Dendron Generation Research Articles

Vibrational spectra study of fluorescent dendrimers built from the cyclotriphosphazene core with terminal dansyl and carbamate groups

The FTIR and FT Raman spectra of the “Janus”-type dendrimers, possessing five carbamate groups on one side and five fluorescent dansyl derivatives on the other side, with amide G 1 and hydrazone G 2 central linkages were studied. These surface-block dendrimers are obtained by the coupling of two different dendrons. The FTIR and FT-Raman spectra of the zero generation dendrons, built from the hexafunctional cyclotriphosphazene core, with five dansyl terminal groups and one carbamate G 0 v and one oxybenzaldehyde function G ′ 0 v have been recorded. The structural optimization and normal mode analysis were performed for dendron G ′ 0 v on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that dendron molecule G ′ 0 v has a concave lens structure with planar –O–C 6 H 4 –CH O fragments and slightly non-planar cyclotriphosphazene core. The experimental IR and Raman spectra of dendron G ′ 0 v were interpreted by means of potential energy distributions. Relying on DFT calculations a complete vibrational assignment is proposed. The strong band 1597 cm −1 show marked changes of the optical density in dependence of substituents in the aromatic ring. The frequencies of ν(N–H) bands in the IR spectra reveal the presence of the different types of H-bonds in the dendrimers.

Constructing polyamidoamine dendrons from poly(poly(ethylene glycol) monomethacrylate) brushes grafted from planar silicon hydride surfaces for biomedical applications

A facile approach was established to construct polyamidoamine (PAMAM) dendrons from polymer brushes of poly(poly(ethylene glycol) monomethacrylate) (Si-g-P(PEGMA-OH)) grafted from a planar silicon hydride surface. First the Si-g-P(PEGMA-OH) brushes were grown via surface-initiated atom transfer radical polymerization with robust Si–C links on silicon surfaces. The side-chain hydroxyl groups of Si-g-P(PEGMA-OH) were chlorinated with thionyl chloride and further chlorines were substituted with amino groups of ethylenediamine, giving terminal primary amines. Borrowing the solution synthesis approach, we constructed second and third generations of PAMAM dendrons on-chip by surface-initiated alternative growth of two monomers, methyl acrylate and ethylenediamine. Two applications of silicon-based PAMAM dendrons were shown: the dense amino groups were activated via a cross-linker, N-succinimidyl-6-maleimidylhexanoate, to capture a free-thiol-carrying peptide of oxytocin and the third generation of PAMAM dendrons was used as a platform to on-chip synthesize a three amino acid peptide of Arg-Gly-Asp (RGD). The above conclusions were mainly derived from a home-built multiple transmission-reflection infrared spectroscopy, and complemented by X-ray photoelectron spectroscopy, UV–Vis spectroscopy and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry.

Hydrophobically Modified Dendrons: Developing Structure−Activity Relationships for DNA Binding and Gene Transfection

This paper develops a structure-activity relationship understanding of the way in which surfactant-like dendrons with hydrophilic spermine surface groups and a variety of lipophilic units at their focal points can self-assemble and subsequently bind to DNA with high affinity. The choice of functional group at the focal point of the dendron and the high tunability of the molecular structure have a very significant impact on DNA binding. Mesoscale modeling of the mode of dendron self-assembly provides a direct insight into how the mode of self-assembly exerts its effect on the DNA binding process. In particular, the hydrophobic unit controls the number of dendrons in the self-assembled micellar structures, and hence their diameters and surface charge density. The DNA binding affinity correlates with the surface charge density of the dendron aggregates. Furthermore, these structure-activity effects can also be extended to cellular gene delivery, as surface charge density plays a role in controlling the extent of endosomal escape. It is reported that higher generation dendrons, although binding DNA less strongly than the self-assembling lower generation dendrons, are more effective for transfection. The impact of the lipophilic group at the focal point is less significant for the DNA binding ability of these larger dendrons, which is predominantly controlled by the spermine surface groups, but it does modify the levels of gene transfection. Significant synergistic effects on gene delivery were observed when employing combinations of the dendrons and polyethyleneimine (PEI, 25 kDa), with transfection becoming possible at low loading levels where the two components would not transfect individually, giving practically useful levels of gene delivery.

