A Structural Study of Bisphosphonate Metal Complexes − Three New Polymeric Structures of the Calcium Complex of Clodronic Acid

Abstract

Three novel calcium complexes of clodronic acid were prepared and their structures determined by single‐crystal X‐ray diffractometry. Previously, a monomeric structure, [Ca{Cl2C(PO3H)2}(H2O)5] (1), has been determined, but the new structures are polymeric: [{Ca2[Cl2C(PO3)2](H2O)6}·4.5H2O]n (2), [{Ca2Na0.5[Cl2C(PO3)2](H2O)8}Cl0.5·4H2O]n (3) and [{Ca5[Cl2C(PO3)2]2(H2O)15}(NO3)2·1.5H2O]n (4); and they provide new, important information about the binding abilities of clodronic acid. Compounds 2−4 crystallise in the triclinic crystal system, the space group being P$\bar 1$ with Z = 2. Compound 2 consists of Ca atoms and Cl2MBP ligands connected to one‐dimensional chains. The chains are held together by hydrogen bonds formed by aqua ligands and lattice water molecules. The structure of 3 consists of similar calcium clodronate chains forming two‐dimensional layers through additional, six‐coordinate Na atoms. Compound 4 consists of two‐dimensional calcium clodronate layers, the calcium atoms are connected by Cl2MBP− and aqua ligands. The nitrate groups and lattice water molecules lie between the layers and hold them together. The layered compounds 3 and 4 reveal substantial porosity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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“…The coordination mode of Ca 2+ is different in polymeric structures of bound clodronate complexes than in the monomeric analogues. [{Ca 2 [Cl 2 C(PO 3 ) 2 ](H 2 O) 6 }⋅4.5H 2 O] n ( 1 ) (Figure ), [{Ca 2 Na 0.5 [Cl 2 C(PO 3 ) 2 ](H 2 O) 8 }Cl 0.5 ⋅4 H 2 O] n ( 2 ), and [{Ca 5 [Cl 2 C(PO 3 ) 2 ] 2 (H 2 O) 15 }(NO 3 ) 2 ⋅1.5 H 2 O] n ( 3 ) revealed that ligands provide seven oxygen donor atoms: four arising from bisphosphonate units and the remaining sites are occupied by water molecules. The geometry is a distorted mono‐capped trigonal prism.…”

“…[59] Within this group, the greatest number of studies have been devoted to etidronate [42,[66][67][68][69][70][71][72][73][74] and clodronate. [67,69,[75][76][77][78][79] Others, such as pamidronate, [59,72,80] alendronate, [59,72,81] tiludronate, [82] or zolendronate [83,84] have been discussed in only af ew research papers. To the best of the author's knowledge,o riginal data for risedronate and ibandronate directly binding to Ca 2 + are not available to date.…”

“…[60,64,67,68,70] It was provenv ia potentiometry that clodronate (NN-BP; Figure 2) forms equimolar complexes as well as dimeric species Ca 2 L. This was studied in ab road pH range (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) in aqueous solution (values of logb listed in Table S1). [68,104] In solid state, four examples-one monomeric [76] and three polymeric [79] structures-ofclodronate complexes with Ca 2 + ions werecharacterized by single-crystal X-ray diffraction. In the monomeric [CaCCl 2 (PO 3 H) 2 ·5 H 2 O] (Figure 3), Ca 2 + was provent ob eh eptacoordinated, bound by two oxygen atoms from aB Pa nion acting as abidentate chelating agent and five water molecules.…”

“…[76] The coordination mode of Ca 2 + is different in polymeric structures of bound clodronate complexes than in the monomeric analogues. [ [79] revealed that ligands provide seven oxygen donor atoms:f our arising from bisphosphonate units and the remaining sites are occupied by water molecules. The geometry is ad istorted mono-capped trigonal prism.…”

“…This shows ad ominant preference of zolendronate oxygen atoms for the Ca 2 + cations. [84] Heptacoordinated calcium ions weref ound in only very few examples of Ca 2 + coordination toward clodronate/ester clodronate, [79,107] but even in those examples only four phosphonic oxygen atoms were involvedinbinding the cation;the remaining three binding sites were occupied by water molecules. That makes the zolendronate/Ca 2 + complexaunique species.…”