Syntheses, crystal structure, thermal behavior, and anti-tumor activity of three ternary metal complexes with 2-chloro-5-nitrobenzoic acid and heterocyclic compounds
-
Zhongyu Zhang
,
Meng Chen
Abstract
Three complexes, namely complex (1), complex (2), and complex (3), were synthesized and characterized by X-ray diffraction, thermogravimetric study, and elemental study. Complex (1) comprises discrete binuclear clusters, where two oxygen atoms of 2-chloro-5-nitrobenzoic acid bridge the two copper atoms. Complex (2) is a six-coordination structure consisting of four nitrogen atoms and two oxygen atoms in 2-chloro-5-nitrobenzoic acid and 1,10-phenanthroline to furnish a twisted octahedron. Complex (3) is a six-coordination structure consisting of four oxygen atoms and two nitrogen atoms from the 2-chloro-5-nitrobenzoic acid, methanol, and 2,2′-dipyridyl to furnish a distorted octahedral geometry. Metal complexes’ anti-tumor activity was also investigated by the MTT assay. Of the complexes tested, complex (1) could induce apoptosis in these A549 lung cancer and Caco-2 colon adenocarcinoma cells and complex (2) could induce apoptosis in Caco-2 colon adenocarcinoma cells. CCDC for complex (1) was 1543354, CCDC for complex (2) was 1546991, and CCDC for complex (3) was 1543417.
1 Introduction
The treatment of cancer has long been a global problem. For years, metallic drugs have been applied clinically. For instance, cisplatin, a platinum compound, is employed in chemotherapy for various cancers [1,2,3]. However, severe side effects, such as ototoxicity, nephrotoxicity, or electrolyte disorders, occur when cisplatin-based chemotherapy is used [4,5]. Therefore, many researchers are trying to design novel anticancer drugs based on potential metals to improve clinical effectiveness, tackle resistance, and reduce toxicity [6]. Heterocyclic compounds play an important role in many biochemical processes and are widespread in nature [7]. These compounds are notable for several reasons, the most important of which is their biological activities. Besides, numerous drugs are heterocyclic compounds [8]. 1,10-Phenanthroline, 2,2′-dipyridyl, and their substituted derivatives interfere with the functions of many biological systems [9,10]. When the N-chelate base without metal is found with the biological activity, it is generally considered to be associated with the separation of trace metals, and the resulting metal complexes are active species. Interests in benzoic acid arise from its biological importance and chemical properties. Benzoic acids show considerable important biological activity (e.g., antibacterial, antifungal, antiviral, herbicide, anti-inflammatory, anti-tumor, and anticancer activities) [11,12]. 2-Chloro-5-nitrobenzoic acid can be combined with various metals (e.g., lead, copper, manganese, and nickel), and it exhibits excellent physical properties [13,14,15].
This study speculates that synthetic forms of Cu(ii), Ni(ii), and Mn(ii) with 2-chloro-5-nitro-benzoic acid and heterocyclic compounds may induce the apoptosis of cancer cells. To verify this hypothesis, three ternary metal complexes were fabricated in anhydrous solvent and their crystal structures were determined. These complexes were characterized and assessed, and their abilities to induce the apoptosis of A549 human lung cancer and Caco-2 human colon adenocarcinoma cells were compared. Among the complexes tested, complex (1) could induce apoptosis in the A549 lung cancer and Caco-2 colon adenocarcinoma cells; complex (2) could induce apoptosis in Caco-2 colon adenocarcinoma cells.
2 Results and discussion
2.1 Method of preparation
The binary metal complexes of 2-chloro-5-nitrobenzoic acid were synthesized by the direct synthesis method, and the second ligand was added to the solution of the aforementioned binary metal complex. The ternary metal complex was synthesized by the component exchange method. Single crystals of the ternary metal complex were obtained by the natural volatilization culture.
2.2 Description of crystal structure
The selected bond lengths and bond angles of complexes are listed in Tables 1 and 2 [16]. The normal chem draw structure of synthesized metal complexes is shown in Figure 1. Crystal structures of the three complexes are presented in Figures 2–4. Besides, packing diagrams of the three complexes are shown in Figures 5–7.
