RETRACTED ARTICLE: Two transition metal coordination polymers: crystal structures and anticancer activity on children’s neuroblastoma

Abstract We, the Editors and Publisher of the journal Inorganic and Nano-Metal Chemistry, have retracted the following article: Xiao-Yi Xiong, Li-Ping Yin & Jun-Kai Zhang (2021) Two transition metal coordination polymers: crystal structures and anticancer activity on children’s neuroblastoma, Inorganic and Nano-Metal Chemistry, 51:10, 1411-1417, DOI: 10.1080/24701556.2020.1835981 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.


Introduction
[7][8] Highly structured and ordered CPs can be synthesized by many different mechanical or chemical procedures such as the solvothermal method, slow evaporation of a precursor solution, layering of solutions or slow diffusion of the components and the mechano-chemical method.[11][12] Structural alterations in CPs have been studied and reported by manipulating reaction conditions such as temperature, solvent, pH and the stoichiometry of the precursors in the synthetic approach.[15] On one hand, the mixed-ligand approach is more convenient for the introduction of functional groups into CPs, from either the carboxylate or Ndonor ligands; On the other hand, the co-existence of the carboxylate and the N-donor ligands could diverse the coordination patterns of the metal ions, which could result in more interesting structures. [16,17]In this study, reactions of Co(NO 3 ) 2 Á6H 2 O or Cu(NO 3 ) 2 Á3H 2 O with N 1 ,N 4 -bis(5-fluoropyridin-3-yl)succinamide (bfps) and 1,2,3-benzenetricarboxylic acid (1,2,3-H 3 BTC) or 1,3,5-benzenetricarboxylic acid (  (2).The CCK-8 assay indicated that compounds 1 and 2 showed the strongest inhibitory effect on M17 children's neuroblastoma cells.Next, the real-time RT-PCR showed compounds 1 and 2 could significantly influence the expression level of the p53, nf-jb, and tnf-a in M17.

Chemicals and measurements
All the chemicals and reagents used for the syntheses of both CPs were commercially available and used without further purification.Infrared spectra (IR) (KBr pellets) were recorded on a Nexus 870 FTIR spectrometer in the range of 400-4000 cm À1 .Elemental analyses (EA) were conducted using a PerkinElmer 240 elemental analyzer.The X-ray data were obtained by utilizing the SuperNova diffractometer.The intensity data was analyzed by utilizing the CrysAlisPro software and converted to the HKL files. [18]he SHELXS program on the basis of direct approach was utilized to create the initial structural models, [19] and the SHELXL-2014 program on the basis of the least-squares approach was modified. [20]The whole non-H atoms were mixed with anisotropic parameters.Then we utilized the AFIX commands to fix the whole H atoms geometrically on the C atoms that they attached.Table 1 details refinement details as well as crystallographic parameters of the two complexes.The selected bond lengths and angles were listed in the Table S1 to S4 in the ESI.

Cell culture
Human cervical cancer cell line HeLa, Chinese hamster ovary cell CHO, liver cancer cell line HepG2, children's neuroblastoma cells M17, breast cancer cell line MDA-MB-231 and the normal human lung epithelial cell line BEAS-2B were purchased from Shanghai Institutes for Biological Sciences, CAS.The HeLa, HepG2, M17, MDA-MB-231 and BEAS-2B cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM)/Ham's F12 medium, and CHO cells were incubated in RPMI-1640 (Gibco, Carlsbad, CA, USA).All cell culture medium was supplemented with 10% fetal bovine serum (FBS), 100 U/mL penicillin and streptomycin (HyClone, UT, USA), and 2% L-glutamine in a 5% CO 2 at 37 C.

CCK-8 assay
The anti-cancer activities of compounds 1 and 2 on serious of cancer cell were determined by CCK-8 assay (96992-500TESTS-F, Sigma-Aldric, USA) according to the protocols as previously reported.Briefly, the cancer cell lines and the normal cell line were plated onto 96-well plates with 1 Â 10 4 cells per well and incubated at 37 C, 5% CO 2 for 12 h.Compounds 1 and 2 were added at different dilutions of 0, 2.5, 5, 10, 25, 50, 100, and 200 lM for further incubation.48 h later, 10 lL CCK-8 reagents were added to each well, followed by measuring the absorbance (optical density, OD) at 450 nm on an enzyme immunoassay analyzer (Bio-Rad, USA).

RNA isolation and RT-PCR detection
The expression of apoptosis related genes, p53, nf-jb, and tnf-a in M17 was determined with real-time RT-PCR according to the manufacturer's instructions.In brief, the cells were seeded into 6-well plates (1 Â 10 5 cells/well) and accepted with different compounds treatment.Then, the total RNA was isolated from the cultured cells using TRIzol Reagent (Sigma, St. Louis, MO, USA).The quality of RNA was evaluated using the OD260/OD280 ratio, followed by the cDNA synthesis using High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Cambridge, MA, Relative expressions of p53, nf-jb, and tnf-a were measured using SYBR Green Master Mix (Roche) in an Applied Biosystems 7300 Sequence Detection System (Applied Biosystems).GAPDH was used as internal control, and data were normalized by using 2 ÀDDCt method as relative quantification from triplicate preformation.

