Coacervation in soft matter: Physicochemical principles and prebiotic implications.

Coacervation is a liquid-liquid phase separation process in which macromolecular, amphiphilic, macroionic, or colloidal components spontaneously demix into a dense coacervate phase and a dilute surrounding phase. In this review, we use the term in a focused physicochemical sense, chiefly for systems in which macromolecular interactions drive the formation of a condensed liquid phase distinct from the surrounding solution. This review examines the physicochemical principles that govern simple and complex coacervation, emphasizing electrostatic interactions, counterion release, hydrogen bonding, hydrophobic forces, pH, ionic strength, temperature, and sequence patterning. We emphasize that coacervation results from a system-dependent balance of enthalpic and entropic contributions, molecular architecture, and environmental conditions. We discuss representative systems including proteins, polysaccharides, peptides, nucleic acids, and synthetic polyelectrolytes, with particular attention to multicomponent systems and molecular composition and sequence-dependent interactions. Special attention is given to how molecular architecture and environmental conditions determine droplet formation, stability, viscoelasticity, and transitions between liquid-like, gel-like, and solid states. We distinguish thermodynamic stability from kinetic persistence and coacervation from related phenomena such as aggregation, desolvation, gelation, and precipitation. Coacervates can concentrate reactants, alter local chemical reactivity, and create microenvironments potentially favorable for prebiotic chemistry. These properties support their use of membrane-free compartmentalization and protocell-like organization, although their relevance to the emergence of life remains hypothesis-dependent. Finally, we highlight unresolved challenges, including the limited predictive capability of current theories and the need to integrate multicomponent, sequence-specific, and nonequilibrium effects into quantitative frameworks. Overall, this review aims to clarify the physicochemical basis of coacervation while distinguishing established behavior from broader hypotheses about soft-matter organization, biomolecular condensates, and the emergence of life.