Thermodynamic Study on Simple Coacervation of Peptide-Inspired Polyguanidinium in Aqueous Media

Cationic arginine residues containing a guanidinium group within disordered protein regions have been identified as enhancers of the liquid−liquid phase separation (LLPS) propensity of proteins. This enhancement is due to their ability to form non-aromatic π–π interactions in aqueous environment. Upon salt screening, the π–π interactions between likely charged guanidinium pairs lead to the simple coacervation of arginine-rich polypeptides in aqueous media. In this study, we designed a peptide-inspired polyguanidinium (G) to investigate the salt-triggered upper critical solution temperature (UCST) behavior in G aqueous solutions. Temperature–composition phase diagrams, the theta temperature (T_θ), and the effective interaction parameter (χ_eff) were characterized as a function of salt concentration and temperature. As the salt concentration increases, the two-phase region of phase diagrams expanded gradually across a wide temperature range. Also, T_θ were precisely controlled by salt screening, and the enthalpic contributions to χ_eff is dominant. These findings suggest that the enthalpically favorable monomer–monomer attractions, driven by π–π interactions between guanidinium pairs, can be a process variable for designing novel materials in complex fluids in aqueous media.