Ti₇-containing, tetrahedral 36-tungsto-4-arsenate(III) [Ti₆(TiO₆)(AsW₉O₃₃)₄]²⁰⁻

Abstract

We have prepared the Ti₇-containing, tetrahedral 36-tungsto-4-arsenate(III) [Ti₆(TiO₆)(AsW₉O₃₃)₄]²⁰⁻ (1) by a simple, one pot procedure. Polyanion 1 contains a novel Ti₇-core, comprising a central TiO₆ octahedron surrounded by six TiO₅ square-pyramids, and capped by four {As^IIIW₉} trilacunary fragments. The title polyanion is solution-stable, as shown by ¹⁸³W NMR and mass spectrometry, and exhibits interesting biological properties.

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Polyoxometalates (POMs) are a well-known class of discrete, molecular metal oxides comprising early transition metal ions in high oxidation states. POMs are of fundamental importance and technological relevance.¹ Lacunary heteropolytungstates can act as inorganic ligands, allowing for incorporation of p-, d-, and f-block metal ions, resulting in products with large structural and compositional versatility and a manifold of properties applicable to catalysis, magnetism, medicine, and materials science.²

The area of Ti⁴⁺-containing POMs is well-established nowadays, and many compounds have been isolated. The ionic radius of Ti⁴⁺ (0.75 Å) is very similar to that of W⁶⁺ (0.74 Å), and hence Ti⁴⁺ fits well into the lacunary site of Keggin or Wells–Dawson type POMs, usually adopting octahedral coordination geometry. In terms of Keggin-derivatives, much progress has been made for mono-, di- and tri-Ti⁴⁺-substituted species,³ ranging from monomers to oligomers, comprising Ti–O–Ti′ bonds between neighbouring Keggin units, such as dimers, trimers, as well as tetramers. Besides, some work has also been carried out on the Ti⁴⁺-containing Keggin-type heteropolytungstates with diverse host/guest features.⁴

A milestone in recent years was the discovery of the di-Ti⁴⁺-containing [Ti₂(OH)₂As₂W₁₉O₆₇(H₂O)]⁸⁻, exhibiting rare five-coordinated Ti⁴⁺ ions.⁵ The two square-pyramidal TiO₄(OH) groups are apparently vital for the unique catalytic properties of this polyanion.⁶

Herein, we report on the synthesis and structure of the novel Ti₇-containing, tetrahedral 36-tungsto-4-arsenate(III) [Ti₆(TiO₆)(AsW₉O₃₃)₄]²⁰⁻ (1, see Fig. 1).

Fig. 1 (a) and (b) Combined polyhedral/ball-and-stick representations of polyanion 1. (c) Ball-and-stick representation of the Ti₇ core in 1. (d) Topological skeleton representation of 1, reflecting the high symmetry as shown by a Ti₆ octahedron and an As₄ tetrahedron. Colour code: WO₆ octahedra (red), TiO₅ square-pyramids and TiO₆ octahedron (light blue), and for the balls: W (black), Ti (light blue), As (yellow), O (red).

Polyanion 1 was prepared as the hydrated sodium salt Na₂₀[Ti₆(TiO₆)(AsW₉O₃₃)₄]·63H₂O (Na-1), by reaction of TiOSO₄ and Na₉[B-α-AsW₉O₃₃]·27H₂O⁷ in NaOAc buffer solution (1 M, pH 4.6) at room temperature (yield 0.105 g, 10%). However, the crystals of Na-1 were not suitable for single crystal X-ray analysis. Therefore, we also isolated the hydrated, mixed sodium–cesium salt Na_17.5Cs_2.5[Ti₆(TiO₆)(AsW₉O₃₃)₄]·72H₂O·2NaCH₃COO (NaCs-1, yield 0.030 g, 3%), which was suitable for X-ray analysis (see Scheme S1 and ESI† for synthetic details)‡. As expected, the FTIR spectra of Na-1 and NaCs-1 are virtually identical in the POM fingerprint region 400–1000 cm⁻¹, indicating the presence of the same polyanion in both cases (see Fig. S1†). Elemental analysis on Na-1 and NaCs-1 suggested 63 vs. 72 water molecules of hydration, respectively (see ESI† for details). Furthermore, for NaCs-1 the presence of two equivalents of cocrystallized sodium acetate was identified, supported by IR (extra peaks at 1559 and 1411 cm⁻¹) and ¹³C NMR (two signals at 181.5 and 23.3 ppm, respectively, see also Fig. S4†). Bond valence sum (BVS) calculations confirmed that 1 is not protonated (Table S3†).⁸ In the present work, all bulk studies were performed on Na-1, due to the higher yield as compared to NaCs-1.

