Calcium Phosphate Prenucleation Complexes in Water by means of ab Initio Molecular Dynamics

Calcium phosphates are the main inorganic components of bone and tooth tissues. The nucleation of calcium phosphates is thought to proceed by aggregation of so called prenucleation clusters (PNCs), which are already present in body fluids before nucleation. This nucleation pathway cannot be fitted in the frame of the Classical Nucleation Theory. We investigated the structure and verified the stability of the PNCs, recently identified as calcium triphosphate complexes [Ca(HPO4)3] 4[1], by means of ab initio Molecular Dynamics with Umbrella Sampling technique. We found the calcium to be seven coordinated by two water molecules, two bidentate phosphates and one monodentate phosphate. Free energy results obtained using umbrella sampling simulations showed that the complex with a Ca:P ratio of 1:3 is the most energetically favoured, and thermodynamically more stable than the free ions. At the moment we are studying the aggregation of Ca and different ratios of PO4 , HPO4 2and H2PO4 ions by means of classical molecular dynamics.