Comprehensive characterization of surface-functionalized poly(amidoamine) dendrimers with acetamide,hydroxyl, and carboxyl groups

Terminal amine groups of poly(amidoamine) (PAMAM) dendrimers can be substituted with different functional groups for various applications. In this study, PAMAM derivatives with acetamide, hydroxyl, and carboxyl termini were synthesized from ethylenediamine (EDA) core generation 4 and 5 primary amine-terminated PAMAM dendrimers. The reaction products were purified with dialysis and subsequently characterized by polyacrylamide gel electrophoresis (PAGE), capillary electrophoresis (CE), size exclusion chromatography (SEC), matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, potentiometric titration, ¹H NMR, and ¹³C NMR. PAGE and CE electropherograms provide data regarding the purity, charge distribution, and electrophoretic mobility of the dendrimers and their derivatives. SEC and MALDI-TOF mass spectrometry detect the average absolute molar mass and the individual mass fractions, respectively. The combination of SEC with potentiometric titration provides quantitative evidence of the degree of the functional group substitution, while NMR techniques (both ¹H NMR and ¹³C NMR) confirmed the changes in dendrimer surface functionalization. This study provides a general example for the comprehensive characterization of surface-functionalized PAMAM dendrimer nanoparticles. The synthesized dendrimer derivatives hold promise for environmental and medical applications.     

Polyelectrolyte behavior and interpolyelectrolyte matching of AstramolTM poly(propylene imine) dendrimers

Polyelectrolyte behavior of Astramol^TM poly(propylene imine) dendrimers of five generations, G1‐G5, namely DAB‐dendr‐(NH₂)_x (where x is equal to 4, 8, 16, 32 or 64) was studied by means of potentiometric titration in salt‐free water solutions and also in the presence of a shielding low molecular electrolyte (NaCI). In addition to x outer primary amine groups the dendrimer molecule contains x‐2 inner tertiary amine groups. The repeating unit, the core molecule and the fifth generation dendrimer structure are shown in the following Scheme.     

Scaling trend in diffusion coefficients of low generation G0–G3 PAMAM dendrimers in aqueous solution at high and neutral pH

Aqueous solution diffusion coefficients for G0–G3 PAMAM dendrimers were determined from DOSY-NMR spectroscopy at high and neutral pH. The study was performed in a dilute regime and diffusion coefficients at infinite dilution (D ₀) were estimated from the variation of diffusion coefficients with dendrimer concentration. Hydrodynamic radii (R _h) for each dendrimer were estimated from D ₀ using the Stoke–Einstein relationship at both pH. According to D ₀ and R _h values, the structure of G0–G1 PAMAM dendrimers is almost insensitive to pH variations, whereas G2–G3 PAMAM dendrimers undergo swelling at neutral pH, due to surface amino groups protonation. Experimental diffusion coefficients show a scaling trend with the number of dendrimer atoms (N), with scaling laws of the type D₀ μ N^a D_{0} \propto N^{\alpha } , where α takes values of −0.39 and −0.50 at pH 12 and 7, respectively. For the first time, experimental data accounts for the scaling behavior of aqueous diffusion coefficients for low generation PAMAM dendrimers, as previously reported from molecular dynamics simulations.     

Synthesis of dicarboxylate oligosaccharide multilayer terminal functionality upon poly(lysine) dendrimer scaffolding

A reactive three‐layered dendrimer containing carboxyl groups was synthesized by the coupling of dicarboxylic acid and a highly reactive, two‐layered glycopeptide dendrimer. Lactose, maltose, or maltotriose was reacted with the poly(lysine) dendrimer in its third and fourth generations by reductive amination and afforded two‐layered glycolysine dendrimers. The reaction was conducted in a borate buffer (pH 9.0). ¹H NMR, ¹³C NMR, and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry analyses were applied for the determination of the structures of the products. When an excess amount of the oligosaccharide and a long reaction time were used, the degree of substitution increased to 1.5–2.0 against an amino group. For the preparation of highly reactive, multilayered dendrimers for an antigen carrier, C6 hydroxy groups of the oligosaccharides were selectively esterified by adipic acid and suberic acid to give 6‐O‐adipoyl oligosaccharide–poly(lysine) dendrimers and 6‐O‐suberoyl oligosaccharide–poly(lysine) dendrimers. The reactivity of these multilayered dendrimers was examined by a model reaction with phenylalanine ethyl ester. The dendrimer showed high reactivity, providing phenylalanine ethyl ester–dicarboxylate oligosaccharide–poly(lysine) dendrimers with a considerably high proportion of phenylalanine residues. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3622–3633, 2002     