Selected bond lengths (Å) of the complexes obtained from experiment
| Complex (1) | Complex (2) | Complex (3) | |||
|---|---|---|---|---|---|
| Bond | Length/Å | Bond | Length/Å | Bond length | Length/Å |
| Cu1a–O3a | 1.977 (3) | Mn–O1 | 2.096 (2) | Ni–O3a | 2.130 (6) |
| Cu1a–O1a | 1.930 (3) | Mn1–O3 | 2.099 (3) | Ni–O3b | 2.130 (6) |
| Cu1a–N1a | 2.018 (4) | Mn1–N4 | 2.245 (3) | Ni–O1a | 2.031 (7) |
| Cu1a–N2a | 2.009 (4) | Mn1–N2 | 2.277 (3) | Ni–O1b | 2.031 (7) |
| Cu1a–O3b | 1.977 (3) | Mn1–N3 | 2.293 (3) | Ni–N2a | 2.060 (8) |
| Cu1b–O3a | 1.977 (3) | Mn1–N1 | 2.326 (3) | Ni–N2b | 2.060 (8) |
| Cu1b–O1b | 1.930 (3) | N1–C24 | 1.314 (5) | O3a–C13a | 1.428 (13) |
| Cu1b–N1b | 2.018 (4) | N1–C25 | 1.357 (5) | O3b–C13b | 1.428 (13) |
| Cu1b–N2b | 2.009 (4) | N2–C15 | 1.325 (5) | O1a–C1a | 1.235 (11) |
| Cu1b–O3b | 1.977 (3) | N2–C16 | 1.357 (5) | O1b–C1b | 1.235 (11) |
| C1b–O1b | 1.283 (6) | N3–C27 | 1.324 (5) | O2a–C1a | 1.258 (12) |
| C1a–O1a | 1.283 (6) | N3–C37 | 1.355 (4) | O2b–C1b | 1.258 (12) |
| C8a–O3a | 1.299 (6) | N4–C36 | 1.325 (5) | N2a–C8a | 1.325 (14) |
| C8b–O3b | 1.299 (6) | N4–C38 | 1.355 (4) | N2a–C12a | 1.337 (12) |
| C8b–O4b | 1.210 (6) | O3–C8 | 1.261 (4) | N2b–C8b | 1.325 (14) |
| C8a–O4a | 1.210 (6) | O1–C1 | 1.269 (4) | N2a–C12b | 1.337 (12) |
| C1a–O2a | 1.223 (6) | O4–C8 | 1.213 (4) | C1a–C2a | 1.510 (13) |
| C1b–O2b | 1.223 (6) | O2–C1 | 1.230 (4) | C1b–C2b | 1.510 (13) |
Selected bond angles (°) of the complexes obtained from experiment
| Complex (1) | Complex (2) | Complex (3) | |||
|---|---|---|---|---|---|
| Bond angle | Angles (°) | Bond angle | Angles (°) | Bond angle | Angles (°) |
| O3a–Cu1a–N1a | 93.17 (16) | O1–Mn1–O3 | 90.16 (10) | O1a–Ni–O1b | 93.7 (4) |
| O3a–Cu1a–N2a | 174.92 (14) | O1–Mn1–N4 | 91.11 (11) | O1b–Ni–O3b | 88.2 (3) |
| O1a–Cu1a–O3a | 90.20 (15) | O3–Mn1–N4 | 108.54 (11) | O1b–Ni–O3a | 87.4 (3) |
| O1a–Cu1a–N1a | 175.31 (15) | O1–Mn1–N2 | 102.06 (10) | O1a–Ni–O3b | 87.4 (3) |
| O1a–Cu1a–N2a | 94.66 (16) | O3–Mn1–N2 | 86.56 (11) | O1a–Ni–O3a | 88.2 (3) |
| N2a–Cu1a–N1a | 81.89 (17) | N4–Mn1–N2 | 160.08 (11) | O1a–Ni–N2a | 172.0 (3) |
| O1a–Cu1a–O3b | 95.494 (137) | O1–Mn1–N3 | 163.76 (11) | O1b–Ni–N2a | 93.5 (3) |
