Bis(ammonium) Zoledronate Dihydrate

Abstract

Neutralization of 2-(1-imidazole)-1-hydroxyl-1,1 -ethylidenediphosphonic acid (zoledronic acid) by an excess of ammonia yielded bis(ammonium) zoledronate dihydrate,The product is readily soluble in water and forms monocrystals for which the X-ray structural analysis was carried out. The zoledronic anion is of double negative charge due to deprotonation of three P-OH groups and protonation of the nitrogen in the imidazole ring. The structure is stabilized by extensive network of N-H⋅ ⋅ ⋅ O and O-H⋅ ⋅ ⋅ O hydrogen bonds expanding through the crystal in plane (002). The imidazole ring is involved in -stacking interactions with its symmetry equivalents related by inversion centers at (1 0 0) and (1 1/2 0), with distances between centroids (Cg-Cg) of 3.819 (2) and 3.881 (2)Å, respectively.

Drug-Inclusive Inorganic–Organic Hybrid Systems for the Controlled Release of the Osteoporosis Drug Zoledronate

“…The “free” forms include two polymorphs (moniclinic and triclinic) of anhydrous zoledronic acid [ 12 ], zoledronic acid monohydrate [ 14 ], and zoledronic acid trihydrate [ 15 , 16 ]. The organic salt forms of zoledronate include the cytosinium zoledronate trihydrate [ 17 ], the dicyclohexylammonium zoledronate [ 18 ] and the bis(ammonium) zoledronate [ 19 ]. The metal-containing forms of zoledronate include structures with metal centers, such as K + [ 20 ], Zn 2+ [ 21 ], Mn 2+ [ 22 ], Fe 3+ [ 22 ], Co 2+ [ 23 ], Ni 2+ [ 23 ], and Cu 2+ [ 24 ].…”