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     

Interaction of G-quadruplex Forming DNA Aptamers with PAMAM Dendrimers Studied by Dynamic Light Scattering and UV-VIS Spectrophotometry**

The complexes of G-quadruplex forming DNA thrombin binding aptamers (TBA) and polyamidoamine dendrimers (PAMAM) were studied with the aim to form a model targeted drug delivery system. Hydrodynamic diameter, zeta potential and melting temperature (T_m) were investigated by dynamic light scattering and UV-VIS spectrophotometry. Non-covalent adsorption by means of electrostatic interaction between positively charged amino groups of dendrimers (+) and negatively charged phosphate groups of aptamers (−) has driven the formation of aggregates. The size of complexes was in the range of 0.2–2 μm and depended on the type of dispersant, charge ratio (+/−) and temperature. Raising the temperature increased the polydispersity, new smaller size distributions were observed indicating the G-quadruplex unfolding. The melting transition temperature of TBA aptamer was affected by the presence of amino-terminated PAMAM rather than carboxylated succinic acid PAMAM−SAH dendrimer, thus supporting the electrostatic nature of interaction that disturbed denaturation of target-specific quadruplex aptamer structure.     

Synthesis of P(MBA-co-MAA) microsphere-grafted PAMAM dendrimers and their application as supporters for gold nanoparticles

Poly(N,N′-methylenebisacrylamide-co-acrylic acid) microsphere-supported polyamidoamine (PAMAM) dendrimers up to third generation (G) were grown onto the surface as well as the gel-layer of P(MBA-co-MAA) microspheres by a divergent method. The P(MBA-co-MAA) supported PAMAM dendrimers were used as heterogeneous stabilizers for the gold nanoparticles by an in situ reduction of HAuCl₄ via the efficient coordination interaction between the amino groups of the supported PAMAM dendrimers and the gold atoms. The effects of the generations of the P(MBA-co-MAA) supported PAMAM dendrimer on the loadings and the catalytic activity of the heterogeneous Au nanoparticles were systematically investigated with the reduction of 4-nitrophenol to 4-aminophenol as a model reaction.     

Amperometric Detection and Quantification of 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) Using Dendrimer Modified Electrodes

8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) detection by high performance liquid chromatography (HPLC) with amperometric detection was studied using a Au electrode modified with different dendrimer based thin films. Gold electrode is thiol‐modified, forming self‐assembled monolayers on which different generation PAMAM dendrimers with terminal functional groups ? COOH and ? NH₂ have been attached using peptidic bonds. Results obtained in synthetic samples show low limits of detection and quantification for 8‐OHdG (1.2×10^?9 and 3.7×10^?9 M respectively), with matrix interference elimination, thus avoiding sample pretreatment. Best results are obtained with electrodes modified with aliphatic amino thiols and 3.5 and 4.5 generation carboxylated dendrimers (Au/AET/DG^3.5 and Au/AET/DG^4.5), demonstrating that these materials constitute a good alternative for 8‐OHdG determination in biological fluids.     

Direct force measurements between adlayers consisting of poly(amidoamine) dendrimers with primary amino groups or quaternary ammonium groups

Adsorption of poly(amidoamine) generation 3 (PAMAM G3) dendrimer with surface amino groups or PAMAM G0 dendrimer with quaternary ammonium groups (C8qbG0) onto glass has been studied by colloidal probe atomic force microscopy. The adlayer-adlayer interactions for these adsorbates are quite different despite the fact that they are almost equal in the hydrodynamic radius. In aqueous PAMAM G3 dendrimer solutions the electrostatic repulsion is predominant. The conformation of the adsorbed layer is flat and the protrusion of the individual dendrimers is negligible. On the other hand, C8qbG0 behaves as a surfactant and the layered structure of C8qbG0 is expected to be a patchy bilayer. Dispersion stability of silica suspensions with the adsorption of these dendrimers can be correlated with the force data obtained.     

