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Acta Cryst. (2009). E65, m1428-m1429    [ doi:10.1107/S1600536809042858 ]

Diaquabis[1-hydroxy-2-(imidazol-3-ium-1-yl)-1,1'-ethylidenediphophonato-[kappa]2O,O']zinc(II)

E. Freire and D. R. Vega

Abstract top

In the title complex, [Zn(C5H9NO7P2)2(H2O)2], the zinc atom is coordinated by two bidentate zoledronate [zoledronate = (2-(1-imidazole)-1-hydroxy-1,1'-ethylidenediphophonate)] ligands and two water molecules. The coordination number is 6. There is one half-molecule in the asymmetric unit with the zinc atom located on a crystallographic inversion centre. The anion exists as a zwitterion with an overall charge of -1; the protonated nitrogen in the ring has a positive charge and the two phosphonates groups each have a single negative charge. There are two intramolecular O-H...O hydrogen bonds. The molecules are linked into a chain by intermolecular O-H...O hydrogen bonds. Adjacent chains are further linked by O-H...O hydrogen bonds involving the aqua ligands. An N-H...O interaction is also observed.

Comment top

The present work is part of a project directed to the preparation and characterization of coordination complexes obtained by the interaction among metals and organic molecules of relevant pharmacological interest like bisphosphonates. Bisphosphonate compounds, which are characterized by a P—C—P backbone, are analogues of naturally occurring pyrophosphates. As effective inhibitors of bone resoption, bisphosphonates are used in the treatment of various bone diseases and disorders of calcium metabolism, osteolityc tumor bone disease, non tumor induced hypercalcemia, Paget and osteoporosis (Fleisch, 2000; Ross et al., 2004; Smith, 2005; Ralston et al., 1989; Reid et al., 2005; Rauch et al., 2005 and Chesnut et al., 2004). The P—C—P base structure allows the bisphosphonates to bind to many metallic cations in particular divalent metal ions and as a result bisphosphonates may stick bone surfaces in vivo (Fleisch et al., 1968). Third generation bisphosphonates, like zoledronate, are characterized by having a cyclic side chain and belong to the nitrogen containing bisphosphonate group which are the most effective for medical treatment (Green et al., 1994). A large number of metal derivatives of other bisphosphonates, like Etidronate and Pamidronate are known where the bisphosphonate ligand displays a variety of coordination modes (Ferńandez, 2002; Li et al., 2008; Chen et al., 2008; Uchtman, 1972). In contrast, few metal derivatives of Zoledronic acid have been reported in CSD (Allen, 2002). The present compound is isostructural with two Co and Ni complexes (Cao et al., 2007).

So, we present herein the crystal structure of a Zinc-Zoledronate complex: monozinc dizoledronate dihydrate, (I), Zn.2(P2O7N2C5H9).2(H2O). We also synthesized a pentacoordinated complex of zinc (II), (Freire & Vega, 2009). The zoledronate anion exists as a zwitterion with an overall charge of -1; the protonated nitrogen in the ring has a positive charge and the two phosphonates groups each have a single negative charge.

The ZnO6 coordination sphere (Fig. 1) is defined by O11, O21, O1W and and their (1 - x, 1 - y, 1 - z) counterparts generated by the inversion center on Zn1. Zn – O distances range from 2.041 (4) to 2.095 (4) Å, and octahedral angles between 86.2 (2) and 92.7 (2)°. The O11—Zn1—O21 zoledronate bite angle is 90.6 (2)° and the angle between two oxygen atoms of different zoledronates is O11A Zn1 O21 89.4 (2)°.

Each phosphonate has one protonated O atom, the extra electronic charge being shared by the remaining two non protonated O atoms. This fact define two distinct types of P—O bonds, as shown by the mean value in the following values of bond distances and angles: P—OH 1,572 (8), P - O 1.503 (5) Å, O—P—OH 109.45 (13), O—P—O 115.60 (14) °, this measure is in agreement with the results found for related molecules (Coiro et al., 1989; Vega et al., 1996; Vega et al., 1998). The phosphonates groups have slighty "staggered" conformations sight in the P1···P2 direction. When this staggering is observed the non bonded torsion angle O13—P1··· P2—O23 is 4.1 °. The imidazol ring is plane, maximum deviation from the L.S. mean plane is 0.0058 Å for C5. The ring and C2 are not coplanar, the angle determined between the plane of the ring and the bond N1—C2 is 3.2 ° and C2 is 0.0861 Å far from the plane of the ring. The torsion angle C1—C2—N1—C3 is of 104.1 (8) ° and it is possible to describe it like + Anti-Clinal (+ac).

