Effect of molecular topology on the transport properties of dendrimers in dilute solution at Theta temperature: a Brownian dynamics study

Structure and transport properties of dendrimers in dilute solution are studied with the aid of Brownian dynamics simulations. To investigate the effect of molecular topology on the properties, linear chain, star, and dendrimer molecules of comparable molecular weights are studied. A bead-spring chain model with finitely extensible springs and fluctuating hydrodynamic interactions is used to represent polymer molecules under Theta conditions. Structural properties as well as the diffusivity and zero-shear-rate intrinsic viscosity of polymers with varied degrees of branching are analyzed. Results for the free-draining case are compared to and found in very good agreement with the Rouse model predictions. Translational diffusivity is evaluated and the difference between the short-time and long-time behavior due to dynamic correlations is observed. Incorporation of hydrodynamic interactions is found to be sufficient to reproduce the maximum in the intrinsic viscosity versus molecular weight observed experimentally for dendrimers. Results of the nonequilibrium Brownian dynamics simulations of dendrimers and linear chain polymers subjected to a planar shear flow in a wide range of strain rates are also reported. The flow-induced molecular deformation of molecules is found to decrease hydrodynamic interactions and lead to the appearance of shear thickening. Further, branching is found to suppress flow-induced molecular alignment and deformation.     

Thermodynamic properties of dendrimers compared with linear polymers: General observations

The pressure‐volume‐temperature and thermal properties of dendrimers based on benzyl ether were measured and compared with literature values for monodisperse, linear polystyrenes. In addition, property measurements are presented for an exact linear analogue to the fifth‐generation dendrimer. The thermodynamic properties' molecular weight behavior for the dendrimers is unique when compared with that of linear polystyrene. All of the evidence presented in this work suggests that some form of structural transition occurs in the bulk at a molecular mass near that for the fourth‐generation dendrimer. No such transition is seen for polystyrene. Dendrimers exhibit an increased packing efficiency as evidenced by a decreased specific volume (increased density) as compared with an exact linear analogue of the fifth‐generation dendrimer analogue, and the dendrimer highlights the entropic differences between the two molecules. In addition, differences in the change in heat capacity with temperature for the two systems further allude to their entropic differences. A crystalline state can be formed for the lower generation dendrimer and linear analogue. This crystalline state is not seen in dendrimers above the third generation. These behaviors compiled with the difference in the glass‐transition temperature for the linear analogue suggest that the dendrimers' microstructure has a significant influence on the bulk thermodynamic state of the material. The Tait equation was fitted to the volume data for comparative purposes; the Tait equation has known limitations but was selected because of its widespread application. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 1766–1777, 2001     

Simplifying the synthesis of dendrimers: accelerated approaches

Dendrimers are highly branched and monodisperse macromolecules that display an exact and large number of functional groups distributed with unprecedented control on the dendritic framework. Based on their globular structure, compared to linear polymers of the same molecular weight, dendrimers are foreseen to deliver extraordinary features for applications in areas such as cancer therapy, biosensors for diagnostics and light harvesting scaffolds. Of the large number of reports on dendrimer synthesis only a few have reached commercial availability. This limitation can be traced back to challenges in the synthetic paths including a large number of reaction steps required to obtain dendritic structures with desired features. Along with an increased number of reaction steps come not only increased waste of chemical and valuable starting materials but also an increased probability to introduce structural defects in the dendritic framework. This tutorial review briefly covers traditional growth approaches to dendrimers and mainly highlights accelerated approaches to dendrimers. A special focus capitalizes on the impact of the click chemistry concept on dendrimer synthesis and the promise it has to successfully accomplish highly sophisticated dendrimers, both traditional as well as heterofunctional, in a minimum number of chemical steps. It is clear that accelerated synthetic approaches are of greatest importance as these will encourage the scientific community to synthesize and access dendrimers for specific applications. The final goal of accelerated synthesis is to deliver economically justified dendritic materials for future applications without compromising the environmental perspective.     

