Dendron Generation Research Articles

Selective ratiometric pH-sensing PAMAM light-harvesting dendrimer based on Rhodamine 6G and 1,8-naphthalimide

The paper reports on the divergent synthesis and fluorescence characteristics of a polyamidoamine (PAMAM) dendron of second generation. Novel compound is configured as a light harvesting antenna where the system surface is labeled with yellow-green emitting 4-(N-piperazinyl)-1,8-naphthalimide “donor” units capable of absorbing light and efficiently transferring the energy to a focal Rhodamine 6G “acceptor”. The energy transfer is calculated to 82%. Furthermore, the 1,8-naphthalimide periphery of the system is designed on the “fluorophore–spacer–receptor” format and is able to act as a molecular fluorescence photoinduced electron transfer based probe. Due to the both effects, photoinduced electron transfer in the periphery of the system and pH dependent rhodamine core absorption, novel antenna is able to act as a highly selective ratiometric pH fluorescence probe. Thus, the distinguishing features of light-harvesting systems (fluorescence resonance energy transfer) were successfully combined with the properties of classical ring-opening sensor systems.

Kinetically Arrested Assemblies of Architecturally Distinct Block Copolymers

The rapid coassembly of linear and linear–dendritic amphiphiles from homogeneous solution and high supersaturation produces kinetically arrested nanoparticles, the morphologies of which are distinct from equilibrium structures. The binary system of poly(d,l-lactide-co-glycolide)-block-poly(ethylene glycol) with a linear or dendritic architecture of the hydrophilic component, forms spherical hybrid nanoparticles regardless of dendron generation or poly(ethylene glycol) length. Controlled variation in nanoparticle size was achieved through a balance of amphiphile architecture, blend composition, and final solvent content. These results demonstrate how kinetic features of the assembly process influence the formation of hybrid copolymer nanoparticles.

N-Acetylgalactosamino Dendrons as Clearing Agents to Enhance Liver Targeting of Model Antibody-Fusion Protein

Dendrimer clearing agents represent a unique class of compounds for use in multistep targeting (MST) in radioimmunotherapy and imaging. These compounds were developed to facilitate the removal of excess tumor-targeting monoclonal antibody (mAb) prior to administration of the radionuclide to minimize exposure of normal tissue to radiation. Clearing agents are designed to capture the circulating mAb, and target it to the liver for metabolism. Glycodendrons are ideally suited for MST applications as these highly branched compounds are chemically well-defined, thus advantageous over heterogeneous macromolecules. Previous studies have described glycodendron 3 as a clearing agent for use in three-step MST protocols, and early in vivo assessment of 3 showed promise. However, synthetic challenges have hampered its availability for further development. In this report we describe a new sequence of chemical steps which enables the straightforward synthesis and analytical characterization of this class of dendrons. With accessibility and analytical identification solved, we sought to evaluate both lower and higher generation dendrons for hepatocyte targeting as well as clearance of a model protein. We prepared a series of clearing agents where a single biotin is connected to glycodendrons displaying four, eight, sixteen or thirty-two α-thio-N-acetylgalactosamine (α-SGalNAc) units, resulting in compounds with molecular weights ranging from 2 to 17 kDa, respectively. These compounds were fully characterized by LCMS and NMR. We then evaluated the capacity of these agents to clear a model (131)I-labeled single chain variable fragment antibody-streptavidin ((131)I-scFv-SAv) fusion protein from blood and tissue in mice, and compared their clearing efficiencies to that of a 500 kDa dextran-biotin conjugate. Glycodendrons and dextran-biotin exhibited enhanced blood clearance of the scFv-SAv construct. Biodistribution analysis showed liver targeting/uptake of the scFv-SAv construct to be 2-fold higher for compounds 1 to 4, as well as for the 500 kDa dextran, over saline. Additionally, the data suggest the glycodendrons clear through the liver, whereas the dextran through reticuloendothelial system (RES) metabolism.

DFT study of Raman spectra of phosphorus-containing dendrons built from cyclotriphosphazene core with terminal carbamate and ester groups

The FT Raman spectra of the zero (Gv0) and first generations (Gv1) of phosphorus-containing dendrons with terminal carbamate groups and one ester function and [2-(4-hydroxyphenyl)ethyl]-carbamic acid tert-butyl ester (C) have been recorded and analyzed. The lines of free ν(CO) bonds are not observed in the experimental Raman spectrum of C and thus association of carbamate groups by hydrogen bonds occur. The frequencies of ν(CO) lines in the experimental Raman spectrum reveal the presence of the different types of H-bonds in the amorphous state of Gv0. Density functional theory (DFT) calculations of C gave geometrical parameters for the t-g-, g-g-, tg-, gg-conformers. The most stable is the gg-conformer. The structural optimization and normal mode analysis were performed for dendrons on the basis of the DFT. The calculated geometrical parameters, harmonic vibrational frequencies and Raman intensities are predicted in a good agreement with the experimental data. The experimental Raman spectra of dendrons were interpreted by means of potential energy distribution. Relying on DFT calculations the lines of a core, repeating units and terminal groups of dendrons were assigned.The polarizabilities and lipophilicity of dendrons were estimated.