In this compound there are two intramolecular hydrogen bonds O1W—H1WA···. O12 and the one generated by the center of symmetry (Fig. 1). These molecules form a chain by means of hydrogen bonds provided by O22—H22··· O23 (-x + 2,-y + 2,-z + 2) and O1—H1··· O23 (-x + 2,-y + 2,-z + 2) (Fig. 2). This chain joins other neighboring and similar chains by means of the hydrogen bonds O1W—H1WB··· O13 (x - 1, y, z), O12—H12··· O13 (-x + 2,-y + 2,-z + 1), and N2—H2··· O21 (-x + 2,-y + 1,-z + 2) (see Table 2), determining a three-dimensional net. In all this hydrogen-bonding network the presence of two homodromic rings (Bernstein et al., 1995) is observed: P2—O22—H22··· O23 (-x + 2,-y + 2,-z + 2) ···H1—O1—C1—P2 (R21(7)), P1—O12—H12··· O13—P1—O12—H12 (-x + 2,-y + 2,-z + 1)··· O13—P1 (R22(8)).

Related literature top

For general background to bisphosphonates, see: Fleisch et al. (1968); Green et al. (1994); Fleisch (2000); Ross et al. (2004); Smith (2005); Ralston et al. (1989); Reid et al. (2005); Rauch et al. (2005); Chesnut et al. (2004). For structures of transition metal (Ni, Co and Cu) complexes with the zoledronate anion, see: Cao et al. (2007, 2008). For metal complexes of other bisphosphonates (Etidronate and Pamidronate), see: Fernández et al. (2002); Li et al. (2008); Chen et al. (2008); Uchtman (1972). For a pentacoordinated zinc(II)–zoledronate complex, see: Freire & Vega (2009). For bond distances and angles in related structures, see: Coiro & Lamba (1989); Vega et al. (1996, 1998). For hydrogen-bond motifs, see: Bernstein et al. (1995).

Experimental top

Zoledronic Acid was obtained from Gador S. A. laboratory. The present compound was obtained as subproduct in a Zoledronate recrystallization process.

Refinement top

The H atoms attached to O were found in a difference Fourier map, further idealized (O—H: 0.82 Å - 0.90 Å) and finally allowed to ride. Those attached to C and N were placed at calculated positions (C—H: 0.93 Å; C—H2: 0.97 Å; N—H2: 0.90 Å) and allowed to ride. Displacement factors were taken as U(H)isot = x.U(host), x: 1.2 (C—H); 1.5 (C—H2, N—H2, O—H).

