Coordination Polymers of Increasing Complexity Derived from Alkali

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Coordination polymers of increasing complexity derived from alkali metal cations and (4-amino-1-hydroxybutylidine)-1,1bisphosphonic acid (alendronic acid): the competitive influences of coordination and supramolecular interactions. Glen Deacon, Craig M. Forsyth, Neil Greenhill, Peter Courtney Junk, and Jun Wang Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.5b00917 • Publication Date (Web): 11 Aug 2015 Downloaded from http://pubs.acs.org on August 13, 2015

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Crystal Growth & Design

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. Glen. B. Deacon,a Craig M. Forsyth,a Neil B. Greenhill,a Peter C. Junkb and Jun Wang.ab a b

Monash University, Clayton 3800, Australia. James Cook University, Townsville 4811, Australia.

Email: [email protected]

Abstract Reactions of (4-amino-1-hydroxybutylidine)-1,1-bisphosphonic acid (alendronic acid = LH5) with one equivalent of the group 1 metal bases KOH, KHCO3, Rb2CO3, RbOH or Cs2CO3 in aqueous solution at pH 4-5 gave the corresponding complexes [M(LH4)(H2O)n].m(H2O), 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(LH4)].3(H2O) (1a) whereas slow crystallisation from water or water/DMSO gave [K2(LH4)2(H2O)2].2H2O (1b phase I). For the rubidium complex 2, rapid crystallisation from water/EtOH gave the analogous [Rb2(LH4)2(H2O)2].2H2O (2b phase I) whereas slow crystallisation from water/DMSO also gave 2b, but as a mixture of phase I and the structural polymorph [Rb(LH4)(H2O)].H2O (2b phase II). In contrast, only [Cs(LH4)(H2O)].H2O (3b phase II) was obtained for the caesium complex 3 under all crystallisation conditions. A second complex type [M(LH4)(LH5)].2H2O (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(O2CH) and LH5 for 5. The crystal structures of the complexes [M(LH4)(H2O)n].m(H2O) 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 M4(LH4)4(H2O)4 subunits arranged in a more close packed 3-D supramolecular network. For [M(LH4)(LH5)].2H2O (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(LH4)(H2O)n].m(H2O) and [M(LH4)(LH5)].2H2O structures display strong PO-H…O(phosphonate) and N-H…O(phosphonate/water) hydrogen bond motifs which significantly impact upon the 1 ACS Paragon Plus Environment


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observed structures. Reactions of LH5 with two equivalents of the group 1 metal bases MOH (M = Na, K, Rb, Cs) at pH 9-10 gave the di-metallated complexes [M2(LH3)(H2O)n].(H2O)m (M = Na 6, K 7, Rb 8, Cs 9). Crystallisation of 6 from water/MeOH gave [Na2(LH3)(H2O)4].H2O (6a) as a single phase. For 7, crystallisation from water/MeOH gave K2(LH3).3(H2O) (7a) as the bulk product, whereas crystals of [K2(LH3)(H2O)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 sheet bisphosphonate coordination polymers, with a high number of coordinated water molecules. However, their 3-D supramolecular structures are distinctive, viz. a pillared array for 6a and a more compact bi-layer structure for 7b. The [M2(LH3)(H2O)n].(H2O)m complexes of the larger group 1 metal cations 8 and 9 each crystallised as a mixture of phases. Crystals of [Rb2(LH3)(H2O)5].(H2O) (8a) and [Cs4(LH3)2(H2O)9].2(H2O) (9a) respectively, were identified as the major component after crystallisation from DMSO/H2O. The lesser hydrates [Rb4(LH3)2(H2O)8].(H2O) (8b) and [Cs2(LH3)(H2O)4] (9b) were also identified, but were not isolated as bulk materials. The structures of 8a, 8b, 9a and 9b each were complex 2-D sheets of bisphosphonate metal coordination polymers, which assembled through the supramolecular interactions into compact 3-D arrays.

Keywords: 1,1-Bisphosphonate; Alendronate; Group 1 metals; Coordination networks; Supramolecular interactions.

Introduction Metal organophosphonate materials have attracted considerable attention due to their rapidly evolving structural diversity and attractive applications in industrial and biomedical arenas.1 An important subset are the 1,1-bisphosphonates (R1)(R2)C(PO(OH)2)2 (eg alendronic acid, Scheme 1), which are a class of pharmaceuticals currently used in the clinical treatment of bone disorders such as osteoporosis, Paget’s disease and hypocalcemia, and are of increasing importance in bone cancer therapy.2 Bisphosphonates are good metalcomplexing agents,3 a property which plays a significant role in the bioactivity of these molecules. Thus they have a high affinity for calcium and are able to target and accumulate in bone mineral as well as interact with specific enzymes through trinuclear metal (Mg2+, Mn2+, Zn2+) coordination in the subsequent inhibition of biochemical processes.4 Molecules such as alendronic acid also offer a number of accessible protonation states within a reasonable pH range and a short carbon chain with a terminal ammonium group. Both these features, whilst critical for their biological function, also present opportunities for crystal engineering of coordination complexes through the formation of strong PO-H…O and NH…O hydrogen bonds. Due to their pharmaceutical relevance, the formation and structures of complexes of alendronate with the Na+ and Ca2+ cations have been studied revealing both 2 ACS Paragon Plus Environment

