Molecular dynamics simulations of hyperbranched poly(ethylene imine)-graphene oxide nanocomposites as dye adsorbents for water purification.

Atomistically detailed molecular dynamics simulations were employed to study the adsorption capacity of graphene-oxide-based (GO) aqueous systems for the methylene blue (MB) dye in the presence of branched poly(ethylene imine) (BPEI) polymers. The polymeric component was either freely mixed or chemically attached to GO. The main focus was the elucidation of the effects originating from the presence of BPEI molecules in the association of MB with the formed GO complexes. The effect of temperature was also examined. It was found that the presence of the cationic BPEI molecules results in the formation of a distinct microenvironment characterized by a polymer-mediated interconnected morphology which promotes the development of larger-sized MB clusters. These clusters were found to form in the vicinity of the GO flakes, increasing thus the adsorption capacity of the dye molecules in the polymer-containing systems. Particularly in the system with the BPEI-functionalized GO flakes, a persistent percolated structure is formed, which results in a more restricted diffusion of the MB molecules, increasing thus significantly their residence time close to the GO surface. The clustering behavior of MB was found to be temperature-dependent in the BPEI-based models, providing useful information regarding the conditions for optimal adsorption performance of such membranes, in nanofiltration processes.

Self-association and complexation of the anti-cancer drug doxorubicin with PEGylated hyperbranched polyesters in an aqueous environment.

Fully atomistic molecular dynamics simulations were employed in order to examine in detail the self-assembly characteristics and the complexation behavior of the anticancer drug doxorubicin with PEGylated hyperbranched polyesters in an aqueous environment. We have examined two variants of the polymeric compound by altering the length of the hydrophilic poly(ethylene glycol) arms attached to the hydrophobic hyperbranched core. By comparing the clustering properties of the drug molecules in a polymer-free system to those in the polymer-containing models, we were able to assess the effects related to the presence and to the structural features of the polymer moiety. In addition, we have distinguished the effects associated with the neutral and protonated drug molecules separately. It was found that, in the presence of the polymeric material, the drug molecules formed clusters preferentially close to the polymer's periphery, the characteristics of which depended on the structural details of the polymeric host and on the charge of the drug molecules. Hydrogen bonding was found to contribute to the polymer/drug complexation, with the nature of the prevailing donor/acceptor pairs depending on the charge of the drug. Dynamic analysis of the drugs' motion revealed that in the polymer-containing systems the drug molecules experienced a larger degree of confinement within the formed clusters compared to that describing their polymer-free analogues, while the structural coherence of the clusters was found to be more persistent in the system with the larger poly(ethylene glycol) arms. The results described in this work, through the monitoring of both static and dynamic aspects of the self-association and the complexation behavior of the neutral and charged molecules of doxorubicin with the polymeric host, may help toward the elucidation of the key parameters that are involved in the formation of effective polymer-based carriers for drug molecules of the anthracycline family used in cancer chemotherapy.

Modeling the formation of ordered nano-assemblies comprised by dendrimers and linear polyelectrolytes: the role of Coulombic interactions.

Models of mixtures of peripherally charged dendrimers with oppositely charged linear polyelectrolytes in the presence of explicit solvent are studied by means of molecular dynamics simulations. Under the influence of varying strength of electrostatic interactions, these systems appear to form dynamically arrested film-like interconnected structures in the polymer-rich phase. Acting like a pseudo-thermodynamic inverse temperature, the increase of the strength of the Coulombic interactions drive the polymeric constituents of the mixture to a gradual dynamic freezing-in. The timescale of the average density fluctuations of the formed complexes initially increases in the weak electrostatic regime reaching a finite limit as the strength of electrostatic interactions grow. Although the models are overall electrically neutral, during this process the dendrimer/linear complexes develop a polar character with an excess charge mainly close to the periphery of the dendrimers. The morphological characteristics of the resulted pattern are found to depend on the size of the polymer chains on account of the distinct conformational features assumed by the complexed linear polyelectrolytes of different length. In addition, the length of the polymer chain appears to affect the dynamics of the counterions, thus affecting the ionic transport properties of the system. It appears, therefore, that the strength of electrostatic interactions together with the length of the linear polyelectrolytes are parameters to which these systems are particularly responsive, offering thus the possibility for a better control of the resulted structure and the electric properties of these soft-colloidal systems.

