Increase In Dendrimer Generation Research Articles

Photochromic Dendrimers for Photoswitched Solid-To-Liquid Transitions and Solar Thermal Fuels.

Dendrimers are well-defined, highly branched macromolecules that have been widely applied in the fields of catalysis, sensing, and biomedicine. Here, we present a novel multifunctional photochromic dendrimer fabricated through grafting azobenzene units onto dendrimers, which not only enables controlled switching of adhesives and effective repair of coating scratches but also realizes high-performance solar energy storage and on-demand heat release. The switchable adhesives and healable coatings of azobenzene-containing dendrimers are attributed to the reversible solid-to-liquid transitions because trans-isomers and cis-isomers have different glass transition temperatures. The adhesion strengths increase significantly with the increase in dendrimer generations, wherein the adhesion strength of fifth-generation photochromic dendrimers (G5-Azo) can reach up to 1.62 MPa, five times higher than that of pristine azobenzenes. The solar energy storage and heat release of dendrimer solar thermal fuels, the isomers of which possess different chemical energies, can be also enhanced remarkably with the amplification of azobenzene groups on dendrimers. The storage energy density of G5-Azo can reach 59 W h kg-1, which is much higher than that of pristine azobenzenes (36 W h kg-1). The G5-Azo fuels exhibit a 5.2 °C temperature difference between cis-isomers and trans-isomers. These findings provide a new perspective and tremendously attractive avenue for the fabrication of photoswitchable adhesives and coatings and solar thermal fuels with dendrimer structures.

Dendrimer size effects on the selective brain tumor targeting in orthotopic tumor models upon systemic administration.

Malignant gliomas are the most common and aggressive form of primary brain tumors, with a median survival of 15–20 months for patients receiving maximal interventions. Advances in nanomedicine have provided tumor‐specific delivery of chemotherapeutics to potentially overcome their off‐target toxicities. Recent advances in dendrimer‐based nanomedicines have established that hydroxyl‐terminated poly(amidoamine) dendrimers can intrinsically target neuroinflammation and brain tumors from systemic administration without the need for targeting moieties. The size of nanocarriers is a critical parameter that determines their tumor‐targeting efficiency, intratumor distribution, and clearance mechanism. In this study, we explore the dendrimer size effects on brain tumor targeting capability in two clinically relevant orthotopic brain tumor models, the 9L rat and GL261 mouse models, which capture differing aspects of gliomas. We show that increasing dendrimers from Generation 4 to Generation 6 significantly enhances their tumor accumulation (~10‐fold greater at 24 hr), tumor specificity (~2–3 fold higher), and tumor retention. The superior tumor targeting effect of G6 dendrimers is associated with its reduced renal clearance rate, resulting in longer circulation time compared to G4 dendrimers. Additionally, the increase in dendrimer generation does not compromise its homogeneous tumor distribution and intrinsic targeting of tumor‐associated macrophages. These results validate the potential for these dendrimers as an effective, clinically translatable platform for effectively targeting tumor‐associated macrophages in malignant gliomas.

Carbazole Dendrimers with Acridone at the Core and Periphery: Synthesis and Properties

AbstractAcridone‐functionalized carbazole dendrimers were synthesized via copper‐catalyzed Ullmann amination and their properties were investigated by spectroscopic and electrochemical measurements, as well as theoretical calculations. The results reveal that the properties of the carbazole dendrimers vary according to the position of acridone. Intramolecular charge transfer between the acridone core and the outer carbazole dendron is observed, accompanying a red shift of the emission maximum and a decline of quantum yields with the rise of the dendrimer generation. Whereas the internal carbazole unit has little influences on the photoluminescence of dendrimers with acridone at the periphery in solution. The electrochemical analysis and theoretical calculations demonstrate a convergence in HOMO and LUMO energy levels in dendrimers bearing the acridone core and a decrease in both of these energy levels in dendrimers with the acridone at the periphery when the dendrimer generation increases.