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1-D and 2-D coordination polymer structures.5-7 These structures also verify the development of 3-D hydrogen bonded networks in these materials through interactions of the pendant cationic alkylammonium group, the phosphonate residues and the lattice water molecules.5-7 More recently, studies of metal coordination compounds of alendronate and related 1,1-bisphosphonate ligands have led to new strategies for their use in the treatment of cancer8 and other medicinal applications,9 as well as developing new materials with magnetic, photochromic, and electrocatalytic properties.10-12 In this current contribution we have investigated the syntheses and structures of a series of new coordination polymers of alendronic acid (LH5, Scheme 1) with a particular focus on cations from the group 1 metals potassium, rubidium and caesium. As described above, the multi-metal binding capabilities of the bisphosphonate group should be well suited to these large oxophilic cations (K-Cs ionic radii are ca 0.36-0.65 Å greater than for Na at CN = 613) which generally exhibit more indiscriminate coordination environments in terms of coordination numbers (typically 6-10), irregular geometries and a wider range of bond distances than the smaller group 1 metals, lithium and sodium. For example, the reported crystal structures of the alendronate complexes [Li(LH4)(H2O)2],14 [Na(LH4)(H2O)].2(H2O),5 and [Na(LH4)],6 show fairly typical four-coordinate tetrahedral Li+ or six-coordinate octahedral Na+ environments. Furthermore, in the absence of a distinct metal-ligand topology for M = K-Cs, the inter-ligand hydrogen bonding interactions may also become more significant and potentially structure-determining. With this in mind, two pH regimes were also investigated, one at pH 4-5 promoting the presence of alendronate as LH4- and possessing at least two residual strong PO-H hydrogen bond donors, and the second at higher pH values, removing one of the PO-H moieties giving LH32- whilst simultaneously increasing the ratio of metal:ligand and the available coordination sites. We now report the synthesis and structural characterisation of three classes of group 1 metal complexes of alendronic acid, (i) [M(LH4)(H2O)n].m(H2O) (M = K 1, Rb 2, Cs 3), (ii) [M(LH4)(LH5)].2(H2O) (M = Rb 4, Cs 5), and (iii) [M2(LH3)(H2O)n].m(H2O) (M = Na 6, K 7, Rb 8, Cs 9). Crystallisation of complexes in classes (i) and (iii) under differing conditions revealed a rich structural chemistry complemented by the observation of multiple phases comprising structural polymorphs or differing hydrates for many of the products. This crystalline diversity provides a challenge in engineering conditions to give single pure phases.

Experimental General Alendronic acid monohydrate was generously provided by pharmaceutical company GenRX Pty Ltd, and was used as received. The group 1 metal salts were obtained from SigmaAldrich or Strem Chemicals and used as received or made up as standardised solutions in water. IR spectra in the region 4000-650 cm-1 were recorded for finely ground powdered 3 ACS Paragon Plus Environment


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samples using an Agilent Cary 630 ATR instrument with ResPro data handling software. Medium or greater intensity absorptions are listed for the region 1250-650 cm-1, full spectra are shown in the ESI (S4.1-S4.10). NMR measurements were obtained for solutions in D2O on a Bruker DPX400 operating at 400 MHz for 1H. Solid state 31P NMR spectra were obtained for powdered samples using standard cross-polarised magic-angle spinning techniques with a spin rate of 10000 Hz on a Bruker ADVANCE 300 MHz solid state spectrometer. Chemical shifts were referenced using external TMS or NH4H2PO4 standards. TGA data were obtained on a Mettler-Toledo TGA/DSC 1 and are listed in Table 1. Elemental analyses were performed in duplicate by the Campbell Microanalytical Laboratories, University of Otago, NZ. X-ray Diffraction Single crystal X-ray data were collected at 123K using an Oxford Gemini Ultra CCD with MoKα (1a, 1b (phase II), 2b (phase II), 4, 5, 6a, 7b) or CuKα (1b (Phase I), 2b (phase I),3b (phase II), 8a, 9a) radiation. The diffraction images were processed using the CrysAlisPro software package.15 Suitable crystals of compounds 8b and 9b were too small for a standard laboratory X-ray diffractometer (typically 95% data coverage. All structures were solved by standard methods and refined by full matrix least squares using the SHELX-97 program.18 Non-hydrogen atoms were refined with anisotropic thermal parameters. Hydrogen atoms attached to C were placed in calculated positions using a riding model with C-H distances of 0.99 Å and Uiso(H) = 1.2×Ueq(C). The approximate positions of acidic hydrogen atoms associated with N or O were located in the difference Fourier maps (except for 1b, see below) and were included in the final refinement cycles as riding atoms with restrained N-H (0.91 Å) or O-H (0.84 Å) distances and Uiso(H) = 1.5×Ueq(N/O).19 For water molecules the H-O-H angles were additionally restrained to ca 109º. For 1b (phase I) several crystals were measured but were invariably twinned. The reported data are the best that was obtained and the structure solved and refined adequately with anisotropic thermal parameters for all non-hydrogen atoms. The results confirmed that the structure was isomorphous with that of 2b (phase I), consistent with the similarity of the solid state spectroscopic results for the two compounds (see below). For the final refinement cycles, the atom coordinates (including hydrogen atoms) from 2b were used as a starting point. The apparent twinning manifests as a number of relatively significant residual electron density peaks in chemically non-sensible positions, presumably contributing to the high R value. Attempts to resolve the twinning using either the twin data processing in CrysAlsiPro15 or the TwinRotMat routine in PLATON20 were not successful. Crystal data and refinement details are listed in Tables 2 and 3. 4 ACS Paragon Plus Environment

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Powder X-ray diffraction data of the bulk compounds were obtained for finely ground samples using Bruker D8 FOCUS instrument (Bragg-Brentano θ-2θ geometry) with CuKα radiation (λ = 1.5406 Å) at room temperature and processed using the Bruker DIFFRAC SUITE software v2.1. The observed patterns were compared with those generated from the single crystal data using Mercury v3.0; slight differences in the peak positions are presumed to result from the different sample temperatures (see ESI, S2.1-2.10). Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary numbers. CCDC 1417947 for 1a, CCDC 1417948 for 1b (phase I) , CCDC 1417949 for 2b (phase I), CCDC 1417950 for 2b (phase II), CCDC 1417951 for 3b (phase II), CCDC 1417952 for 4, CCDC 1417953 for 5, CCDC 1417954 for 6a, CCDC 1417955 for 7b, CCDC 1417956 for 8a, CCDC 1417957 for 8b, CCDC 1417958 for 9a, CCDC 1417959 for 9b, CCDC 1417960 for [Na(LH4)(H2O)].2(H2O) (see ESI) Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: +44 (0) 1223 336033; e-mail: [email protected]).

