Zoledronate complexes. III. Two zoledronate complexes with alkaline earth metals: [Mg(C₅H₉N₂O₇P₂)₂(H₂O)₂] and [Ca(C₅H₈N₂O₇P₂)(H₂O)]_n

Abstract

Diaquabis[dihydrogen 1-hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonato-kappa(2)O,O']magnesium(II), [Mg(C(5)H(9)N(2)O(7)P(2))(2)(H(2)O)(2)], consists of isolated dimeric units built up around an inversion centre and tightly interconnected by hydrogen bonding. The Mg(II) cation resides at the symmetry centre, surrounded in a rather regular octahedral geometry by two chelating zwitterionic zoledronate(1-) [or dihydrogen 1-hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonate] anions and two water molecules, in a pattern already found in a few reported isologues where the anion is bound to transition metals (Co, Zn and Ni). catena-Poly[[aquacalcium(II)]-mu(3)-[hydrogen 1-hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonato]-kappa(5)O:O,O':O',O''], [Ca(C(5)H(8)N(2)O(7)P(2))(H(2)O)](n), consists instead of a Ca(II) cation in a general position, a zwitterionic zoledronate(2-) anion and a coordinated water molecule. The geometry around the Ca(II) atom, provided by six bisphosphonate O atoms and one water ligand, is that of a pentagonal bipyramid with the Ca(II) atom displaced by 0.19 A out of the equatorial plane. These Ca(II) coordination polyhedra are ;threaded' by the 2(1) axis so that successive polyhedra share edges of their pentagonal basal planes. This results in a strongly coupled rhomboidal Ca(2)-O(2) chain which runs along [010]. These chains are in turn linked by an apical O atom from a -PO(3) group in a neighbouring chain. This O-atom, shared between chains, generates strong covalently bonded planar arrays parallel to (100). Finally, these sheets are linked by hydrogen bonds into a three-dimensional structure. Owing to the extreme affinity of zoledronic acid for bone tissue, in general, and with calcium as one of the major constituents of bone, it is expected that this structure will be useful in modelling some of the biologically interesting processes in which the drug takes part.

Calcium‐Mediated Secondary Cross‐Linking of Bisphosphonated Oligo(poly(ethylene glycol) Fumarate) Hydrogels

“…This complete cycle was repeatable, indicating that the interactions formed were reversible. BP clustering and precipitation in the presence of Ca 2+ has been reported in the literature, and several mechanisms have been proposed based on the formation of coordination complexes with divalent metallic ions including Ca 2+ and Mg 2+ . Irrespective of the structure of these complexes, our results show for the first time that the BP‐Ca 2+ coordination bonds can be used as structural components in PEG‐based hydrogels.…”

Human isoprenoid synthase enzymes as therapeutic targets

“…Lipophilicity-dependent aggregation of moderately (or poorly) hydrophilic compounds is the most common factor responsible for false experimental data and can affect both in vitro and cell-based assays (Owen et al, 2012). The ability of bisphosphonates to form stable, high-order complexes in solution, particularly in the presence of metal ions, is a well-documented phenomenon, exploited in a number of biomedical applications (Kunnas-Hiltunen et al, 2009; Freire et al, 2010; Giger et al, 2013). Large lipophilic compounds, and particularly the non-bisphosphonate inhibitors, are more likely to suffer from solvent-induced hydrophobic interaction than the small polar N-BP drugs.…”

Zoledronic Acid and Its Calcium-contain Complexes in Treatment of Experimental Osteoporosis in Wistar Female Rats

“…In these complexes, Zol is coordinated to calcium by two oxygen atoms of phosphonic groups ( Figure 1). This assumption is supported by the fact that in calcium complexes with Zol and in complexes of alkali and 3d-metals with Zol in the crystalline state, the nitrogen atom of the imidazole ring of the ligand are not involved in coordination to the metal ion [19][20][21]. Using the calculated formation constants of calcium complexes with Zol, a diagram of the equilibrium distribution of complexes of different composition as a function of pH in the system Ca(NO 3 ) 2 : Zol=1:1 has been constructed ( Figure 2 Analysis of BMD indices in female rats after bilateral oophorectomy which received only calcium and vitamin D supplementation with diet did not reveal their positive dynamics at the spine and total body in 1 and 3 months of observation ( Table 2).…”