Effect of pH on Eosin Y/PAMAM interactions studied from absorption spectroscopy and molecular dynamics simulations

Absorption spectroscopy experiments were carried out to examine the 1:1 supramolecular interaction between Eosin Y (EOS) and low generation G0-G3 poly(amido amine) (PAMAM) dendrimers at neutral and basic media, aimed at gaining insight about the role of pH and dendrimer generation on EOS-PAMAM binding. Our results revealed that EOS complexation is favored under neutral pH conditions, and that the supramolecular interaction strengthens as the dendrimer generation increases. Further molecular-level information regarding EOS-PAMAM systems was obtained from Molecular Dynamics (MD) simulations, Non-Covalent Interaction (NCI) analysis and MM/PBSA binding free energy calculations, which were carried out to examine the role of the generation, charge, and protonation state of PAMAM on the structure, conformation, and preferable interactions with EOS at neutral and basic pH conditions. Theoretical predictions were in high agreement with experimental results, showing that neutral pH allows a faster, deeper, and more stable complexation of the dye within dendrimer cavities, and that higher generation dendrimers induce a larger affinity towards EOS. According to MD results, the binding mode of the dye favors the interaction of the xanthene moiety within internal dendrimer cavities through the establishment of attractive van der Waals contacts. On the other hand, the carboxylate moiety interacts with the outermost dendrimer branches and remains exposed towards the solvent in G0-G2 PAMAM. These results support the validity of using MD simulations as auxiliary tools to deal with supramolecular complexation phenomena involving PAMAM dendrimers as host molecules.

Synthesis, Photophysical, Electrochemical Studies, and Antioxidant Properties of Fluorescein‐Linked Glycodendrimers

AbstractFluorescein‐linked glycodendrimers 1, 2, 3, and 4 were synthesized up to the third generation with glucose surface groups and triazole as the bridging unit by using a CuI‐catalyzed click chemistry protocol. All the synthesized glycodendrimers showed comparable antioxidant behavior to that of the standard with ascorbic acid when tested with both the DPPH (1,1‐diphenyl‐2‐picryl hydrazyl) scavenging assay and HO radical scavenging assay methods. Higher generation glycodendrimers exhibited superior antioxidant activity than the lower generation glycodendrimers owing to the presence of a greater number of triazole units and multivalent glucose units. The fluorescence and UV absorption intensity increases with the increase in dendrimer generation. All the dendrimers 1–4 showed reduction peaks with negative potentials in their cyclic voltammograms.

Prolonged drug delivery system of an antifungal drug by association with polyamidoamine dendrimers.

Introduction:The potent antifungal agent amphotericin B (AmB) is not freely soluble in water. The clinical use of AmB is limited by nephrotoxicity and poor water solubility. Polyamidoamine (PAMAM) dendrimer offers an identical carrier for drug binding that has the capacity to attach and discharge drugs in numerous ways.Materials and methods:In this research work, we explored the potential of PAMAM dendrimers to improve the solubility of AmB.Results and discussion:The experimental results indicated that the solubility of AmB was greatly enhanced in the presence of PAMAM dendrimer solutions. Results indicated that the solubility of AmB enhanced with increase in dendrimer generations as well as concentration. In vitro release studies of AmB in the presence of the third generation of PAMAM dendrimers was performed by the dialysis method. Our research work revealed that binding of drug into dendrimers led to sustained release of AmB in vitro.Conclusion:Based on the stability studies, it was concluded that the drug dendrimer complex should be stored in a dark place at a cool temperature.

Complexation of Mefenamic Acid by Low‐Generation PAMAM Dendrimers: Insight from NMR Spectroscopy Studies and Molecular Dynamics Simulations

The complexation of mefenamic acid (MA) with poly(amido amine) dendrimers of the second and third generation (PAMAM‐G2 and PAMAM‐G3) at pH 7.0 is studied by aqueous solubility experiments, DOSY and 2D‐NOESY spectroscopy, and fully atomistic molecular dynamics (MD) simulations. Solubility profiles account for the formation of MA:PAMAM complexes of the type 10:1 and 15:1, for PAMAM‐G2 and PAMAM‐G3, respectively, with a maximum solubilization enhancement of 14.6 mol of MA per mol dendrimer. Diffusion ordered sepectroscopy (DOSY) and nuclear Overhauser effect spectroscopy (NOESY) experiments suggest that MA association occurs through both external electrostatic interactions with the PAMAM surface and internal encapsulation into the deep dendrimer cavities. MD simulations are consistent with these experimental findings and show that the internal drug encapsulation is enhanced as the dendrimer generation increases. The involvement of internal and external interactions in the complexation of MA with low‐generation PAMAM dendrimers differs from the general behavior expected for acidic anionic guests, for which external electrostatic contacts with the positively charged PAMAM surface have been postulated as the most relevant factor for drug association. image