Syntheses General Syntheses of [M(LH4)(H2O)m].n(H2O) complexes. Aqueous solutions of 1, 2 and 3 were prepared by addition of LH5.H2O (10-100 mmol), either as a solid, or as a suspension in water, to aqueous solutions of MOH, MHCO3 or M2CO3 in a 1:1 acid to metal ratio. When the carbonate reagents were utilized, evolution of CO2 was observed. After addition of the acid, the reaction mixtures were heated to ensure complete reaction, and then cooled to room temperature. The complexes were isolated from the final solution as described below. 2[K(LH4)].3(H2O) 1a. EtOH (ca 40 mL) was added to a solution of 1, prepared from LH5.H2O 27.4 g, 105 mmol and KHCO3 10.5 g, 105 mmol in ca 300 mL of water, resulting in the formation of a white precipitate. The mixture was then stirred at room temperature and the solid was collected by filtration and washed with EtOH and dried to constant weight under vacuum giving 30.0 g (91 %) of 2[K(LH4)].3(H2O) 1a as a white powder. IR (ν, cm-1): 1242(m), 1150(m), 1123(m), 1061(m), 1038(s), 1018(s), 948(m), 901(vs), 861(s), 826(m), 756(mbr). 1H NMR (ppm): 2.93 (m, 4H, CH2N), 1.89 (m, 8H, CH2CH2). 31P MAS NMR (ppm): 23.0 (s), 21.3(s), 15.4(s), 12.8(s). MS (+ve ES, m/z): selected peaks 288 [15%, K(LH5)+], 326 [100, K2(LH4)+], 364 [27, K3(LH3)+], 402 [2, K4(LH2)+]. Elemental analyses (%). Found: C 15.56, H 4.87, N 4.39. Calcd. for C8H30K2N2O17P4: C 15.29, H 4.81, N 4.46. In an analogous synthesis, 1a was also prepared by slow addition of a solution of K2CO3 4.4 g, 32 mmol in 20 mL of water to a suspension of LH5.H2O 17.2 g, 66 mmol and in ca 100mL of hot water and was isolated as above giving 17.2 g (85%) of 1a (identified by PXRD). Crystals of 1a for X-ray crystallography were grown by addition of DMSO (ca 5 mL) to a solution of 1, prepared from LH5.H2O 4.3 g, 16 mmol and KOH 16 mL of a 1.0 M solution, 16 mmol, in ca 25 mL of water until a permanent precipitate had formed. The mixture was then heated until clear, filtered and allowed to cool overnight resulting in a colourless crystalline mass that was collected by filtration and dried under 5 ACS Paragon Plus Environment


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ambient conditions giving 4.0 g (80 %) of 1a. The PXRD of the bulk material was identical with that obtained for 1a above. [K2(LH4)2(H2O)2].2(H2O) 1b (phase I). DMSO (ca 5 mL) was added drop-wise to a solution of 1a (2.1 g, 6.7 mmol) in 40 mL of water. The mixture was heated, filtered and then allowed to cool to room temperature. After several days, colourless needle-like crystals formed which were collected by filtration and dried under ambient conditions giving 1.81 g (84 %) of [K2(LH4)2(H2O)2].2(H2O) 1b (phase I). IR (ν, cm-1): 1127(vs), 1015sh(m), 959(m), 910(vs), 860(m), 826(m),753(m). 31P MAS NMR (ppm): 22.7 (s), 19.9(s), 18.5(s), 17.6(s) (see ESI, Fig. S3.4). Elemental analyses (%). Found: C 15.00, H 4.97, N 4.36. Calcd. for C8H32K2N2O18P4: C 14.86, H 4.99, N 4.33. [Rb2(LH4)2(H2O)2].2(H2O) 2b (phase I). A solution of 2, prepared from LH5.H20 2.75 g, 10.4 mmol and Rb2CO3 1.20 g, 5.2 mmol in 10 mL of water, was reduced in volume to ca 5 mL and EtOH was added until a precipitate formed. The resulting white precipitate was collected by filtration, and washed with EtOH then dried in air to constant weight yielding 3.70 g (95 %) of [Rb2(LH4)2(H2O)2].2(H2O) 2b (phase I) as a white powder. IR (ν, cm-1): 1128(vs), 1084sh(s), 1056sh(s), 1016sh(m), 958(m), 902(vs), 867sh(s), 720(m). 1H NMR (ppm): 2.99 (m, 4H, CH2N), 1.95 (m, 8H, CH2CH2). 31P NMR (ppm): 18.0 (s). 31P MAS NMR (ppm): 21.1(s), 19.5(d, JPP = 60 Hz), 18.4(s), 17.3(s). Elemental analyses (%). Found: C 13.31, H 4.45, N 3.79. Calcd. for C8H32N2O18P4Rb2: C 13.00, H 4.36, N 3.79. A mixture of small, colourless, prismatic crystals of 2b (phase I) and 2b (phase II) were obtained by recrystallisation of a small portion of the product from DMF/H2O. Rb(LH4).2(H2O) 2b (phase I/phase II). DMSO (ca 5 mL) was added drop-wise to a solution of 2, prepared from LH5.H20 4.3 g, 16 mmol and Rb2CO3 1.84 g, 8.0 mmol in 20 mL, until a small amount of a permanent precipitate formed and the resulting mixture was heated until clear and then cooled slowly to room temperature. A crystalline mass formed after several days and was collected by filtration, washed with DMSO and dried under vacuum giving 4.40 g (75 %) of Rb(LH4).2(H2O) 2b, as a mixture of phase I (major) and phase II (minor). The IR spectrum and PXRD pattern matched that of 2b (phase I) above. 31P MAS NMR (ppm): 21.1(s), 20.3 (s), 19.3(s), 18.2(s), 17.3(s), 13.3(s) ppm (see ESI, Fig. S3.5). Approximately 2.0 g of the product was redissolved in 40 mL of water and 5 mL of DMSO was added. The resulting mixture was filtered and allowed to stand for several days after which colourless crystals had formed which were collected by filtration and dried in air giving 1.28 g (64 %) of 2b, as a mixture of phase I (minor) and phase II (major). 31P MAS NMR (ppm): 21.0(s), 20.3 (s), 19.5(s), 18.2(s), 17.3(s), 13.3(s) ppm (see ESI, Fig. S3.6). [Cs(LH4)(H2O)].H2O 3b (phase II). A solution of 3, prepared from LH5.H2O 5.34 g, 20.0 mmol and Cs2CO3 3.26 g, 10.0 mmol in 50 mL, of water was reduced in volume to ca 5 mL and allowed to stand overnight giving a colourless oil. The product was isolated after removing the remaining solvent under vacuum and drying to constant weight in a vacuum desiccator giving 7.94 g (95 %) of [Cs(LH4)(H2O)].H2O 3b (phase II) as a white powder. IR (ν, cm-1): 6 ACS Paragon Plus Environment