Comparing dendritic and self-assembly strategies to multivalency—RGD peptide–integrin interactions

This paper compares covalent and non-covalent approaches for the organisation of ligand arrays to bind integrins. In the covalent strategy, linear RGD peptides are conjugated to first and second generation dendrons, and using a fluorescence polarisation competition assay, the first generation compound is demonstrated to show the most effective integrin binding, with an EC(50) of 125 μM (375 μM per peptide unit). As such, this dendritic compound is significantly more effective than a monovalent ligand, which does not bind integrin, even at concentrations as high as 1 mM. However, the second generation compound is significantly less effective, demonstrating that there is an optimum ligand density for multivalency in this case. In the non-covalent approach to multivalency, the same RGD peptide is functionalised with a hydrophobic C12 chain, giving rise to a lipopeptide which is demonstrated to be capable of self-assembly. This lipopeptide is capable of effective integrin binding at concentrations of 200 μM. These results therefore demonstrate that covalent (dendritic) and non-covalent (micellar self-assembly) approaches have, in this case, comparable efficiency in terms of achieving multivalent organisation of a ligand array.

Effect of Enzyme Modification by Well-Defined Multi-Armed Poly(Ethylene Glycol) Synthesized Using Polyamidoamine Dendron

Egg white lysozyme was chemically modified by PEGylated PAMAM 1st, 2nd and 3rd generation dendrons, which had 2, 4 and 8 PEG arms, respectively. The number of PEG chains introduced to the lysozyme molecule drastically increased with an increase in dendron generation, although the number of PEGylated PAMAM dendrons introduced decreased due to steric repulsion. The lytic activity of lysozyme to Micrococcus luteus cells was effectively inhibited by conjugating PEGylated PAMAM dendron to the lysozyme, indicating steric stabilization of PEG chains at the surface of lysozyme molecule. In addition, the enzymatic reaction of the lysozyme with oligosaccharide substrate was apparently accelerated by a substrate condensation effect due to the multi-armed structure of PEG.

Water-soluble dendritic-linear triblock copolymer-modified magnetic nanoparticles: preparation, characterization and drug release properties

One route has been employed to prepare dendritic-linear block copolymer modified superparamagnetic iron oxide nanoparticles (SPIONs), which consist of a Fe3O4 magnetic nanoparticle core and a dendritic-linear block copolymer, the focal point polyamidoamine-type dendron-b-poly(2-dimethylaminoethyl methacrylate)-b-poly(N-isopropylacrylamide) (PAMAM-b-PDMAEMA-b-PNIPAM) shell by two-step atom transfer radical polymerization (ATRP). Firstly, Fe3O4 nanoparticles were prepared by a high-temperature solution phase reaction in the presence of iron(III) acetylacetonate [Fe(acac)3], oleic acid and oleylamine. Then propargyl focal point PAMAM-type dendron (generation 2.0, denoted as propargyl-D2.0) with four carboxyl acid end groups as a cap displaced the oleic acid and oleylamine on the surfaces. Subsequently, an initiator for ATRP was introduced onto the propargyl-D2.0-modified Fe3O4 nanoparticle surfaces via click chemistry with 2′-azidoethyl-2-bromoisobutylate (AEBIB). PDMAEMA and PNIPAM were grown gradually from nanoparticle surfaces using two-step copper-mediated ATRP. Finally, a crosslinking reaction between PDMAEMA block with 1,2-bis(2-iodoethoxy)ethane (BIEE) was used to stabilize the nanoparticles and reverse aggregation. The modified nanoparticles were subjected to detailed characterization using FT-IR, DLS, XRD and TGA. Magnetization measurements confirmed the characteristic superparamagnetic behavior of all magnetic nanoparticles under room temperature. In addition, doxorubicin (DOX) as an anticancer drug model was loaded into the dendritic-linear block copolymer shell of the modified nanoparticles, and subsequently the drug release was performed in phosphoric acid buffer solution (pH 7.4) at 25 °C or 37 °C. The results verify that dendritic-linear block copolymer-modified nanoparticles as a drug carrier possess thermosensitive drug release behaviors. Furthermore, a methyl tetrazolium (MTT) assay of DOX-loaded dendritic-linear block copolymer-modified nanoparticles against Hela cells was evaluated. The results show that the modified nanoparticles can be used for drug delivery.

Singlet molecular oxygen generation by water-soluble phthalocyanine dendrimers with different aggregation behavior

Phthalocyanines having hydrophilic or lipophilic dendrons were synthesized to investigate the efficiencies of singlet molecular oxygen (1Δg) formation. The introduction of higher generation of dendrons to the central metal ( Si ) of phthalocyanine in vertical direction to their ring plane has resulted in the successful improvement in avoiding aggregate formation that resulted in efficient generation of 1Δg even in water.

