Stable Prenucleation Calcium Carbonate Clusters Define Liquid–Liquid Phase Separation

Liquid–liquid phase separation (LLPS) is an intermediate step during the precipitation of calcium carbonate, and is assumed to play a key role in biomineralization processes. Here, we have developed a model where ion association thermodynamics in homogeneous phases determine the liquid–liquid miscibility gap of the aqueous calcium carbonate system, verified experimentally using potentiometric titrations, and kinetic studies based on stopped‐flow ATR‐FTIR spectroscopy. The proposed mechanism explains the variable solubilities of solid amorphous calcium carbonates, reconciling previously inconsistent literature values. Accounting for liquid–liquid amorphous polymorphism, the model also provides clues to the mechanism of polymorph selection. It is general and should be tested for systems other than calcium carbonate to provide a new perspective on the physical chemistry of LLPS mechanisms based on stable prenucleation clusters rather than un‐/metastable fluctuations in biomineralization, and beyond.