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1149(m), 1135(m), 1066(m), 1049(ssh), 1031(s), 954(m) 891(vs), 864(s), 808(m), 760(m), 745(m). 1H NMR (ppm): 2.99 (m, 2H, CH2N), 1.96 (m, 4H, CH2CH2). 31P MAS NMR (ppm): 19.5(s), 11.8(s). Elemental analyses (%). Found: C 11.60, H 3.88, N 3.20. Calcd. for C4H16CsNO9P2: C 11.52, H 3.87, N 3.36. Crystals suitable for X-ray crystallography were grown from a DMSO/water solution. [Rb(LH4)(LH5)].2(H2O) 4. Rb2CO3 (0.92 g, 4.0 mmol) was dissolved in 5 mL of water and the solution was added drop-wise to a stirred suspension of LH5.H2O (4.3 g, 16 mmol) in 20 mL of water at 60 ⁰C. After complete addition, the mixture was heated until a clear colourless solution was obtained. On cooling to room temperature and standing overnight, colourless crystals deposited and were collected by filtration and dried under ambient conditions giving 2.2 g of LH5.H2O. The filtrate was allowed to slowly reduce in volume under ambient conditions for several days after which large colourless crystals deposited which were collected by filtration and dried under ambient conditions giving 0.50 g (10 %) of [Rb(LH4)(LH5)].2(H2O) 4. IR (ν, cm-1): 1197(m), 1112(s), 1064(s), 1031(s), 1016(s), 968(s), 935(vs), 823(m), 739(m). 31P MAS NMR (ppm): 19.1(s), 17.5(s), 16.9(s). Elemental analyses (%). Found: C 15.62, H 4.69, N 4.47. Calcd. for C8H29N2O16P4Rb: C 15.53, H 4.72, N 4.53. [Cs(LH4)(LH5)].2(H2O) 5. Cs(O2CH) (2.84 g, 16.0 mmol) was dissolved in 10 mL of water and the solution was added drop-wise to a stirred suspension of LH5.H2O (4.3 g, 16 mmol) in 20 mL of water at 60 ⁰C. After complete addition, the mixture was heated until a clear colourless solution was obtained. After cooling to room temperature, DMSO ca 5 mL was added and the mixture was filtered and the filtrate was allowed to stand overnight. Large colourless crystals deposited and were collected by filtration and dried under ambient conditions giving 4.4 g (82 %) of [Cs(LH4)(LH5)].2(H2O) 5. IR (ν, cm-1): 1135(m), 1053(s), 1014(s), 964(s), 928(s), 908(vs), 806(m). 31P MAS NMR (ppm): 19.7(s), 16.3(s), 15.6(d, JPP = 28 Hz), 15.0(s). Elemental analyses (%). Found: C 14.58, H 4.48, N 4.14. Calcd. for C8H29CsN2O16P4: C 14.43, H 4.39, N 4.21. General Syntheses of [M2(LH3)(H2O)m].n(H2O) complexes. Aqueous solutions of 6, 7, 8 and 9 were prepared by addition of LH5.H2O (10-100 mmol), either as a solid, or as a suspension in water, to aqueous solutions of MOH in a 1:2 acid to metal ratio. After complete addition of the acid, the reaction mixtures were heated to ensure complete reaction, and then cooled to room temperature. The measured pH values were in the range 9.0-9.5. The complexes were isolated from the final solution as described below. [Na2(LH3)(H2O)4].H2O 6a.A solution of 6 (prepared from LH5.H2O 26.7 g, 100 mmol and NaOH 8.0 g, 200 mmol) in 100 mL of water was reduced in volume to ca 20 mL and MeOH (ca 30 mL) was added giving a white precipitate. The solid was collected by filtration and washed with MeOH, then purified by dissolution in hot water, filtration and re-precipitation with MeOH. The final product was collected by filtration and dried under vacuum to constant weight giving 38.0 g (99 %) of [Na2(LH3)(H2O)4].H2O 6a as a white powder. IR (ν, cm-1 ): 1145(m) , 1108(s), 1073(s), 1016(vs), 972(s), 943(s), 910(s), 871(m). 1H NMR (ppm): 3.00 (t, 7 ACS Paragon Plus Environment


