Physical origin underlying the prenucleation-cluster-mediated nonclassical nucleation pathways for calcium phosphate

Area of Science:

• Materials Science
• Chemical Physics
• Crystallization Theory

Background:

• Prenucleation clusters (PNCs) are implicated in nonclassical nucleation, but their quantitative understanding remains limited.
• Key aspects like formation, stability, and impact on nucleation barriers require further investigation.

Purpose of the Study:

• To elucidate the formation mechanism and stability of PNCs in calcium phosphate crystallization.
• To quantitatively analyze the role of PNCs in nucleation barriers and the transition to amorphous calcium phosphate (ACP).

Main Methods:

• Advanced free energy calculations with over 5 μs cumulative simulation time.
• Free energy decomposition analysis to understand solvent effects and ion interactions.
• Atomic-level simulations of ion association and PNC aggregation.

Main Results:

• Identified a thermodynamically favored pathway for PNC-mediated calcium phosphate nucleation, initiated by ion pair association.
• Demonstrated PNC formation through coordination of phosphate to calcium, including same-sign ion association.
• Revealed that water's role in ion association depends on calcium ion hydration shells.
• Showed that PNC aggregation into ACP is triggered by the uptake of an additional calcium ion, lowering energy barriers.

Conclusions:

• The study provides quantitative explanations for experimental observations in nonclassical nucleation of calcium phosphate.
• Developed computational methods offer a general approach to study aqueous solution crystallization at the atomic level.
• The findings advance the understanding of PNCs' role in phase transitions and crystallization processes.