Redefined ion association constants have consequences for calcium phosphate nucleation and biomineralization

• Published in: Nature communications Vol. 15; no. 1; p. 3359
• Main Authors: McDonogh, David P., Gale, Julian D., Raiteri, Paolo, Gebauer, Denis
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 639/638/298/54/991; 639/638/440/951; 639/638/563/981; Bones; Calcium ions; Calcium phosphates; Clustering; Humanities and Social Sciences; Hydroxyapatite; Ion association; Ions; Mathematical models; Mineralization; multidisciplinary; Nucleation; Orthophosphate; Orthophosphates; pH effects; Phase separation; Revisions; Science; Science (multidisciplinary); Speciation; Tricalcium phosphate
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-47721-7

Calcium orthophosphates (CaPs), as hydroxyapatite (HAP) in bones and teeth are the most important biomineral for humankind. While clusters in CaP nucleation have long been known, their speciation and mechanistic pathways to HAP remain debated. Evidently, mineral nucleation begins with two ions interacting in solution, fundamentally underlying solute clustering. Here, we explore CaP ion association using potentiometric methods and computer simulations. Our results agree with literature association constants for Ca 2+ and H 2 PO 4 − , and Ca 2+ and HPO 4 2- , but not for Ca 2+ and PO 4 3− ions, which previously has been strongly overestimated by two orders of magnitude. Our data suggests that the discrepancy is due to a subtle, premature phase separation that can occur at low ion activity products, especially at higher pH. We provide an important revision of long used literature constants, where association of Ca 2+ and PO 4 3− actually becomes negligible below pH 9.0, in contrast to previous values. Instead, [CaHPO 4 ] 0 dominates the aqueous CaP speciation between pH ~6–10. Consequently, calcium hydrogen phosphate association is critical in cluster-based precipitation in the near-neutral pH regime, e.g., in biomineralization. The revised thermodynamics reveal significant and thus far unexplored multi-anion association in computer simulations, constituting a kinetic trap that further complicates aqueous calcium phosphate speciation. While clusters in calcium orthophosphate nucleation have long been known, their speciation and mechanistic pathways to hydroxyapatite remain debated. Here the authors report a revision of ion association in the calcium phosphate system and explore the consequences thereof on the early stages of phase separation.