Generation-Dependent Molecular Recognition Controls Self-Assembly in Supramolecular Dendron−Virus Complexes

In this work molecular dynamics simulation identifies a clear link between the dendron-virus multivalent molecular recognition and the nature of the consequent self-assembly. Data demonstrate how a weak hydrophobic association is transformed in an electrostatic self-assembly, orders of magnitude stronger, depending on the dendron generation used to assemble the viruses. This opens a new frontier in the engineering of hierarchical self-assemblies, potentially enabling the control of the supramolecular properties by acting at the single-molecule level.

DFT study of structure, IR and Raman spectra of the first generation dendron built from cyclotriphosphazene core

The FTIR and FT-Raman spectra of the first generation dendron built from the cyclotriphosphazene core, five arms O C 6H 4 CH N N(CH 3) P(S)< with 10 oxybenzaldehyde terminal groups and one ester function G v 1 ′ have been recorded. The structural optimization and normal mode analysis were performed for dendron on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that G v 1 ′ has a concave lens structure with planar O C 6H 4 CH N N(CH 3) P(S)< fragments and slightly non-planar cyclotriphosphazene core. The oxybenzaldehyde groups attached to different arms show significant deviations from a symmetrical arrangement relative to the local planes of repeating units. The experimental IR spectra of G v 1 ′ dendron was interpreted by means of potential energy distributions. Relying on DFT calculations a complete vibrational assignment is proposed. The strong band 1597 cm −1 show marked changes of the optical density in dependence of the aldehyde (−СН О), ester (−OС O−) or azomethyne (−СН N−) substituents in the aromatic ring.

Synthesis and physicochemical characterization of branched poly(monomethyl itaconate)

AbstractThe synthesis and characterization of branched polymers derived from poly (monomethyl itaconate) (PMMI) are reported. Important changes in the properties of the functionalized products were found with respect to the base polymer, establishing a close relationship with the hydrophobic/hydrophilic balance of the products. The intrinsic viscosity of the branched PMMI showed an increment in its hydrodynamic volume due to the insertion of branched molecules, which correspond to a first generation of dendrons. Their incorporation into the polymer chain caused a change in the surface energy values of the sample films and enabled the products to form stable monolayers at the air-water interface

Amphiphilic dendronized homopolymers

A series of second generation of amphiphilic dendronized homopolymers are efficiently synthesized, and their thermoresponsiveness in aqueous solutions and secondary structures in methanol solutions are described. These polymers are constructed in each repeat unit with various generations of hydrophobic 4-aminoproline and hydrophilic oligoethylene glycol (OEG)-based dendrons, and their over-all hydrophilicity is tuned by varying these dendron generations. Polymers with or without the first generation of proline dendron show good water solubility at room temperature, but exhibit typical thermoresponsive behaviors at elevated temperatures as characterized by turbidity measurements using UV-vis spectroscopy, while the polymer with the secondary generation of proline dendron is not soluble in water. All polymers show ordered secondary structures as evidenced by the optical rotation and circular dichroism experiments. Finally, assembly of these amphiphilic homopolymers into porous films via breath figure (BF) technique is described, and polymer structures are found to show significant influence on the morphology of porous film.

Photophysical investigation of microenvironment in glycerol based dansylated polyether dendrons

Photophysical studies of four generations of polyglycerol dendrons with isopropylidene end groups and dansyl moiety as a fluorophore attached at the focal point were carried out. All the four generations showed similar behaviour in their absorption transitions but the emission maximum for all generations of dendrons showed strong dependence on the solvent polarity. The solvatochromic shift of emission maximum showed linearity in the Lippert–Mataga plot, indicating the dominant importance of general solvent effect in all generations of dendrons. Photophysical parameters such as fluorescence quantum yield, fluorescence lifetime and radiative decay rate constant showed solvent polarity dependence. The detailed photophysical study reveals that due to the increased influence of the repeating dendron units of the higher order dendrons on the dansyl microenvironment, it becomes less and less influenced by the solvent.

