VO²⁺–hydroxyapatite complexes as models for vanadyl coordination to phosphate in bone

Abstract

We describe a 1D and 2D electron spin echo envelope modulation investigation of VO²⁺ adsorbed on hydroxyapatite (HA) at different concentrations and compare with VO²⁺–triphosphate (TPH) complexes studied previously in detail, in an effort to provide more insight into the structure of VO²⁺ coordination in bone. Structures of this interaction are important because of the role of bone in the long-term storage of administered vanadium, and the likely role of bone in the steady-state release of vanadium leading to the chronic insulin-enhancing anti-diabetic effects of vanadyl complexes. Three similar sets of cross-peaks from phosphorus nuclei observed in the ³¹P hyperfine sublevel correlation (HYSCORE) spectra of VO²⁺–HA, VO²⁺–TPH and VO²⁺–bone suggest a common tridentate binding motif for triphosphate moieties to the vanadyl ion. The similarities between the systems present the possibility that in vivo vanadyl coordination in bone is relatively uniform. Experiments with HA samples containing different amounts of adsorbed VO²⁺ demonstrate additional peculiarities of the ion–adsorbent interaction which can be expected in vivo. The HYSCORE spectra of HA samples show varying relative intensities of ³¹P lines from phosphate ligands and ¹H lines, especially lines from protons of coordinated water molecules. This result suggests that the number of equatorial phosphate ligands in HA could be different depending on the water content of the sample and the VO²⁺ concentration; complexes of different structures probably contribute to the spectra of VO²⁺–HA. Similar behaviour can also be expected in vivo during VO²⁺ accumulation in bones.

Keywords:

• hydroxyapatite
• oxovanadium(IV)
• diabetes
• bones
• EPR
• two-dimensional ESEEM (HYSCORE)

Acknowledgements

We thank Kinetek Pharmaceuticals Inc., the Canadian Institutes of Health Research (CIHR), the Science Council of British Columbia (GREAT programme, BDL) and the Natural Sciences and Engineering Research Council (NSERC) of Canada for support of this research. CO acknowledges many fruitful discussions with Prof. J. H. McNeill and the Canada Council for the Arts for a Killam Research Fellowship (2011–2013). This work was supported in part by NIH Grant No. GM062954 to SAD.