Coacervate (/koʊəˈsɜːrvət/ or /koʊˈæsərveɪt/) is an aqueous phase rich in macromolecules such as synthetic polymers, proteins or nucleic acids. It forms through liquid-liquid phase separation (LLPS), leading to a dense phase in thermodynamic equilibrium with a dilute phase. The dispersed droplets of dense phase are also called coacervates, micro-coacervates or coacervate droplets. These structures draw a lot of interest because they form spontaneously from aqueous mixtures and provide stable compartmentalization without the need of a membrane—they are protocell candidates.

The term coacervate was coined in 1929 by Dutch chemist Hendrik G. Bungenberg de Jong and Hugo R. Kruyt while studying lyophilic colloidal dispersions. The name is a reference to the clustering of colloidal particles, like bees in a swarm. The concept was later borrowed by Russian biologist Alexander I. Oparin to describe the proteinoid microspheres proposed to be primitive cells (protocells) on early Earth. Coacervate-like protocells are at the core of the Oparin-Haldane hypothesis.

A reawakening of coacervate research was seen in the 2000s, starting with the recognition in 2004 by scientists at the University of California, Santa Barbara (UCSB) that some marine invertebrates (such as the sandcastle worm) exploit complex coacervation to produce water-resistant biological adhesives. A few years later in 2009 the role of liquid-liquid phase separation was further recognized to be involved in the formation of certain membraneless organelles by the biophysicists Clifford Brangwynne and Tony Hyman. Liquid organelles share features with coacervate droplets and fueled the study of coacervates for biomimicry.

Coacervates are a type of lyophilic colloid; that is, the dense phase retains some of the original solvent – generally water – and does not collapse into solid aggregates, rather keeping a liquid property. Coacervates can be characterized as complex or simple based on the driving force for the LLPS: associative or segregative. Associative LLPS is dominated by attractive interactions between macromolecules (such as electrostatic force between oppositely charged polymers), and segregative LLPS is driven by the minimization of repulsive interactions (such as hydrophobic effect on proteins containing a disordered region).

The thermodynamics of segregative LLPS can be described by a Flory-Huggins polymer mixing model (see equation). In ideal polymer solutions, the free-energy of mixing (Δ_mixG) is negative because the mixing entropy (Δ_mixS, combinatorial in the Flory-Huggins approach) is positive and the interaction enthalpies are all taken as equivalent (Δ_mixH or χ = 0). In non-ideal solutions, Δ_mixH can be different from zero, and the process endothermic enough to overcome the entropic term and favor the de-mixed state (the blue curve shifts up). Low molecular-weight solutes will hardly reach such non-ideality, whereas for polymeric solutes, with increasing interactions sites N and therefore decreasing entropic contribution, simple coacervation is much more likely.

${\displaystyle \Delta _{mix}G={\frac {\phi }{N}}\ln \phi +(1-\phi )\ln(1-\phi )+\Delta _{\operatorname {mix} }H}$

${\displaystyle \Delta _{mix}G=k_{B}T\left[{\frac {\phi }{N}}\ln \phi +(1-\phi )\ln(1-\phi )\right]+\Delta _{\operatorname {mix} }H}$

${\displaystyle \Delta _{\operatorname {mix} }H=\chi \phi (1-\phi )}$