Photo-induced electron transfer between a dendritic zinc(II) phthalocyanine and methyl viologen

The intermolecular electron transfer between the carboxylic dendritic zinc(II) phthalocyanines [ G 1 -ZnPc(COOH) 8 and G 2 -ZnPc(COOH) 16 ] and methyl viologen ( MV 2+ ) is studied by steady-state fluorescence and UV/Vis absorption spectroscopic method. The effect of dendron generation of this series of dendritic phthalocyanines on intermolecular electron transfer is investigated. The results show that the fluorescence emission of these dendritic phthalocyanines could be greatly quenched by MV 2+ upon excitation at 610 nm. The Stern–Volmer constant ( K SV ) of electron transfer is decreased with increasing dendron generations. Our study suggests that these dendritic phthalocyanines are an effective new electron donor and transmission complex and could be used as a potential artificial photosynthesis system.

Dendronized polystyrene via orthogonal double‐click reactions

ABSTRACTDendronized copolymers bearing two different dendrons as side chains have been synthesized using a modular orthogonal “double‐click” reaction based strategy. The orthogonality of the Huisgen‐type azide‐alkyne cycloaddition and the Diels–Alder reaction was utilized to attach different dendrons to the polymer backbone via the “graft‐to” strategy. First through third generations of polyaryl ether dendrons appended with an alkyne group and polyester dendrons possessing a furan‐protected maleimide group at their focal point were reacted with a styrene based copolymer containing azide and anthracene moieties as side chains. The efficiency and selectivity of the orthogonal dendronization of the copolymers were examined via various analytical methods such as 1H NMR spectroscopy, FTIR and gel permeation chromatography. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 5029–5037

DFT study of Raman spectra of phosphorus-containing dendrons built from cyclotriphosphazene core

The FT-Raman spectra of the zero and first generations of phosphorus-containing dendrons with terminal oxybenzaldehyde and PCl groups and one ester function have been recorded and analyzed. The structural optimization and normal mode analysis were performed for dendrons 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 dendrons were interpreted by means of potential energy distribution. Relying on DFT calculations the lines of the core, repeating units and terminal groups of dendrons 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 dendrons the information, usually inaccessible is obtained. The polarizabilities and lipophilicity of dendrons were estimated. The strong line at 1600cm−1 show marked changes of intensity in dependence of aldehyde (СНО), ester (OСO) or azomethyne (СНN) substituents in the aromatic ring.

The synthesis and study of fluorescent PAMAM-based dendritic molecules

New water soluble and fluorescent PAMAM-based dendritic molecules based on the naphthalimide derivative 7H-benz[de]benzimidazo[2,1-a]isoquinoline-7-one as the fluorescent unit, have been prepared and their photophysical properties studied in aqueous solution over a wide pH range. The dendrons are all strongly fluorescent through an intramolecular charge transfer (ICT) excited state, but this can be modulated by photoinduced electron transfer (PeT) processes, which increases with higher PAMAM dendron generation.

Novel Monodisperse PEGtide Dendrons: Design, Fabrication, and Evaluation of Mannose Receptor-Mediated Macrophage Targeting

