Solid-state NMR of bisphosphonates adsorbed on hydroxy apatite

Solid-state ³¹P and ¹³C magic angle spinning (MAS) NMR spectra were used to characterize pure bisphosphonates and also bisphosphonates adsorbed on hydroxyapatite. Four geminal bisphosphonates, including the clinically used compounds ethane-1-hydroxy-1,1-diphosphonic acid, 3-amino-1-hydroxypropane-l,l-diphosphonic acid and 4-amino-1-hydroxybutane-1,1-diphosphonic acid, five α,ω-bisphosphonates and phosphonoacetic acid were investigated. NMR spectra of pure and adsorbed bisphosphonates differ in the observed linewidths and in the isotropic chemical shifts. The broad lines reflect mainly the poor crystallinity of the adsorbed compounds. Shifts of δ_iso in both directions do not reveal a correlation with the molecular structures. The molar ratio of phosphonates adsorbed on hydroxyapatite determined by ³¹P spectra without cross-polarization (CP) is approximately two times larger for geminal bisphosphonates than for α,ω-bisphosphonates and phosphonoacetic acid. ¹³C CP/MAS spectra of pure and adsorbed bisphosphonates recorded in two cases for identification of adsorbed compounds give additional information about the state of adsorbed compounds. Disodium α,ω-dihydroxypolymethylene-α,ω-bisphosphonates in the solid state show characteristic ¹³C chemical shifts which are indicative of either odd or even numbers of CH₂ groups.