Computing details top

Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1988); cell refinement: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1988); data reduction: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1988); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. : Molecular view of (I), showing the labeling scheme used. Hydrogen bonding is shown in dashed lines.
[Figure 2] Fig. 2. : View of the intra chain H-bonds in (I).
Diaquabis[1-hydroxy-2-(imidazol-3-ium-1-yl)-1,1'-ethylidenediphophonato- κ2O,O']zinc(II) top
Crystal data top
[Zn(C5H9N2O7P2)2(H2O)2]Z = 1
Mr = 643.57F(000) = 328
Triclinic, P1Dx = 1.999 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.457 (1) ÅCell parameters from 42 reflections
b = 8.408 (2) Åθ = 8–18°
c = 9.843 (2) ŵ = 1.54 mm−1
α = 105.06 (3)°T = 293 K
β = 112.23 (3)°Prism, colorless
γ = 97.05 (3)°0.18 × 0.11 × 0.05 mm
V = 534.5 (2) Å3
Data collection top
Rigaku AFC6 Difractometer
diffractometer		1236 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.050
graphiteθmax = 25.5°, θmin = 2.4°
ω/2θ scansh = −9→9
Absorption correction: ψ scan
(North et al., 1968)		k = −1→10
Tmin = 0.82, Tmax = 0.92l = −11→11
2426 measured reflections3 standard reflections every 150 reflections
1990 independent reflections intensity decay: <3%
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.052Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.152H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0781P)2]
where P = (Fo2 + 2Fc2)/3
1990 reflections(Δ/σ)max < 0.001
160 parametersΔρmax = 0.84 e Å−3
0 restraintsΔρmin = −0.94 e Å−3
Crystal data top
[Zn(C5H9N2O7P2)2(H2O)2]γ = 97.05 (3)°
Mr = 643.57V = 534.5 (2) Å3
Triclinic, P1Z = 1
a = 7.457 (1) ÅMo Kα radiation
b = 8.408 (2) ŵ = 1.54 mm−1
c = 9.843 (2) ÅT = 293 K
α = 105.06 (3)°0.18 × 0.11 × 0.05 mm
β = 112.23 (3)°
Data collection top
Rigaku AFC6 Difractometer
diffractometer		1236 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)		Rint = 0.050
Tmin = 0.82, Tmax = 0.92θmax = 25.5°
2426 measured reflections3 standard reflections every 150 reflections
1990 independent reflections intensity decay: <3%
Refinement top
R[F2 > 2σ(F2)] = 0.052H-atom parameters constrained
wR(F2) = 0.152Δρmax = 0.84 e Å−3
S = 1.04Δρmin = −0.94 e Å−3
1990 reflectionsAbsolute structure: ?
160 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Zn10.50000.50000.50000.0266 (4)
P10.8731 (2)0.77240 (19)0.52403 (17)0.0172 (4)
P20.8422 (2)0.77671 (19)0.82873 (17)0.0186 (4)
O110.7109 (6)0.6106 (5)0.4453 (4)0.0211 (9)
O120.7749 (6)0.9268 (5)0.5228 (5)0.0242 (10)
H120.84031.01490.52640.036*
O131.0242 (6)0.7849 (5)0.4574 (5)0.0217 (9)
O210.6875 (6)0.6116 (5)0.7361 (5)0.0253 (10)
O220.7342 (6)0.9253 (5)0.8129 (5)0.0254 (10)
H220.80211.02160.86910.038*
O230.9654 (7)0.8002 (5)0.9969 (5)0.0249 (10)
O11.1578 (6)0.9545 (5)0.8097 (5)0.0261 (10)