| O3a–Cu1a–O3b | 78.345 (131) | O3–Mn1–N3 | 93.90 (10) | O1a–Ni–N2b | 93.5 (3) |
| N1a–Cu1a–O3b | 88.402 (148) | N4–Mn1–N3 | 72.69 (10) | O1a–Ni–N2b | 172.0 (3) |
| N2a–Cu1a–O3b | 102.599 (145) | N2–Mn1–N3 | 93.89 (10) | O3a–Ni–O3b | 173.6 (4) |
| C8a–O3a–Cu1a | 115.3 (3) | O1–Mn1–N1 | 92.25 (10) | N2a–Ni–O3a | 95.4 (3) |
| C1a–O1a–Cu1a | 123.1 (3) | O3–Mn1–N1 | 158.34 (12) | N2a–Ni–O3b | 89.6 (3) |
| C25a–N1a–Cu1a | 112.7 (3) | N4–Mn1–N1 | 92.94 (12) | N2b–Ni–O3b | 95.4 (3) |
| C24a–N1a–Cu1a | 129.5 (3) | N2–Mn1–N1 | 71.89 (12) | N2b–Ni–O3a | 89.6 (3) |
| C24a–N1a–C25a | 117.8 (4) | N3–Mn1–N1 | 89.75 (9) | N2a–Ni–N2b | 79.4 (5) |
| C26a–N2a–Cu1a | 112.5 (3) | C8–O3–Mn1 | 134.4 (2) | C1b–O1b–Ni | 124.2 (7) |
| C15a–N2a–Cu1a | 129.8 (3) | C1–O1–Mn1 | 129.6 (2) | C13b–O3b–Ni | 120.4 (7) |
| O3b–Cu1b–N1b | 93.17 (16) | C24–N1–C25 | 117.9 (3) | C12b–N2b–Ni | 114.9 (7) |
| O3b–Cu1b–N2b | 174.92 (14) | C24–N1–Mn1 | 126.8 (3) | C8b–N2b–Ni | 124.8 (7) |
| O1b–Cu1b–O3b | 90.20 (15) | C25–N1–Mn1 | 115.3 (3) | C1a–O1a–Ni | 124.2 (7) |
| O1b–Cu1b–N1b | 175.31 (15) | C36–N4–C38 | 118.5 (3) | C13a–O3a–Ni | 120.4 (7) |
| O1b–Cu1b–N2b | 94.66 (16) | C36–N4–Mn1 | 125.0 (2) | C12a–N2a–Ni | 114.9 (7) |
| N2b–Cu1b–N1b | 81.89 (17) | C38–N4–Mn1 | 116.5 (2) | C8a–N2a–Ni | 124.8 (7) |
| O1b–Cu1b–O3a | 95.494 (137) | C27–N3–C37 | 118.2 (3) | C8a–N2a–C12a | 120.1 (9) |
| O3b–Cu1b–O3a | 78.345 (131) | C27–N3–Mn1 | 126.8 (3) | O5a–N1a–O4a | 123.8 (10) |
| N1b–Cu1b–O3a | 88.402 (148) | C37–N3–Mn1 | 115.0 (2) | O5a–N1a–C6a | 116.9 (10) |
| N2b–Cu1b–O3a | 102.599 (145) | C15–N2–C26 | 118.4 (3) | O4a–N1a–C6a | 119.3 (9) |
| C8b–O3b–Cu1b | 115.3 (3) | C15–N2–Mn1 | 124.8 (3) | C8b–N2b–C12b | 120.1 (9) |
| C1b–O1b–Cu1b | 123.1 (3) | C26–N2–Mn1 | 116.8 (2) | O5b–N1b–O4b | 123.8 (10) |
| C25b–N1b–Cu1b | 112.7 (3) | N4–C38–C33 | 122.1 (4) | O5b–N1b–C6b | 116.9 (10) |
| C24b–N1b–Cu1b | 129.5 (3) | N4–C38–C37 | 118.1 (3) | O4b–N1b–C6b | 119.3 (9) |
| C24b–N1b–C25b | 117.8 (4) | C33–C38–C37 | 119.8 (3) | O1a–C1a–O2a | 126.6 (9) |
| C26b–N2b–Cu1b | 112.5 (3) | C7–C2–C3 | 118.4 (4) | O1b–C1b–O2b | 126.6 (9) |
| C15b–N2b–Cu1b | 129.8 (3) | C7–C2–C1 | 118.2 (3) | O2a–C1a–C2a | 116.3 (8) |
Chemical structures of synthesized metal complexes.
