Physicochemical properties of quaternized poly(amidoamine) dendrimers with alkyl groups and of their mixtures with sodium dodecyl sulfate

The physicochemical properties of quaternized poly(amidoamine) dendrimers (generation 4) with methyl or octyl groups and of their mixtures with sodium dodecyl sulfate (SDS) in aqueous solutions have been investigated using several techniques including surface tension, fluorescence of pyrene, and dynamic light scattering. In the single systems of the dendrimers, the dendrimer with octyl groups shows lower surface tension and lower micropolarity than the dendrimer with methyl groups. The hydrodynamic radii of two quaternized poly(amidoamine) dendrimers are considerably large, indicating the formation of aggregates. In the mixed systems of quaternized poly(amidoamine) dendrimers and SDS, the dendrimer with octyl groups-SDS mixed system shows very low surface tension and low micropolarity even in the presence of extremely low SDS concentration compared to those of the dendrimer with methyl groups-SDS mixed system. Maximum turbidity for both systems is observed at around the mixed molar ratio of dendrimer:SDS=1:1.5 where distinct changes have also been confirmed by surface tension, fluorescence of pyrene, and electrical conductivity measurements.     

Dendrimers as potential drug carriers; encapsulation of acidic hydrophobes within water soluble PAMAM derivatives

This paper describes the synthesis of three neutral water soluble poly(amidoamine) (PAMAM) dendrimer derivatives. The ability of the two larger dendrimers to bind small acidic hydrophobic molecules is reported. Spectroscopic data and pH behaviour suggested that the acidic hydrophobes were forming stable ion pairs with the dendrimer's internal, basic tertiary nitrogens. With respect to forming 1:1 and 2:1 substrate/dendrimer complexes, both of the larger dendrimers were equally efficient at binding. All dendrimer/substrate complexes were completely miscible with water in all proportions (i.e. infinitely water soluble). When the bound substrates are drug moieties, then the resulting complexes could be considered as potential drug delivery systems. Flow calorimetry demonstrated that the dendrimers were able to release their hydrophobic guests when in contact with a biological cell.     

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     

Synthesis of poly(ester‐amide) dendrimers based on 2,2‐Bis(hydroxymethyl) propanoic acid and glycine

Water‐soluble, biodegradable, and biocompatible poly(ester‐amide) dendrimers with hydroxyl functional groups are synthesized from previously prepared AB₂ adduct of 2,2‐bis(hydroxymethyl) propanoic acid (bis‐MPA) and glycine as a repeating unit. Two esterification procedures using different coupling reagent/catalyst systems (DCC/DPTS or EDC/DMAP) are studied with respect to efficiency, ease of products purification, and quality of the final products. Both procedures have their own benefits and drawbacks, depending on dendrimer generation. The synthesized poly(ester‐amide) dendrimers as well as commercially available bis‐MPA dendrimers, poly(ester‐amide) hyperbranched polymer, and poly(vinyl alcohol) are used for preparation of solid dispersions of sulfonylurea antidiabetic drug glimepiride to improve its poor water‐solubility. In vitro dissolution studies show in comparison with pure glimepiride in crystalline or amorphous form, to the same extent improved glimepiride solubility for solid dispersions based on dendritic polymers, but not for poly(vinyl alcohol). The amount of glimepiride complexed with both dendrimer types increases with dendrimer generation. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3292–3301     

Electrocatalytical properties of polymethylferrocenyl dendrimers and their applications in biosensing

The electrochemical characterization of polymethylferrocenyl dendrimers deposited onto a platinum electrode and their applications as hydrogen peroxide and glucose sensor are described. The redox dendrimers consist of flexible poly(propileneimine) dendrimer cores functionalised with octamethylferrocenyl units. Amperometric biosensors for glucose were prepared by immobilization of glucose oxidase onto these modified electrodes. The influence of the dendrimer generation and the thickness of the dendrimer layer, the effect of the substrate concentration, and the interferences and reproducibility on the response of the sensors were investigated.     

N‐Boc‐Protected 1,2‐Diphenylethylenediamine‐Based Dendritic Organogels with Multiple‐Stimulus‐Responsive Properties

A new class of poly(benzyl ether) dendrimers, decorated in their cores with N‐Boc‐protected 1,2‐diphenylethylenediamine groups, were synthesized and fully characterized. It was found that the gelation capability of these dendrimers was highly dependent on dendrimer generation, and the second‐generation dendrimer (R,R)‐G₂DPENBoc proved to be a highly efficient organogelator. A number of experiments (SEM, TEM, FTIR spectroscopy, ¹H NMR spectroscopy, rheological measurements, UV/Vis absorption spectroscopy, CD, and XRD) revealed that these dendritic molecules self‐assembled into elastically interpenetrating one‐dimensional nanostructures in organogels. The hydrogen bonding, π–π, and solvophobic interactions were found to be the main driving forces for formation of the gels. Most interestingly, these dendritic organogels exhibited smart multiple‐stimulus‐responsive behavior upon exposure to environmental stimuli such as temperature, anions, and mechanical stress.     