Interaction of nucleic acids with carbon nanotubes and dendrimers

Nucleic acid interaction with nanoscale objects like carbon nanotubes (CNTs) and dendrimers is of fundamental interest because of their potential application in CNT separation, gene therapy and antisense therapy. Combining nucleic acids with CNTs and dendrimers also opens the door towards controllable self-assembly to generate various supra-molecular and nano-structures with desired morphologies. The interaction between these nanoscale objects also serve as a model system for studying DNA compaction, which is a fundamental process in chromatin organization. By using fully atomistic simulations, here we report various aspects of the interactions and binding modes of DNA and small interfering RNA (siRNA) with CNTs, graphene and dendrimers. Our results give a microscopic picture and mechanism of the adsorption of single- and double-strand DNA (ssDNA and dsDNA) on CNT and graphene. The nucleic acid-CNT interaction is dominated by the dispersive van der Waals (vdW) interaction. In contrast, the complexation of DNA (both ssDNA and dsDNA) and siRNA with various generations of poly-amido-amine (PAMAM) dendrimers is governed by electrostatic interactions. Our results reveal that both the DNA and siRNA form stable complex with the PAMAM dendrimer at a physiological pH when the dendrimer is positively charged due to the protonation of the primary amines. The size and binding energy of the complex increase with increase in dendrimer generation. We also give a summary of the current status in these fields and discuss future prospects.

Complexation of siRNA with Dendrimer: A Molecular Modeling Approach

This paper reports the structural behavior and thermodynamics of the complexation of siRNA with poly(amidoamine) (PAMAM) dendrimers of generation 3 (G3) and 4 (G4) through fully atomistic molecular dynamics (MD) simulations accompanied by free energy calculations and inherent structure determination. We have also done simulation with one siRNA and two dendrimers (2×G3 or 2×G4) to get the microscopic picture of various binding modes. Our simulation results reveal the formation of stable siRNA−dendrimer complex over nanosecond time scale. With the increase in dendrimer generation, the charge ratio increases and hence the binding energy between siRNA and dendrimer also increases in accordance with available experimental measurements. Calculated radial distribution functions of amines groups of various subgenerations in a given generation of dendrimer and phosphate in backbone of siRNA reveals that one dendrimer of generation 4 shows better binding with siRNA almost wrapping the dendrimer when compared to the...

Diffusion and NOE NMR Studies on Multicationic DAB‐Organoruthenium Dendrimers: Size‐Dependent Noncovalent Self‐Assembly to Megamers and Ion Pairing

New multicationic organoruthenium dendrimers (RuPF(6)-Dabn, n = 2, 4, 8, 16) have been synthesized by coupling of [Ru(eta(6)-p-cymene)(kappa(3)-dpk-OCH(2)CH(2)OH)]X (1PF(6), dpk = 2,2'-dipyridyl ketone, X = PF(6)) with 1,4-diaminobutane (DAB) and polypropylenimine dendrimer DAB-dendr-(NH(2))(n) {n=4, 8, 16} mediated by 1,1'-carbonyldiimidazole (CDI). The intermediate in the synthesis, [Ru(eta(6)-p-cymene)(kappa(3)-dpk-OCH(2)CH(2)OC(O)Im]X (2PF(6), Im = imidazole, X = PF(6)) has been isolated and characterized by single-crystal XRD. The intra- and supramolecular structures in a solution of RuPF(6)-Dabn dendrimer have been investigated by multidimensional and multinuclear NMR techniques. Diffusion NMR experiments on dilute solutions indicated that the linear distance between two metal centers (14.9-22.1 A depending on the dendrimer generation) is much greater than the diameter of 1PF(6) (9.9 A). (19)F,(1)H-HOESY NMR experiments (HOESY = heteronuclear Overhauser effect spectroscopy) showed that the counterion is positioned on the surface of the dendrimers and assumes the same relative anion-cation orientation as in 2PF(6). Diffusion NMR experiments on RuPF(6)-Dabn dendrimers in CD(2)Cl(2) at different concentrations revealed a process of supramolecular assembly of dendrimers to megamers that is strongly favored for the highest generations. Megamer formation is coupled with an increased fraction of free ions (alpha) and a consequent reduction in ion-paired ruthenium centers. Graphs of alpha versus C(Ru) (the concentration of ruthenium centers) showed a minimum for RuPF(6)-Dab4, RuPF(6)-Dab8, and RuPF(6)-Dab16 at a position coinciding with the significant presence of supramolecular dendritic dimers. The tendency to ion pairing decreases as the dendrimer generation increases.