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2H, CH2N), 1.93 (m, 4H, CH2CH2). 31P MAS NMR (ppm): 21.2 (s), 20.2(s). MS (+ve ES, m/z): selected peaks 272 [27%, Na(LH5)+], 294 [55, Na2(LH4)+], 316 [31, Na3(LH3)+], 338 [9, Na4(LH2)+]. Elemental analyses (%). Found: C 12.75, H 5.43, N 3.70. Calcd. for C4H21NNa2O12P2: C 12.54, H 5.52, N 3.66. Crystals suitable for X-ray crystallography were grown in the mother liquor after separation of the bulk product. K2(LH3)(H2O)3 7a. A solution of 7 (prepared from LH5.H2O 2.67 g, 10.0 mmol and KOH (85 % purity) 1.35 g, 20.4 mmol) in 50 mL of water was reduced in volume to approximately 30 mL and then MeOH (ca 20 mL) was added until incipient precipitation. The mixture was heated until clear and then cooled to 4 ºC and the resulting white precipitate was collected by filtration and dried under vacuum to constant weight giving 2.28 g of K2(LH3)(H2O)3 7a (60 % yield) as a white powder. IR (ν, cm-1 ): 1157(m), 1147(m), 1091(s), 1040(vs), 1026(vs), 971(vs), 931(s), 840(m), 826(m), 724(s), 683(s). 1H NMR (ppm): 2.99 (m, 2H, CH2N), 1.93 (m, 4H, CH2CH2). 31P NMR (ppm): 18.1(s). 31P MAS NMR (ppm): 24.8 (d, JPP = 40 Hz), 16.8(d, JPP = 39 Hz). MS (+ve ES, m/z): selected peaks 39 [100%, K+], 288 [1, K(LH5)+], 326 [8, K2(LH4)+], 364 [3, K3(LH3)+]. Elemental analyses (%). C 12.70, H 4.67, N 3.58. Calcd. for C4H17K2NO10P2: C 12.67, H 4.52, N 3.70. Crystals of [K2(LH3)(H2O)6] 7b were grown from a DMSO/H2O solution and were characterised by X-ray crystallography. [Rb2(LH3)(H2O)5].H2O 8a. A solution of 8 (prepared from LH5.H2O 1.76 g, 6.59 mmol and RbOH.H2O 1.74 g, 14.4 mmol) in 50 mL of water was reduced to approximately 25 mL under vacuum and then MeOH was added until incipient precipitation. The mixture was heated until clear and then cooled to 4 ºC. The resulting white microcrystalline material was collected by filtration and washed with MeOH and dried in air giving 2.40 g (70 %) of [Rb2(LH3)(H2O)5].H2O 8a as a free flowing white powder. IR (ν, cm-1 ): 1167(s), 1080(s), 1053(vs), 1027(vs), 963(vs), 925(s), 833(m), 781(mbr), 737(s), 656(s). 1H NMR (ppm): 3.00 (s, 2H, CH2N), 1.92 (m, 4H, CH2CH2). 31P MAS NMR (ppm): 19.4(d, JPP = 34 Hz), 17.9(d, JPP = 28 Hz). Elemental analyses. Found: C 9.48, H 4.30, N 2.69. Calcd. for C4H23NO13P2Rb2: C 9.13, H 4.41, N 2.66. Recystallisation of a portion of the bulk product (ca 200 mg) from DMSO/H2O (1:5) gave a mixture of colourless crystals of 8a and a small amount of a colourless oil. The latter partially crystallised on standing yielding crystals of [Rb4(LH3)2(H2O)8].(H2O) 8b. [Cs4(LH3)2(H2O)9].2(H2O) (9a). A solution of 9 (prepared from LH5.H2O 3.54 g, 13.3 mmol and CsOH.H2O (>90 % purity) 4.72 g, 25.3 mmol) in 50 mL of water was reduced to approximately 25 mL under vacuum. MeOH was added until incipient precipitation then the mixture was heated and allowed to cool to room temperature then stored at 4 ºC. The resulting white precipitate was collected by filtration and washed with MeOH and dried in air giving 6.06 g (78 %) of [Cs4(LH3)2(H2O)9].2(H2O) 9a as a free flowing white powder IR (ν, cm-1 ): 1157(s), 1075(s), 1058(s), 1037(vs), 1019(vs), 967(vs), 940(m), 922(m), 897(m), 848(m), 669(m). 1H NMR (ppm): 3.01 (s, 4H, CH2N), 1.94 (m, 8H, CH2CH2). 31P CPMAS NMR (ppm): 24.0(s), 18.8(s), 15.9(s). MS (+ve ES, m/z): selected peaks 133 [100%, Cs+], 514 [2, Cs2(LH4)+]. Elemental analyses. Found: C 8.07, H 3.66, N 2.28. Calcd. for C8H44Cs4N2O25P4: C 8 ACS Paragon Plus Environment

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7.85, H 3.62, N 2.29. Crystals of 9a, suitable for X-ray crystallography were grown from a DMSO/H2O solution of the bulk material. Crystals of [Cs2(LH3)(H2O)4] 9b were obtained from an analogous preparation in which the initial product had formed as an oil that partially crystallised on standing.

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Results and Discussion Alendronic acid reacted readily with the group 1 metal bases MOH, MHCO3 or M2CO3 in water in a 1:1 metal to acid ratio to yield complexes of the form M(LH4).n(H2O) (M = K 1, Rb 2, Cs 3, Scheme 1). The pH values of the final solutions were in the range 4-5, consistent with the presence of alendronate as LH4-.21 The bulk products were initially isolated in high yield by precipitation with MeOH or EtOH (1 and 2) or by evaporation of the solution to dryness (3) which gave materials with the compositions 2[K(LH4)].3(H2O) (1a), Rb(LH4).2(H2O) (2b) and Cs(LH4).2(H2O) (3b). Elemental analyses were in agreement with the proposed formulae and TGA data (Table 1) displayed mass losses in the temperature range 120-170 ºC corresponding to elimination of approximately three (1a) or two (2b, 3b) water molecules respectively. In addition, solid state 31P MAS NMR data (see below) confirmed that each of these materials was a single phase. Crystals of 1a and 3b were grown from water/DMSO were characterised by single crystal structure determination (see below), and the calculated PXRD pattern matched those obtained for the initially isolated bulk products (see ESI, S2.1S2.10). However, further crystallisation experiments for the K and Rb complexes 1 and 2 under differing conditions revealed a more rich structural variety. Slow recrystallization of 1a from a dilute water/DMSO mixture gave colourless needles of [K2(LH4)2(H2O)2].2H2O 1b. Similarly, recrystallization of a small sample of 2b from water/DMF gave a mixture of crystal types, corresponding to two structural polymorphs (herein after referred to as phase I and phase II). Both phases were characterised by single crystal structure determination with the phase I structure isomorphous with that of the K complex 1b, whereas the phase II structure is isomorphous with that of 3b. The calculated PXRD pattern for 2b (phase I) matched that obtained for the bulk isolated product, suggesting that the latter is pure phase I, and this was confirmed by the solid state 31P MAS NMR data (see below). Attempts to isolate a bulk sample of 2b (phase II) appeared to yield only mixtures of phase I and phase II in varying proportions. During the course of the crystallisation experiments, crystals of a second complex type [M(LH4)(LH5)].2H2O (M = Rb 4, Cs 5) were observed in isolated instances and usually only as a minor product. A bulk sample of 4 was isolated in low yield from a reaction of Rb2CO3 and four equivalents of LH5.H2O by fractional crystallisation. In contrast, reaction of LH5.H2O with Cs(O2CH) gave 5 in high yield, irrespective of the use of a 1:1 metal-acid ratio. The reactions of alendronic acid with the group 1 metal hydroxide salts, MOH were also performed with a 1:2 acid to metal ratio to yield complexes of the form M2(LH3).n(H2O) (M = Na 6, K 7, Rb 8, Cs 9). The final pH of the solutions prior to precipitation of the products was between 9-10 consistent with the presence of LH32-.21 The reaction for M = Na 6 straightforwardly gave [Na2(LH3)(H2O)4].H2O (6a) in high yield after precipitation of the bulk product with MeOH. The PXRD and 31P MAS NMR data were consistent with the crystal structure (from crystals grown from the mother liquor - see below) indicating that the bulk product was a single phase material. Elemental analyses were satisfactory and TGA data (Table 1) indicated a sharp single step mass loss at 123 ºC, corresponding to elimination of 10 ACS Paragon Plus Environment

