Two new Mg₃(II)-cluster-based coordination polymers: their synthesis, crystal structures and inhibiting activity on the human spinal tumor cells

Crystal structure description

Yellow prism crystals for 1 with the formula of [Mg₃(tatb)(MeOH)(DMA)](DMA)₂ could be obtained by a solvothermal reaction of H₃tatb and Mg(NO₃)₂·6H₂O in a mixed solvent of DMA and MeOH. It should be noted that the addition of HNO₃ could promote the crystallization of complex 1, whereas no crystalline products could be formed without the addition of HNO₃. An X-ray single structural determination demonstrates that 1 is located in the monoclinic crystal system, space group P2₁/n and reveals a 2D layered network structure. The building unit of 1 is formed by two independent Mg²⁺ ions (one with full occupancy and the other with half occupancy), one tatb³⁻ linker, one coordinated DMA and one coordinated MeOH molecule. As described in Figure 2A, six carboxylic O atoms from six different tatb³⁻ ligands form the [MgO6] tetrahedral coordination geometry of the Mg1 ion. Meanwhile, the coordination surrounding of Mg2 is shaped by four O atoms from three different tatb³⁻ ligands, with the leaving sites completed by two O atoms on the coordinated MeOH and DMA molecules. The observed Mg-O bond distances are in the range of 2.030(2)–2.185(2) Å, which are comparable with those observed in the Mg-based coordination polymers. The three Mg²⁺ ions are held together by the six carboxylic groups via the sys-bridging modes to afford the linear Mg₃ cluster-based secondary building unit with the Mg-Mg distance of 3.615 Å. In 1, each tatb³⁻ ligand connects with six Mg²⁺ ions by using three deprotonated carboxylate groups, with each showing a μ²-η₁: η₁, μ²-η₁: η₁ and μ²-η₂: η₁ bridging/chelating mode (Figure 2B). Each Mg₃ cluster is connected with six different tatb²⁻ ligands in the ab plane to afford the 2D layered structure, with the coordinated MeOH and DMA molecules pointing toward the outside of the plane (Figure 2C). These 2D layers are further stacked along the c axis to afford the porous 3D supermolecular network with two different types of 1D channels running along the b axis and the c axis (Figure 2D). The effective solvent accessible free volume is 44.8% within the consideration of the coordinated MeOH and DMA molecules, as calculated via the software PLATON. A 3,6-connected kgd-type topology could be used to express the network of 1.

Figure 2:

The crystal structure for compound 1.

(A) The Mg3 cluster in 1 (symmetric code: A 1−x, 1−y, −z); (B) the binding pattern of the tatb³⁻ ligand; (C) the 2D layered network of 1; (D) View for the 1D channels of the stacking supermolecular structure.

The solvothermal reaction of Mg(NO₃)₂·6H₂O with the H₂tatab ligand using a mixed solvent of DMA and water leads to the formation of compound 2. A structural determination via the X-ray single-crystal diffraction crystallography technique shows that the complex 2 is situated in the cubic crystal system, Pa3̅ space group with a=20.2869 Å. Its molecular building unit consists of one third tatab ligand, two Mg²⁺ ions (one with a third occupancy and the other with a sixth occupancy) and one coordinated water molecule. Figure 3A shows the coordination surrounds of the six-coordinated Mg₁ and Mg₂ ions with disordered octahedral [MgO6] geometries, which are shaped by six O atoms from six different carboxylic groups and three carboxylic O atoms with three coordinated water molecules, respectively. The O-Mg bond lengths range from 2.082(3) to 2.727(2) Å, which are comparable with the observed values in the Mg-base coordinated polymers. The three Mg²⁺ ions are held together by the six carboxylic groups via the sys-bridging modes to afford the linear Mg₃ cluster-based secondary building unit with the Mg-Mg distance of 3.34 Å. As for the tatab³⁻ ligand, it binds with six Mg²⁺ ions via the three carboxylic arms in a μ²-η₂ pattern (Figure 3B). Each Mg₃ cluster binds with the six tatab³⁻ ligands and each tatab³⁻ ligand connects with six different Mg₃ clusters. This generates a 3D framework with a large solvent accessible void of 44.7%, as calculated via the software PLATON (Figure 3C). The framework of 1 could be judged as a pyr/pyrite-type (3,6)-connected net with the point symbol of {6^12.8^3}{6^3}2 (Figure 3D).