The structure of complex (1) and the atom-numbering scheme.
The structure of complex (2) and the atom-numbering scheme.
The structure of complex (3) and the atom-numbering scheme.
Packing diagram of the unit cell of complex (1).
Packing diagram of the unit cell of complex (2).
Packing diagram of the unit cell of complex (3).
Figure 2 shows that complex (1) is a binuclear Cu(ii) complex. The copper atom is coordinated with three oxygen atoms and two nitrogen atoms from the 2-chloro-5-nitrobenzoic acid and 1,10-phenanthroline to form a twisted square cone configuration. The two Cu(ii) centers are bridged together by the two oxygen atoms from 2,2-chloro-5-nitrobenzoic acid molecules. The oxygen atom of the deprotonated COOH groups is bridged the two Cu(ii) centers directly. This bridge keeps together the two Cu(ii) centers forming complex (1). In the complex (1), the bond angles of O3a–Cu1a–N1a, O3a–Cu1a–N2a, O1a–Cu1a–O3a, O1a–Cu1a–N1a, O1a–Cu1a–N1a, O1a–Cu1a–O3b and N1a–Cu1a–O3b are 93.179(16)°, 174.92(14)°, 90.20(15)°, 175.31(15)°, 95.494(137)° and 88.402(148)°, respectively, the Cu(ii) is five coordinated by threeoxygen and two nitrogen atoms from the three 2-chloro-5-nitrobenzoic acid ligands, and 1,10-phenanthroline to furnish a distorted square-pyramidal geometry. Figure 5 shows that the molecules are connected in stretched chains parallel to axis a and axis c via short contact and intermolecular π–π interactions. The three-dimensional structure of complex (1) is constituted by van der Waals bonds [17,18].
Figure 3 shows that complex (2) is a neutral mononuclear complex. Complex (2) is a six-coordination structure consisting of two oxygen atoms and four nitrogen atoms in 2-chloro-5-nitrobenzoic acid and 1,10-phenanthroline to furnish a twisted octahedron. There are two five-element chelating rings (ring 1: Mn–N2–C26–C25–N1 ring 2: Mn–N3–C37–C38–N4). In the complex (2), the bond angles of N4–Mn1–N2, O1–Mn1–N3, and O3–Mn1–N1 are 160.08 (11)° 163.76 (11)°, 158.34 (12)° respectively. The Mn(ii) is six coordinated by two oxygen and four nitrogen atoms from the two 2-chloro-5-nitrobenzoic acid ligands and two 1,10-phenanthroline to furnish a distorted octahedron geometry. Figure 6 shows that the molecules are connected in stretched chains parallel to axis a and axis b by intermolecular π–π interactions and via van der Waals bonds. The three-dimensional structure of complex (2) is assembled by short contact [19,20].
Figure 4 shows that complex (3) is a neutral mononuclear complex as well. In complex (3), Ni(ii) locates in a distorted octahedral geometry coordinated with six-bond 2N atoms from 2,2′-dipyridyl, 2O atoms from methanol, and two carboxylate O atoms from 22-chloro-5-nitrobenzoic acid molecules. There is one five-membered chelate ring [ring 1: Ni–N2a–C12a–C12b–N2b]. In the complex (3), the bond angles of O1a–Ni–N2a, O1a–Ni–N2b, and O3a–Ni–O3b are 172.0 (3)°, 172.0 (3)°, 173.6 (4)° respectively. The Ni (ii) is six coordinated by four oxygen and two nitrogen atoms from the 2-chloro-5-nitrobenzoic acid ligands, methanol and 1,10-phenanthroline to furnish a distorted octahedron geometry. Figure 7 shows that the molecules are connected in stretched chains parallel to axis a and axis c by intermolecular π–π interactions and via van der Waals bonds. The three-dimensional structure of complex (3) is assembled by short contact [21].
2.3 Thermal studies
In the presence of N2, the thermal analysis of the complexes was conducted at a temperature from 25 to 1,000°C [22]. As shown in Figure 8, the TGA curve of complex (1) reveals that the mass decreases in two steps with the rise in temperature and the thermal stability of the compound can be up to 226°C. The TGA curve of complex (2) suggests that the mass decreases in two steps with the rise in temperature and the thermal stability of the compound can reach 270°C. The TGA curve of complex (3) reveals that the mass decreases in two steps with the rise in temperature and the thermal stability of the compound can be up to 120°C [23].