Nanoscale protein pores modified with PAMAM dendrimers

We describe nanoscale protein pores modified with a single hyperbranched dendrimer molecule inside the channel lumen. Sulfhydryl-reactive polyamido amine (PAMAM) dendrimers of generations 2, 3 and 5 were synthesized, chemically characterized, and reacted with engineered cysteine residues in the transmembrane pore alpha-hemolysin. Successful coupling was monitored using an electrophoretic mobility shift assay. The results indicate that G2 and G3 but not G5 dendrimers permeated through the 2.9 nm cis entrance to couple inside the pore. The defined molecular weight cutoff for the passage of hyperbranched PAMAM polymers is in contrast to the less restricted accessibility of flexible linear poly(ethylene glycol) polymers of comparable hydrodynamic volume. Their higher compactness makes sulfhydryl-reactive PAMAM dendrimers promising research reagents to probe the structure of porous membrane proteins with wide internal diameters. The conductance properties of PAMAM-modified proteins pores were characterized with single-channel current recordings. A G3 dendrimer molecule in the channel lumen reduced the ionic current by 45%, indicating that the hyperbranched and positively charged polymer blocked the passage of ions through the pore. In line with expectations, a smaller and less dense G2 dendrimer led to a less pronounced current reduction of 25%. Comparisons to recordings of PEG-modified pores revealed striking dissimilarities, suggesting that differences in the structural dynamics of flexible linear polymers vs compact dendrimers can be observed at the single-molecule level. Current recordings also revealed that dendrimers functioned as ion-selectivity filters and molecular sieves for the controlled passage of molecules. The alteration of pore properties with charged and hyperbranched dendrimers is a new approach and might be extended to inorganic nanopores with applications in sensing and separation technology.     

Analysis of the shape of dendrimers under shear

Nonequilibrium molecular-dynamics simulations are used to investigate the molecular shape of dendrimers and linear polymers in a melt and under shear. Molecules are modeled at the coarse-grained level using a finitely extensible nonlinear elastic bead-spring model. The shape of dendrimers and linear polymers at equilibrium and undergoing planar Couette flow is analyzed quantitatively and it is related to the shear viscosity. The shape of dendrimers responds differently to the influence of shear compared with linear polymers of equivalent molecular mass. However, in both cases the transition from Newtonian to non-Newtonian viscosity behavior corresponds to significant changes in molecular symmetry. This suggests that a shape analysis could be used to estimate the onset of shear thinning in polymers.     

Nanoscopic supermolecules with linear-dendritic architecture: Their preparation and their supramolecular behavior

The design, synthesis, and properties of supermolecules consisting of well defined assemblies of linear and globular macromolecules is studied. Therefore, several families of hybrid block polymers based on polyether dendrimers linked to well-defined blocks of polyethylene oxide, polyethylene glycol, polyester, or polystyrene have been prepared. The unique topological macromolecules that result from the assembly of such components having different shapes and internal densities can assemble in highly stable supramolecular micelles whose characteristics vary as a function of the medium. The hybrid macromolecules are usually prepared by the nucleophilic displacement of a reactive functionality located at the focal point of a convergent polyether dendrimer, with a nucleophilic anion located at one or both chain ends of a linear polymer. Alternately, the focal point of the dendrimer may be used to attach a polymerizable vinyl group affording a dendritic macromonomer that may be used to create variety of copolymers. Finally, the focal point of the convergent dendrimer may serve as an initiator in the polymerization of a linear chain thereby affording the hybrid linear-dendritic entity. In the latter case the unique microenvironment provided by the dendrimer is useful in the prevention of undesirable side-reactions during growth of the linear block. This demonstrates that the differences between the globular and linear fragments of these unique molecules can be used to design nanoscale reactors that perform functions not normally achieved with small molecules. The very unusual solution properties of the dendritic-linear supermolecules are a direct result of the forced combination of their dissimilar building blocks.     