Figure 3:

The crystal structure for compound 2.

(A) The Mg3 cluster in 2 (symmetric code: A 1−x, 2−y, 1−z); (B) the binding pattern of the tatab³⁻ ligand; (C) the 3D network of 2; (D) pyr/pyrite-type (3,6)-connected net for 2.

To check the purities of the as-synthesized samples, the room temperature PXRD patterns were collected to compare them with the simulated ones from the crystal data. As shown in Figure 4, the collected curves reveal a considerable match between the ones from the crystal data, thus showing the high phase purity of the as-prepared two complexes.

Figure 4:

The PXRD patterns for 1 and 2.

Anticancer activity

In order to explore the low cytotoxicity of complexes 1 and 2in vitro, oral epidermal cells (normal cells) were chosen to incubate with complexes 1 and 2 under different concentrations. As shown in Figure 5A, the cell viabilities all remained above 90% even at a concentration of 100 μg/mL of complexes 1 and 2. Thus, both complexes showed low cytotoxicity in the oral epidermal cells. The in vitro antitumor activities of the as-prepared two metal-organic complexes as well as the two organic ligands and Mg(NO₃)₂·6H₂O have been evaluated against the human spinal tumor cell lines U-266 via the standard MTT assay under different concentrations (0–100 μg/mL) for 24 h. As shown in Figure 5B, the cell viabilities are all above 90% even at the concentration of 80 μg/mL of the ligands and Mg(NO₃)₂·6H₂O, thus indicating that they are unable to kill the cancer cells. In comparison, both complexes show obvious cancer cell growth inhibition, with 44% and 55% U-266 cells killed, respectively, at the concentration of 80 μg/mL. Moreover, increasing the concentration of these two complexes could lead to more cancer cell death, indicating the anticancer activities of these two complexes are dose-dependent. Notably, the mixture of Mg(NO₃)₂ and the organic ligand in an equal molar ratio do not show obvious anticancer activity, revealing that the observed anticancer activity of compounds 1 and 2 could not be achieved by simply mixing the metal ions with the organic ligands (Figure 5C). These results further indicate that the anticancer activities of both complexes are better than their organic and inorganic compositions, and that the anticancer activity of both complexes comes from the coordination of the metal ions with the organic ligands. In addition, the complex 2 shows a better anticancer activity than complex 1, indicating that the N sites that are free have a positive effect on the anticancer activity. This finding is similar to a result reported in the literature (Liu et al., 1999). To gain a better insight on the anticancer activities of both complexes, the cytotoxicity of cisplatin against the title cancer cell has also been recorded. The results reveal that the complex 2 shows a comparable anticancer activity compared with that of cisplatin, thus suggesting its promising anticancer activity (Figure 5D).

Figure 5:

In vitro cell viabilities after incubation for 24 h with different complexes under different concentrations.

(A) Oral epidermal cell viability for 1 and 2; (B) the cancer cell viability for 1, 2, organic ligands and the Mg(NO₃)₂; (C) the cancer cell viability for the mixture of the Mg(NO₃)₂·6H₂O and the organic ligand; (D) a comparison of the cancer cell viability for 2 and cisplatin.

