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, H(2)N(CH(2))(n)C(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 both liquid ((1)H, (13)C, (31)P-NMR) and solid state ((13)C, (15)N and (31)P-CPMAS NMR) were determined.