Dendrimer Ligands Research Articles

Single-molecule displacement assay reveals strong binding of polyvalent dendrimer ligands to telomeric G-quadruplex

Binding between a ligand and a receptor is a fundamental step in many natural or synthetic processes. In biosensing, a tight binding with a small dissociation constant (Kd) between the probe and analyte can lead to superior specificity and sensitivity. Owing to their capability of evaluating competitors, displacement assays have been used to estimate Kd at the ensemble average level. At the more sensitive single-molecule level, displacement assays are yet to be established. Here, we developed a single-molecule displacement assay (smDA) in an optical tweezers instrument and used this innovation to evaluate the binding of the L2H2-6OTD ligands to human telomeric DNA G-quadruplexes. After measuring Kd of linear and dendrimer L2H2-6OTD ligands, we found that dendrimer ligands have enhanced binding affinity to the G-quadruplexes due to their polyvalent geometry. This increased binding affinity enhanced inhibition of telomerase elongation on a telomere template in a Telomerase Repeated Amplification Protocol (TRAP). Our experiments demonstrate that the smDA approach can efficiently evaluate binding processes in chemical and biological processes.

Unique transport behaviour of Am(III)/Eu(III) ions across a supported liquid membrane containing a TREN-based diglycolamide dendrimer ligand

Abstract Appropriately functionalized dendrimers are exotic ligands and are expected to give rise to better extraction/transport results than the corresponding monofunctional ones. Diglycolamide- (DGA) based dendrimers and their transport studies are rarely reported. Transport of Am(III) and Eu(III) was studied across a PTFE- (polytetrafluoroethylene) based flat sheet supported liquid membrane containing a tris(2-aminoethyl)amine (TREN) dendrimer ligand containing six DGA pendent arms (termed as TREN-G1-DGA) in 5% isodecanol modified n-dodecane. The transport results were compared with those of the monofunctional ligand TODGA (N,N,N′,N′-tetra-n-octyl diglycolamide). In case of a 5.75 × 10−4 M TREN-G1-DGA solution, Am(III) transport was slower than that of Eu(III) under identical conditions. In case of TREN-G1-DGA the role of acid on the metal ion transport was less important than that while using TODGA as a carrier. However, a nitric acid medium is much more suitable for metal ion transport than a mixture containing sodium nitrate as the major component. Insight into the extraction and transport of the Eu(III) complexes was obtained from luminescence spectroscopic studies.

Sub-5 nm Anisotropic Pattern Transfer via Colloidal Lithography of a Self-Assembled GdF3 Nanocrystal Monolayer.

Patterning materials with nanoscale features opens many research opportunities ranging from fundamental science to technological applications. However, current nanofabrication methods are ill-suited for sub-5 nm patterning and pattern transfer. We demonstrate the use of colloidal lithography to transfer an anisotropic pattern of discrete features into substrates with a critical dimension below 5 nm. The assembly of monodisperse, anisotropic nanocrystals (NCs) with a rhombic-plate morphology spaced by dendrimer ligands results in a well-ordered monolayer that serves as a 2D anisotropic hard mask pattern. This pattern is transferred into the underlying substrate using dry etching followed by removal of the NC mask. We exemplify this approach by fabricating an array of pillars with a rhombic cross-section and edge-to-edge spacing of 4.4 ± 1.1 nm. The fabrication approach enables broader access to patterning materials at the deep nanoscale by implementing innovative processes into well-established fabrication methods while minimizing process complexity.

A New Cu(II) Complex of PAMAM Dendrimer Modified with 1,8-Naphthalimide: Antibacterial and Anticancer Activity

A new fluorescent PAMAM copper complex ([Cu2(D)(NO3)4]) has been synthesized and identified. The formation of the complex has been investigated by fluorescence spectroscopy which revealed two copper ions to be bound to the dendrimer ligand. That has also been confirmed upon subjecting the solid copper complex to electron paramagnetic spectroscopy. The antimicrobial activity of the copper complex against Gram-negative bacterium Pseudomonas aeruginosa in light and the dark has been studied. The results demonstrate an increase in its activity when irradiated with daylight. This activity of the copper complex is retained even after being loaded onto a cotton cloth. The antitumor activity of the copper complex and dendrimer ligand against triple-negative breast cancer MDA-MB-231 cells has been investigated as well.