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four water molecules. For M = K 7, the bulk product precipitated by addition of MeOH, K2(LH3)(H2O)3 (7a) has a different composition from crystals of [K2(LH3)(H2O)6] (7b) grown from water/DMF. The latter readily lost water on standing and attempts to prepare a bulk sample of 7b were unsuccessful. The subsequent loss of all three water molecules from 7a was shown by TGA (Table 1) to occur at a temperature well above 100 ºC. Crystallisation of the products for M = Rb 8 or Cs 9 from water/EtOH gave the corresponding complexes [Rb2(LH3)(H2O)5].(H2O) (8a) and [Cs4(LH3)2(H2O)9].2(H2O) (9a). Crystals of both complexes were grown from water/DMSO solutions as the major component in each case. However, a second crystal form was observed in both systems and corresponded to a lesser hydrate of each complex, [Rb4(LH3)2(H2O)8].(H2O) (8b) and [Cs2(LH3)(H2O)4] (9b). The calculated PXRD patterns for 8a and 9a corresponded with those of the bulk products and the elemental analyses and TGA data were consistent with the formula. However, spectroscopic data suggested (see below) that for 8a, the bulk material was contaminated with 2b (phase II). The metal alendronate products were characterised by solid state spectroscopic techniques. The IR spectra of the M(LH4) complexes each display a weak broad absorption centred at approximately 3200-3000 cm-1 attributable to OH and NH stretching vibrations (see ESI S4.1S4.4). These absorptions are considerably more intense in the spectra of the corresponding M2(LH3) compounds (see ESI S4.6-S4.10), presumably reflecting the higher numbers of coordinated water molecules in the latter. A complex series of absorption bands between 1250-750 cm-1 was also observed in all the spectra, and these are in the typical region for P-O stretching vibrations.22 From the crystal structures (see below) the alendronate anion in the M(LH4) complexes is zwitterionic, having one -NH3+ and two -PO2(OH)- groups, whereas the M2(LH3) complexes have instead one -PO32- and one -PO2(OH)- group. The interpretation of these P-O stretching vibrations is further complicated by the differing coordination modes of each phosphonate group in the individual complexes. However, the spectra of the M(LH4) complexes with closely related structures, eg 1a, and 2b/3b (phase II) are very similar with each showing three groups of multiple absorption bands centred at ca 1150, 1050 and 900 cm-1 whereas the spectra of 1b/2b (phase I) were somewhat different showing two intense broad absorptions at ca 1130 and 900 cm-1. The M2(LH3) complexes 6a, 7a, 8a and 9a also have multiple P-O stretching bands similar to those of the M(LH4) complexes with an additional strong absorption near 960 cm-1, plausibly indicative of the -PO32- group.22a The current M(LH4), M(LH4)(LH5) and M2(LH3) complexes were also analysed by solid state P MAS NMR. Data for several 1,1-bisphosphonate molecules in their acid form has shown distinguishable isotropic shifts for the -PO(OH)2 and -PO2(OH)- sites (eg. for LH5.H2O we observed two peaks at δ 15.5 (d, JPP 44 Hz) and 14.8 (br s) ppm, cf Lit.23a 16.6 and 15.9 ppm).4c However, for metal complexes, the dominant influence on the isotropic 31P MAS NMR shifts is most likely to be the metal-phosphonate coordination modes and the number of peaks generally correlates with the number of unique phosphonate sites in the corresponding crystal structure.8c,9b,24,25 As shown in ESI Figures S3.1-3.3, the data obtained 31



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for the three structural variants 1a, 2b (phase I) and 3b (phase II) (corresponding to the bulk products) are distinctive, and the number of isotropic peaks matches the number of crystallographically unique phosphorus atoms in the relevant crystal structures. In some cases, peaks are split into doublets due to P-P coupling with JPP ~ 30-60 Hz. The spectrum of 1a (Fig. S3.1) shows four single resonances at δ 23.0, 21.3, 15.4 and 12.8 ppm corresponding to two different phosphonate groups of the two independent alendronate ligands in the structure (see below). Similarly, the spectrum of 2b (phase I) (Fig. S3.2) also shows four resonances at δ 21.1, 19.5, 18.4 and 17.3 ppm and these are very similar to those (δ 22.7, 19.9, 18.5 and 17.6 ppm, (see ESI, Fig. S3.4) observed for the isomorphic complex 1b (phase I) that was obtained from recrystallization of 1a. In contrast, the spectrum of 3b (phase II) (Fig. S3.3) shows only two peaks at δ 19.5 and 11.8 ppm consistent with the single crystallographically unique alendronate ligand. The spectra for samples of 2b from the crystallisation experiments (see ESI, Fig. S3.5-6) show the four peaks observed for phase I with two additional peaks at δ 20.3 and 13.3 ppm corresponding to the phase II component. The spectra also show that the proportion of phase II could be enriched, but we were unable to obtain a pure 2b (phase II) sample. Consistent with the above observations, the spectrum for [Cs(LH4)(LH5)].2(H2O) 5, (see ESI, Fig. S3.8) shows four peaks, two for the LH5 ligand and two for the LH4- ligand. In contrast for the analogous complex [Rb(LH4)(LH5)].2(H2O) 4 (Fig. S3.7) there are three resonances in the same chemical shift range and presumably there is coincidental overlap of two peaks in this case. The 31P MAS NMR data for the M2(LH3) complexes (Figures S3.9-3.12) appears to be largely consistent with the observed crystal structures with complex 6a showing two peaks at δ 20.2 and 21.2 ppm (Fig. S3.9) and complex 9a showing three peaks at δ 24.0, 18.8, 15.9 ppm, the latter presumably two pairs of peaks that are partially overlapped (Fig. S3.12). Complex 7a, which was not structurally characterised (see below), displayed only two resonances at δ 16.8 and 24.8 ppm (both as doublets, JPP 38-40 Hz) (Fig. S3.10). The data for the bulk sample of the Rb complex 8a showed two main peaks at δ 19.5 and 17.9 ppm (both as doublets, JPP 28-34 Hz), consistent with the observed structure (see below), with an additional small peak at δ 13.3 ppm (Fig. S3.11). The latter is plausibly due to an impurity of [Rb(LH4)(H2O)].(H2O) 2b (phase II) (Fig. S3.6) (there is a small shoulder on the δ 19.5 peak which may correspond to the 20.3 ppm peak of 2b). For the remaining two complexes 8b and 9b we were unable to obtain sufficient amounts for NMR characterisation. Description of Crystal Structures [K2(LH4)2].3(H2O) 1a. Complex 1a comprises a set of two different 2-D coordination polymer sheets of [K(LH4)] in which each 2-D sheet contains solely one or the other of the two unique potassium atoms K(1) and K(2), with the layers alternating in the 3D structure (Figure 1a). The building blocks of the 2D sheets are edge-shared polyhedral chains of K+ cations (Figure 1b), propagated through pairs of bridging phosphonate groups and successive parallel chains are connected through bridging bisphosphonate ligands. Thus each ligand binds four 12 ACS Paragon Plus Environment

