Unexpected Like-Charge Self-Assembly of a Biguanide-Based Antimicrobial Polyelectrolyte

Polyelectrolyte chains dissolved in good solvent are expected to collapse in compact configurations in the presence of multivalent ions. Here, we show that a weakly charged, hydrophilic polyelectrolyte containing biguanide groups self-assembles in water also in the presence of monovalent counterions, even at low salt concentrations. The polymer assembles in a compact, ordered, hairpin-like shape that, with increasing the ionic strength of the solution, can collapse further in three- or five-folded structures. Neither water nor ions mediate the self-assembly which, instead, is driven by the like-charge pairing of the biguanide units. The thermodynamics of the self-assembly show that the self-association is enthalpically driven, is isodesmic (at least at low aggregation number), and is favored by increasing salt concentration. This unique self-assembly behavior may be linked to the well-known polymer’s antimicrobial properties and could help in rationalizing its biological activity

Extended Charge-On-Particle Optimized Potentials for Liquid Simulation Acetone Model: The Case of Acetone–Water Mixtures

It is well-known that classical molecular dynamics simulations of acetone–water mixtures lead to a strong phase separation when using most of the standard all-atom force fields, despite the well-known experimental fact that acetone is miscible with water in any proportion at room temperature. We describe here the use of a charge-on-particle model for accounting for the induced polarization effect in acetone–water mixtures which can solve the demixing problem at all acetone molar fractions. The polarizability effect is introduced by means of a virtual site (VS) on the carbonyl group of the acetone molecule, which increases its dipole moment and leads to a better affinity with water molecules. The VS parameter is set by fitting the density of the mixture at different acetone molar fractions. The main novelty of the VS approach lies on the transferability and universality of the model because the polarizability can be controlled without modifying the force field adopted, like previous efforts did. The results are satisfactory also in terms of the transport properties, that is, diffusivity and viscosity coefficients of the mixture

Solvent Structuring and Its Effect on the Polymer Structure and Processability: The Case of Water–Acetone Poly-ε-caprolactone Mixtures

One of the most common processes to produce polymer nanoparticles is the solvent-displacement method, in which the polymer is dissolved in a “good” solvent and the solution is then mixed with an “anti-solvent”. The polymer processability is therefore determined by its structural and transport properties in solutions of the pure solvents and at the intermediate compositions. In this work, we focus on poly-ε-caprolactone (PCL) which is a biocompatible polymer that finds widespread application in the pharmaceutical and biomedical fields, performing full atomistic molecular dynamics simulations of one PCL chain of different molecular weight in a solution of pure acetone (good solvent), of pure water (antisolvent), and their mixtures. Our simulations reveal that the nanostructuring of one of the solvents in the mixture leads to an unexpected identical polymer structure irrespectively of the concentration of the two solvents. In particular, although in pure solvents the behavior of the polymer is, as expected, very different, at intermediate compositions, the PCL chain shows properties very similar to those found in pure acetone as a result of the clustering of the acetone molecules in the vicinity of the polymer chain. We derive an analytical expression to predict the polymer structural properties in solution at different solvent compositions and show that the solvent clustering affects in an unpredictable way the polymer diffusion coefficient. These findings have important consequences on the optimization of the nanoparticle production process and in the implementation of continuum modeling techniques to model it