Tell me something I do not know. Multiscale molecular modeling of dendrimer/ dendron organization and self-assembly in gene therapy.

Due to the relative easy synthesis and commercial availability, nanovectors based on dendrimers and dendrons are among the most utilized non-viral vectors for gene transfer. Contextually, recent advances in molecular simulations and computer architectures not only allow for accurate predictions of many structural, energetical, and eventual self-assembly features of these nanocarriers per se, but are able to yield vital (and perhaps otherwise unattainable) molecular information about the interactions of these nanovectors with their nucleic acid cargoes. In the present work, we aim at reviewing our own efforts in the field of multiscale molecular modeling of these interesting materials. In particular, our originally developed computational recipes will be presented, and the link between simulations and experiments will be described and discussed in detail. This review is written by computational scientists for experimental scientists, with the specific purpose of illustrating the potentiality of these methodologies and the usefulness of multiscale molecular modeling as an innovative and complementary tool in their current research.

Modeling of hyperbranched polyesters as hosts for the multifunctional bioactive agent Shikonin.

We employ fully atomistic molecular dynamics simulations to study in detail the mechanisms involved in the non-covalent association of the bioactive agent Shikonin with the commercially available hyperbranched polyesters (Boltorn®), in ethanol solutions. We examine effects of the (pseudo)generation of the hyperbranched polyester and mimic two different concentrations, under conditions corresponding to excess drug availability. The two mechanisms participating in the polymer/drug complexation are hydrogen bonding and spatial constriction of the drug molecules within the hyperbranched structure. Based on static, as well as on dynamic information obtained by the analysis performed, it is demonstrated that apart from the size of the polyester, factors like the degree of structural flexibility, the intrapolymer hydrogen bonding and the polymer concentration may affect decisively the polyester/shikonin associative behavior, as well as the behavior of the drug-molecules in the solution. The results from the present study offer a detailed picture of the relative importance of those parameters affecting the complexation, and may serve as a basis for the understanding of the behavior of more complex multi-polyester systems.

Investigation of thermodynamic properties of hyperbranched aliphatic polyesters by inverse gas chromatography.

Thermodynamic properties of a series of commercial hyperbranched aliphatic polyesters (Boltorn H20, H30 and H40) were examined for the first time by inverse gas chromatography (IGC) using 13 different solvents at infinite dilution as probes. Retention data of probes were utilized for an extensive characterization of polymers, which includes the determination of the Flory-Huggins interaction parameter, the weight fraction activity coefficient as well as the total and partial solubility parameters. Analysis of the results indicated that the total and partial solubility parameters decrease with increase of temperature. Furthermore, upon increase of the molecular weight, while the hydrogen bonding component decreases, no influence on the total solubility parameter is noticed within the experimental error margins. Results from the present study while providing new insight to the thermodynamic characteristics of the examined systems, they are also expected to reflect more general aspects of the behavior of hyperbranched polymers bearing similar end-groups.

Molecular dynamics simulations of polyamidoamine dendrimers and their complexes with linear poly(ethylene oxide) at different pH conditions: static properties and hydrogen bonding.