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K+ cations, and the metal-ligand connectivity is shown in Figure S5.1. For K(1), the bisphosphonate ligand is µ4-1κ2(O,OH):2κ3(OH,O’,O’’):3κ2(OH’,O’’’):4κ2(O’’’,COH) whilst for K(2), the 1κ2(O,OH) and 3κ2(OH’,O’’’) connections convert to unidentate by not having the K-O(H)-P bond. Hence the coordination number is reduced from nine for K(1) to seven for K(2). The K-O bond distances (K(1) 2.603(2)-3.119(2) Å, K(2) 2.675(2)-3.001(2) Å) are in the normal range observed for analogous complexes.26,27 The change in coordination number from K(1) to K(2) is related to differences in the strong (1.67(1)-1.75(1) Å) phosphonate hydrogen bond patterns within each of the 2-D sheets. Four bisphosphonate ligands surround each K(1) or K(2) centre with a change in the connectivity between two ligands from a phosphonate…water…phosphonate linkage around K(1) to a direct phosphonate…phosphonate linkage for K(2). A consequent twist in the orientation of the coordinated phosphonate groups lengthens two of the K-OH distances to non-bonding, ca 4.0 Å. The interlayer region also shows a distinctive hydrogen bond pattern in which the 4ammoniobutylidene chains protrude above and below the planes of metal atoms. Pairs of alendronate ligands are connected head-to-tail through N-H…phosphonate interactions in a ܴଶଶ (16) ring motif and this feature is ubiquitous through all the subsequent structures described below. These rings form pillars between successive potassium-bisphosphonate sheets and the interlayer spacing is ca 9.6 Å. Lattice water molecules occupy the vacancies between the 4-ammoniobutylidene chains and form additional hydrogen bonded bridges between the layers. Potassium complexes with related bisphosphonate ligands (eg [K(L)(H2O)].H2O, L = RC(OH)(PO2(OH)-)2, where R = CH2pyH+ or CH2imH+)27,28 similarly show 2D sheet coordination polymer structures but with different metal-ligand connectivity from that of 1a. However, these structures also form layers through N-H…phosphonate hydrogen bonds in the same head-to-tail ܴଶଶ (16) ring motif, albeit with additional π-π interactions of the parallel heterocyclic rings and a larger interlayer spacing (ca 14.1, 13.3 Å respectively). [M2(LH4)2(H2O)2].2(H2O) M = K 1b (phase I), M = Rb 2b (phase I). The phase I structures of 1b and 2b comprise a supramolecular array of 1-D coordination polymeric ribbon-like chains (Figure 2a) composed of repeating parallel tetra-nuclear [M2(LH4)2(H2O)2]2 substructures (Figure 2b) which are assembled into infinite chains through bridging bisphosphonate groups. There are two unique M+ sites, M(1), which lies on the edges of the polymer ribbon, and M(2) which is part of the C2-symmetric central pair. Each M+ has a coordinated water molecule, and the four M+ centres are connected through bridging -PO2(OH) groups. The metal ligand connectivity for the two unique ligands for each structure is shown in Figure S5.2. One bisphosphonate ligand is µ3-1κ(O):2κ2(O’,O’’):3κ2(O’’’,COH), whilst the second is µ5-1κ3(O,O’,OH):2κ(O’):3κ2(O’’,O’’’):4κ(O’’’):5κ(COH). However, analysis of the M-O bond distances shows two additional longer interactions in the 3.4-3.6 Å range for each complex, as indicated in Figure S5.2. Comparable data for group 1 metal phosphonate complexes that possess similar lamella topographies, [M(HO3P-R-PO3H2)] R = CH2CH2,29 C6H4C6H4,30 [Rb(HEDP)].2(H2O) (HEDP = MeC(OH)(PO3H)2)31 show metal-oxygen bond distances typically 2σI) wR(all data) 0.079 0.279 0.060 0.073 0.102 GoF 1.034 1.120 1.031 1.062 1.099 a Data for 1b (phase I) showed signs of twinning that could not be resolved (see experimental). However, the structure is isomorphous with that of 2b (phase I).

Table 3. Crystal data and refinement details for the M(LH4)(LH5) complexes 4 and 5 and the M2(LH3) salts 6a and 7b.

formula fw cryst sys sp gp a (Å) b (Å) c (Å) α (º) β (º) γ (º) 3 V (Å ) Z Nt N(Rint) No R1(I>2σI) wR(all data) GoF

4 C8H29N2O16P4Rb 618.68 monoclinic P21/c 20.4874(11) 7.2929(3) 14.7879(9) 90 109.949(6) 90 2076.92(19) 4 11625 5549(0.030) 4600 0.035 0.079 1.047

5 C8H29CsN2O16P4 666.12 triclinic P-1 7.3560(4) 7.3955(4) 19.7674(9) 90.296(4) 90.613(4) 97.621(5) 1065.79(10) 2 14572 6882(0.026) 6157 0.027 0.060 1.103

6a C4H21NNa2O12P2 383.14 monoclinic P21/n 13.1262(3) 6.9000(1) 15.7837(4) 90 95.052(2) 90 1423.99(5) 4 18068 4770(0.033) 3842 0.032 0.080 1.040

