The study of phase equilibria is of ubiquitous importance, with applications ranging from chemical process design to the understanding of biological systems. In our current work, the behaviour of aqueous solutions of the pharmaceutically relevant [1], and prototypical biopolymer, polyethylene glycol (PEG) is considered. The focus here is to develop a model to study and reproduce the experimentally observed closed-loop re-entrant fluid-phase behaviour of water-PEG systems [2] using molecular dynamic simulation. The resulting coarse-grain (CG) model enables the study of the larger length and times scales required to observe polymer phase separation phenomena in simulation.
Lobanova et al. [3] have demonstrated that the group contribution statistically association fluid theory (SAFT-γ Mie) [4] can be used as a CG methodology to develop (non-associating) models for the study of carbon dioxide + water + n-alkanes mixtures through simulation. We apply this SAFT CG methodology to polymer-water systems with the aim to study liquid-liquid immiscibility. A CG model of PEG is developed to be used inconjunction with the CGW2-bio water model developed by Lobanova et al. [5].
The intermolecular parameters are estimated using the SAFT-γMie approach from target pure component vapour pressure and saturated liquid density data of smaller molecules as well as liquid-liquid equilibrium data of water-PEG mixtures. A temperature independent CG potential is unable to reproduce the full closed-loop phase behaviour; only capturing the upper critical solution temperature. A temperature dependent unlike interaction between the polymer and water beads is introduced to account for changes in the hydrogen bonding between water and the polymer; this phenomena is responsible for the lower critical solution temperature behaviour [6]. Work by Rahman et al. [7] on alkanes suggests that including bonded interactions improves the accuracy of the prediction of structural and transport properties. Initial simulations, in which the alkane bond constraints developed by Rahman et al. [7] are implemented for PEG, indicate that bonded interactions have a large impact on the phase behaviour of water-PEG systems. Bespoke bonded potentials for PEG are developed from atomistic simulations to create a semi-flexible model to compare with the SAFT theory. The models are used to study the behaviour of water-PEG in molecular dynamic simulations allowing for the prediction of structural properties such as the radius of gyration, which are not directly obtainable from the SAFT theory.
[1] Harris,J.M., N.E. Martin, M. Modi. Clin Pharmacokinet 40, 539 (2001)
[2] Saeki, S., N. Kuwahara, M. Nakata, M.Kaneko. Polymer 17, 685-689 (1976)
[3] Lobanova,O., A. Mejía, G. Jackson, E.A. Müller. J. Chem. Thermo. 93, 320 (2016)
[4] Papaioannou,V., T. Lafitte, C. Avendaño, C.S. Adjiman, G. Jackson, E.A. Müller, A. Galindo.J. Chem. Phys. 140, 054107 (2014)
[5] Lobanova, O., C. Avendaño, T. Lafitte, E.A. Müller. Mol. Phys 113, 1228-1249 (2015)
[6] Clark, G.N.I., A. Galindo, G. Jackson, S.Rogers, A.N. Burgess. Macromolecules 41, 6582 (2008)
[7] Rahman, S., O. Lobanova, C. Braga, V. Raptis, E.A. Müller,G. Jackson, A. Galindo, J. Phys. Chem. B (Submitted for Publication).
Advances in molecular simulation , Challenges and advances in fluid phase equilibria
