Polyelectrolyte compaction by pH-responsive agents.

Compaction of negatively charged polyanions by polycations with different characteristics is investigated using Monte Carlo simulation in a coarse-grain model. Two different routes are tested and the results compared. In one, the polycation/polyanion charge ratio is varied by increasing the amount of polycations, keeping all the chain characteristics constant. In the other, the linear charge density of the polycations is altered but their number is kept constant. The set of systems in which the linear charge density changes is used as a model for a system comprising chains with different degrees of ionization under different pH conditions. In both cases, polycation/polyanion charge ratios ranging from 0.25 to 1.25 are addressed. The system with unitary charge ratio is common to both routes. It is seen that, although the overall trends followed by the two sets of systems are similar, marked differences can be discerned both for low charge ratios, and for the higher ones, where the systems are overcharged. Coexistence regimes are clearly detected in some of the systems. The results obtained computationally can be used to guide practical applications.

Structure of microemulsion-ABA triblock copolymer networks.

Structural equilibrium properties of transient networks formed by microemulsion droplets and ABA triblock copolymers in solution have been studied by Monte Carlo simulation. The droplets were represented by soft spheres, and the polymers were represented by junctions connected by harmonic bonds with an angular potential regulating the intrinsic chain stiffness. The interaction parameters were selected such that the end A-blocks were localized inside the droplets and the middle B-block in the continuous phase. The influence of (i) the polymer concentration, (ii) the polymer stiffness, and (iii) the contour length of the middle B-block on the formation and the structure of the microemulsion-polymer network were investigated using polymer end-to-end separation probability distribution functions, droplet radial distribution functions, droplet-droplet nearest-neighbor probability distribution functions, and network connectivity indicators. An increase of the polymer-droplet number ratio had a strong impact on the network formation. Under typical conditions and at an intermediate polymer-droplet number ratio, (i) the fraction of polymers forming bridges between droplets increased from essentially zero to unity and (ii) the fraction of polymers that were forming loops decreased as the ratio of the polymer end-to-end separation and the surface-to-surface separation between neighboring droplets for a hypothetical homogeneous droplet distribution was increased from 0.5 to 2. For long and flexible polymers, a mesoscopic segregation triggered by a depletion attraction between droplets appeared, and, furthermore, for sufficiently stiff chains, only bridge conformations occurred. The percolation probability could be represented as a function of the average droplet cluster size only, across all systems.

Interaction of omeprazole with a methylated derivative of beta-cyclodextrin: phase solubility, NMR spectroscopy and molecular simulation.

PURPOSE: Cyclodextrins are known to be good solubility enhancers for several drugs, improving bioavailability when incorporated in pharmaceutical formulations. In this work we intend to assess and characterize the formation of inclusion complexes between omeprazole (OME) and a methylated derivative of beta-cyclodextrin, methyl-beta-cyclodextrin (MbetaCD). A comparison with results obtained from the most commonly used natural cyclodextrin, beta-cyclodextrin (betaCD) is also presented in most cases. MATERIALS AND METHODS: The interaction of OME with the mentioned cyclodextrins in aqueous solutions was studied by phase solubility studies, 1D (1)H and 2D rotating frame nuclear overhauser effect NMR spectroscopy (ROESY) and Molecular Dynamics. RESULTS: The solubility of OME was significantly increased by formation of inclusion complexes with each cyclodextrin. Phase solubility studies and continuous variation plots revealed that OME forms an inclusion complex in a stoichiometry of 1:1 with both cyclodextrins. (1)H NMR and ROESY spectra of the inclusion complexes indicated that the benzimidazole moiety is included within the cyclodextrins cavities. Molecular dynamics showed that OME is more deeply included in the MbetaCD than in betaCD cavity, in agreement with a larger apparent stability constant (K (S)) obtained for the inclusion complex with MbetaCD. CONCLUSIONS: MbetaCD proved to be an efficient enhancer of OME solubility, thus possessing characteristics for being an useful excipient in pharmaceutical formulations of this drug.

Polyelectrolytes in solutions with multivalent salt. Effects of flexibility and contour length.

It has been experimentally observed that trivalent ions are capable of promoting compaction of semi-flexible polyelectrolyte chains. In this work we perform Monte Carlo simulations on single chain model systems with varying chain size and stiffness and evaluate the action of multivalent salt on the chain conformation. It is observed that longer chains tend to achieve relatively more compact conformations than shorter ones, and the dimensions of the collapsed structures do not significantly vary with contour length. The influence of contour length and intrinsic stiffness in the process of ion condensation is studied by analysis of the ion-ion nearest-neighbor distribution. The general trend is an increase of the degree of ion condensation as the chain length increases, in accordance with experimental evidence. A decreased importance of end-effects and, especially, larger volume charge densities are responsible for such behavior. The influence of chain stiffness is nontrivial, and depends on salt concentration. The results emphasize the complex nature of ion-correlation phenomena in flexible or semi-flexible chains and call for the development of more sophisticated analytical theories.

Coil-globule coexistence and compaction of DNA chains.

In this work we discuss different factors governing coil-globule coexistence in the compaction process of DNA. We initially analyse the role played by fluctuations in the degree of binding of an external compacting agent in the conformational behavior of the chain backbone. The analysis relies both on Monte Carlo simulation results and simple statistical approaches. Compacting agents of various binding characteristics are taken into consideration and the degree of charge neutralization upon the chain is related to conformational indicators. Selected model systems comprising stiff chains in the presence of multivalent ions are employed to assess intrinsic single-chain conformational fluctuation, in the presence of external agents but not resulting from differences in binding. It is shown that trends found for a variety of compacting agents, including the extension of the coil-globule coexistence regions, can be rationalised on the basis of this analysis.