Models consisting of an amine-terminated poly(amidoamine) (PAMAM) dendrimer with and without the presence of a linear poly(ethylene oxide) (PEO) chain were studied in aqueous solutions by means of fully atomistic molecular dynamics simulations. Dendrimers of two generations, 3rd and 4th and at different pH conditions were examined, in order to address issues associated with characteristics pertinent to the shape of the dendrimers in the presence or absence of PEO as well as to the volume fraction of the penetrating solvent molecules and counterions as compared to recent experimental studies. In addition, hydrogen-bonding characteristics such as the intensity and the longevity of intra- and intermolecular hydrogen-bonded pairs are examined for the first time in these systems. It was found that the volume fraction of the penetrating solvent molecules increased upon decrease of pH, but no dependence on the size of the molecules was observed. The density of the solvent within the dendritic interior did not exceed that of the bulk, while the corresponding number of counterions entering the dendrimer boundaries exhibited a marked increase between the 3rd and the 4th generation of the dendrimers. Intramolecular hydrogen bonding was favored at high pH conditions, while intermolecular hydrogen bonding between PAMAM and the solvent or the PEO was significantly enhanced upon protonation of the dendrimer's amines. The presence of PEO imparted appreciable changes in the dendrimer's shape particularly in the physiological pH conditions. In addition, it incurred a decrease in intramolecular hydrogen bonding and acted antagonistically to the formation of water/dendrimer hydrogen bonds. The higher degree of hydrogen bonding between PAMAM and PEO was observed at low pH levels, indicating that under these conditions the formed complexes are expected to be more stable. The findings of the present study were found to be in good agreement with the relevant experimental findings where available, thus assessing the role of several structural and conformational details in the manifested behavior and providing further insight of the effects of non-covalent complexation of PAMAM dendrimers with linear poly(ethylene oxide).

Association of a weakly acidic anti-inflammatory drug (ibuprofen) with a poly(amidoamine) dendrimer as studied by molecular dynamics simulations.

In this work, we report results from fully atomistic molecular dynamics simulations regarding the associative behavior of a third-generation poly(amidoamine) dendrimer with ibuprofen, a weakly acidic nonsteroidal anti-inflammatory drug, in aqueous solutions and at different pH conditions. Employing a combined static and dynamic approach, we describe the specifics of the complexation/encapsulation of the drug within the dendritic structure. In addition, information regarding the dynamic behavior is provided for the self- and the collective motion of the drug molecules. The detail afforded by the present molecular-level description of the relevant associative mechanisms (i.e., electrostatic complexation, hydrogen-bonding), provides a deeper insight for the interpretation of recent experimental findings regarding the behavior of dendrimer/ibuprofen systems in an aqueous environment.

Molecular dynamics simulations of a hyperbranched poly(ester amide): statics, dynamics, and hydrogen bonding.

Fully atomistic molecular dynamics simulations are employed in order to examine static and dynamic characteristics of a hyperbranched poly(ester amide), Hybrane, in the bulk state. The force field used is validated via a comparison to available static, dynamic, and thermodynamic data. Properties pertinent to both local and global length scales like atomic and molecular spatial arrangement, bond-reorientation dynamics, shape and size fluctuations, rotational motion of the whole molecule, and diffusional motion are examined in detail in order to assess the relation between microscopic mechanisms and macroscopic behavior. The atomistic-level detail of the model utilized allows a close examination of the intra- and intermolecular hydrogen-bonding formation and the relevant residence time scales; these are among the key factors that determine the behavior of such polymers in the nanoscale, important for a wide range of applications. The detailed nature of the present investigation will provide insight in a more general basis for the behavior of nonregularly branched polymers of comparable molecular weight and similar chemical composition.

Dynamics of counterions in dendrimer polyelectrolyte solutions.

Molecular dynamics simulations were employed in models of peripherally charged dendrimers in solutions of explicit solvent and monovalent counterions in order to explore aspects of the dynamic behavior of counterions. The present study explores the effects of varying strength of electrostatic interactions for models of two dendrimer generations, in explicit solvent solutions below the dendrimer overlap concentration. Counterion diffusional motion as well as residence lifetimes of pairs formed by charged dendrimer beads and condensed counterions is monitored in the different electrostatic regimes. Spatiotemporal characteristics of self- and collective counterion motion are explored by means of space-time Van Hove correlation functions. A characteristic scaling law is found to describe the counterion diffusion coefficient as a function of Bjerrum length in the strong electrostatic regime, independent of the size of the dendrimer molecules at the examined volume fractions. The change noted in the diffusional motion of counterions in the range of strong Coulombic interactions is also reflected to their relevant residence times. Development of dynamic heterogeneities in counterion self-motion is observed during the gradual increase in the strength of electrostatic interactions, characterized by the emergence of distinct counterion populations in terms of their mobility. The time scale for the development of such a mobility contrast in the self-motion of the counterions can be correlated with that describing their collective motion as well. The latter increases with Bjerrum length but remains shorter compared to the time scale at which free diffusional motion sets in. Findings from the present study provide further insight on the mechanisms pertinent to ion migration in macroion dispersions and may serve as a basis for the interpretation of ionic motion in a broader range of polyelectrolyte systems.

