Systematic study of the physicochemical properties of a homologous series of aminobisphosphonates

Aminobisphosphonates, e.g., alendronate and neridronate, are a well known class of molecules used as drugs for various bone diseases. Although these molecules have been available for decades, a detailed understanding of their most important physicochemical properties under comparable conditions is lacking. In this study, ten aminobisphosphonates, H₂N(CH₂)_nC(OH)P(O)(OH)₂]₂, in which n = 2-5, 7-11 and 15 have been synthesized. Their aqueous solubility as a function of temperature and pH, pK_a-values, thermal stability, IR absorptions, and NMR spectral data for bothliquid (¹H, ¹³C, ³¹P-NMR) and solid state (¹³C, ¹⁵N and ³¹P-CPMAS NMR) were determined.