Thermosensitive properties of poly(amidoamine) dendrimers with peripheral phenylalanine residues

Dendrimers are unique polymers with globular shapes and well-defined structures. We previously prepared poly(amidoamine) (PAMAM) dendrimers having phenylalanine (Phe) residues at every chain end of the dendrimer as efficient gene carriers. In this study, we found that Phe-derivatized PAMAM dendrimers change their water solubility depending on temperature. The dendrimers were soluble in aqueous solutions at low temperatures, but they became water-insoluble at temperatures above a specific threshold, which is termed the lower critical solution temperature (LCST). Although the LCST of Phe-modified dendrimers decreased with increasing dendrimer generation, these dendrimers exhibited an LCST of 20-30 degrees C under physiological conditions. In addition, the LCST of the dendrimers was controlled by introducing isoleucine (Ile) residues at chain ends of dendrimers at varying ratios with respect to Phe residues. The PAMAM dendrimers are known to encapsulate various drug molecules. For these reasons, temperature-sensitive dendrimers might be useful as efficient drug carriers with controlled size and temperature-responsive properties.     

Dendritic polymers: from efficient catalysis to drug delivery

Dendritic polymers constitute an intriguing class of macromolecules that offer tremendous potential in designing new materaisl for applications in areas such as catalysis and small molecule loading and delivery. Synthesis of a variety of dendritic polymers using a simple and highly versatile synthetic methodology has enabled us to carry out a detailed investigation of dendritic effects in transition metal catalyzed organic transformations. Small dye molecules such as p-nitroaninline and DR1 could be loaded into the intrinsic cavities of the backbone of 3,5-dihydroxybenzyl alcohol based dendrimers, leading to a change in physical properties of both the dye and the dendrimer. We are also exploring the use of dendrimers as templates to prepare network carriers containing cavities of predetermined size and disposition.     

Dynamics of Dendrimeric Molecules Undergoing Simple Shear Flow: A Nonequilibrium Brownian Dynamics Study

Nonequilibrium Brownian dynamics (NEBD) simulations are used to model the dynamics of six generations of dendrimers undergoing shear flow. A coarse‐grained bead‐spring model is proposed, which incorporates springs with stretching and bending potentials. The bending constant is used as one of the primary independent variables to control the deformability of the molecules. Rheological and conformational properties, such as viscosity, normal stress differences, visco‐elastic moduli, flow birefringence, mean square radius of gyration, and degree of prolateness, are observed under both transient (startup and cessation of flow) and steady‐state conditions. Comparisons are made with the corresponding linear chain analogs of the same molecular weight. The model qualitatively describes many of the experimentally observed effects in these systems, most notably a Newtonian viscosity profile (no shear thinning) and a maximum in the dependence of the intrinsic viscosity on the molecular weight. The dendrimers are also characterized by negligible start‐up overshoots in the transient viscosity and birefringence.     

Charge inversion of dendrimers in complexes with linear polyelectrolytes in the solutions with low pH

Complexes of fully ionized third-generation dendrimers with oppositely charged linear polyelectrolyte chains are studied by the Brownian dynamics method. A freely jointed model of a dendrimer and a linear chain is used. Electrostatic interactions are considered within the Debye-Hückel approximation with the Debye radius exceeding the dimensions of a dendrimer. In these systems, the phenomenon of charge inversion is observed, and the degree of “overcharging” is higher as compared with that taking place in analogous complexes formed by dendrimers in which only terminal groups are charged. The dependence of the amount of chain units adsorbed on a dendrimer on the polyelectrolyte chain length is nonmonotnic and agrees qualitatively with the predictions of the theory proposed by Nguyen and Shklovskii for a complex composed of a spherical macroion with an oppositely charged linear chain. This nonmonotonic character also manifests itself for certain other structural characteristics of the complexes. Upon the formation of a complex, a chain is shown to penetrate deeply into a dendrimer.     

