the sol-gel structure. In films made of larger (150-nm) particles with correspondingly larger pores, concentration-jump experiments showed that larger dendrimers are excluded from more of the intraparticle pore space than small dendrimers. Similarly, fluorescence-correlation measurements showed that the diffusion of smaller dendrimers exhibited greater tortuosity than larger dendrimers in the interparticle pores of the film. The smaller dendrimers explore a greater volume of smaller, more convoluted pores, whereas larger dendrimers penetrate a smaller volume of larger, more open pores.

Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores.

Large macromolecular MRI contrast agents with albumin or dendrimer cores are useful for imaging blood vessels. However, their prolonged retention is a major limitation for clinical use. Although smaller dendrimer-based MRI contrast agents are more quickly excreted by the kidneys, they are also able to visualize vascular structures better than Gd-DTPA due to less extravasation. Additionally, unlike Gd-DTPA, they transiently accumulate in renal tubules and thus also can be used to visualize renal structural and functional damage. However, these dendrimer agents are retained in the body for a prolonged time. The purpose of this study was to obtain information from which a macromolecular dendrimer-based MRI contrast agents feasible for use in further clinical studies could be chosen. Six small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole-body retention, and dynamic MRI were evaluated in mice to determine an optimal agent in comparison to Gd-[DTPA]-dimeglumine. Diaminobutane (DAB) dendrimer-based agents cleared more rapidly from the body than polyamidoamine (PAMAM) dendrimer-based agents with the same numbers of branches. Smaller dendrimer conjugates were more rapidly excreted from the body than the larger dendrimer conjugates. Since PAMAM-G2, DAB-G3, and DAB-G2 dendrimer-based contrast agents showed relatively rapid excretion, these three conjugates might be acceptable for use in further clinical applications.

Ferrocenyl Dendrimers Incorporated into Mesoporous Silica: New Hybrid Redox-Active Materials

A novel type of redox-active materials, which to our knowledge are the first examples of mesoporous silica hosts containing dendritic guest molecules within their highly ordered channels, is presented. A simple and efficient synthetic route has been used to incorporate poly(propyleneimine) dendrimers containing 4, 8, and 64 amidoferrocenyl moieties (1−3) into MCM-41. In these new composite materials (dend-n-MCM-41, n = 1−3) the integrity of the guest after the inclusion process is maintained (as confirmed by elemental analyses, IR, and 13C CP MAS NMR spectroscopy), resulting in stable dendrimer−matrix complexes. X-ray diffraction, nitrogen adsorption isotherms, and transmission electron microscopy are consistent with the full occupancy of the channels by the smallest dendrimer, whereas less effective inclusion is obtained with the bulkier macromolecules. One significant feature of these new composite materials is that the guest dendrimers, containing a controlled number of ferrocenyl units, are easily acc...

Conformations of dendrimers in dilute solution

Conformations of isolated homo-dendrimers of G=1–7 generations with D=1–6 spacers have been studied in the good and poor solvents, as well as across the coil-to-globule transition, by means of a version of the Gaussian self-consistent method and Monte Carlo simulation in continuous space based on the same coarse-grained model. The latter includes harmonic springs between connected monomers and the pair-wise Lennard-Jones potential with a hard core repulsion. The scaling law for the dendrimer size, the degrees of bond stretching and steric congestion, as well as the radial density, static structure factor, and asphericity have been analyzed. It is also confirmed that while smaller dendrimers have a dense core, larger ones develop a hollow domain at some separation from the center.

Fast Adsorption on Nonideal Surfaces

The initial adsorption kinetics in stagnant flow of both rigid spherical poly(propylene imine) dendrimers as well as of flexible branched poly(ethylene imine) with similar building-blocks on glass are quantitatively described as Smoluchowski−Levich convective-diffusion-controlled up to concentrations cb ≈ 10 mg/L using a sticking probability β, defined as the ratio between the experimental adsorption rate and the theoretical prediction. This parameter β accounts for the nonideality of the substrate: There is only a limited amount of surface sites in the glass gel-layer available for adsorption, and this affects the collision efficiency. β is on the order of 0.03 for the small spheres and 0.8 for the flexible polyelectrolyte, perfectly in line with the expectation that the flexible polyelectrolyte, able to conform along the surface, has a much higher chance of finding a site within its contact area than the small dendrimers. At higher concentrations, the experimental data no longer show the predicted line...

Redox Potential Selection in a New Class of Dendrimers Containing Multiple Ferrocene Centers

The preparation and electrochemical properties of four new dendrimers, compounds 1, 2, 3, and 4, containing eight, seven, four, and four ferrocene residues, respectively, are described. These small dendrimers were prepared with the building block bis(ferrocenylmethyl)alkylamine, which contains the tether −CH2−N(R)−CH2− linking two ferrocene units. The resulting dendrimers are multiferrocene compounds in which the peripheral ferrocene residues are paired. Partial protonation or N-methylation of the connecting nitrogen atoms allows the selection of the ferrocene oxidation potentials between two different values (∼0.4 and ∼0.6 V vs Ag/AgCl). The observed voltammetric pattern for ferrocene oxidation can be reversibly switched among several states depending on the number of protonated centers within each dendritic structure. Crystallographic and electrochemical data confirm that the electronic communication between two equivalent ferrocene centers is lessened after protonation or N-methylation of the connectin...