7b C4H23K2NO13P2 433.37 triclinic P-1 6.9859(5) 9.1723(10) 26.4883(18) 95.782(8) 91.213(6) 92.422(7) 1686.6(2) 4 19453 10363(0.032) 8382 0.035 0.081 1.043


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Table 4. Crystal data and refinement details for the M2(LH3) salts 8a, 8b, 9a and 9b.

formula fw cryst sys sp gp a (Å) b (Å) c (Å) α (º) β (º) γ (º) V (Å3) Z Nt N(Rint) No R1(I>2σI) wR(all data) GoF

8a C4H23NO13P2Rb2 526.11 monoclinic P21/n 6.8174(5) 26.990(2) 9.3643(7) 90 98.805(7) 90 1702.7(2) 4 15275 2983(0.062) 2791 0.043 0.109 1.061

8b C8H40NO23P4Rb4 998.18 triclinic P-1 6.816(4) 13.509(5) 17.821(5) 104.03(2) 98.21(2) 94.69(3) 1563.2(12) 2 19523 5492(0.104) 4559 0.065 0.170 1.045

9a C8H44Cs4N2O25P4 1223.97 triclinic P-1 6.9204(4) 14.4826(8) 17.7931(11) 81.983(5) 82.274(5) 88.484(5) 1749.81(18) 2 19217 6200(0.054) 5562 0.040 0.107 1.042

9b C4H19Cs2NO11P2 584.96 triclinic P-1 6.8740(14) 9.3880(19) 12.775(3) 88.97(3) 88.32(3) 81.42(3) 814.8(3) 2 27549 4119(0.056) 3972 0.027 0.069 1.083



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Scheme 1. Syntheses group 1 metal alendronate complexes. Crystallisation conditions: a) H2O/EtOH, b) H2O/DMSO, c) H2O/evaporation, d) H2O/MeOH, e) air, f) minor product.


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a)

b)

Figure 1. (a) Polyhedral representation of 2[K(LH4)].3(H2O) 1a as viewed down the b axis. Lattice water molecules have been omitted for clarity. (b) Side view of part of the coordination polymer chain containing K(1).



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a)

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b)

Figure 2. (a) Polyhedral representation of phase I structure of [M2(LH4)2(H2O)2].2(H2O) , M = K 1b, M = Rb 2b, as viewed down the coordination polymer chain along the b axis. Lattice water molecules have been omitted for clarity. (b) View of the C2-symmetric M4(LH4)4(H2O)4 substructure (for M = Rb).


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a)

b)

Figure 3. (a) Polyhedral representation of the phase II structures of [M(LH4)(H2O)].H2O M = Rb 2b, M = Cs 3b, as viewed down the b axis. Lattice water molecules have been omitted for clarity. (b) Side view of part of the coordination polymer chain in 3b



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a)

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b)

Figure 4. Bisphosphonate hydrogen bond network in a) 2b/3b and b) [Na(LH4)(H2O)].2(H2O) showing the relative positions of the metal atoms within the networks.


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a)

b)

Figure 5. (a) Polyhedral representation of the structures of [M(LH4)(LH5)].2(H2O), M = Rb 4, M = Cs 5, as viewed down the b axis. Lattice water molecules have been omitted for clarity. (b) Side view of part of the coordination polymer in 5.



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a)

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b)

c)

Figure 6. (a). Polyhedral representation of [Na2(LH3)(H2O)4].H2O (6a) as viewed down the b axis. Lattice water molecules have been omitted for clarity. (b) Ball and stick representation of part of the Na2(LH3) chain and showing the coordination environment of Na(1). (c) End view of the polymer showing the disposition of Na(2) above and below the central chain.


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a)

b)

Figure 7. (a) Polyhedral representation of [K2(LH3)(H2O)6] (7b), as viewed down the a axis and showing the ends of the coordination polymer chains. (b) Ball and stick representation of part of the coordination polymer for one of the two very similar unique components in the structure and showing the coordination environment of K(1) and K(2).



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a)

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b)

c)

Figure 8. (a) Polyhedral representation of [Rb2(LH3)(H2O)5].(H2O) 8a as viewed down the a axis. Lattice water molecules have been omitted for clarity. (b) Ball and stick representation of the chain substructure A in 8a (one coordinated water molecule O(8) has been omitted for clarity) (c) Ball and stick representation of part of the sheet substructure B in 8a.


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a)

b)

c)

Figure 9. (a) Polyhedral representation of [Rb4(LH3)2(H2O)8].(H2O) 8b as viewed down the a axis. (b) Ball and stick representation of the part of the chain substructure A in 8b. (c) Side view of the chain substructure A and the sheet substructure B in 8b.



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a)

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b)

c)

Figure 10. (a) Polyhedral representation of [Cs4(LH3)2(H2O)9].2(H2O) 9a. (b) Side view of the chain substructure in 9a showing the coordination environment of Cs(1). (c) End view of the ladder substructure A (left) and the sheet substructure B (right) in 9a showing the coordination environments of Cs(2), Cs(3) and Cs(4).


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a)

b)

c)

Figure 11. (a) Polyhedral representation [Cs2(LH3)(H2O)4] (9b) as viewed down the a axis. (b) The primary substructure in 9b, comprising two parallel Cs(1)(LH3)(H2O) chains with central Cs(2)(H2O)3 units bound through bridging phosphonate oxygen atoms . (c) Seven-coordinate Cs(2) centres are

bound via a κ2(O,O’) phosphonate group from one chain and two unidentate phosphonate groups from the other chain as well as to three water molecules, O(9), O(10) and O(11).



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Table of Contents: 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. Glen. B. Deacon, Craig M. Forsyth, Neil B. Greenhill, Peter C. Junk and Jun Wang. Reactions of alendronic acid (= LH5) with group 1 metal bases KOH, KHCO3, Rb2CO3, RbOH or Cs2CO3 gave the corresponding complexes [M(LH4)(H2O)n].m(H2O), M = K, Rb or Cs. Crystallisation of the products under varying conditions yielded differing hydrates and/or polymorphic phases.

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ACS Paragon Plus Environment

Coordination Polymers of Increasing Complexity Derived from Alkali

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