Nature of Bisphosphonates Binding onto Hydroxyapatite in the Aqueous Phase

In many studies I've read, bisphosphonates (first image) are said to bind remarkably onto bone hydroxyapatite (second image) crystals. It was reported by J. Roelofs et al., (2008) that this mechanism occurs in a bidentate fashion, where both phosphate groups act as a monodentate ligand to coordinate with the hydroxyapatite. But how specifically does this occur? In other words, what atoms in the bisphosphonate act as the electron donors, and what atoms in the hydroxyapatite act as the electron acceptors? I suspect that the electron donor in the bisphosphonate are the oxygen groups after being deprotonated, though verification would be appreciated!


[![Structure of Bisphosphonate, from https://www.google.com/url?sa=i&url=https%3A%2F%2Fbiovinc.com%2Fbisphosphonate-101%2F&psig=AOvVaw1m-4Cdw5m4WK6I66yplxly&ust=1641581665316000&source=images&cd=vfe&ved=0CAwQjhxqFwoTCIC97bfmnfUCFQAAAAAdAAAAABAJ](https://i.stack.imgur.com/ypyOa.png)](https://i.stack.imgur.com/ypyOa.png)


[![Structure of hydroxyapatite](https://i.stack.imgur.com/K3hoG.jpg)](https://i.stack.imgur.com/K3hoG.jpg)￼ ￼ ￼


[![enter image description here](https://i.stack.imgur.com/k5sEf.jpg)](https://i.stack.imgur.com/k5sEf.jpg)


Image 1 depicts the structure of a generalized bisphosphonate


Image 2 depicts the ball-and-stick structure of hydroxyapatite, from Rajitanapanich et al., 2014.


Image 3 depicts an additional representation of hydroxyapatite, from Selvaraj et al., 2019.


