Recent advances in coacervation and underlying noncovalent molecular interaction mechanisms

Coacervation is a liquid-liquid phase separation phenomenon. It involves the formation of a dense coacervate phase, rich in concentrated materials, and a co-existing immiscible dilute supernatant. This phenomenon can occur either from a homogeneous aqueous solution (simple coacervation) or when two different macromolecular aqueous solutions (proteins, polymers, and colloids) are brought into contact (complex coacervation). Coacervation has historical significance as it may have played a role in the origin of life, concentrating nutritious materials through liquid-liquid phase separation. It also reveals the underlying mechanisms of many biological phenomena such as intracellular biomolecular condensates, extracellular matrices, squid beak's gradient properties, sessile organism's wet adhesion, Alzheimer's diseases, and more. Coacervation provides insights and inspires promising solutions in areas like artificial cells/tissues, gradient materials, gene/drug delivery, underwater adhesives, and beyond. The driving forces of coacervation are noncovalent molecular interactions, often referred to as ‘chemistry beyond the molecule’, including hydrophobic interaction, electrostatic interaction, hydrogen-bonding interaction, cation-π interaction, π-π interaction, multivalency, etc. In this work, we have systematically reviewed the underlying noncovalent molecular interactions of simple coacervation and complex coacervation, respectively. We summarize commonly used materials and their corresponding molecular structures, discussing their applications. Some remaining challenge issues and perspectives for future studies are also presented. Understanding the underlying noncovalent molecular interactions of coacervation, alongside insights into molecular compositions and structures, can better guide the design of novel materials, elucidate various biological phenomena, and contribute to the development and optimization of relevant engineering technologies.