Bathochromic shift of the fluorescence spectral maximum with increasing generation of dansyl labeled Newkome type dendrimers

Dansyl moiety attached to the core of Newkome-type dendrimers shows a bathochromic shift of the fluorescence emission spectrum with increase in dendrimer generation. However the E T(30) plots in different solvents show a decrease in slope with increasing generation. This has been explained in terms of modification of transition energies and progressive shielding of the fluorophore with increasing generation.

PGSE NMR Studies on DAB-Organo-Rhodium Dendrimers: Evaluation of the Molecular Size, Self-Aggregation Tendency, and Surface Metal Density

PGSE NMR measurements have been carried out for DAB-dendr-(NH2)n [n = 4 (Dab4), 8 (Dab8), 16 (Dab16), 32 (Dab32), and 64 (Dab64)] and DAB-dendr-[NH(O)COCH2CH2OC(O)C5H4Rh(NBD)]n [n = 4 (Rh-Dab4), 8 (Rh-Dab8), 16 (Rh-Dab16), 32 (Rh-Dab32), and 64 (Rh-Dab64)] in CD2Cl2 and CD3OD as a function of the concentration. The hydrodynamic radius (rH) and, consequently, the hydrodynamic volume (VH) of all the species are determined from the measured translational self-diffusion coefficients (Dt). In CD2Cl2, both Dab and Rh-Dab dendrimers show a tendency toward self-aggregation that increases with the generations. In addition, while the radii rH for Dab dendrimers is ca. 20−30% higher in CD3OD than in CD2Cl2, the rH values for Rh-Dab dendrimers are only slightly influenced by solvent variation. To estimate the Rh−Rh spatial proximity (dRh/Rh) on the surface, the internal radius (rint) of the Dab skeleton in Rh-Dab dendrimers was (i) considered equal to that of the Dab dendrimers (model A) or (ii) evaluated assuming that the additional solvent molecules derived from the attachment of Rh to Dab dendrimers were incorporated into the elongated dendritic skeleton (model B). It was found that dRh/Rh decreases from 17.2−19.8 Å (Rh-Dab4) to about 14.0 Å (Rh-Dab64) with the increase in dendrimer generation.

Binding of monomeric and dimeric Concanavalin A to mannose-functionalized dendrimers

Because of the central role of Concanavalin A (Con A) in the study of protein-carbohydrate interactions, a thorough understanding of the multivalent functions of Con A is imperative. Here, the association of monomeric and dimeric derivatives of Con A with mannose-functionalized generation two through six PAMAM dendrimers is reported. Hemagglutination assay results indicate relatively low activity of the dendrimers for monomeric Con A, with small increases as the dendrimer generation increases. Isothermal titration microcalorimetry experiments indicate monovalent binding by the dendrimers with monomeric Con A and divalent binding by the dendrimers with dimeric Con A. Continuous (and comparable) but narrowing increases in enthalpy and entropy and the slight increase in association constants with monomeric Con A as the dendrimer generation increases suggest favorable proximity effects on binding. Both the hemagglutination assay and the calorimetry experiments suggest that statistical binding enhancements can be observed with monomeric Con A. The results described here should allow for a more quantitative evaluation of the enhancements that are often observed in protein-carbohydrate interactions for glycosylated frameworks binding to Con A.

Synthesis of axially chiral dendrimers containing meta-terphenyl peripheral groups and a chiral binol core

Fréchet-type poly(arylether) dendritic bromides carrying m-terphenyl peripheral groups were synthesised up to second generation by convergent methodology. Simple O-alkylation of chiral (S)-BINOL with the dendritic bromides afforded the corresponding axially chiral dendrimers. The molar optical rotation values of the dendrimers become increasingly negative as the dendrimer generation increases.

