Cluster-mediated formation of amorphous calcium carbonate: compositional gatekeepers, bindings partners of biomineralization proteins, and agents in spinodal demixing

Which mechanisms underlie the formation of amorphous calcium carbonate, and how do organic compounds and foreign ions — such as biomineralization proteins or Magnesium — impact these processes? In addressing these outstanding questions, we conducted a comprehensive set of studies, adopting a molecular perspective. A particular emphasis has been placed on so-called prenucleation clusters and their as-yet elusive impact on calcium carbonate formation. These dynamic clusters, composed of interconnected chains of carbonato-calcium units, have been interpreted as proto-nucleation germs, a nonclassical crystallization species that remains debated. The present study demonstrates their role as compositional gatekeepers of the later ACC phase for organic inclusions and foreign elements, e.g., giving rise to notably low Mg distribution coefficients. In addition, we show distinct interaction with characteristic low-complexity repeat regions typical for biomineralization proteins, revealing clusters as putative binding partners, thereby deorphanising a wide range of biomineralization proteins. From a synthetic perspective, these coordination polymers can thus undergo supramolecular interactions, which breaks new ground for further expansion towards phase separation pathways uncommon for ionic and sparingly soluble mineral systems. With controlled fast flow chemistry, which ensures turbulent mixing, we even achieve spinodal demixing on larger scales, forming characteristic nanosized bicontinuous networks in various cluster-forming inorganic systems. The presented results emphasize the chemical nature of these pre-critical solution species, particularly their specific molecular interaction with organic compounds and their capability to generate supramolecular assemblies.