Surface-Initiated Ring-Opening Metathesis Polymerization (SI-ROMP): Synthesis and Electropolymerization of Terthiophene-Functionalized Olefin Peripheral Dendrons

We report on the synthesis and electrodeposition of peripheral olefin dendrons with electropolymerizable focal point terthiophene units. These films were utilized for surface initiated ring-opening metathesis polymerization (SI-ROMP) of norbornene to form grafted polynorbornene brushes. The dendrons were first electrodeposited on an electrode surface, forming a highly dense and uniform polythiophene-type film, and their electrochemical behavior was investigated. Subsequently, after activation with a transition metal metathesis catalyst, polynorbornene brushes were grown from the electrodeposited films which were found to be highly dependent on the density of exposed olefin functional groups and dendron generation. The change in film morphology was examined by atomic force microscopy (AFM). X-ray photoelectron spectroscopy (XPS) was used to prove polynorbornene brush film growth and composition on top of the electropolymerized layer. Brush growth kinetics experiments were also carried out to understand the...

Nanoparticle Formation and Ultrathin Film Electrodeposition of Carbazole Dendronized Polynorbornenes Prepared by Ring-Opening Metathesis Polymerization

We report on the synthesis, electropolymerization, and nanoparticle formation of a series of electroactive carbazole-terminated dendronized linear polynorbornenes prepared by living ring-opening metathesis polymerization (ROMP). The molecular weight (MW) of the dendronized polymers was controlled by varying the feed ratio between the dendronized monomer and first-generation Grubbs' catalyst. Ultrathin films were prepared by electrodeposition. The electrochemical behavior and viscoelastic properties of such films were found to be highly dependent on the dendron generation and linear polymer MW as studied by electrochemical quartz crystal microbalance (E-QCM). Moreover, nanoparticle formation and size/shape control were observed by tuning the surface wetting properties of the substrate during adsorption and by intramolecular cross-linking via chemical oxidation in solution.

Facile Iterative Synthesis of Biphenyl Dendrons with a Functionalized Focus

An iterative procedure gives 1,3,5-phenyl-linked dendrons of up to the fourth generation and enables the formation of different generations of iridium(III) complex-cored dendrimers. The convergent synthesis uses N,N'-1,8-naphthyl-3,5-dibromophenylboronamide as the key building block. The iterative synthesis cycle involves deprotection of the boronamide-focused dendron to form a boronic acid and subsequent Suzuki coupling either with the N,N'-1,8-naphthyl-3,5-dibromophenylboronamide to give the next dendron generation or with an activated core to form a dendrimer.

Synthesis and Aggregation Properties of Dansylated Glycerol‐Based Amphiphilic Polyether Dendrons

AbstractGlycerol‐based amphiphilic polyether mono azide third‐generation dendrons were synthesized through a divergent strategy. A repetitive synthetic sequence of O‐alkylation and isopropylidene deprotection reaction was adopted for the synthesis, pentamethylene was used as spacer. Dansyl chloride was attached to the focal point as a fluorophore. The photophysical property in aqueous solution of the protected dendrons showed self‐association behaviour from second generation onwards even at a very low concentration (1 × 10–8 M). A hypsochromic shift of around 60 nm in the emission maximum, significant increase in fluorescence intensity, almost ten‐fold increase in the fluorescence anisotropy and a fourfold increase in average fluorescence lifetime of dansyl moiety were observed on going from first generation dendron to higher generation dendrons in aqueous medium. The absence of such behavior in the corresponding unprotected, relatively hydrophilic dendritic units clearly indicated that the aggregation is due to the presence of hydrophobic isopropylidene end groups. Quenching studies of the dendrimersin aqueous solution using a hydrophilic quencher Ag+ revealed that the dansyl moiety in protected higher generations dendritic units is significantly shielded from the surroundings, which further rendered support to the fact that higher order dendrons undergo aggregation in aqueous medium.

A New Family of Nonionic Dendritic Amphiphiles Displaying Unexpected Packing Parameters in Micellar Assemblies

In this paper we report on the synthesis of a new family of nonionic dendritic amphiphiles that self-assemble into defined supramolecular aggregates. Our approach is based on a modular architecture consisting of different generations of hydrophilic polyglycerol dendrons [G1-G3] connected to hydrophobic C(11) or C(16) alkyl chains via mono- or biaromatic spacers, respectively. All amphiphiles complex hydrophobic compounds as demonstrated by solubilization of Nile Red or pyrene. The structure of the supramolecular assemblies as well as the aggregation numbers are strongly influenced by the type of the dendritic headgroup. While the [G1] amphiphiles form different structures such as ringlike and fiberlike micelles, the [G2] and [G3] derivatives aggregate toward spherical micelles of low polydispersity clearly proven by transmission electron microscopy (TEM) measurements. In the case of the biaromatic [G2] derivative, the structural persistence of the micelles allowed a three-dimensional structure determination from the TEM data and confirmed the aggregation number obtained by static light scattering (SLS) measurements. On the basis of these data, molecular packing geometries indicate a drastic mass deficit of alkyl chains in the hydrophobic core volume of spherical micelles. It is noteworthy that these highly defined micelles contain as little as 15 molecules and possess up to 74% empty space. This behavior is unexpected as it is very different from classical detergent micelles such as sodium dodecyl sulfate (SDS), where the hydrophobic core volume is completely filled by alkyl chains.