Shear-induced effects in hyperbranched-linear polyelectrolyte complexes.

Static and dynamic properties of complexes formed by hyperbranched polymers with linear polyelectrolytes are studied under the influence of steady shear flow by means of Brownian dynamics simulations. Models of peripherally charged hyperbranched molecules bearing two extreme topological structures and different molecular weights complexed with linear neutralizing chains are subjected to a range of shear rates starting from a low-shear regime toward the complex-breaking point. Examination of the stability limit, shape and mass distribution parameters, and dynamics in different lengths and timescales is performed as a function of the applied shear. The results described illustrate features of the generic behavior that should be expected from such systems under conditions of steady shear flow.

Effects of topology and size on statics and dynamics of complexes of hyperbranched polymers with linear polyelectrolytes.

Brownian dynamics simulations with explicit hydrodynamic interactions have been employed to study generic effects of size and topology in noncovalent (Coulombic-driven) complexes formed by irregular-shaped hyperbranched polymers and linear polyelectrolytes. The behavior of the complexes was explored in detail in terms of static and dynamic properties, both in local and in the entire complex scale. The results were compared to previous studies on perfect dendrimers and other hyperbranched molecules where available. It was found that both molecular weight and structure may impart significant changes to key factors known to be associated with the ability of these systems to take part in relevant nanoscale applications.

Non-Gaussian nature of glassy dynamics by cage to cage motion.

A model based on a single Brownian particle moving in a periodic effective field is used to understand the non-Gaussian dynamics in glassy systems of cage escape and subsequent recaging, often thought to be caused by a heterogeneous glass structure. The results are compared to molecular-dynamics simulations of systems with varying complexity: quasi-two-dimensional colloidlike particles, atactic polystyrene, and a dendritic glass. The model nicely describes generic features of all three topologically different systems, in particular around the maximum of the non-Gaussian parameter. This maximum is a measure for the average distance between cages.

Local polymer dynamics under strong connectivity constraints: the dendrimer case.

The characteristics of local motion are explored by molecular dynamics simulations in a series of AB(2)-type dendrimer melts. Systems of generations 3-5 were simulated in a wide temperature range, allowing the assessment of effects associated with molecular size, proximity to the detected glasslike transitions, and the strong connectivity constraints imposed by the dendritic topology. Investigation of the mechanisms involved in local motion at short temporal and spatial scales revealed the connection between the non-Gaussian nature of monomer displacements to alpha-relaxation and the caging/decaging process under different degrees of confinement. In the latter mechanism, two characteristic localization lengths were identified: at the low temperature limit spatial localization was realized within approximately 10% of the nearest neighbor distance while at temperatures higher than the glass transition, the existence of an analogous length scale is ascribed to the geometric constraints due to the dense connectivity pattern. As the results from this study are discussed in comparison to the behavior observed in linear polymers and supercooled liquids, new insight is provided on the universal/specific mechanisms involved in local dynamics of different glass-forming systems.

Nanoscopic-confinement effects on local dynamics

The segmental dynamics of 1.5-2.0 nm polymer films confined between parallel solid surfaces is investigated with dielectric spectroscopy in polymer/silicate intercalated nanocomposites. The confinement effect is evident by the observation of a mode, much faster than the bulk-polymer alpha relaxation and exhibiting much weaker temperature dependence. This is discussed in relation to either the interlayer spacing restricting the cooperative volume of the alpha relaxation or to the dominance of the more mobile interphase regions as predicted by simulations; the data qualitatively support the former.