Prenucleation Species Dictate Foreign Ion Incorporation in the Biomineral Precursor Amorphous Calcium Carbonate

ABSTRACT Amorphous calcium carbonate (ACC) is a central precursor in biomineralization, paleoclimate archives, and functional carbonate materials. Yet, how foreign ions regulate ACC nucleation and composition remains unclear. Here, we show that Mg 2 + , Sr 2 + , and Ba 2 + modulate ACC formation through ion‐specific mechanisms that defy simple solubility and classical nucleation arguments. All three ions incorporate into supra‐ionic coordination clusters that act as compositional gatekeepers from which ACC forms by aggregation. Integration of Ba into clusters stabilizes the solution entropically, leading to progressive nucleation inhibition with increasing Ba/Ca ratios— counterintuitive, given the lower solubility of Ba‐ vs. Ca‐carbonate. Sr exhibits retrograde behavior, inhibiting nucleation at low Sr/Ca ratios but promoting it at higher ratios. Mg is distinct: Mg shows formation of two cluster populations, and ACC nucleation proceeds presumably mainly from Mg‐depleted clusters. Mg acts hereby as a two‐stage regulator, first delaying nucleation through cluster integration and subsequently being expelled from clusters during cluster phase separation. Together, these findings reveal a spectrum of ion‐specific nucleation interferences that challenge classical nucleation concepts: entropic nucleation inhibition (Ba), ratio‐sensitive induction/inhibition (Sr), and nucleation‐induced compositional change (Mg). Beyond fundamental insight, they provide chemical levers to program nucleation pathways, tune material composition, and decode biomineralization control mechanisms.