The TGA curve for the complexes.
2.4 Study on anti-tumor activity
Some important anti-tumor drugs (e.g., cisplatin) have a metal center. These drugs have been employed for years to treat all types of human cancers [24,25]. In a previous study, some Mn(ii) and Cu(ii) complexes that suppress the proliferation of cancer cells were reported [26,27]. Here, whether the three novel complexes (1), (2), and (3) can suppress the proliferative abilities was studied. A549 and Caco-2 cells were exposed to 5, 10, 20, 40, and 60 µM of each complex for 24 h, and then, they were analyzed by the MTT assay. Dimethyl sulfoxide (DMSO)-treated cells were classified as control group. The result is shown in Figure 9. For A549 cells, complexes (2) and (3) were found with similar growth-suppressive activity, leading to only 47.09, and 40.26% suppression at 60 µM, respectively. However, complex (1) showed 75.70% suppression at 20 µM after 24 h of treatment. And the IC50 of complex (1) is 8.82 µM. When Caco-2 cells were used, complexes (1) and (2) were found exhibiting a similar growth-suppressive activity, leading to 72.70 and 59.57% suppression at 20 µM. At 60 µM, however, complex (3) triggered less than 5.02% suppression. And the IC50 of complexes (1) and (2) is 0.00053 and 1.69 µM, respectively.
2,3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for Caco-2 cells (a) and A549 cells (b).
It has also been reported that some copper and cadmium complexes can inhibit proteasomes and induce apoptosis in cancer cells. Proteasome inhibition might be effective strategy in anticancer therapy due to the fact that the cancer cells are much more dependent on these processes as compared to normal cells, and proteasome inhibition leads to apoptosis selectively in cancer cells. We will further investigate the mechanism by which complex (1) acts as inhibitors of proteasome activity to induce apoptosis in tumor cells.
3 Conclusion
Three complexes, namely C52H28Cl4Cu2N8O16·2CH3OH (1), C38H22Cl2MnN6O8 (2), and C26H20Cl2N4NiO10 (3), were fabricated and characterized by X-ray diffraction, thermogravimetric study, and elemental study. For complex (1), the crystal crystallizes in triclinic, suggesting that it is a binuclear Cu(ii) complex. For complex (2), the crystal crystallizes in orthorhombic, revealing that it is a neutral mononuclear complex. For complex (3), the crystal crystallizes in monoclinic, suggesting that it is also a neutral mononuclear complex.
In the presence of N2, the thermal analysis of the complexes was conducted at a temperature from 25 to 1,000°C. Based on their curves, compounds (1), (2), and (3) have thermal stability up to 226, 270, and 120°C, respectively.
The anti-tumor activity of three metal complexes was studied. It was found that complex (1) can induce the proliferation of A549 cells and Caco-2 cells, and complex (2) can induce the proliferation of Caco-2 cells. The results suggest that metal complexes with 2-chloro-5-nitrobenzoic acid and heterocyclic compounds could be developed into new anticancer drugs.
4 Experimental
4.1 Materials and physical measurement
In the present study, all chemicals were applied without purification. 1,10-Phenanthroline, 2,2′-dipyridyl, and 2-chloro-5-nitrobenzoic acid were bought from Aladdin. DMSO and MTT were bought from Sigma-Aldrich. All metal complexes were prepared as 50 mM stocks in DMSO and deposited at 4°C. FBS was bought from Aleken Biologicals. RPMI-1640, DMEM/F12 (1:1), and penicillin/streptomycin were bought from Invitrogen.
The elemental analysis was conducted with a 2400 PerkinElmer analyzer [28]. The X-ray diffraction data were collected with a Bruker Smart CCD single-crystal X-ray diffractometer. Thermogravimetric measurements were performed using a METTLER TGA/DSC 3 + instrument. The programmed heating rate was 15°C min−1, the protection flow was N2, and the flow rate was 40 mL min−1. Infrared spectra were recorded as KBr pellets on a Nicolet 170SX spectrophotometer in the 4,000–400 cm−1 region. The UV spectra were performed on a Unicam UV2 spectrometer. Molar conductivity was measured with a WTWLF model 330 conductivity meters, using a prepared solution of the complex in DMSO.