Properties of Oligothiophene Dendrimers as a Function of Molecular Architecture and Generation Number

Density functional and time‐dependent density functional calculations using the B3LYP method combined with the 6‐31G(d) and 6‐311++G(d,p) basis sets are performed on symmetric and unsymmetric all‐thiophene dendrimers containing up to 45 thiophene rings. Calculations consider both the neutral and the oxidized states of each dendrimer. The results are used to examine the molecular geometry, the ionization potential, the lowest π–π* transition energy, and the shape of the frontier orbitals. The molecular and electronic properties of these systems depend not only on the number of thiophene rings, as typically occurs for linear oligothiophenes, but also on their symmetric/unsymmetric molecular architecture. Two mathematical models developed to predict the lowest π–π* transition energy of all‐thiophene dendrimers that are inaccessible to quantum mechanical calculations are tested on a dendrimer with 90 thiophene rings.     

Multiscale modeling and simulation methods with applications to dendritic polymers

Dendrimers and hyperbranched polymers represent a novel class of structurally controlled macromolecules derived from a branches-upon-branches structural motif. The synthetic procedures developed for dendrimer preparation permit nearly complete control over the critical molecular design parameters, such as size, shape, surface/interior chemistry, flexibility, and topology. Dendrimers are well defined, highly branched macromolecules that radiate from a central core and are synthesized through a stepwise, repetitive reaction sequence that guarantees complete shells for each generation, leading to polymers that are mono-disperse. This property of dendrimers makes it particularly natural to coarsen interactions in order to simulate dynamic processes occurring at larger length and longer time scales. In this paper, we describe methods to construct 3-dimensional molecular structures of dendrimers (Continuous Configuration Boltzmann Biased direct Monte Carlo, CCBB MC) and methods towards coarse graining dendrimer interactions (NEIMO and hierarchical NEIMO methods) and representation of solvent dendrimer interactions through continuum solvation theories, Poisson–Boltzmann (PB) and Surface Generalized Born (SGB) methods. We will describe applications to PAMAM, stimuli response hybrid star-dendrimer polymers, and supra molecular assemblies crystallizing to A15 colloidal structure or Pm6m liquid crystals.     

结合丝组二肽的树状多肽对λDNA的切割

以Fmoc手工固相合成法合成了以多聚赖氨酸为骨架, 表面结合丝组二肽的四分支和二分支树状多肽, 以高效液相色谱提纯, 电喷雾电离质谱表征, 并通过凝胶电泳法研究了其对λDNA的切割活性.     

Dendrimer as a versatile platform for biomedical application: A review

Modern chemistry is vastly fascinated by dendrimer chemistry, an area that is rapidly expanding and brimming with potential applications. Dendrimers are highly branched polymers that have multiple peripheral groups, interior cavities and they have many structural properties therefore Dendrimers play a crucial role in the fields of nanotechnology, pharmaceuticals, and medicinal chemistry. The terminal functional groups of dendrimers may be chemically linked to other moieties in order to adjust surface properties for applications such as biomimetic nanodevices. A variety of biologically active agents can be incorporated into dendrimers to create biologically active conjugates, including novel drug carriers, by utilizing the homogeneity of their three-dimensional architecture. The purpose of this review is to provide a brief overview of bio-inspired dendrimer applications, highlighting their use as drug and gene delivery agents, and biomedical diagnostic agents. In addition, the review mentions briefly some dendrimer applications in cosmetics, agrochemicals, and catalyst.     

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

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

Extension of the chain‐end,free‐volume theory for predicting glass temperature as a function of conversion in hyperbranched polymers obtained through one‐pot approaches