Synthesis and characterization of fluorescent PAMAM dendrimer modified with 1,8-naphthalimide units and its Cu(II) complex designed for specific biomedical application

A new fluorescent dendrimer was obtained by modifying the periphery of a PAMAM dendrimer from zero generation. The modification involves substitution at the C-4 position with 1,8-naphthalimide units containing N-methylpiperazine and the addition of Cu(II) ions forming the metallodendrimer [Cu2(D)(NO3)2]. The dendrimer ligand and metallodendrimer were subjected to UV–vis, fluorescence spectroscopy, FT-IR, NMR, and SEM investigations to define their precise structure. The photophysical characteristics of the yellow-green fluorescent dendrimer were studied in organic solvents of different polarity. Results show that polar solvents favour a photoinduced electron transfer (PET) process. Experiments on the effect of pH in an ethanol - water solution (1:4 v/v) revealed the fluorescence of the dendrimer to be more than seventeen times higher than that in an acidic medium. Electron paramagnetic resonance (EPR) studies were performed to characterize the complexing ability of the dendrimer towards Cu(II) by varying the [Cu(II)/dendrimer external sites] molar ratio in DMSO solution. The EPR results suggest that Cu(II) formed a Cu-N2O2 square-planar coordination with nitrogen sites (N-CH3 sites of 1,8-methylpiperazine, and amine and amide groups) at the dendrimer internal/external interface, and 2 solvent molecules. The Cu(II) complex was characterized by restricted mobility conditions. Copper (II) ions were distributed between the dendrimer interface and the external surface; saturation of the nitrogen sites at the interface occurred at a 1:2 M ratio between Cu(II) and methylpiperazine units. These results are useful in view of the use of this metallodendrimer as anticancer and antimicrobial drugs. The antimicrobial activity of dendrimer ligand and its Cu(II) complex was tested against several model strains bacteria and yeasts in agar, in liquid medium, and after their deposition onto a cotton fabric. The results showed good antibacterial effect of dendrimer ligand, which was enhanced by its Cu(II) complexation.

Sequestration of tetravalent neptunium from acidic feeds using diglycolamide-functionalized dendrimers in a room temperature ionic liquid: extraction, spectroscopic and electrochemical studies

Extraction of Np(iv) was studied using RTIL containing two poly(propyleneimine) based dendrimer ligands from HNO3 solutions. Studies of the extracted complexes were also carried out by Vis-NIR and cyclic voltammetry.

Fouling decline and retention increase of polyethersulfone membrane by incorporating melamine-based dendrimer amine functionalized graphene oxide nanosheets (GO/MDA)

Graphene oxide (GO) nanosheets were prepared using modified Hummers method and then amino-functionalized with melamine-based dendrimer amines (MDA). The resulted nanofiller (GO/MDA) was incorporated into the polyethersulfone (PES) membrane matrix with the phase inversion technique. The effects of this incorporation on membrane properties were studied in different terms including hydrophilicity, porosity, surface and cross-sectional morphology, mean pore radius, permeability, fouling resistance and nanofiltration performance. The resulted membranes presented enhanced hydrophilicity, porosity and permeability due to the presence of super hydrophilic GO/MDA nanocomposite in the membrane matrix. The pure water flux of the PES membranes under the operating pressure of 0.3 MPa was increased from 19.9 kg/m2 h for the bare PES to 38.1 kg/m2 h and 53.9 kg/m2 h for the optimum contents of GO and GO/MDA, respectively. The flux recovery ratio (FRR) was enhanced from 50.4% for the bare PES to 78.5% for the membrane containing the optimum content of GO/MDA (0.25 wt%). This membrane also presented the minimum total and irreversible fouling ratios. Nanofiltration performance of the membranes was proved with near total rejection of anionic dye reactive red 198, alongside the remarkable retention of divalent ions (77.4% and 56.4% for Na2SO4 and MgSO4, respectively) and slight retention of monovalent ion NaCl (18.9%). Eventually, the results of the present study introduced MDAs as ideal dendrimer ligands for the preparation of highly hydrophilic and antifouling nanofillers.