Single crystal X-ray analysis revealed that polyanion 1 contains a novel Ti₇-core, comprising a central TiO₆ octahedron surrounded by six TiO₅ square-pyramids, capped by four {As^IIIW₉} trilacunary fragments, leading to an assembly with T_d point-group symmetry (see Fig. 1a and b). The structure of 1 somewhat resembles the tetra-Keggin polyanion [Nb₄O₆(Nb₃SiW₉O₄₀)₄]²⁰⁻,⁹ as well as the Wells–Dawson based tetramer {(Ti₃P₂W₁₅)₄},¹⁰ which also has an overall tetrahedral shape. However, in 1 the lone pair of electrons on the As hetero atom in {B-α-AsW₉O₃₃} does not allow formation of a tri-Ti⁴⁺-substituted Keggin unit. As a result, the four {B-α-AsW₉O₃₃} units in 1 are linked via six square-pyramidally coordinated TiO₅ groups, with the apical oxo ligand O12T (d_Ti2–O12T = 1.75(2) Å) pointing at the centre of the polyanion, and bridging to the central, unique Ti⁴⁺ ion, which is hence octahedrally coordinated. As a result, 1 contains Ti⁴⁺ ions in two different coordination geometries, square-pyramidal and octahedral. In the other known polyanions containing square-pyramidal TiO₅ groups the apical oxygen is terminal.^5,11 The central Ti₇ core in 1 has an octahedral shape, with ideal bond angles of 90° and 180°, respectively, around the central Ti1 (see Fig. 1c). For structural clarity, we can simplify the four {B-α-AsW₉O₃₃} groups in 1 as the four vertices of a regular tetrahedron, with the six five-coordinated Ti⁴⁺ ions being located at the edge centers, thus forming an ideal octahedron, surrounding the central, unique Ti⁴⁺ ion (see Fig. 1d).

As Na-1 is well-soluble in water, we also performed ¹⁸³W NMR in D₂O/H₂O. The resulting spectrum (see Fig. 2) consists of two singlets at −129.3 and −138.1 ppm, respectively, with relative intensities of 1 : 2, in complete agreement with the solid state structure of 1, indicating that the tetrahedral assembly is maintained in solution.

Fig. 2 Room temperature ¹⁸³W NMR spectrum of Na-1 in D₂O/H₂O. The signal at −129.3 ppm originates from the 12 capping tungsten atoms (green, WO₆ octahedra), whereas the signal at −138.1 ppm corresponds to the 24 equatorial tungsten atoms (blue, WO₆ octahedra).

These observations are further supported by UV-vis spectroscopy. The UV-vis spectrum of Na-1 dissolved in water displays an absorption maximum at 256 nm (see Fig. S5a†), and we demonstrated that polyanion 1 is stable in water and LiOAc solution at pH 4–7 for at least 24 hours (see Fig. S5b–d†).