4.2 Preparation of complexes
2.0 mmol of 2-chloro-5-nitrobenzoic acid was dissolved in 30.0 mL of anhydrous methanol. 1.0 mmol of metal salt [M(OAc)2·nH2O M = Cu(ii), Mn(ii), and Ni(ii)] was dissolved in 20.0 mL of anhydrous methanol. The solution of metal salt was dripped in the above 2-chloro-5-nitrobenzoic acid solution and then stirred at 55°C for 4 h. Subsequently, 1.0 mmol of the second ligand (1,10-phenanthroline or 2,2′-dipyridyl) was dissolved in 10.0 mL of anhydrous methanol. The solution of the second ligand was dripped in the above solution and stirred at 55°C for 4 h. Then, the experiment was stopped, cooled to ambient temperature, and filtered. The filtrate evaporates slowly at ambient temperature. Twenty days later, the crystals were formed.
4.2.1 Copper complex (1)
The overall yield of the reaction was 60%. Anal. calc. (%) for C52H28Cl4Cu2N8O16·2CH3OH (1): N, 8.278; H, 2.68; C, 47.90. Found (%): N, 8.26; H, 2.70; C, 47.95. UV: λ max (nm): 241, 306. IR data (KBr, cm−1): 3419.68, υ(–OH); 1500.36, υ as(–NO2); 1330.01, υ s(–NO2); 1628.36, υ as(COO–); 1437.68, υ s(COO–); 507.82, υ(Cu–N); 438.69, υ(Cu–O).
4.2.2 Manganese complex (2)
The overall yield of the reaction was 63%. Anal. calc. (%) for C38H22Cl2MnN6O8 (2): N, 10.29; H, 2.71; C, 55.90. Found (%): N, 10.27; H, 2.74; C, 55.93. UV: λ max (nm): 249, 302. IR data (KBr, cm−1): 1508.42, υ as(–NO2); 1321.17, υ s(–NO2); 1630.78, υ as(COO–); 1432.26, υ s(COO–); 510.32, υ(Mn–N); 440.13, υ(Mn–O).
4.2.3 Nickel complex (3)
The overall yield of the reaction was 70%. Anal. calc. (%) for C26H20Cl2N4NiO10 (3): N, 8.26; H, 2.97; C, 46.05. Found (%): N, 8.30; H, 2.99; C, 46.02. UV: λ max (nm): 250, 301. IR data (KBr, cm−1): 1510.37, υ as(–NO2); 1341.17, υ s(–NO2); 1631.69, υ as(COO–); 1440.58, υ s(COO–); 498.21, υ(Ni–N); 429.73, υ(Ni–O).
4.3 Crystallographic data collection and structure determination
Under a graphite monochromatic Mo-Kα radiation at 298(2) K, we collected X-ray diffraction data with a Bruker Smart CCD diffractometer. Data were collected in a series of ω–2θ scan. The crystal structure was solved directly by SHELXS-97 [29]. Non-hydrogen atoms were defined by Fourier synthesis. To refine the position parameters and thermal parameters to make them converge, the full matrix least square method was employed. Crystallographic information is listed in Table 3 [30].