Spectral characterization, antimicrobial and antibiofilm activity of poly(propylene imine) metallodendrimers in solution and applied onto cotton fabric

Poly(propylene imine) dendrimers from first and third generation modified with 1,8-naphthalimide units and their Cu(II) complexes have been characterized by fluorescence and EPR spectroscopy. Cotton fabric has been modified with these dendrimers and their color characteristics were determined. The antimicrobial activity of dendrimer ligands and their Cu(II) complexes in solution and after their deposition on a cotton fabric was investigated. Good antibacterial effect of dendrimer ligands has been obtained, which is enhanced at their Cu(II) complexes. After their deposition on cotton fabric metallodendrimers exhibit good antibiofilm activity.

Dendrimer Ligand Directed Nanoplate Assembly.

Many studies on nanocrystal (NC) self-assembly into ordered superlattices have focused mainly on attractive forces between the NCs, whereas the role of organic ligands on anisotropic NCs is only in its infancy. Herein, we report the use of a series of dendrimer ligands to direct the assembly of nanoplates into 2D and 3D geometries. It was found that the dendrimer-nanoplates consistently form a directionally offset architecture in 3D films. We present a theory to predict ligand surface distribution and Monte Carlo simulation results that characterize the ligand shell around the nanoplates. Bulky dendrimer ligands create a nontrivial corona around the plates that changes with ligand architecture. When this organic-inorganic effective shape is used in conjunction with thermodynamic perturbation theory to predict both lattice morphology and equilibrium relative orientations between NCs, a lock-and-key type of mechanism is found for the 3D assembly. We observe excellent agreement between our experimental results and theoretical model for 2D and 3D geometries, including the percent of offset between the layers of NCs. Such level of theoretical understanding and modeling will help guide future design frameworks to achieve targeted assemblies of NCs.

Improved Chemical and Colloidal Stability of Gold Nanoparticles through Dendron Capping

Nanoparticle (NP) stability is imperative for commercialization of nanotechnology. In this study, we compare the stability of Au NPs with surfaces functionalized with oleylamine, dodecanethiol, and two dendritic ligands of different generations. Dendrimer ligands provide a significant increase in the chemical stability of Au NPs when analyzed by cyanide-induced NP decomposition as well as an investigation into their colloidal stability at ambient conditions. These results were supported by absorption measurements, transmission electron microscopy, thermogravimetric analysis, nuclear magnetic resonance, and small-angle transmission X-ray scattering and show that dendrimers play a key role in improving the chemical and colloidal stability of NPs.

Synthesis, spectral characterization, and in vitro antimicrobial activity in liquid medium and applied on cotton fabric of a new PAMAM metallodendrimer

ABSTRACTA new polyamidoamine metallodendrimer modified with eight 1,8-naphthalimide units was synthesized. The Cu(II) complex has been investigated by EPR spectroscopy and it has shown that 17 copper ions have involved in the dendrimer complex. To confirm the presence of metallodendrimers on the cotton surface, scanning electron microscopy characterization has been used. In vitro antimicrobial activity of the metallodendrimer against different pathogens was investigated and compared to the dendrimer ligand free of copper ions. Both dendrimers were deposited on a cotton fabric and antibacterial activity of the treated cotton samples was investigated against model Gram-positive and Gram-negative bacteria. It has been shown that the studied dendrimers reduce bacterial growth and prevent the formation of biofilms. The metallodendrimer showed stronger antimicrobial and biofilm inhibiting abilities than those of the free of Cu(II) ions ligand.

Multifunctional Dendrimer Ligands for High-Efficiency, Solution-Processed Quantum Dot Light-Emitting Diodes.

We present multifunctional dendrimer ligands that serve as the charge injection controlling layer as well as the adhesive layer at the interfaces between quantum dots (QDs) and the electron transport layer (ETL) in quantum dot light-emitting diodes (QLEDs). Specifically, we use primary amine-functionalized dendrimer ligands (e.g., a series of poly(amidoamine) dendrimers (PADs, also referred to PAMAM)) that bind to the surface of QDs by replacing the native ligands (oleic acids) and also to the surface of ZnO ETL. PAD ligands control the electron injection rate from ZnO ETL into QDs by altering the electronic energy levels of the surface of ZnO ETL and thereby improve the charge balance within QDs in devices, leading to the enhancement of the device efficiency. As an ultimate achievement, the device efficiency (peak external quantum efficiency) improves by a factor of 3 by replacing the native ligands (3.86%) with PAD ligands (11.36%). In addition, multibranched dendrimer ligands keep the QD emissive layer intact during subsequent solution processing, enabling us to accomplish solution-processed QLEDs. The approach and results in the present study emphasize the importance of controlling the ligands of QDs to enhance QLED performance and also offer simple yet effective chemical mean toward all-solution-processed QLEDs.

