Thionation of Structurally Isomeric Polymers for Tuning the Thermoresponsive Behavior

Lower critical solution temperature (LCST) behavior in water-soluble polymers arises from a delicate balance between polymer–water and polymer–polymer interactions, which in turn depend on the backbone and side-chain structure. Recently, thionation (the replacement of the amide carbonyl oxygen by sulfur) was introduced as a new tool to adjust LCST behavior in poly(2-oxazoline)s by weakening hydrogen bonding and reducing polarity. However, it remains unclear how this approach translates across different amide-based polymers and their LCST mechanisms. The effect of thionation on a set of structurally isomeric homopolymers having secondary, tertiary, and cyclic amide motifs and distinct phase-transition behaviors is systematically studied. By combining thionation with solution characterization techniques and molecular dynamics simulations, we examine how modifying the amide functionality influences polymer hydration, aggregation, and phase separation. This comparative approach reveals how thionation acts not only as a cloud-point modifier but also as a structure-dependent alteration that reshapes polymer–water interaction, polymer–polymer interaction, and agglomeration pathways.