A structural study of metal binding of gem-diphosphonates, bone growth regulators

Abstract

The crystal structures of sodium dichloromethylenediphosphonate tetrahydrate and calcium dichloromethylenediphosphonate pentahydrate, determined from single crystal X-ray diffractometer data, are compared with those of other bone growth regulators ( gem-diphosphonates and pyrophosphates). Na 2CCl 2(PO 3H) 2·4H 2O crystallizes triclinic (P 1 with Z = 2 formula units in a cell of constants: a = 11.27(2), b = 9.18(2), c = 5.91(1) Å, α = 88.57(2)°, β = 92.69(2)°, γ = 90.58(2)°; final R = 0.0359 and R w = 0.0453. The two crystallographically independent sodium ions both show octahedral coordination, but, while one of them is coordinated by two couples of oxygens from two chelating diphosphonate anions plus a chlorine atom and a water molecule, the other is surrounded by three oxygen atoms from three different diphosphonate anions and three water molecules. Two couples of these octahedra, sharing edges, form tetrameric clusters joined together by diphosphonate bridges. CaCCl 2(PO 3H) 2·5H 2O crystallizes orthorhombic ( Pnma) with unit cell dimensions: a = 10.278(2), b = 10.872(2), c = 11.899(2) Å, Z = 4; final R = 0.0389 and R w = 0.0449. Calcium is heptacoordinated by two oxygen atoms from a diphosphonate anion acting as a bidentate chelating agent, and five water molecules. The coordination polyhedron can be described as a distorted monocapped trigonal prism. Chlorine is not involved in coordination to the metal. In both compounds the diphosphonate anion interacts with the cation through deprotonated oxygen atoms and assumes a nearly eclipsed conformation which gives a O⋯O bite distance as short as 3.06–3.27 Å which seems particularly suitable for a bidentate chelation to calcium and is characteristic of this class of calcium phosphate metabolism regulators.