Novel PEGtide dendrons of generations 1 through 5 (G1.0–5.0) containing alternating discrete poly(ethylene glycol) (dPEG) and amino acid/peptide moieties were designed and developed. To demonstrate their targeting utility as nanocarriers, PEGtide dendrons functionalized with mannose residues were developed and evaluated for macrophage targeting. PEGtide dendrons were synthesized using 9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS) protocols. The N-α-Fmoc-N-ε-(5-carboxyfluorescein)-l-lysine (Fmoc-Lys(5-FAM)-OH) and monodisperse Fmoc-dPEG6-OH were sequentially coupled to Fmoc-β-Ala-resin to obtain the resin-bound intermediate Fmoc-dPEG6-Lys(5-FAM)-β-Ala (1). G1.0 dendrons were obtained by sequentially coupling Fmoc-Lys(Fmoc)-OH, Fmoc-β-Ala-OH, and Fmoc-dPEG6-OH to 1. Dendrons of higher generation, G2.0–5.0, were obtained by repeating the coupling cycles used for the synthesis of G1.0. Dendrons containing eight mannose residues (G3.0-mannose8) were developed for mannose receptor (MR) mediated macrophage targeting by conjugating α-d-mannopyranosylphenyl isothiocyanate to G3.0 dendrons. In the present study PEGtide dendrons up to G5.0 were synthesized. The molecular weights of the dendrons determined by MALDI-TOF were in agreement with calculated values. The hydrodynamic diameters measured using dynamic light scattering (DLS) ranged from 1 to 8 nm. Cell viability in the presence of G3.0 and G3.0-mannose8 was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and was found to be statistically indistinguishable from that of untreated cells. G3.0-mannose8 exhibited 12-fold higher uptake than unmodified G3.0 control dendrons in MR-expressing J774.E murine macrophage-like cells. Uptake was nearly completely inhibited in the presence of 10 mg/mL mannan, a mannose analogue and known MR substrate. Confocal microscopy studies demonstrated the presence of significant intracellular punctate fluorescence colocalized with a fluid endocytosis marker with little surface fluorescence in cells incubated with G3.0-mannose8. No significant cell-associated fluorescence was observed in cells incubated with G3.0 dendrons that did not contain the targeting ligand mannose. The current studies suggest that PEGtide dendrons could be useful as nanocarriers in drug delivery and imaging applications.

New cyclodextrin derivative containing poly(L-lysine) dendrons for gene and drug co-delivery

To develop a multifunctional polymeric carrier for gene and drug co-delivery, a new cyclodextrin derivative containing poly(L-lysine) dendrons was prepared by the click conjugation of per-6-azido-β-cyclodextrin with propargyl focal point poly(L-lysine) dendron of third generation and then characterized by FTIR, 1H NMR, and GPC analyses. It was found that such a conjugate could form colloidally stable nanocomplexes with plasmid DNA in aqueous system and exhibited high gene transfection efficiency. Moreover, it could load efficiently methotrexate drug with anticancer activity and showed a sustained release behavior. Different from commonly used amphiphilic copolymers with cationic character, the as obtained cyclodextrin derivative may be used directly for the combinatorial delivery of nucleic acid and lipophilic anticancer drugs without a complicated micellization process.

Photoinduced surface patterning of azobenzene-containing supramolecular dendrons, dendrimers and dendronized polymers

Ionic complexes of azobenzenes and dendritic structures are shown to exhibit efficient light-induced mass transport upon irradiation with a light interference pattern. Surface-relief gratings (SRGs) with modulation depths of up to 550 nm were successfully inscribed. We compare the SRG formation in three generations of supramolecular dendrons, dendrimers, and dendronized polymers and demonstrate that the grating formation process is destructed by the existence of self-assembled structures as well as by overly large size of the dendronic complexes.

Photophysics of Delocalized Excitons in Carbazole Dendrimers

The photophysical properties in solution of three generations of carbazole-based dendrons and dendrimers with fluorenyl surface groups were studied using steady-state, time-resolved femtosecond transient absorption and anisotropy, and coherent two-dimensional ultraviolet spectroscopy. It was found that increasing the generation caused a switch in the nature of the emissive state between the first-generation compounds and the second- and third-generation dendrimers. Time-resolved anisotropy measurements revealed low initial anisotropies that decreased with increasing dendrimer generation consistent with increasing intradendrimer interchromophore coupling. Two-dimensional UV spectroscopy showed that the signal from the second- and third-generation dendrimers is the product of multiple chromophores interacting. The maximum number of interacting chromophores is reached by the second generation.

Dendron–polymer conjugates via the diels–alder “click” reaction of novel anthracene‐based dendrons

ABSTRACTDiblock and triblock dendron–polymer conjugates containing biodegradable polyester dendron blocks and polyethylene glycol (PEG) polymer were synthesized using the Diels–Alder “click” cycloaddition reaction. PEG polymers with furan‐protected maleimide functionality were synthesized and reacted with biodegradable polyester dendrons containing an anthracene moiety at their focal point. First through third generations of biodegradable polyester dendrons containing an anthracene unit at their focal point were synthesized using a divergent strategy. Efficient conjugation of the dendrons to polymers was demonstrated using 1HNMR and size exclusion chromatography. This modular approach provides an easy access to the design of multivalent PEG conjugates. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3191–3201

Structural characterization and thermal behavior of dendritic-linear PGMA-HPAM-r-PS copolymers in a self-assembled microporous matrix