H11.10191.03260.81400.039*
N11.2533 (8)0.6520 (6)0.8864 (6)0.0224 (11)
N21.3599 (9)0.5904 (8)1.0957 (7)0.0372 (15)
H21.36780.53881.16180.045*
C11.0088 (9)0.7937 (7)0.7310 (6)0.0183 (13)
C21.1243 (10)0.6535 (8)0.7302 (7)0.0271 (15)
H2A1.02880.54390.67190.032*
H2B1.20670.66800.67590.032*
C31.2149 (10)0.5438 (9)0.9533 (8)0.0315 (16)
H31.10520.45090.90840.038*
C51.4298 (10)0.7711 (8)0.9896 (8)0.0319 (16)
H51.49290.86110.97220.038*
C41.4926 (12)0.7303 (10)1.1212 (8)0.042 (2)
H41.60680.78851.21270.051*
O1W0.3851 (6)0.7142 (6)0.4904 (6)0.0349 (12)
H1WA0.46450.80740.52730.052*
H1WB0.27030.72450.46680.052*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Zn10.0278 (7)0.0212 (6)0.0247 (6)0.0057 (5)0.0079 (5)0.0030 (5)
P10.0177 (8)0.0145 (8)0.0173 (8)0.0054 (6)0.0056 (7)0.0043 (6)
P20.0194 (8)0.0157 (8)0.0150 (8)0.0029 (7)0.0048 (7)0.0008 (6)
O110.020 (2)0.024 (2)0.014 (2)0.0010 (19)0.0059 (18)0.0015 (17)
O120.026 (2)0.020 (2)0.035 (3)0.0118 (19)0.016 (2)0.015 (2)
O130.022 (2)0.019 (2)0.025 (2)0.0082 (18)0.0116 (19)0.0051 (18)
O210.029 (3)0.021 (2)0.017 (2)0.000 (2)0.006 (2)0.0027 (18)
O220.028 (2)0.020 (2)0.024 (2)0.0100 (19)0.009 (2)0.0019 (19)
O230.035 (3)0.021 (2)0.015 (2)0.005 (2)0.007 (2)0.0037 (18)
O10.021 (2)0.018 (2)0.030 (2)0.0008 (19)0.007 (2)0.0003 (19)
N10.023 (3)0.022 (3)0.021 (3)0.010 (2)0.006 (2)0.008 (2)
N20.052 (4)0.039 (4)0.032 (3)0.018 (3)0.020 (3)0.025 (3)
C10.023 (3)0.017 (3)0.017 (3)0.010 (3)0.007 (3)0.007 (2)
C20.029 (4)0.023 (3)0.019 (3)0.010 (3)0.002 (3)0.004 (3)
C30.027 (4)0.031 (4)0.044 (4)0.013 (3)0.016 (3)0.022 (3)
C50.027 (4)0.026 (4)0.037 (4)0.008 (3)0.007 (3)0.012 (3)
C40.048 (5)0.042 (5)0.025 (4)0.020 (4)0.000 (3)0.013 (3)
O1W0.018 (2)0.022 (2)0.059 (3)0.007 (2)0.013 (2)0.011 (2)
Geometric parameters (Å, °) top
Zn1—O11i2.042 (4)O1—H10.8201
Zn1—O112.042 (4)N1—C31.317 (8)
Zn1—O212.079 (4)N1—C51.379 (8)
Zn1—O21i2.079 (4)N1—C21.478 (7)
Zn1—O1Wi2.096 (4)N2—C31.323 (9)
Zn1—O1W2.096 (4)N2—C41.341 (9)
P1—O111.501 (4)N2—H20.8600
P1—O131.509 (4)C1—C21.543 (8)
P1—O121.567 (4)C2—H2A0.9700
P1—C11.847 (6)C2—H2B0.9700
P2—O211.498 (4)C3—H30.9300
P2—O231.502 (4)C5—C41.352 (9)
P2—O221.578 (4)C5—H50.9300
P2—C11.850 (6)C4—H40.9300
O12—H120.8200O1W—H1WA0.8200
O22—H220.8200O1W—H1WB0.8200
O1—C11.448 (7)
O11i—Zn1—O11180.0C1—O1—H1109.4
O11i—Zn1—O2189.35 (16)C3—N1—C5108.8 (6)
O11—Zn1—O2190.65 (16)C3—N1—C2126.2 (6)
O11i—Zn1—O21i90.65 (16)C5—N1—C2125.0 (5)
O11—Zn1—O21i89.35 (16)C3—N2—C4109.7 (6)
O21—Zn1—O21i180.0C3—N2—H2125.1
O11i—Zn1—O1Wi86.18 (18)C4—N2—H2125.1
O11—Zn1—O1Wi93.82 (18)O1—C1—C2106.5 (5)
O21—Zn1—O1Wi87.37 (18)O1—C1—P1108.5 (4)
O21i—Zn1—O1Wi92.63 (18)C2—C1—P1105.0 (4)
O11i—Zn1—O1W93.82 (18)O1—C1—P2110.8 (4)
O11—Zn1—O1W86.18 (18)C2—C1—P2112.6 (4)
O21—Zn1—O1W92.63 (18)P1—C1—P2113.1 (3)
O21i—Zn1—O1W87.37 (18)N1—C2—C1114.5 (5)
O1Wi—Zn1—O1W180.000 (1)N1—C2—H2A108.6
O11—P1—O13115.5 (2)C1—C2—H2A108.6