Novel ultrafiltration membranes with the least fouling properties for the treatment of veterinary antibiotics in the pharmaceutical wastewater

Dendrimers have received more attention in all fields of research these days. In the present study, polyamidoamine (PAMAM) dendrimers were synthesized on the acrylic ultrafiltration membranes to minimize fouling as an important deficiency in the separation process. The antifouling activity of these dendrimers with different generations (G0‐3) was tested to restrict three macrolides (tylvalosin, tylosin, and tulathromycin) and two pleuromutilins (tiamulin and valnemulin) as veterinary antibiotic drugs with amine groups and positive charges at pH = 7 of the membrane surface. These compounds are risky for human consumption. Due to having several amine functional groups and branches, PAMAM dendrimers can be a great coating agent for antifouling. G3 PAMAM dendrimer‐coated membranes had the best performance (water flux: 130.7 L/m²·h, rejection of tulathromycin: 91.4%, flux recovery ratio: 86.3%). The function of this ultrafiltration process depended on pore size and also charge surface. A significant reduction for irreversible and reversible fouling was observed for this new ultrafiltration membrane (F_ir: 14.5%, F_re: 21.9%). This observation was confirmed by the power law model. Three 5‐hour cycle ultrafiltration processes were carried out for veterinary antibiotic wastewater that showed 3.18% loss of initial water flux (for the third cycle), final cleaning efficiency of 96.82%, and tylvalosin rejection of 94.1%.     

SiO2–poly(amidoamine) dendrimer inorganic/organic hybrids

SiO₂–poly(amidoamine) (PAMAM) dendrimer hybrids were synthesized via (1) a Michael addition reaction between the dendrimer and 3‐(trimethoxysilyl) propyl acrylate, (2) the dissolution of the formed compound in methanol, and (3) the mixing of the latter solution with a methanol solution of partly hydrolyzed tetraethylorthosilicate (TEOS) and its casting on a glass substrate. ¹H NMR indicated that in the first step, 77% of the secondary amines were converted into tertiary amines when the fourth‐generation dendrimer was employed and 46% were converted when the second‐generation dendrimer was used. The final SiO₂–PAMAM dendrimer hybrids were obtained via the hydrolysis and condensation of the compound obtained via the Michael addition and the methanol solution of partly hydrolyzed TEOS. The compartmentalized structure of the hybrids due to the compartments of the dendrimers could be controlled by changing the dendrimer and the amount of TEOS. Scanning electron microscopy and transmission electron microscopy micrographs provided information about the structure of the hybrids. Like the PAMAM dendrimer, the SiO₂–PAMAM dendrimer hybrids exhibited a high metal ion complexing capacity because of the presence of the compartments of the dendrimer; they can be, however, much more easily handled, and, as demonstrated by thermogravimetric experiments, have much higher thermal resistance. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1443–1449, 2000     

Preparation and characterization of silicone rubber through the reaction between γ‐chloropropyl and amino groups with siloxane polyamidoamine dendrimers as cross‐linkers

A novel heat‐curable silicone rubber (MCSR/Si‐PAMAM) was prepared by using siloxane polyamidoamine (Si‐PAMAM) dendrimers as cross‐linkers and polysiloxane containing γ‐chloropropyl groups as gums. The chemical cross‐linking occurs through the reaction between Si‐PAMAM dendrimers and polysiloxane containing γ‐chloropropyl groups. The effect of various amounts of cross‐linkers on mechanical properties of MCSR/Si‐PAMAM was discussed in this paper. MCSR/Si‐PAMAM exhibits favorable mechanical properties with a tensile strength of 10.06 MPa and a tear strength of 47.9 kN/m when the molar ratio r of [N‐H]/[CH₂CH₂CH₂Cl] is 1:1. These excellent mechanical properties can be attributed to the formation of concentrative cross‐linking from Si‐PAMAM dendrimers in the cross‐linking networks, along with the introduction of Si–O–Si units in the internal structure of dendrimers. The introduction of Si–O–Si units reduces the steric hindrance of molecular structure, which facilitates the N–H bonds in the interior layers of dendrimers to react with γ‐chloropropyl groups. In addition, thermogravimetric analysis results indicate that MCSR/Si‐PAMAM is thermally stable even at high temperatures in a nitrogen atmosphere. Differential scanning calorimetry analysis reveals that the glass transition peak of MCSR/Si‐PAMAM is not identified in the temperature range −150 to −30°C, only a melting endothermic peak at −40°C.     

Preparation of PAMAM- and PPI-metal (silver, platinum, and palladium) nanocomposites and their catalytic activities for reduction of 4-nitrophenol

Dendrimer-metal (silver, platinum, and palladium) nanocomposites are prepared in aqueous solutions containing poly(amidoamine) (PAMAM) dendrimers with surface amino groups (generations 3, 4, and 5) or poly(propyleneimine) (PPI) dendrimers with surface amino groups (generations 2, 3, and 4). The particle sizes of the metal nanoparticles obtained are almost independent of the generation as well as the concentration of the dendrimer for both the PAMAM and the PPI dendrimers; the average sizes of silver, platinum, and palladium nanoparticles are 5.6-7.5, 1.2-1.6, and 1.6-2.0 nm, respectively. It is suggested that the dendrimer-metal nanocomposites are formed by adsorbing the dendrimers on the metal nanoparticles. Studies of the reduction reaction of 4-nitrophenol by these nanocomposites show that the rate constants are very similar between PAMAM and PPI dendrimer-silver nanocomposites, whereas the rate constants for the PPI dendrimer-platinum and -palladium nanocomposites are greater than those for the corresponding PAMAM dendrimer nanocomposites. In addition, it is found that the rate constants for the reduction of 4-nitrophenol involving all the dendrimer-metal nanocomposites decrease with an increase in the dendrimer concentrations, and the catalytic activity of dendrimer-palladium nanocomposites is highest.     