A series of dendritic-linear copolymers, composed of poly(glycidyl methacrylate-grafted- 3,3′-dimethyl-(4-hydroxyphenylazanediyl) bis(2-methylpropanoate))-random-polystyrene (PGMA-HPAM-r-PS), were successfully synthesized via a macromonomer route. Characterization of the copolymers and investigation of their thermal behavior revealed a significant influence of the dendritic GMA-HPAM segment. The thermal degradation temperature (Td) of the dendritic-linear PGMA-HPAM-r-PS copolymer was elevated as the weight percentage of dendritic segment (GMA-HPAM) increased. The glass transition temperatures of the copolymers exhibited a strong, complex dependence on the dendritic GMA-HPAM segment, with three behavioral ranges. DSC data were attributed to two distinct effects of the dendritic segment: (i) the effect of the dendritic segment grafting on copolymer chains, and (ii) intermolecular interactions between the dendritic and styrene segments. Microporous dendritic-linear PGMA-HPAM-r-PS copolymer matrices were prepared using solvent-induced phase separation at room temperature. The self-assembled surface morphology was affected by (i) the micellar domains of the dendritic and styrene segments and (ii) inter- and intramolecular interactions between the dendritic and styrene segments. An interesting relationship between thermal behavior and surface morphology was discovered, which can provide a simple, accurate and rapid means of finding the optimum dendritic segment content for producing a hexagonally ordered microporous matrix for different dendron generations.

Photochemical Generation of Light Responsive Surfaces

AbstractThe preparation of patterned photoswitchable surfaces by employing the nitrile imine‐mediated tetrazole ene cycloaddition (NITEC) photoinduced reaction in the presence of dipolarophiles based on photoresponsive azobenzene moieties is reported. The dipolarophile used is a maleimide carrying either an azobenzene unit or a first generation dendron containing two azobenzene units. X‐ray photoelectron spectroscopy (XPS) is employed to analyze the functionalized silicon wafers, while time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) evidences the spatial control of the functionalization of the surface achieved by using a micropatterned shadow mask. Water contact angle measurements and optical inspection observing the behavior of a water droplet demonstrate the photoinduced change on wettability of the structured functionalized surfaces due to the reversible trans‐to‐cis isomerization of the azobenzene moities.

Synthesis of Cylindrical Polymer Brushes with Umbrella-Like Side Chains via a Combination of Grafting-from and Grafting-onto Methods

Cylindrical polymer brushes with umbrella-like side chains have been synthesized by a combination of grafting-from and grafting-onto methods. First, the polymer brushes with azido end-functionalized poly(tert-butyl acrylate) (PtBA-N3) side chains, PBIEM-g-(PtBA-N3), were prepared by atom transfer radical polymerization (ATRP) of tBA monomers using polyinitiator PBIEM followed by a substitution of bromo-side terminals with sodium azide. Subsequently, polyamidoamino dendrons of three generations with a propargyl focal point (Gn) were introduced onto the brush-shaped PtBA-N3 by copper-catalyzed azide–alkyne cycloaddition (CuAAC) coupling reaction. The efficiency of CuAAC between PtBA-N3 side chains and Gn has showed a dependence on generation number n of the dendrons. At the feed ratio of [Gn]:[N3] = 1:1, the grafting efficiency of the first generation dendron (G1) reached above 95%, whereas that of G2 and G3 was at least 84% and 73%, respectively. AFM images indicated that diameter of the brushes hybridized...

Photoresponsive Dendronized Copolymers of Styrene and Maleic Anhydride Pendant with Poly(amidoamine) Dendrons as Side Groups

A series of photoresponsive dendronized polymers PGn-NB (n = 1, 2, 3) were synthesized by attaching o-nitrobenzyl alcohol-terminated amidoamine dendrons (G1–G3) to the alternating styrene and maleic anhydride copolymer (PSt-alt-PMAh). The structures and the molecular weights of the obtained polymers were characterized by 1H NMR and FTIR measurements. It is found that the coverage degrees of the dendrons are 74%, 42%, and 26%, respectively, indicating that the numbers of the appended dendrons decrease in the order of G1 > G2 > G3 due to the steric hindrance of higher generation dendrons with more branches. The photocleavable behavior of G1–G3 was detected by UV–vis and 1H NMR measurements. As a result, G2 showed a faster cleavage rate compared to G1 and G3. The critical aggregation concentration (CAC) of PGn-NB (n = 1, 2, 3), measured by using pyrene as a fluorescence probe, were 0.05 mg/mL (PG1-NB), 0.01 mg/mL (PG2-NB), and 0.03 mg/mL (PG3-NB), which displayed that the structure of PG2-NB was in favor of forming aggregates at lower concentrations. Light scattering study indicated that both the apparent molecular weight and the chain density of the aggregates formed by PG2-NB decreased with the irradiation time. Atomic force microscope (AFM) measurements also showed that the size of the aggregates increased dramatically from 15 to 70 nm before and after UV irradiation, evidencing that the UV light induced structure change. Nile Reds, as the guest molecules, were loaded in the aggregates from PG2-NB, and the release profiles upon UV stimulus were monitored by the fluorescence spectroscopy.

