Temporal Control Over Complex, Simple, and Multiphase Coacervates Using Ureolysis and Ammonium Carbonate Decomposition

ABSTRACT Active compartmentalization is a fundamental property of life, as well as a key element in cell regulation. In order to build synthetic systems with emergent cell‐like properties, we need to develop active compartments that form, disappear, and change properties autonomously over time. Here, we report a new strategy to induce temporal changes in coacervates using the urea‐urease reaction. This reaction triggers the dissolution of complex coacervates after a controllable delay, as it increases ionic strength through the production of ammonium carbonate. This delayed dissolution can be directly used for a broad range of complex coacervates without any synthetic effort. Furthermore, ammonium carbonate can also decompose over time, evaporating from the solution. This combination of enzymatic synthesis and spontaneous decomposition of salt leads to transient coacervate dissolution, which can be used for the controlled release of cargo and for the modulation of a compartmentalized reaction. Cycles of dissolution/reformation can be repeated multiple times without any waste generation, although the number of cycles is limited by the denaturation of urease. Finally, by combining polyelectrolytes with a protected dipeptide, ureolysis can trigger the formation of multiphase coacervates, as well as the sequential formation, dissolution, and aggregation of simple and complex coacervates.