Simultaneous Spectrophotometric Determination of Group B Vitamins Using Parallel Factor Analysis: PARAFAC

In this work, a simple and rapid analytical procedure was applied for simultaneous determination of folic acid (vitamin B₀), thiamin (vitamin B₁), riboflavin (vitamin B₂) and pyridoxal (vitamin B₆) based on the absorbance data in the pH range 2.0‐12.0 at 25 °C using parallel factor analysis (PARAFAC). The effect of the pH as the most important factor on the sensitivity of the determination was studied. The spectral data were recorded in 400‐650 nm intervals and a 2‐12 pH range for all four vitamins. The calibration set was constructed in the concentration ranges of 4‐22, 1‐20, 6‐26, and 4‐20 μg mL^?;1 for B₆,B₂,B₁ and B₀, respectively. The root mean squares errors of prediction for the prediction set, (RMSEP), are 0.65, 0.63, 1.13 and 0.34 for B₀,B₁,B₂ and B₆, respectively. The recovery percent for the validation set are in the range of 90.6 to 107.0%. The effect of the experimental conditions and diverse species were discussed. The optimum values of these factors were searched according to the relative standard deviation of the prediction set of mixtures solutions.     

A Penicillamine Biosensor Based on Tyrosinase Immobilized on Nano‐Au/ PAMAM Dendrimer Modified Gold Electrode

Gold electrodes were modified with submonolayers of 3‐mercaptopropionic acid and further reacted with poly(amidoamine) (PAMAM) dendrimers to obtain thin films. The high affinity of PAMAM dendrimer for nano‐Au with its amine groups was used to realize the role of nano‐Au as an intermediator to immobilize the enzyme of tyrosinase. The characterization of the modified electrode was investigated by cyclic voltammetry, electrochemical impedance spectroscopy and atomic force microscopy (AFM). Tyrosinase can catalyze the oxidation of catechol to o‐benzoquinone. When penicillamine was added to the solution, it reacted with o‐benzoquinone to form the corresponding thioquinone derivatives, which resulted in decrease of the reduction current of o‐benzoquinone. Based on this, a new electrochemical sensor for determination of penicillamine has been developed.     

Interaction forces between poly(amidoamine) (PAMAM) dendrimers adsorbed on gold surfaces

Interaction forces between two gold surfaces with adsorbed poly(amidoamine) (PAMAM) dendrimers (generations G3.0 and G5.0) have been investigated using colloidal probe atomic force microscopy (AFM). In the absence of dendrimers or at their low concentrations, an attractive force derived from the van der Waals interaction was observed. On the other hand, this attractive interaction changed to repulsion with increasing dendrimer concentration. The origin of the repulsion can be attributed to either an electric double layer interaction or a steric effect of the adsorbed dendrimers, depending on the concentration of dendrimer. The steric hindrance was also influenced by the generation of the dendrimer; the force-detectable distance in the presence of PAMAM G5.0 dendrimer was slightly longer than that in the presence of G3.0 dendrimer. In order to estimate the occupied area of each dendrimer adsorbed on gold, quartz crystal microbalance (QCM) measurement was also carried out.     

Zinc Substitution of Cobalt in Vitamin B12: Zincobyric acid and Zincobalamin as Luminescent Structural B12‐Mimics

Replacing the central cobalt ion of vitamin B₁₂ by other metals has been a long‐held aspiration within the B₁₂‐field. Herein, we describe the synthesis from hydrogenobyric acid of zincobyric acid ( Znby ) and zincobalamin ( Znbl ), the Zn‐analogues of the natural cobalt‐corrins cobyric acid and vitamin B₁₂, respectively. The solution structures of Znby and Znbl were studied by NMR‐spectroscopy. Single crystals of Znby were produced, providing the first X‐ray crystallographic structure of a zinc corrin. The structures of Znby and of computationally generated Znbl were found to resemble the corresponding Co^II‐corrins, making such Zn‐corrins potentially useful for investigations of B₁₂‐dependent processes. The singlet excited state of Znby had a short life‐time, limited by rapid intersystem crossing to the triplet state. Znby allowed the unprecedented observation of a corrin triplet (E^T=190 kJ mol^?1) and was found to be an excellent photo‐sensitizer for ¹O₂ (Φ_Δ=0.70).     