Enhanced cellular internalization and gene silencing with a series of cationic dendron‐multiwalled carbon nanotube:siRNA complexes

One of the major obstacles to the clinical development of gene silencing by small interfering RNA (siRNA) is its effective cytoplasmic delivery. Carbon nanotubes have been proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We recently demonstrated in a proof-of-principle study that amino-functionalized multiwalled carbon nanotubes (f-MWNT) can effectively deliver in vivo an siRNA sequence, triggering cell apoptosis that results in human lung xenograft eradication and prolonged survival. In the present study, we demonstrate how a newly synthesized series of polycationic dendron-MWNT constructs with a precisely tailored number of amino functions (dendron generations) can complex and effectively deliver double-stranded siRNA to achieve gene silencing in vitro. A systematic comparison between the f-MWNT series in terms of cellular uptake, cytotoxicity, and siRNA complexation is offered. Significant improvement in siRNA delivery with the dendron-MWNT conjugates is shown, and gene silencing was obtained in 2 human cell lines using 2 different siRNA sequences. The study reveals that through f-MWNT structure-biological function analysis novel nanotube-based siRNA transfer vectors can be designed with minimal cytotoxicity and effective delivery and gene-silencing capabilities.

One-pot sonochemical synthesis of dendron-stabilized gold nanoparticles as promising nano-hybrid with potential impact in biological application

Dihydroxy fatty acid-based (DF) dendron-stabilized gold nanoparticles (AuNps) were synthesized without adding any external reducing or stabilizing agent. Each DHA base dendron (G1, G2, or G3) possesses a single thiol at the focal point and free –OH groups at the other terminal and as a result can be used to reduce AuCl 4 − to Au 0 and stabilize the nascent AuNps by the thiol group. The size and distribution of the AuNp produced can also be correlated with the rate of Au (III) reduction. TEM images vividly demonstrate the specific morphology of gold nanoparticles with different sizes and shapes obtained by using different generations of DF dendrons.

Synthesis and structural characterization of dendritic-linear PMA-APM-r-PS copolymers for a self-assembled microporous matrix

A set of dendritic-linear copolymers, poly(maleic anhydride-grafted-3,3′-dimethyl-(4-aminophenylazanediyl)bis(2-methylpropanoate))-random-polystyrene (PMA-APM-r-PS), was successfully prepared by copolymerization of the novel dendritic macromonomer, 4-(4-(bis(3-(4-(bis(3-methoxy-2-methyl-3-oxopropyl)amino)phenylamino)-2-methyl-3-oxopropyl)amino)phenylamino)-4-oxobut-2-enoic acid (MA-APM), with styrene monomer. The dendritic MA-APM macromonomer dendron 3,3′-dimethyl-(4-aminophenylazanediyl)bis(2-methylpropanoate) (APM) was then grafted by using the divergent growth method. FTIR, 1H NMR, and 13C NMR spectra were used to identify the structures of the dendron, the dendritic macromonomer, and the dendritic-linear PMA-APM-r-PS copolymer. Furthermore, microporous dendritic-linear PMA-APM-r-PS copolymer films were prepared by using solvent-induced phase separation at room temperature. We investigated the phase separation behavior and morphological structures of the dendritic-linear copolymer film as functions of dendritic GMA-HPAM segments in the content using SEM. Self-assembly of the dendritic-linear PMA-APM-r-PS copolymer in the MG2-X system, which represented the second generation dendron containing X wt % of the dendritic MA-APM segment, resulted in submicron phase segregation. Interestingly, the submicron phase segregation morphology of the MG2–43 sample presented a uniform size distribution of ordered-array structures. The results of this study demonstrate that controlling the appropriate macromonomer content via the grafting of a three-dimensional structure results in a self-assembly process that is capable of providing an ordered-array microporous morphology in a polymer film. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3290–3301, 2010