Diffusion of Dendritic Polymers Through Concentrated Polymer Solutions

AbstractDiffusional dynamics of polymers can be very sensitive to polymer architecture. Polymers with novel (or time-varying) architectures could facilitate the release of therapeutic compounds from gels or concentrated polymer solutions with unusual or novel kinetic profiles. Towards this end, we are studying the behavior of model dendritic polymers, the poly(amidoamine)(PAMAM) dendrimers, in aqueous solutions and in concentrated solutions of a “matrix” polymer, poly(ethylene oxide)(PEO). Fluorescence measurements of the environmental polarity of the dendrimers provide evidence for pH-induced confomational changes in mid-sized (generation 6), but not in small (generation 2) dendrimers. In aqueous solution, dendrimer diffusion measurements reveal the fractal-like growth of these molecules, but measurements in aqueous PEO solutions failed to detect any pH dependence of the diffusion coefficient. Specific chemical interactions between the PEO and the PAMAM molecules may dominate their dynamic behavior.

Cayley Tree Random Walk Dynamics

AbstractWe investigate diffusion on newly synthesized molecules with dendrimer structures. We model these structures with geometrical Cayley trees. We focus on diffusion properties, such as the excursion distance, the mean square displacement of the diffusing particles, and the area probed, as given by the walk parameter SN, the number of the distinct sites visited, on different coordination number, z, and different generation order g of a dendrimer structure. We simulate the trapping kinetics curves for randomly distributed traps on these structures, and compare the finite and the infinite system cases, and also with the cases of regular dimensionality lattices. For small dendrimer structures, SN approaches the overall number of the dendrimer nodes, while for large trees it grows linearly with time. The average displacement R also grows linearly with time. We find that the random walk on Cayley trees, due to the nature ot these structures, is indeed a type of a “biased” walk. Finally we find that the finite-size effects are particularly important in these structures.

An EPR Study of the Interactions between Starburst Dendrimers and Polynucleotides

Interactions of nitroxide-labeled polyamidoamine dendrimers of generations 2 and 6 (2SBD-T and 6SBD-T, respectively) with double-stranded polynucleotidesCalf Thymus DNA (C.T.DNA), poly(deoxyadenylic−deoxythymidylic acid) (termed Poly(AT)), poly(deoxyguanylic−deoxycytidylic acid) (termed Poly(GC)), and a double-stranded oligonucleotide of 12 base pairs (DNA-12mer)were investigated by EPR. Computer-aided analysis of the EPR spectra provided information on the mobility of the nitroxide labels and their partition in different environments, which, in turn, gave information on the interactions between dendrimers and polynucleotides. After complexes were formed between DNA and SBD, the labels retained fast mobility at room temperature. On the basis of EPR analysis at 258 K, interaction of oligo- or polynucleotides with SBDs decreased in the following order: DNA-12mer > C.T.DNA > Poly(GC) > Poly(AT). Small dendrimers (2SBD-T) at low pH (5.5) showed significant interaction with the polynucleotides, which decreased with an increase in concentration due to self-aggregation of dendrimer molecules. Conversely, interaction between large dendrimers (6SBD-T) and polynucleotides increased with an increase in SBD concentration until saturation of the interacting sites occurred. Comparison with previous studies on nSBD-T−vesicle systems indicated that interaction of dendrimers with vesicles is stronger than dendrimer−polynucleotide interaction. This study provides some insights into dendrimer−DNA interactions of particular interest in understanding the mechanism of gene transfer to mammalian cells by SBDs.

A comparison of two convergent routes for the preparation of metalloporphyrin-core dendrimers: direct condensationvs. chemical modification

Porphyrin-core dendrimers consisting of benzyl ether dendrons assembled around a porphyrin core have been prepared by two different convergent syntheses. The first involves the direct condensation of convergent dendrons having 3,5-disubstituted benzaldehyde focal points with an equivalent amount of pyrrole. This route which requires very mild conditions is especially useful for the rapid assembly of small dendrimers but suffers from steric limitations as the size of the dendrons increases above the fourth generation. The second route involves the attachment of pre-formed benzyl bromide dendrons to a functionalized porphyrin through a simple Williamson synthesis. This route is also very practical but it requires careful purification of the final product from the partially functionalized porphyrin dendrimers that are also obtained. MALDI mass spectrometry proved to be a very useful tool both for monitoring the formation of the dendritic porphyrins and for their characterization.

Hexamethylhydrazinocyclotriphosphazene N3P3(NMeNH2)6: Starting reagent for the synthesis of multifunctionalized species, macrocycles, and small dendrimers

Hexamethylhydrazinocyclotriphosphazene N3P3(NMeNH2)6: Starting reagent for the synthesis of multifunctionalized species, macrocycles, and small dendrimers

Electrochemical Reduction of CO2 Catalyzed by Small Organophosphine Dendrimers Containing Palladium

The sequential addition of diethyl vinylphosphonate to primary phosphines followed by reduction with lithium aluminum hydride can be used to synthesize small dendrimers containing up to 15 phosphorus atoms. A second approach uses the addition of bis((diethylphosphino)ethyl)phosphine to tetravinylsilane to produce a dendrimer containing 12 phosphorus atoms. The connectivities of these ligands are established unambiguously by {sup 31}P NMR spectroscopy. These dendrimers react with [Pd(CH{sub 3}CN){sub 4}](BF{sub 4}){sub 2} to produce metalated dendrimers which catalyze the electrochemical reduction of CO{sub 2} to CO. Relationships between catalytic properties and dendrimer structure are discussed.