Synthesis and electrochemical properties of dendrimers containing meta-terphenyl peripheral groups and a 4,4′-bipyridinium core

Fréchet-type poly(arylether) dendrons carrying m-terphenyl peripheral groups were synthesized up to second generation by convergent methodology. Simple quarternisation of 4,4′-bipyridine with the dendritic bromides afforded the corresponding dendrimers containing a 4,4′-bipyridine core. The electrochemical parameters were obtained for all the dendrimers and the half-wave potentials of both the first and second redox processes shift to less-negative values as the dendrimer generation increases.

Copper-free monomeric and dendritic palladium catalysts for the Sonogashira reaction: substituent effects, synthetic applications, and the recovery and re-use of the catalysts.

A series of bis(tert-butylphosphine)- and bis(cyclohexylphosphine)-functionalized Pd(II) monomers and polyamino (DAB) dendritic catalysts were synthesized and investigated for Sonogashira carbon-carbon coupling reactions in a copper-free procedure. The influence of phosphine substituents (tBu versus Cy) on the reaction kinetics was investigated by a GPC technique to monitor the reactions. The dendritic catalysts containing the cyclohexylphosphine ligands could be recovered and reused without loss of efficiency until the fifth cycle. The dendritic Pd(II) catalysts show a negative dendritic effect, that is, the catalyst efficiency decreases as the dendrimer generation increases.

Photochemical and Photophysical Properties of C60 Dendrimers Studied by Laser Flash Photolysis

Photochemical and photophysical properties of fullerene dendrimers, in which the fullerene-moiety was connected via an acetylene bond with benzyl-ether type dendrons from the second to fourth generation, have been investigated by time-resolved fluorescence and time-resolved absorption methods, in addition to steady-state spectra. The photophysical properties of the dendrimers such as lifetimes of the singlet and triplet excited states were essentially the same, regardless of the dendrimer generation. However, the rate constants of intermolecular processes such as triplet−triplet annihilation, triplet energy transfer, and electron transfer via the triplet states decreased with the increase in dendrimer generation. The relation between the free energy changes and the quenching rate constants revealed long-range electron transfer processes due to steric hindrance of the dendron groups. Furthermore, it was revealed that the solvation of radical ion pairs is also affected by size of the dendron groups. Back el...

Dendrimers Functionalized with a Single Fluorescent Dansyl Group Attached “Off Center”: Synthesis and Photophysical Studies

A series of three new fluorescent dendrimers containing a single, focally located dansyl group and 3 (1), 9 (2), and 27 (3) carboxylic acid groups in their peripheries were synthesized and characterized. The photophysical properties of these dendrimers were investigated in aqueous solution. The host−guest interactions of the dendrimers through their dansyl subunits with β-cyclodextrin and polyclonal anti-dansyl antibodies were also investigated by various methods. Photophysical measurements on the dendrimers demonstrate that the dansyl residue is progressively shielded from the solvent as the dendrimer generation increases, resulting in marked changes in spectral features, fluorescence quantum yields, excited-state fluorescence lifetimes, radiative and nonradiative decay rates, and rotational reorientation times. The excited-state intensity decay kinetics for 1−3 are well described by a single exponential. Contrary to the popularly held belief that lower generation dendrimers are “floppy” species in solut...

Solvent Dependence of the Hydrodynamical Volume of Dendrimers with a Rubicene Core

Four generations of a dendrimer with a fluorescent core consisting of a rubicene moiety are synthesized. The biexponential nature of fluorescence decay in toluene indicates the presence of two emitting conformations. Molecular modeling suggests that a conformation where the dendrons interact with the core is not improbable. The relative weight of the two decay times indicates that the contribution of that conformation in toluene increases as the dendrimer generation increases. In acetone and acetonitrile however the fluorescence decay is, except for the fourth generation, monoexponential. The hydrodynamical volume of the dendrimer is determined in toluene, a good solvent, acetone, a medium quality solvent, and acetonitrile, a poor solvent, with the time-resolved fluorescence depolarization technique. No change of the hydrodynamical volume is found in toluene in a temperature range between 20 and 94 °C. This suggests that the dendrimers of all the generations are fully expanded in this solvent. In acetonitrile however the hydrodynamical volume of the dendrimers is substantially smaller than in toluene and acetone. This effect is most clear for the fourth-generation dendrimer. For this compound the hydrodynamical volume is only a few percentages larger than the excluded volume.