CRYSTAL STRUCTURES OF SYMMETRICAL DIETHYL (DICHLOROMETHYLENE) -BISPHOSPHONATE AND ITS MAGNESIUM, CALCIUM AND STRONTIUM COMPLEXES
Markku Ahlgrén1, Sirpa Peräniemi1, Jouko Vepsäläinen2 and Eija Vuokila1
1 University of Joensuu, Department of
Chemistry, P.O. Box 111, FIN-80101 Joensuu, Finland
2 University of Kuopio, Department of
Chemistry, P.O. Box 1627, FIN-70211 Kuopio, Finland
Email: markku.ahlgren@joensuu.fi
Bisphosphonates are widely used for the treatment of diseases in the skeletal system, bone formation and resorption disorders, as well as for the treatment of diseases in soft tissues. Clodronate is one of the best documented bisphosphonates used in the treatment of these diseases, buth both the therapeutic index and absorption are poor. In attempt to tackle these problems number of new bisphosphonate derivatives have been synthetized and they are expected to be better drugs[1,2].
Symmetrical diethyl (dichloromethylene)bisphosphonate diperidinium salt was synthesized as described earlier[3]. For X-ray diffraction studies suitable colourless single crystals of the compound were obtained by slow evaporation from water/ethanol solution of diethyl (dichloromethylene)-bisphosphonate diperidinium salt. The compound crystallized in triclinic space group P-1.
Earth metal complexes of diethyl (dichloromethylene)bisphosphonate were prepared by gel crystallization method using 10% tetramethylsiloxane gel[4]. Diethyl (dichloromethylene)bisphosphonate diperidinium and suitable metal salt were separately dissolved in water and liquids were brought together in test tube. Tetramethylsiloxane was added and mixture was shaken untill homogenized. After gel formation acetone was added above the gel surface and after a while crystals were grown in gel.
Magnesium complex crystallizes in triclinic space group P-1. The complex is polymeric, formed of chains, and contains two independent six coordinated magnesium atoms which lie at centres of symmetry. Mg(1) is surrounded by two water molecules and two chelating bisphosphonate ligands which also connect Mg(1) to adjacent Mg(2) atoms. The octahedral geometry of Mg(2) is completed by four aqua ligands. Calcium and strontium complexes of diethyl (dichloromethylene)-bisphosphonate are similar. Both complexes crystallize in orthorhombic space group Cmca. Complexes are dimeric containing two seven coordinated metal atoms bridged by two bisphosphonate ligands. The rest of the coordination sites of each metal atom are occupied by three aqua ligands.