Starburstr̀ dendrimers — Nanoscopic supermolecules according to dendritic rules and principles

Construction of dendritic macromolecules based on the mimicry of macroscopic branching patterns found in trees is reviewed. From this mimicry, synthetic strategies have been developed for the preparation of precise macromolecular building blocks referred to as Starburstr̀/Cascade dendrimers. These dendrimer constructions involve the amplifications of matter (mass) by organizing monomer units around initiator cores according to geometrically driven mathematical rules and principles. The predictable precision of mass and valency (i.e., number of reactive surface groups) displayed by these dendrimers, as a function of generation, validates their proposed role as fundamental nanoscopic building blocks (i.e., particle sizes of 10 −1000Å). This emerging area of “structure-controlled polymers” is defining a fourth new major class of macromolecular architecture. Ideal, defect free structures of Starburst^r̀ polyamidoamine (PAMAM) dendrimers (e.g., NH₃ core; generation = 2.0, MWt. 2,414) have been synthesized in kilogram quantities with overall yields of 60-70%. The precise masses and surface valencies associated with these dendrimer structures allow one to view these entities as “nanoscopic analogues” to atoms. As such, basic rules of chemical combination between dendrimers to give definite, stoichiometric compositions can be defined much as first noted by Dalton for atoms. The use of these nanoscopic building blocks (i.e., 10–1000Å species) to construct supramolecular/supermolecular structures such as nanoscopic compounds, clusters and macro-lattices will be reviewed. Registered trademark of Dendritech Inc.     

Synthesis and characterization of polyaniline–polyamidoamine dendrimer blends

A novel conductive blend of polyaniline (PANI) with polyamidoamine dendrimer (PAMAM (G 2.0)) was prepared by different blending procedure. The PANI‐PAMAM blended polymers were characterized by UV–vis, FTIR, and electron paramagnetic resonance (EPR) spectra. The effect of varying the blending procedure on structure and EPR properties of PANI‐PAMAM blended polymers was investigated. Varying the blending procedure and temperature has a direct effect on the structure and EPR parameters (ΔH_PP, g factor, N_S, T₂, and A/B ratio). EPR spectroscopic studies suggested the presence of chemical interaction between PANI and PAMAM. Electron localization effects in PANI‐PAMAM blended polymers can therefore be studied using the technique of EPR. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1–8, 2006     

Synthesis,Redox Activity of Rigid Ferrocenyl Dendrimers,and Isolation of Robust Ferricinium and Class‐II Mixed‐Valence Dendrimers

The coupling reactions of ethynylferrocene with trihalogenoarenes do not lead to ethynylferrocenyl arenes that are soluble enough to form the basis of a suitable construction of stiff ferrocenylethynyl arene‐cored dendrimers, which explains the previous lack of reports on stiff ferrocenyl dendrimers. However, rigid ferrocenyl‐terminated dendrimers have been synthesized from 1,3,5‐tribromo‐ and triiodobenzene through Sonogashira and Negishi reactions with 1,2,3,4,5‐pentamethyl‐1′‐ethylnylferrocene ( 1 a ), according to 1→2 connectivity. With compound 1 a , the construction of a soluble dendrimer ( 10 a ) that contained 12 ethynylpentamethylferrocenyl termini was achieved. Stiff dendrimer 10 a shows a single, reversible cyclic voltammetry (CV) wave (with adsorption), which disfavors the hopping heterogeneous electron‐transfer mechanism that is postulated for redox‐terminated dendrimers that contain flexible tethers. The selectivity of these Sonogashira reactions allows the synthesis of an arene‐cored dendron ( 2 c ) that contains both ethynylferrocenyl and 1,2,3,4,5‐pentamethyl‐ferrocenylethynyl redox groups, thus leading to the construction of a dendrimer ( 7 c ) that contains both types of differently substituted ferrocenyl groups with two well‐separated reversible CV waves. Upon selective oxidation, this mixed dendrimer ( 7 c ) leads to a class‐II mixed‐valence dendrimer, 7 c [PF₆]₃, as shown by Mössbauer spectroscopy, whereas oxidation of the related fully pentamethylferrocenylated dendrimer ( 7 a ) leads to the all‐ferricinium dendrimer, 7 a [PF₆]₆.