Instruments and chemicals

The Rigaku D/MAX 2500V diffractometer (Rigaku, Tokyo, Japan) was used to collect the Powder X-ray diffraction (PXRD) curves. An Oxford Xcalibur E diffractometer (Oxford, UK) was employed to collect the single crystal XRD data. The Perkin Elmer Model 240C instrument (PerkinElmer, MA, USA) was employed to obtain the element analyses (C, H and N) results. All the chemicals in this study were commercially available and purchased from the Bai Ling Wei Company (Beijing, China).

Preparation and characterization of [Mg₃(tatb)(MeOH)₂(DMA)₂](DMA)₂ (1) and [Mg₃(tatab)₂(H₂O)₆](DMA)₂ (2)

Into a 50 mL beaker, H₃tatb (0.11 mmol, 48 mg) and Mg(NO₃)₂·6H₂O (0.2 mmol, 52 mg) were added, followed by DMA (4 mL) and MeOH (2 mL) with vigorous stirring for 1 h at room temperature. After the addition of 1 drop of HNO₃ (1 m, aq), the solution was transferred into a vial, kept at 105°C for 72 h and then cooled to room temperature with a cooling rate of 5°C/h. The light yellow prism crystals of 1 were obtained after cooling the reaction system to room temperature, washed with MeOH and air-dried. Yield: 36.4% based on the H₃tatb linker. Elemental analysis Calcd (%) for 1 (C₆₁H₅₅Mg₃N₉O₁₆): H, 4.46; C, 58.94; N, 10.14. Found: H, 4.59; C, 59.02; N, 10.36. The compound 1 could not be dissolved in water and DMF but can be well dispersed in the DMSO solution.

Into a 50 mL beaker, H₃tatab (0.11 mmol, 53 mg) and Mg(NO₃)₂·6H₂O (0.2 mmol, 52 mg) was added, followed by DMA (4 mL) and distilled water (2 mL) with vigorous stirring for 1 h at room temperature. After the addition of 1 drop of HNO₃ (1 m, aq), the solution was transferred into a vial, kept at 80°C for 72 h and then cooled to room temperature with a cooling rate of 5°C/h. The light yellow cubic crystals of 2 were obtained after cooling the reaction system to room temperature, washed with water and air-dried. Yield: 39.6% based on the H₃tatab linker. Elemental analysis Calcd (%) for 2 (C₅₆H₆₀Mg₃N₁₄O₂₀): H, 4.57; C, 50.88; N, 14.83. Found: H, 4.29; C, 51.02; N, 14.36. The compound 2 could not be dissolved in water and DMF but can be well dispersed in the DMSO solution.

Structural determination via X-ray diffraction

An Oxford Xcalibur E diffractometer with graphite monochromatized Mo radiation (0.71073 Å) was used to collect the reflection data of 1 and 2 at 298 K. The direct method in the XS program was used to obtain the initial structural modes, and the least-squares method in XL program (Sheldrick, 2015) was used to refine the structural models. All the H atoms were poisoned at their ideal locations and refined using the AFIX commands according to their C atoms attached. All the non-hydrogen atoms in the two structures were treated anistropically. Table 1 shows the crystal data and the structural refinements.

Antitumor activity

The antitumor activities of the as-prepared two metal-organic complexes (1 and 2) were studied on the human spinal tumor cell lines U-266 by using the MTT assay. In this work, the targeted cells were seeded in the Dulbecco’s Modified Eagle’s Medium (DMEM), which was supplemented with 10% fetal calf serum (FCS) and 1% penicillin/streptomycin (P/S, Boster), and then cultured in a humidified incubator overnight. The conditions of the incubator were set to 5% CO₂ atmosphere and 37°C. Subsequently, a 96-well plate was used to house the two complexes with various concentrations, respectively, and the incubation time was set to 24 h. Then 10 mL of MTT (3.0 mg/mL) solution was added to each well and then incubated for 4 h. Then, the supernatant was replaced with 150 μL of dimethyl sulfoxide (DMSO) for each well to dissolve the MTT formazan crystals. The absorbances at 490 nm were used to calculate the cell viability.