Simulation of Calcium Phosphate Prenucleation Clusters in Aqueous Solution: Association beyond Ion Pairing.

Natalya A Garcia,Nico A J M Sommerdijk,Raffaella Demichelis,Riccardo Innocenti Malini,Paolo Raiteri,Colin L Freeman,John H Harding,Julian D Gale

doi:10.1021/acs.cgd.9b00889

Abstract

Classical molecular dynamics simulations and free energy methods have been used to obtain a better understanding of the molecular processes occurring prior to the first nucleation event for calcium phosphate biominerals. The association constants for the formation of negatively charged complexes containing calcium and phosphate ions in aqueous solution have been computed, and these results suggest that the previously proposed calcium phosphate building unit, [Ca(HPO4)3]4–, should only be present in small amounts under normal experimental conditions. However, the presence of an activation barrier for the removal of an HPO42– ion from this complex indicates that this species could be kinetically trapped. Aggregation pathways involving CaHPO4, [Ca(HPO4)2]2–, and [Ca(HPO4)3]4– complexes have been explored with the finding that dimerization is favorable up to a Ca/HPO4 ratio of 1:2.

Highlights

Calcium phosphate minerals are ubiquitous in nature and are found extensively in both geological settings and within living systems
Classical molecular dynamics simulations were used to probe the formation of calcium and hydrogen phosphate complexes and their subsequent aggregation using a force field parametrized with a thermodynamic focus.[32]
Given that the experimental results suggest that negatively charged [Ca(HPO4)3]4− complexes form prior to nucleation[21] and that calcium-deficient amorphous calcium phosphate (ACP)[20,21] forms subsequently, it is important to probe the mechanisms by which these complexes can form and their relative stabilities in aqueous solution

Summary

Introduction

Calcium phosphate minerals are ubiquitous in nature and are found extensively in both geological settings and within living systems. A carbonated form of HA is found in human bones where it is crucial as a structural element and as a mineral reservoir It has been extensively studied due to its wide range of properties, which leads to a wealth of potential applications including the development of new biomaterials or engineered bone tissue replacement,[1,2] catalysis,[3] liquid column chromatography,[4] and heavy metal removal from soils.[5] the pathway by which this mineral nucleates from solution is still under debate, and understanding the molecular mechanism behind this process is essential to improve our ability to control the structure and tailor the final properties of this mineral for a desired application. Recent work by Smeets et al.[10] indicates that the clusters are unstable at high concentrations leading to the formation of a dense liquid phase, implying a two-step approach to the nucleation problem.[11]

Methods

Results

Conclusion