Dendrimers as Nd3+ ligands: Effect of Generation on the Efficiency of the Sensitized Lanthanide Emission

We have designed two novel dendrimers with cyclam cores with appended poly(amido amine) (PAMAM) dendrons, decorated at the periphery with four and eight dansyl chromophores, respectively. The photophysical properties of the dendrimers and their Nd³⁺ complexes have been investigated. The energy‐transfer efficiency to the lanthanide ions from these dendrimers has been studied as a function of the generation. It has been observed that an increase in the dendrimer generation as well as the number of amide units enhances the energy transfer to the lanthanide ion.     

Metallocorrole dendrimers: sensitive corrole-chromium(V)-nitride spin probes for studying the solution structure of dendrimers

The corrole-chromium(V)-nitrido moiety is introduced as a uniquely sensitive EPR spin probe. We describe a series of corrole-centered poly(amidoamine) (PAMAM) dendrimers and the selective incorporation of the chromium(V)-nitrido moiety. The chromium-corrole cores are reactive toward both neutral and charged reagents, and the accessibility of the dendrimer cores enables easy manipulation of the spin probe. The spin probe reveals a pronounced solvent dependence of the solution-phase structure of the dendrimers.     

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.     

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.     

Dendrimers as photochemical reaction media. Photochemical behavior of unimolecular and bimolecular reactions in water-soluble dendrimers

Synthesis and studies of poly(alkyl aryl ether) dendrimers, possessing carboxylic acid functionalities at their peripheries, are reported. 5-Bromopentyloxy methylisophthalate was utilized as the monomer to O-alkylate the phenolic hydroxyl groups of poly(alkyl aryl ether) dendrimers. Dendrimers of first, second, and third generations, possessing 6, 12, and 24 carboxylic acids, respectively, were thus prepared. These dendrimers were soluble in alkaline aqueous solutions, and the ensuing microenvironmental properties of the aqueous solutions were assessed by pyrene solubilization studies. Upon establishing the presence of nonpolar microenvironments within the dendritic structures, solubilizations of few organic substrates were conducted and their photochemical behaviors were assessed. Specifically, the photolysis of 1-phenyl-3-p-tolyl-propan-2-one and benzoin ethyl ether and photodimerization of acenaphthylene were conducted. These studies revealed that the product distribution and the "cage effect" were more distinct and efficient for the third generation dendrimer, than for the first and second generation dendrimers. The photochemical studies of carboxylic acid functionalized dendrimers were compared to that of hydroxyl group terminated poly(alkyl aryl ether) dendrimers.     

Degradable dual pH- and temperature-responsive photoluminescent dendrimers

Poly(β-aminoester) dendrimers have been prepared. These systems represent the first degradable dual pH- and temperature-responsive dendrimers displaying photoluminescence. The pH/temperature sensitivities are interrelated; the lower critical solution temperature of the dendrimer decreases as the pH of the solution is increased. The sensitivities are mainly due to phase changes of the surface groups with changes in pH or temperature. These dual-responsive dendrimers are very useful in drug delivery. They may be loaded with a hydrophobic drug at low temperature without using organic solvents. The loaded drug is released very slowly and steadily at 37 °C and physiological pH, but can be quickly released at acidic pH, for example the lysosomal pH (pH 4-5), for intracellular drug release. These dendrimers also display strong photoluminescence, which can be exploited for monitoring drug loading and release. Thus, poly(β-aminoester) dendrimers constitute ideal drug carriers since their thermal sensitivity allows the loading of drugs without using organic solvents, their pH sensitivity permits fast intracellular drug release, and their photoluminescence provides a means of monitoring drug loading and release.     

Platinum ion uptake by dendrimers: an NMR and AFM study

The reaction of generation 2 and generation 4 poly(amidoamine) (PAMAM) dendrimers with K2PtCl2 was studied by several NMR methods. The time dependency of the Pt(II) complexation was followed with 195Pt NMR for both dendrimers and the equilibrium product was further characterized with (1)H NMR, and indirectly detected 13C NMR, in the case of the generation 2 dendrimer. After 2 days, a black precipitate of Pt(0) was observed, half the original 195Pt signal was lost, and approximately 20% of the initial Pt(II) was coordinated to the tertiary and secondary nitrogens of the generation 2 dendrimer. The uptake of Pt(II) by the generation 4 dendrimer was much slower, consistent with the steric crowding of the surface groups on the generation 4 dendrimer compared to the more open generation 2. After 10 days, 80% of the Pt(II) was deep within the generation 4 dendrimer; the remaining 20% was unreacted or bound near the surface nitrogens of a single dendrimer. The location and time course of the platinum ion uptake by the dendrimers provides valuable insight into the formation of Pt(0) nanoparticles made in the presence of dendrimers as stabilizers, visualized by atomic force microscopy.     

