Mathew Mathai, Fowler Bruce O., Breuer Eli, Golomb Gershon, Alferiev Ivan S., Eidelman Naomi
Paffenbarger Research Center, American Dental Association Health Foundation, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, National Institute of Dental Research's Craniofacial and Skeletal Diseases Branch Research Associate Program at the National Institute of Standards and Technology, Gaithersburg, Maryland 20899, Department of Pharmaceutical Chemistry, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel, Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel, and Department of Pediatrics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Inorg Chem. 1998 Dec 14;37(25):6485-6494. doi: 10.1021/ic980374h.
A new bis(acylphosphonate), glutarylbis(phosphonate) (GlBP), was synthesized. Sodium and calcium salts of the GlBP, disodium dihydrogen glutarylbis(phosphonate), NaHO(3)PC(O)(CH(2))(3)C(O)PO(3)HNa, and dicalcium glutarylbis(phosphonate) dihydrate, Ca(2)[O(3)PC(O)(CH(2))(3)C(O)PO(3)].2H(2)O, were prepared and characterized by chemical analyses, thermogravimetry and Fourier transform infrared spectroscopy (FTIR). The crystal structure of the Ca salt was determined by single-crystal X-ray diffraction. The crystals are orthorhombic with a = 10.970(1) Å, b = 23.694(2) Å, c = 5.580(1) Å, space group Pnma, and Z = 4. This study provides the first example of a structure of a calcium complex involving a nongeminal bis(phosphonate). The structure can be described in terms of a covalently pillared layer-type arrangement of neutral Ca-GlBP-Ca units along the b-axis. Each oxygen atom of the phosphonate group is bonded to a different Ca ion, and each Ca in turn is linked to three phosphonate groups. The Ca octahedra and the phosphonate tetrahedra form a two-dimensional polar sheet perpendicular to the b-axis. The chelate bonds involving the keto groups appear to be important links in the stabilization of the structure and, in turn, to the biological activity of bis(acylphosphonates). A near-perfect lattice match, found between the Ca phosphonate layer and the major crystal faces of hydroxyapatite, indicates that epitaxial growth or incorporation of GlBP can occur on the apatitic surface which may be the mode of action in the inhibition of calcification.
合成了一种新型双（酰基膦酸酯）——戊二酰双（膦酸酯）（GlBP）。制备了GlBP的钠盐和钙盐，即戊二酰双（膦酸酯）二氢二钠（NaHO(3)PC(O)(CH(2))(3)C(O)PO(3)HNa）和戊二酰双（膦酸酯）钙二水合物（Ca(2)[O(3)PC(O)(CH(2))(3)C(O)PO(3)].2H(2)O），并通过化学分析、热重分析和傅里叶变换红外光谱（FTIR）对其进行了表征。通过单晶X射线衍射确定了钙盐的晶体结构。晶体为正交晶系，a = 10.970(1) Å，b = 23.694(2) Å，c = 5.580(1) Å，空间群Pnma，Z = 4。本研究提供了涉及非偕二双（膦酸酯）的钙配合物结构的首个实例。该结构可描述为中性Ca - GlBP - Ca单元沿b轴的共价柱撑层状排列。膦酸酯基团的每个氧原子与不同的Ca离子键合，每个Ca又与三个膦酸酯基团相连。Ca八面体和膦酸酯四面体形成垂直于b轴的二维极性片层。涉及酮基的螯合键似乎是结构稳定以及双（酰基膦酸酯）生物活性的重要连接。在钙膦酸酯层与羟基磷灰石的主要晶面之间发现了近乎完美的晶格匹配，这表明GlBP可在外延生长或掺入磷灰石表面，这可能是其抑制钙化的作用方式。
