Complexing ability and activity of N-containing bisphosphonates in bone cancer treatment

Abstract

The nitrogen-containing bisphosphonates (N-BPs), 4-amino-1-hydroxy-1,1-butylidenebisphosphonic acid, or Alendronate, (ALN) and 6-amino-1-hydroxy-1,1-hexylidenebisphosphonic acid, or Neridronate (NED), were studied with metal ions Mg(II), Ca(II), Cd(II) and Pb(II) at ionic strength 0.15 M at 25 oC in NaCl. The complexes of ALN and NED with Mg(II) and Ca(II) were studied by glass electrode potentiometry (GEP), and with Cd(II) and Pb(II) by sampled direct current polarography (DCP) and normal pulse polarography (NPP) at fixed total ligand to total metal concentration ratios and varied pH values. Virtual potential was used in the modelling of the metal ligand-system derived from DCP and NPP. Protonation constants and complex formation constants for ligands ALN and NED with metal ions are reported. The structures of metal-complexes proposed were compared to the reported crystal structures of the metal-complexes of the ligands ALN and NED. The linear free energy relationships (LFER) that include stability constants log KML for Mg(II), Ca(II) and Cd(II) with ligands ALN and NED were used to estimate log KML values for Sm(III) and Ho(III) with ALN and NED. The stability constants estimated here might be regarded as not reliable due to the few points available for that purpose.