Coordination Polymers of Increasing Complexity Derived from Alkali Metal Cations and (4-Amino-1-hydroxybutylidine)-1,1-bisphosphonic Acid (Alendronic Acid): The Competitive Influences of Coordination and Supramolecular Interactions

Abstract

Reactions of (4-amino-1-hydroxybutylidine)-1,1-bisphosphonic acid (alendronic acid = LH 5 ) with one equivalent of the group 1 metal bases KOH, KHCO 3 , Rb 2 CO 3 , RbOH or Cs 2 CO 3 in aqueous solution at pH 4-5 gave the corresponding complexes [M(LH 4 )(H 2 O) n ].m(H 2 O), M = K (1), Rb (2) or Cs (3). Crystallisation of the products under varying conditions yielded differing hydrates and/or polymorphic phases. Rapid crystallisation of the potassium complex 1 from water/EtOH or water/DMSO gave 2[K(LH 4 )].3(H 2 O) (1a) whereas slow crystallisation from water or water/DMSO gave [K 2 (LH 4 ) 2 (H 2 O) 2 ].2H 2 O (1b phase I). For the rubidium complex 2, rapid crystallisation from water/EtOH gave the analogous [Rb 2 (LH 4 ) 2 (H 2 O) 2 ].2H 2 O (2b phase I) whereas slow crystallisation from water/DMSO also gave 2b, but as a mixture of phase I and the structural polymorph [Rb(LH 4 )(H 2 O)].H 2 O (2b phase II). In contrast, only [Cs(LH 4 )(H 2 O)].H 2 O (3b phase II) was obtained for the caesium complex 3 under all crystallisation conditions. A second complex type [M(LH 4 )(LH 5 )].2H 2 O (M = Rb 4, Cs 5), incorporating an additional coordinated alendronic acid molecule was also observed for the larger metals Rb and Cs as a minor product in some syntheses and isolated by fractional crystallisation for 4, but as the sole product from Cs(O 2 CH) and LH 5 for 5. The crystal structures of the complexes [M(LH 4 )(H 2 O) n ].m(H 2 O) 1a, 2b (phase II) and 3b (phase II) comprise edge-shared or corner-shared polyhedral chains that are linked by bridging bisphosphonate ligands into 2-D sheets. The 4-ammoniobutylidene chains protrude above and below the coordination layers and interact with neighbouring layers through hydrogen bonding of the terminal ammonium group forming distinctive supramolecular 3-D arrays. The phase I structure of 1b and 2b comprises ribbons of parallel M 4 (LH 4 ) 4 (H 2 O) 4 subunits arranged in a more close packed 3-D supramolecular network. For [M(LH 4 )(LH 5 )].2H 2 O (M = Rb 4, Cs 5), isolated M + cations, bridged by bisphosphonate ligands, are arranged into 2-D sheets, with the pendant 4-ammoniumbutylidene chains resulting in a 3-D lamellar network similar to those of 1a and 2b/3b (phase II). All of the [M(LH 4 )(H 2 O) n ].m(H 2 O) and [M(LH 4 )(LH 5 )].2H 2 O structures display strong PO-H…O(phosphonate) and N-H…O(phosphonate/water) hydrogen bond motifs which significantly impact upon the observed structures. Reactions of LH 5 with two equivalents of the group 1 metal bases MOH (M = Na, K, Rb, Cs) at pH 9-10 gave the di-metallated complexes [M 2 (LH 3 )(H 2 O) n ].(H 2 O) m (M = Na 6, K 7, Rb 8, Cs 9). Crystallisation of 6 from water/MeOH gave [Na 2 (LH 3 )(H 2 O) 4 ].H 2 O (6a) as a single phase. For 7, crystallisation from water/MeOH gave K 2 (LH 3 ).3(H 2 O) (7a) as the bulk product, whereas crystals of [K 2 (LH 3 )(H 2 O) 6 ] (7b) were grown from water/DMSO solutions. On standing, the crystals of 7b were converted into the bulk product 7a. The structures of 6a and 7b are chain rather than ...

Analysis of supramolecular interactions in alendroniate alkali metal salts: synthesis, structure, and properties of novel sodium alendronate polymorph

“…The 3D molecular self-assemblies of alendronate salts are distinguishable. The structures revealed one-dimensional and two-dimensional pseudo-coordination (1) polymeric architectures and in structure (1) has intermediate character between the anhydrous polymorph determined from the powder data [13] and hydrated sodium salts [14,15]. The R 2 2 (20) synthon is observed in all sodium alendronate salts.…”

“…The P-C bond distances 1.834(3) and 1.864(3) Å and P-C-P bond angle of As has already been reported, these systems demonstrate diverse complexity, which increases with the central cation radius. Lithium alendronate salts revealed four-coordinate tetrahedral Li + cation [16]; sodium salts, six-coordinate octahedral Na + [13][14][15]; potassium salts, seven-coordinated K + [14]; and rubidium, 6/7/8-coordinated Rb + [14]; while cesium, 7/8/9-coordinated Cs + [14]. Surprisingly, Na + cation in (1) is surrounded by a fivecoordinated sphere through three of the hydroxyl (-OH) and two oxygen atoms of the phosphonate (P=O) groups.…”

“…The diffraction patterns were obtained at room temperature with step size of 0.0167°and counting time 20 s/step over angular range 3°-60°(2θ) using Bragg-Brentano geometry and a rotating flat-plate sample holder. The comparisons of diffraction patterns of new polymorph (1) and reported earlier anhydrous sodium alendronate [14] are shown in Fig. S2.…”

“…search of literature and the Cambridge Crystal Structure Database (CSD Version 5.38, May 2017 release) [12] revealed the following salts with alkali cations such as the following: sodium, represented by CSD reference codes-UTOKAQ [13], PUQHAM, TEHWOS01 [14], TEHWOS [15]; lithium-EJEZUP [16]; potassium-PUQFOY, PUQFUE, PUQHEQ [14]; rubidium-PUQGAL, PUQGAL01, PUQGOZ, PUQHIU, PUQHOA [14]; and cesium-PUQGIT, PUQGUF, PUQHUG, PUQJAO [14]. Besides, alendronic acid crystal structures signed by CSD reference codes GOWZEX [17] and KOJGUL [18] were included into the analysis.…”

“…Besides, alendronic acid crystal structures signed by CSD reference codes GOWZEX [17] and KOJGUL [18] were included into the analysis. So far, there were reports that the title compound exists in dehydrated [14,15] and trihydrate [14] forms. Interestingly, in a new polymorph, the Na + is fivecoordinated in contrast to the other sodium salts, in which the cation is surrounded by six-coordinated sphere.…”