Crystallographic data and structure refinement for complexes
| Identification code | Complex (1) | Complex (2) | Complex (3) |
|---|---|---|---|
| Nomenclature | (1,10-Phenanthroline-κ2 N,N′)-di (2-chloro-5-nitrobenzoat)-κ2O:O-bis (2-chloro-5-nitrobenzoic acid-κ1O) copper (ii)-methanol (2/2) | Bis (1,10-phenanthroline-κ2 N,N′)-bis (2-chloro-5-nitrobenzoat-κ1O) manganese(ii) | (2,2′-Dipyridyl-κ2 N,N′)-bis (2-chloro-5-nitrobenzoat -κ1O)-bis (methanol) nickel(ii) |
| Empirical formula | C54H36Cl4Cu2N8O18 | C38H22Cl2MnN6O8 | C26H20Cl2N4NiO10 |
| Formula weight | 1353.79 | 816.45 | 678.07 |
| Temperature/K | 296.15 | 296 (2) | 296.15 |
| Crystal system | Triclinic | Orthorhombic | Monoclinic |
| Space group | P1̄ | Pna21 | C2/c |
| a/Å | 9.905 (7) | 17.881 (3) | 6.617 (6) |
| b/Å | 11.685 (10) | 10.5472 (17) | 29.36 (3) |
| c/Å | 13.049 (11) | 18.318 (3) | 14.453 (12) |
| α/° | 64.996 (12) | 90 | 90 |
| β/° | 79.725 (15) | 90 | 101.514 (11) |
| γ/° | 84.949 (13) | 90 | 90 |
| Volume/Å3 | 1346.6 (19) | 3454.7 (10) | 2751 (4) |
| Z | 1 | 4 | 4 |
| ρ calc g/cm3 | 1.669 | 1.570 | 1.637 |
| μ/mm−1 | 1.074 | 0.603 | 0.965 |
| F (000) | 686.0 | 1660.0 | 1384.0 |
| Crystal size/mm3 | 0.27 × 0.25 × 0.23 | 0.24 × 0.23 × 0.21 | 0.23 × 0.2 × 0.18 |
| Radiation | MoKα (λ = 0.71073) | MoKα (λ = 0.71073) | MoKα (λ = 0.71073) |
| 2Θ range for data collection/° | 3.486–51.012 | 4.448–49.998 | 3.996–52.142 |
| Index ranges | −9 ≤ h ≤ 11, −14 ≤ k ≤ 13, −15 ≤ l ≤ 15 | −20 ≤ h ≤ 21, −10 ≤ k ≤ 12, −21 ≤ l ≤ 19 | −7 ≤ h ≤ 8, −25 ≤ k ≤ 36, −17 ≤ l ≤ 17 |
| Reflections collected | 7,848 | 19,531 | 8,306 |
| Independent reflections | 4980 [R int = 0.0542, R sigma = 0.1033] | 5791 [R int = 0.0326, R sigma = 0.0367] | 2690 [R int = 0.0971, R sigma = 0.1080] |
| Data/restraints/parameters | 4,980/7/390 | 5,791/1/496 | 2,690/0/196 |
| Goodness-of-fit on F 2 | 0.952 | 1.025 | 1.122 |
| Final R indexes [I > = 2σ (I)] | R 1 = 0.0599, wR 2 = 0.1387 | R 1 = 0.0293, wR 2 = 0.0611 | R 1 = 0.1058, wR 2 = 0.2897 |
| Final R indexes [all data] | R 1 = 0.1083, wR 2 = 0.1687 | R 1 = 0.0403, wR 2 = 0.0665 | R 1 = 0.1375, wR 2 = 0.3055 |
| Largest diff. peak/hole/e Å−3 | 0.73/−0.70 | 0.20/−0.22 | 1.31/−0.79 |
4.4 Cell culture
Caco-2 human colon adenocarcinoma cells and A549 human lung cancer cells originated from the American Type Culture Collection. A549 cells and Caco-2 cells underwent incubation in RPMI-1640 medium and DMEM/F-12 (1:1) medium, respectively. All media were added with 100 µg/mL of streptomycin, 10% FBS, and 100 U/mL of penicillin. All cells were incubated in a humidified environment with 5% CO2 at 37°C [31].
4.5 Cell proliferation assay
MTT assay was performed for the detection of the effects of metal complexes on cell proliferation. In brief, A549 cancer cells and Caco-2 cancer cells were seeded in a 96-well plate in triplicate and then incubated to 70–80% confluent at 37°C. Subsequently, the indicated concentrations of the complexes were exploited to treat cancer cells for 24 h [32]. The culture medium was removed, and MTT solution (1 mg/mL) was introduced for 2 h. Subsequently, MTT solution was removed, and 100 µL of DMSO was introduced to dissolve the metabolite formazan. Finally, the absorbance value was measured with the Victor 3 multi-label plate reader.
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Funding information: This research was supported by the Bidding subject of Dezhou University (No. 3010040205), the Talent Introduction Program of Dezhou University (No. 2016kjrc17), and the National Natural Science Foundation of China (No. 21806019).
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Conflict of interest: Authors state no conflict of interest.
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Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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