Detecting the adsorption of dye molecules in homogeneous poly(propylene imine) dendrimer monolayers by surface plasmon resonance sensor

In this work, we studied guest-host interactions between various dye molecules and the fifth-generation poly(propylene imine) (PPI-5) dendrimers in aqueous solutions using a surface plasmon resonance (SPR) sensor. The effect of the properties of guest and host molecules (e.g., charge and shape) and media (e.g., pH and ion strength) on affinity between guest and host molecules was investigated. Based on an immobilized homogeneous monolayer of PPI-5 dendrimer tethered to carboxyl-terminal self-assembled monolayers, the adsorption behavior of a group of dye molecules in PPI-5 was obtained. Results show that the strong affinity of PPI-5 to Rose Bengal and erythrosine B is attributed to the good match in charge and shape between the cavities of the dendrimer and the dye molecules. Maximum adsorption around a pH value of 7 was observed. The kinetic behaviors of different dye molecules in dendrimers were also studied. A fundamental understanding of guest-host interactions in dendrimers will guide the design of new-generation sensors and drug delivery carriers.     

Preparation of gold-, gold/silver-dendrimer nanocomposites in the presence of benzoin in ethanol by UV irradiation

Gold- and gold/silver-dendrimer nanocomposites have been synthesized by UV irradiation of their salts dissolved in ethanol containing dendrimers. As dendrimers, poly(amidomaine) PAMAM dendrimers and poly(propyleneimine) PPI dendrimers of various generations were used. The photoreduction of their salts is greatly accelerated by using benzoin as a photoinitiator. The sizes of gold in the nanocomposites are affected by the concentration of benzoin as well as the concentration of dendrimers, but are hardly changed with the kind of dendrimers. For gold/silver-dendrimer nanocomposites, the absorption spectra of gold/silver nanoparticles in the nanocomposites are very similar to the theoretical spectra of gold/silver alloy nanoparticles, suggesting the formation of gold/silver alloy nanoparticles. From the comparison of TEM and DLS measurements, it is found that the metal-dendrimer nanocomposites consist of metal nanoparticles covering by dendrimer molecules.     

Synthesis of new dendrimers—trimesic acid derivatives

The efficient synthesis of new dendrimeric polyesters up to generation 3 that consist of 1,3,5-benzenetricarboxylic acid building blocks with potential applications in drug delivery is described. The dendrimers possess hydroxy or allyl functional groups on the surface and were prepared through a divergent approach using readily available 2-(hydroxymethyl)-2-ethylpropan-1,3-diol and 1,3,5-benzenetrimethanol as central cores, with 3,5-bis[(allyloxy)methyl]benzoic acid being an essential unit of the dendrimer. The latter compound was synthesized, in high yield, from 1,3,5-benzenetricarboxylic acid, applying selective hydrolysis of the corresponding triester as the key step.     

Bienzyme sensors based on novel polymethylferrocenyl dendrimers

Amperometric bienzyme electrodes with horseradish peroxidase (HRP) and glucose oxidase (GOx) co-immobilized on polymethylferrocenyl dendrimers deposited onto platinum electrodes have been used for determination of the hydrogen peroxide produced by the oxidase during the enzymatic reaction. The redox dendrimers consist of flexible poly(propylenimine) dendrimer cores functionalised with octamethylferrocenyl units. The effects of dendrimer generation, the thickness of the dendrimer layer, substrate concentration, interferences, and reproducibility on the response of the sensors were investigated. The new bienzyme biosensors respond to substrate at work potential values between 200 and 50 mV (vs. SCE), have good sensitivity, and are resistant to interferences. Figure     

New Dendrimers: Synthesis and Characterization of Popam - Pamam Hybrid Dendrimers

Recently developed multifunctional cancer therapeutic nano-device production is based on poly(amidoamine) PAMAM generation 5 (G5) dendrimer as a carrier 1-5. Scale up synthesis of this nano-device is limited because of long reaction sequence (12 reaction steps) and long and not easy work up of the products after each reaction step. Combination of poly(propyle-imine) and poly(amidoamine) synthesis can improve the production of the drug carrier.In this paper we give a general overview of the synthesis and characterization of a series of novel hybrid dendrimers which we coined as novel POMAM hybrid dendrimers, constructed from poly(propylene-imine) (PPI or POPAM) core and poly(amidoamine) PAMAM shells. The synthesis was accomplished by a divergent reiterating method involving repeating subsequent Michael addition and amidation reactions. Each generation of the newly synthesized dendrimer was characterized by using HPLC, GPC, NMR and AFM.     

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     

Synthesis of phosphorus dendrimers bearing chromophoric end groups: toward organic blue light-emitting diodes

Several series of phosphorus dendrimers decorated by potential fluorescent end groups (naphthalene, anthracene, and pyrene) have been synthesized. Unexpectedly, we found that it is absolutely necessary to link the fluorophore to the dendrimer through an alkyl link, and not directly through heteroelements such as oxygen or nitrogen, in order to preserve the fluorescence. One series of dendrimers from generation 1 (6 pyrene end groups) to generation 4 (48 pyrene end groups) has been tested for the elaboration of organic light-emitting diodes (OLEDs). The threshold voltage for the emission of light is high (over 20 V), however, electroluminescence is observed in all cases.