Adsorption of uranium from aqueous solution by PAMAM dendron functionalized styrene divinylbenzene

A new polymeric chelating resin was prepared by growing third generation poly(amido)amine (PAMAMG3) dendron on the surface of styrene divinylbenzene (SDB) and characterized by FTIR, TGA and SEM. The ideal branching of dendron in the chelating resin was determined from potentiometric titration. Adsorption of uranium (VI) from aqueous solution using PAMAMG3-SDB chelating resin was studied in a series of batch experiments. Effect of contact time, pH, ionic strength, adsorbent dose, initial U(VI) concentration, dendron generation and temperature on adsorption of U(VI) were investigated. Kinetic experiments showed that U(VI) adsorption on PAMAMG3-SDB followed pseudo-second-order kinetics model appropriately and equilibrium data agreed well with the Langmuir isotherm model. Thermodynamic parameters (ΔH°, ΔS°, ΔG°) were evaluated from temperature dependent adsorption data and the uranium adsorption on PAMAMG3-SDB was found to be endothermic and spontaneous in nature. The sticking probability value (5.303×10−9), kinetic and isotherm data reveal the chemisorption of uranium on PAMAMG3-SDB and adsorption capacity of the chelating resin was estimated to be 130.25mgg−1 at 298K. About 99% of adsorbed U(VI) can be desorbed from PAMAMG3-SDB by a simple acid treatment suggesting that the chelating resin is reusable.

Synthesis and Characterization of Novel Dendrons Bearing Amino-Nitro-Substituted Azobenzene Units and Oligo(ethylene glycol) Spacers: Thermal, Optical Properties, Langmuir Blodgett Films and Liquid-Crystalline Behaviour

In this work, we report the synthesis and characterization of a novel series of first and second generation Fréchet type dendrons bearing amino-nitro substituted azobenzene units and tetra(ethylene glycol) spacers. These compounds were fully characterized by FTIR, 1H and 13C-NMR spectroscopies, and their molecular weights were determined by MALDI-TOF-MS. The thermal properties of the obtained dendrons were studied by TGA and DSC and their optical properties by absorption spectroscopy in solution and cast film. Molecular calculations were performed in order to determine the optimized geometries of these molecules in different environments. Besides, Langmuir and Langmuir Blodgett films were prepared with the first generation dendrons that were shown to be amphiphilic. Finally, some of the dendrons showed a liquid crystalline behaviour, which was studied by light polarized microscopy as a function of the temperature in order to determine the transition temperatures and the structure of the mesophase.

Janus PEG-Based Dendrimers for Use in Combination Therapy: Controlled Multi-Drug Loading and Sequential Release

The increasing use of drug combinations to treat disease states, such as cancer, calls for improved delivery systems that are able to deliver multiple agents. Herein, we report a series of novel Janus dendrimers with potential for use in combination therapy. Different generations (first and second) of PEG-based dendrons containing two different "model drugs", benzyl alcohol (BA) and 3-phenylpropionic acid (PPA), were synthesized. BA and PPA were attached via two different linkers (carbonate and ester, respectively) to promote differential drug release. The four dendrons were coupled together via (3 + 2) cycloaddition chemistries to afford four Janus dendrimers, which contained varying amounts and different ratios of BA and PPA, namely, (BA)(2)-G1-G1-(PPA)(2), (BA)(4)-G2-G1-(PPA)(2), (BA)(2)-G1-G2-(PPA)(4), and (BA)(4)-G2-G2-(PPA)(4). Release studies in plasma showed that the dendrimers provided sequential release of the two model drugs, with BA being released faster than PPA from all of the dendrons. The different dendrimers allowed delivery of increasing amounts (0.15-0.30 mM) and in exact molecular ratios (1:2; 2:1; 1:2; 2:2) of the two model drug compounds. The dendrimers were noncytotoxic (100% viability at 1 mg/mL) toward human umbilical vein endothelial cells (HUVEC) and nontoxic toward red blood cells, as confirmed by hemolysis studies. These studies demonstrate that these Janus PEG-based dendrimers offer great potential for the delivery of drugs via combination therapy.