Overcoming antibiotic resistance in Pseudomonas aeruginosa biofilms using glycopeptide dendrimers.

Antibiotic resistance in the opportunistic pathogen Pseudomonas aeruginosa is partly caused by biofilms forming a physical barrier to antibiotic penetration. Here we focused on modifying tetravalent glycopeptide dendrimer ligands of P. aeruginosa lectins LecB or LecA to increase their biofilm inhibition activity. First heteroglycoclusters were investigated displaying one pair each of LecB specific fucosyl groups and LecA specific galactosyl groups and binding simultaneously to both lectins, one of which gave the first fully resolved crystal structure of a peptide dendrimer as LecB complex providing a structural model for dendrimer-lectin interactions (PDB ; 5D2A). Biofilm inhibition was increased by introducing additional cationic residues in these dendrimers but resulted in bactericidal effects similar to those of non-glycosylated polycationic antimicrobial peptide dendrimers. In a second approach dendrimers displaying four copies of the natural LecB ligand Lewisa were prepared leading to slightly stronger LecB binding and biofilm inhibition. Finally synergistic application of a LecB specific non-bactericidal antibiofilm dendrimer with the antibiotic tobramycin at sub-inhibitory concentrations of both compounds allowed effective biofilm inhibition and dispersal.

Poly(propylenamine) dendrimers modified with 4-amino-1,8-naphthalimide: Synthesis, characterization and in vitro microbiological tests of their Cu(II) and Zn(II) complexes

The paper describes the modification of the periphery of first and third generation poly(propylenamine) dendrimers with 4-amino-1,8-naphthalimide units as well as the formation of their Cu(II) and Zn(II) complexes. The new dendrimers and metal complexes have been characterized by electronic (UV–Vis and fluorescence), FTIR and NMR and MALDI-TOF analytical methods. The results have shown that the Cu(II) and Zn(II) ions form complexes with the dendrimer ligands. Photophysical experiments have been performed in organic solvents of different polarity. The metal complexes formed between the dendrimers and Cu(II) and Zn(II) ions have been studied with regards to potential microbiological activity. In vitro antimicrobial screening of the newly synthesized metallodendrimers revealed promising antimicrobial activity, and the minimum inhibitory concentrations (MICs) of the complexes were determined. The results suggest that the new metal complexes could find application in designing new antimicrobial preparations to control the spread of infections.

Synthesis and spectral characterization of a new PPA dendrimer modified with 4-bromo-1,8-naphthalimide and in vitro antimicrobial activity of its Cu(II) and Zn(II) metal complexes

This article describes the peripheral modification of a polypropylene amine dendrimer of second generation with eight 4-bromo-1,8-naphthalimide units and its copper and zinc complexes. The new dendrimer and its metal complexes have been characterized by electronic (UV–vis and fluorescence) and vibrational (IR and Raman) spectral methods in view of their antibacterial and antifungal activity. The results have shown that the two metal ions form complexes with the dendrimer ligand. In vitro antimicrobial screening of the newly synthesized metallodendrimers showed promising antimicrobial activities against some pathogenic Gram-positive and Gram-negative bacteria and the yeasts Candida lipolytica. The results suggest that the new metal complexes could find application in designing new antimicrobial preparations to control the spread of infections caused especially by Acinetobacter, Micrococcus and Candida species.

ChemInform Abstract: Magic Number Pt13 and Misshapen Pt12 Clusters: Which One is the Better Catalyst?

AbstractPtn (n = 12, 13) clusters are synthesized with atomic‐level precision by using a dendrimer ligand as the macromolecular template.

Magic Number Pt13 and Misshapen Pt12 Clusters: Which One is the Better Catalyst?