Electrospray-ionization mass spectrometry (ESI-MS) has proven to be a valuable analytical technique, allowing extraction of structural information of POMs.¹² The major peaks observed in the ESI-MS spectrum of Na-1 dissolved in water showed an ensemble of adducts derived from [Na_xH_yTi₇As₄W₃₆O₁₃₈(H₂O)_z]^{(20−x−y)−} with different numbers of sodium ions, protons and water molecules associated with polyanion 1 (see Fig. 3). For instance, the most intense peaks centred at m/z 1375.17 and 1608.02, respectively, can be assigned to the −7 charged [Na₂H₁₁Ti₇As₄W₃₆O₁₃₈(H₂O)₆]⁷⁻ and the −6 charged [Na₃H₁₁Ti₇As₄W₃₆O₁₃₈(H₂O)₆]⁶⁻ adducts. These results indicate that 1 is also stable in the gas phase, as expected based on our solution ¹⁸³W NMR and UV-vis studies.

Fig. 3 Negative ion mass spectrum of Na-1 in water showing a series of species derived from [Na_xH_yTi₇As₄W₃₆O₁₃₈(H₂O)_z]^{(20−x−y)−}.

We have also performed biological studies on 1. It has been shown previously that Ti⁴⁺-containing POMs can exhibit anticancer activities.¹³ We investigated the cytotoxicity of 1 in the epidermoid carcinoma cell line A431 (see Fig. 4). These in vitro studies indicated low cytotoxicity of 1 (EC₅₀ ∼ 2.5 mg mL⁻¹ after 24 hours), in agreement with other Ti⁴⁺-containing POMs.¹⁴ However, there was neither cell growth nor death detectable. A reason for this could be poor cellular accumulation of 1. Hence, it is likely that the main mechanism of the pharmacological effect of 1 is based on inhibiting the binding of native ligands to membrane receptors such as growth factors. Such possible interference in cell signaling and proliferation can be beneficial in cancer treatment.

Fig. 4 LDH (top) and XTT (bottom) assays of A431 cells incubated with 1 for different incubation times. Activity is expressed in percent (compared to control) and is related to the appropriate protein content. Data are means of 6 replicates for each POM concentration. SD ± 15%.

In summary, we have prepared [Ti₆(TiO₆)(AsW₉O₃₃)₄]²⁰⁻ (1), comprising a Ti₇ core composed of five- and six-coordinated Ti⁴⁺ ions, surrounded by four {B-α-AsW₉O₃₃} capping units, resulting in a tetrahedral assembly. The novel polyanion 1 was characterized by various analytical methods including single crystal X-ray diffraction, FTIR, UV-vis, TGA, NMR and ESI-MS. In vitro studies revealed low cytotoxicity in a model cancer cell line, but cell proliferation was inhibited. Currently we investigate these and other properties in more detail.

U. K. thanks the German Research Council (DFG), Jacobs University, and CMST COST Action CM1203 (PoCheMoN) for support. K.-Y. W. thanks the China Scholarship Council (CSC) and A. H. thanks the German Academic Exchange Council (DAAD) for a doctoral fellowship, allowing for Ph.D. studies at Jacobs University. J. C. thanks the National Natural Science Foundation of China (21371025), the 111 Project (B07012) and the Fundamental Research Grant (20121942006) by the Beijing Institute of Technology. K. V. thanks the Helmholtz Virtual Institute NanoTracking (Agreement Number VH-VI-421) for generous financial support. We thank Ms Annika Moje (Jacobs University) for performing the C elemental analysis.

Notes and references

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Footnotes

† Electronic supplementary information (ESI) available: Synthetic details, XRD data, selected bond lengths and angles, FTIR, TGA, ¹³C NMR, UV-vis, bond valence sum calculations, and toxicity test results. See DOI: 10.1039/c4dt02494j

‡ Crystallographic data for NaCs-1: C₄H₁₅₀As₄Cs_2.5Na_19.5O₂₁₄Ti₇W₃₆, λ = 0.71073 Å, M = 11657.39, cubic, space group Fd3̄m, a = 38.955(2) Å, V = 59114(9) ų, Z = 8, T = 100 K, D_calc = 2.620 g cm⁻³, μ = 14.985 mm⁻¹, 199 037 total reflections, 2403 unique [R_int = 0.2058], final R₁ = 0.0482, wR₂ = 0.1217 [I > 2σ(I)]. CSD number: 427928.

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