O11—P1—O12108.9 (2)N1—C2—H2B108.6
O13—P1—O12109.9 (2)C1—C2—H2B108.6
O11—P1—C1108.2 (3)H2A—C2—H2B107.6
O13—P1—C1107.9 (3)N1—C3—N2108.0 (6)
O12—P1—C1106.0 (3)N1—C3—H3126.0
O21—P2—O23115.7 (2)N2—C3—H3126.0
O21—P2—O22108.0 (3)C4—C5—N1106.1 (6)
O23—P2—O22110.9 (2)C4—C5—H5127.0
O21—P2—C1107.4 (3)N1—C5—H5127.0
O23—P2—C1109.4 (3)N2—C4—C5107.4 (6)
O22—P2—C1104.9 (3)N2—C4—H4126.3
P1—O11—Zn1134.2 (2)C5—C4—H4126.3
P1—O12—H12117.6Zn1—O1W—H1WA118.1
P2—O21—Zn1132.6 (3)Zn1—O1W—H1WB130.4
P2—O22—H22116.2H1WA—O1W—H1WB110.8
O13—P1—O11—Zn1167.0 (3)O12—P1—C1—P263.4 (3)
O12—P1—O11—Zn1−68.8 (4)O21—P2—C1—O1177.3 (4)
C1—P1—O11—Zn146.0 (4)O23—P2—C1—O1−56.4 (4)
O21—Zn1—O11—P1−30.0 (4)O22—P2—C1—O162.6 (4)
O21i—Zn1—O11—P1150.0 (4)O21—P2—C1—C2−63.6 (5)
O1Wi—Zn1—O11—P1−117.4 (4)O23—P2—C1—C262.7 (5)
O1W—Zn1—O11—P162.6 (4)O22—P2—C1—C2−178.3 (4)
O23—P2—O21—Zn1−172.3 (3)O21—P2—C1—P155.2 (4)
O22—P2—O21—Zn162.8 (4)O23—P2—C1—P1−178.5 (3)
C1—P2—O21—Zn1−49.8 (4)O22—P2—C1—P1−59.5 (3)
O11i—Zn1—O21—P2−147.8 (4)C3—N1—C2—C1104.1 (7)
O11—Zn1—O21—P232.2 (4)C5—N1—C2—C1−72.1 (8)
O1Wi—Zn1—O21—P2126.0 (4)O1—C1—C2—N162.2 (6)
O1W—Zn1—O21—P2−54.0 (4)P1—C1—C2—N1177.1 (4)
O11—P1—C1—O1−176.6 (3)P2—C1—C2—N1−59.4 (6)
O13—P1—C1—O157.8 (4)C5—N1—C3—N20.4 (8)
O12—P1—C1—O1−59.9 (4)C2—N1—C3—N2−176.3 (6)
O11—P1—C1—C269.9 (4)C4—N2—C3—N10.3 (8)
O13—P1—C1—C2−55.8 (4)C3—N1—C5—C4−0.9 (8)
O12—P1—C1—C2−173.4 (4)C2—N1—C5—C4175.8 (6)
O11—P1—C1—P2−53.3 (4)C3—N2—C4—C5−0.9 (9)
O13—P1—C1—P2−178.9 (3)N1—C5—C4—N21.1 (8)
Symmetry codes: (i) −x+1, −y+1, −z+1.
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O22—H22···O23ii0.821.902.676 (6)159
O12—H12···O13iii0.821.792.607 (6)176
O1—H1···O23ii0.822.282.910 (6)134
O1W—H1WA···O120.822.433.078 (6)137
O1W—H1WB···O13iv0.821.942.745 (6)167
N2—H2···O21v0.861.902.740 (7)164
Symmetry codes: (ii) −x+2, −y+2, −z+2; (iii) −x+2, −y+2, −z+1; (iv) x−1, y, z; (v) −x+2, −y+1, −z+2.
Table 1
Selected geometric parameters (Å, °) top
Zn1—O112.042 (4)Zn1—O1W2.096 (4)
Zn1—O212.079 (4)
O11—Zn1—O2190.65 (16)O21—Zn1—O1W92.63 (18)
O11—Zn1—O1W86.18 (18)
Table 2
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O22—H22···O23i0.821.902.676 (6)159
O12—H12···O13ii0.821.792.607 (6)176
O1—H1···O23i0.822.282.910 (6)134
O1W—H1WA···O120.822.433.078 (6)137
O1W—H1WB···O13iii0.821.942.745 (6)167
N2—H2···O21iv0.861.902.740 (7)164
Symmetry codes: (i) −x+2, −y+2, −z+2; (ii) −x+2, −y+2, −z+1; (iii) x−1, y, z; (iv) −x+2, −y+1, −z+2.
Acknowledgements top

We acknowledge PICT 25409, the Spanish Research Council (CSIC) for providing us with a free-of-charge licence to use the CSD system (Allen, 2002) and Professor Judith Howard for the donation of a Rigaku AFC6S four-circle diffractometer. EF is a member of the research staff of Conicet. The authors are grateful to: aboratorios Gador for providing the zoledronic acid.

references
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