Role of interaction anisotropy in polymer cononsolvency: insights from the Flory–Huggins–Potts framework

Abstract

Cononsolvency occurs when mixing two good solvents creates poor-solvent conditions for polymers over specific composition ranges, causing macroscopic phase separation or microscopic chain collapse. Despite its technological and biophysical relevance, the connection between macroscopic and microscopic manifestations of cononsolvency remains unclear. A key challenge is identifying which interactions govern cononsolvency: coarse-grained analyses like standard Flory–Huggins models assume purely isotropic interactions, while atomistic simulations contain complex anisotropic interactions that cannot be precisely controlled or isolated. Here, we address the role of interaction anisotropy using the Flory–Huggins–Potts framework, which yields χ as a thermodynamic average over both configurational and internal-state coarse-grained degrees of freedom. This enables controlled comparison between systems with isotropic versus orientation-dependent interactions that share identical effective χ parameters, either driving cononsolvency by strong solvent–cosolvent affinity or preferential polymer–cosolvent affinity. While pairs of systems exhibit equivalent macroscopic phase behavior, lattice Monte Carlo simulations reveal that those featuring anisotropic or orientation-dependent interactions generate distinct collapse signatures, particularly in reentrant coil–globule transitions or characteristics of the solvation structure. These results demonstrate how microscopic interactions influences cononsolvency behavior beyond what effective χ parameters alone predict.