Phenol release from pNIPAM hydrogels: scaling molecular dynamics simulations with dynamical density functional theory.

We employed molecular dynamic simulations (MD) and the Bennett's acceptance ratio method to compute the free energy of transfer, ΔGtrans, of phenol, methane, and 5-fluorouracil (5-FU), between bulk water and water-pNIPAM mixtures of different polymer volume fractions, ϕp. For this purpose, we first calculate the solvation free energies in both media to obtain ΔGtrans. Phenol and 5-FU (a medication used to treat cancer) attach to the pNIPAM surface so that they show negative values of ΔGtrans irrespective of temperature (above or below the lower critical solution temperature of pNIPAM, Tc). Conversely, methane switches the ΔGtrans sign when considering temperatures below (positive) and above (negative) Tc. In all cases, and contrasting with some theoretical predictions, ΔGtrans maintains a linear behavior with the pNIPAM concentration up to large polymer densities. We have also employed MD to compute the diffusion coefficient, D, of phenol in water-pNIPAM mixtures as a function of ϕp in the diluted limit. Both ΔGtrans and D as a function of ϕp are required inputs to obtain the release halftime of hollow pNIPAM microgels through Dynamic Density Functional Theory (DDFT). Our scaling strategy captures the experimental value of 2200 s for 50 µm radius microgels with no cavity, for ϕp ≃ 0.83 at 315 K.

A coil-to-globule transition capable coarse-grained model for poly(N-isopropylacrylamide).

We present a model for mesoscopic molecular dynamics simulations of poly(N-isopropyl-acrylamide) (pNIPAM). The model uses a coarse-grained scheme based on the explicit-solvent Martini force field. The mapping of the polymer accounts for three beads per monomer. Similarly to the Martini water bead, the amide moieties of the polymer include an electric dipole. The model is tested by building polymer chains of different sizes and proved to accurately capture the thermal response of pNIPAM without including any temperature-dependent parameters. The critical temperature of the model is observed at (302.1 ± 1.1) K for a 35-mer and it keeps invariant when increasing the chain length. We deployed a series of replica-exchange molecular dynamics simulations that evidence the oligomer reaches thermodynamic equilibrium irrespective of the starting configuration. Finally, the model is applied to a membrane structure of pNIPAM where a good agreement with previous atomistic simulations is observed.

P-NIPAM in water-acetone mixtures: experiments and simulations.

The lower critical solution temperature (LCST) of poly-N-isopropylacrylamide (p-NIPAM) diminishes when a small volume of acetone is added to the aqueous polymer solution, and then increases for further additions, producing a minimum at a certain acetone concentration. Here this behavior is observed through the variation of the hydrodynamic radius RH of p-NIPAM microgels with temperature, measured by dynamic light scattering (DLS), when adding increasing amounts of acetone in the molar fraction range of 0.00 to 0.25. This size trend of microgels with temperature is well captured by all-atom molecular dynamic simulations, which are implemented for a single 30-mer, at similar solvent and temperature conditions. Both DLS measurements and simulations indicate that the shrunken state continuously augments its size with increasing acetone content. This, in turn, leads to a minimum of the globule-to-coil transition temperature, which should correspond to the minimum of the LCST. Furthermore, density profiles, as obtained by considering a membrane arrangement of oligomers, reveal a preferential interaction of the polymer with acetone to the detriment of water. We observe how the membrane loses water content as the temperature is increased while keeping a similar amount of acetone in its interior. This competition between water and acetone for the polymer surface plays a major role in the enthalpy driven dependence of the critical temperature with acetone concentration.