Compared with linear polymers, more factors may affect the glass‐transition temperature (T_g) of a hyperbranched structure, for instance, the contents of end groups, the chemical properties of end groups, branching junctions, and the compactness of a hyperbranched structure. T_g's decrease with increasing content of end‐group free volumes, whereas they increase with increasing polarity of end groups, junction density, or compactness of a hyperbranched structure. However, end‐group free volumes are often a prevailing factor according to the literature. In this work, chain‐end, free‐volume theory was extended for predicting the relations of T_g to conversion (X) and molecular weight (M) in hyperbranched polymers obtained through one‐pot approaches of either polycondensation or self‐condensing vinyl polymerization. The theoretical relations of polymerization degrees to monomer conversions in developing processes of hyperbranched structures reported in the literature were applied in the extended model, and some interesting results were obtained. T_g's of hyperbranched polymers showed a nonlinear relation to reciprocal molecular weight, which differed from the linear relation observed in linear polymers. T_g values decreased with increasing molecular weight in the low‐molecular‐weight range; however, they increased with increasing molecular weight in the high‐molecular‐weight range. T_g values decreased with increasing log M and then turned to a constant value in the high‐molecular‐weight range. The plot of T_g versus 1/M or log M for hyperbranched polymers may exhibit intersecting straight‐line behaviors. The intersection or transition does not result from entanglements that account for such intersections in linear polymers but from a nonlinear feature in hyperbranched polymers according to chain‐end, free‐volume theory. However, the conclusions obtained in this work cannot be extended to dendrimers because after the third generation, the end‐group extents of a dendrimer decrease with molecular weight. Thus, it is very possible for a dendrimer that T_g increases with 1/M before the third generation; however, it decreases with 1/M after the third generation. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1235–1242, 2004     

Starburst pamam dendrimers: Synthetic approaches,surface modifications,and biomedical applications

Dendrimers are having novel three dimensional, synthetic hyperbranched, nano-polymeric structure. Among all of the dendrimers, Poly-amidoamine (PAMAM) dendrimer are used enormously applying materials in supramolecular chemistry. This review described the structure, characteristic, synthesis, toxicity, and surface modification of PAMAM dendrimer. Various strategies in supramolecular chemistry of PAMAM for synthesizing it at commercial and laboratory scales along with their limitations and applications has also discussed. When compared to other nano polymers, the characteristics of supramolecular PAMAM dendrimers in nanopolymer science has shown significant achievement in transporting drugs for molecular targeted therapy, particularly in host–guest reaction. It also finds its applications in gene transfer devices and imaging of biological systems with minimum cytotoxicity. From that viewpoint, this review has elaborated the structural and safety aspect of PAMAM for targeted drug delivery with pharmaceuticals in addition to the biomedical application.     

Dendrimers in drug research

Dendrimers are versatile, derivatisable, well-defined, compartmentalised chemical polymers with sizes and physicochemical properties resembling those of biomolecules e.g. proteins. The present critical review (citing 158 references) briefly describes dendrimer design, nomenclature and divergent/convergent dendrimer synthesis. The characteristic physicochemical features of dendrimers are highlighted, showing the effect of solvent pH and polarity on their spatial structure. The use of dendrimers in biological systems are reviewed, with emphasis on the biocompatibility of dendrimers, such as in vitro and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers may be used as drugs for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host-guest binding motifs directed towards medical applications is described. Other specific examples are the use of dendrimers as 'glycocarriers' for the controlled multimeric presentation of biologically relevant carbohydrate moieties which are useful for targeting modified tissue in malignant diseases for diagnostic and therapeutic purposes. Finally, the use of specific types of dendrimers as scaffolds for presenting vaccine antigens, especially peptides, for use in vaccines is presented.     

Molecular simulation of dendrimers and their mixtures under shear: comparison of isothermal-isobaric (NpT) and isothermal-isochoric (NVT) ensemble systems

Flow properties of dendrimers are studied with the aid of nonequilibrium molecular dynamics techniques. Simulations are performed in the NpT ensemble using the NpT-SLLOD algorithm [P. J. Davis and D. J. Evans, J. Chem. Phys. 100, 541 (1994)] and are compared to the results from simulations performed in the NVT ensemble reported earlier [J. T. Bosko, B. D. Todd, and R. J. Sadus, Chem. Phys. 121, 12050 (2004)]. Shear thickening observed at high strain rates vanishes in systems kept under constant pressure. Also the exponents in the power-law dependencies of the viscosity and the normal stress coefficients change. The variations are significant only at high strain rates and do not affect largely microscopic properties such as shape, alignment, or rotation of molecules. The NpT-SLLOD algorithm has been applied to study various systems including dendrimers in solution and their blends with linear chain molecules of the same molecular mass, and some results for these systems are presented.