A relationship between the size of metal particles and their catalytic activity has been established over a nanometer scale (2-10 nm). However, application on a subnanometer scale (0.5-2 nm) is difficult, a possible reason being that the activity no longer relies on the size but rather the geometric structure as a cluster (or superatomic) compound. We now report that the catalytic activity for the oxygen reduction reaction (ORR) significantly increased when only one atom was removed from a magic number cluster composed of 13-platinum atoms (Pt13). The synthesis with an atomic-level precision was successfully achieved by using a dendrimer ligand as the macromolecular template strictly defining the number of metal atoms. It was quite surprising that the Pt12 cluster exhibited more than 2-fold catalytic activity compared with that of the Pt13 cluster. ESI-TOF-mass and EXAFS analyses provided information about the structures. These analyses suggested that the Pt12 has a deformed coordination, while the Pt13 has a well-known icosahedral atomic coordination as part of the stable cluster series. Theoretical analyses based on density functional theory (DFT) also supported this idea. The present results suggest potential activity of the metastable clusters although they have been "missing" species in conventional statistical synthesis.

Preferential Binding of a Novel Polyhistidine Peptide Dendrimer Ligand on Quantum Dots Probed by Capillary Electrophoresis

Fluorescence detection coupled to capillary electrophoresis (CE-FL) effectively separates molecules in solution and at the same time allows monitoring of the fluorescence spectrum of each individual species. The integration of separation and fluorescence detection results in a powerful method superior to the ensemble in-cuvette fluorescence measurement, in probing the binding interaction between ligands and quantum dots (QDs) in complex solutions. Förster resonance energy transfer (FRET) between fluorescent ligands and QDs could be readily detected by CE-FL, which together with the migration times of the fluorescent peaks provides an indication of the binding interaction between ligands and QDs. In the present study, the binding interaction between a multivalent ligand, polyhistidine peptide denderimer (PHPD), and CdSe-ZnS QDs was probed by CE-FL using the monovalent hexahistidine peptide as a control. Cy5 labeled PHPD assembles on glutathione capped QDs, showing a higher FRET signal than that of the assembly between Cy5 labeled hexahistidine peptide and QDs. Capillary electrophoresis further revealed that PHPD outcompetes other QD binding small molecules, peptides, and proteins in cell lysate. Our study demonstrates the power of CE-FL in analyzing the binding interaction between ligands and QDs in a complex binding solution. It also shows that clustering surface binding motifs yields multivalent ligands that can preferentially assemble with nanoparticles.

Synthesis and grafting of folate–PEG–PAMAM conjugates onto quantum dots for selective targeting of folate-receptor-positive tumor cells

We report the design and synthesis of folate–poly(ethylene glycol)–polyamidoamine (FPP)-functionalized CdSe/ZnS quantum dots (QDs), in which the QD plays a key role in imaging, whereas the folate–poly(ethylene glycol) (PEG) conjugates of the polyamidoamine (PAMAM) dendrimer serve as a system targeted to folate receptors in tumor cells. Dendrimer ligands such as folate–PEG grafted PAMAM of generation 3.5 are found to encapsulate and solubilize luminescent QDs through direct ligand-exchange reactions. Because of membrane expression of FA receptors in tumor cells, this class of ligand-exchanged QDs is able to target tumor cells. We have evaluated FPP-coated QDs and QDs without folate in HeLa cells and shown that cellular uptake of FPP-coated QDs is more significant than that non folate QDs in vivo imaging experiment. In particular, QDs coated with FPP are initially bound to tumor cell surfaces, followed by slow endosomal escape and release into the tumor cells. These insights are important for the design and development of nanoparticle agents for optical detection of tumor cells and bio-imaging.

Iron‐Containing Poly(propylene imine) Dendromesogens with Photoactive Properties

AbstractHere, we report the first results of investigation the local structure and photoactive properties of iron‐containing dendromesogens based on decyloxybenzoate substituted poly(propylene imine) dendrimers of the first to fifth generations. Iron ions existing in a high‐spin state are coordinated in dendrimer ligands by two kinds of iron‐complexing sites with an octahedral and a tetrahedral symmetry. Octahedral (high‐symmetry) centers are located at the border of the dendrimeric core, while the tetrahedral centers with strong rhombic distortion of iron environment are distributed throughout all branching of the dendrimeric core. It has been found that all iron‐containing dendromesogens exhibit light‐harvesting and fluorescence properties.magnified image