Crystal structures
The structural solution and refinement results based on the single crystal data collected around room temperature show that complex 1 crystallizes in the triclinic space group P-1 and the asymmetric unit contains half of a [Co 3 (bfps) ( ] unit with a crystallographic center of symmetry located at the midpoint of the Co1ÁÁÁCo1B separation (Figure 1b).This unit is further interconnected to its equivalent ones by the bridging bfps ligands and the [Co(H 2 O) 4 ] species along two directions, thereby generating a 2D layer structure extending approximately along the bc plane (Figure 1c).The lattice H 2 O molecules are located inbetween the 2D layers via the H-bonding interactions with the coordinated H 2 O molecules around Co2 (Figure 1d).The distance between the neighboring layers was calculated to be 6.34 Å.For the four-coordinated Co1  18) Å) are close to those found in other Co(II) CPs having the similar coordination surroundings. [21]From the topological point of view, Co2 and the bfps ligand could be viewed as 2-conncted nodes, Co1 and the 1,2,3-BTC could be considered as 3-connected nodes, so the whole framework of 1 could be simplified into a 3-connected fes-type network with the point symbol of f4.8 Ù 2g.

R E T R A C T E D
directions, producing a double-layer 2D network extending along the [0, À1, 1] plane (Figure 2c).The distance between the neighboring layers was calculated to be 7.26 Å.The mean Cu-N and Cu-O bond lengths (2.153(3) Å vs 2.150(2) Å) are slightly longer than those of the corresponding ones found in other Cu(II)-based coordination polymers.The lattice H 2 O molecules are situated in-between the 2D layers via the H-bonding interactions with the C═O group of the bfps linker, COOH and COO groups of the 1,3,5-HBTC dianions of the neighboring layers (Figure 2d).From the topological point of view, the dinuclear Cu 2 (CO 2 ) 4 cluster could be viewed as a 4-connected node and all the ligands could be treated as the 2-connected linkers, so the whole framework of 2 could be judged as a 4-connected sql-type network with the point symbol of f4^4.6^2g.
To check the phase purity of the products, powder X-ray diffraction (PXRD) experiments have been carried out for these complexes (Figure 3a).The peak positions of the experimental and simulated PXRD patterns are in good agreement with each other, indicating that the crystal structures are truly representative of the bulk crystal products.The differences in intensity may be owing to the preferred orientation of the crystal samples. [22]The thermal stabilities of coordination polymers 1 and 2 were determined in the temperature range of 25 À 700 C with a heating rate of 10 C/min in the N 2 atmosphere (Figure 3b).The TGA

R E T R A C T E D
curve of complex 1 shows a weight loss of 15.2% from 83 to 152 C, which could be attributed to the removal of six coordinated and four lattice water molecules in the framework (calcd: 14.8%).After removing the solvents, the solvent-free framework of 1 could be thermally stable up to 257 C, after which there is a second sharp weigh loss observed, indicating the decomposition of the organic ligands along with the collapse of the whole framework.The TGA curve of complex 2 shows a sight weight loss of 3.2% from 98 to 214 C, which is related to the escape of one lattice water molecule (calcd: 3.0%).After the temperature of 242 C, a second weight loss could be observed, corresponding to the decomposition of the organic ligands.

Cytotoxicity of compounds 1 and 2 on cancer cells
The in vitro antitumor capabilities of compounds 1 and 2 were evaluated with the CCK8 assays.After treated with serially diluted compounds 1 and 2, the cancer cells viability was measured at the absorbance of 570 nm.As results shown in Figure 4, compounds 1 and 2 showed excellent anti-proliferation activity against most cancer cells, but not HeLa cells.Compounds 1 and 2 showed the strongest inhibitory effect on M17 children's neuroblastoma cells.

Apoptotic genes expression after compounds treatment
It has been proved that compounds 1 and 2 exhibited superior anti-cancer activates on M17 cells, we presumed this effect may due to the induction of cell apoptosis.Hence, we detected the relative expression of apoptotic genes via RT-PCR.In Figure 5, we can see, after incubated with compounds 1 and 2 for 48 h, the expression level of p53, nf-jb, and tnf-a are significantly upregulated to 4.52 ± 0.69, 5.64 ± 0.39, 6.56 ± 0.64 and 2.6 ± 0.38, 2.95 ± 0.28, 2.28 ± 0.37.There is a significant difference compared with control group (p < 0.05).

Conclusion
In summary, we have successfully prepared two transition metal coordination polymers by applying the mixed-ligand approach.The single crystal X-ray diffraction study shows that both complexes show two-dimensional layer structures derived from interconnecting dinuclear [Co 2 (

Figure 4 .
Figure 4. Cancer cell proliferation after compounds treatment.The Cell viability curves measured by CCK8 assay after compounds 1 and 2 treatment.

Figure 5 .
Figure 5. Compounds 1 and 2 stimulate apoptotic genes expression.After treated with compounds 1 and 2, the p53, nf-jb, and tnf-a gene expression in mRNA level was detected with RT-PCR.

Table 1 .
Refinement details and crystallographic parameters for complexes 1 and 2.
1,2,3-BTC) 2 (H 2 O) 2 ] units through the bfps bridges and the [Co(H 2 O) 4 ] species (1) or interlinking dinuclear [Cu 2(1,3,5-HBTC) 2 ] units via pairs of bfps bridges and pairs of 1,3,5-HBTC dianions(2).The compounds exhibit highest selectivity on M17 children's neuroblastoma cells, especially compound 1, having the IC 50 of 1.64 ± 0.06 Mm.The RT-PCR results revealed the underlining mechanism of compounds, which could up-regulate the relative expression of p53, nfjb, and tnf-a apoptotic genes and finally exert anti-tumor capabilities.All data from the present study suggest that compared with compound 2, compound 1 is a more attractive and promising candidate for developing anti-cancer drug targeting children's neuroblastoma.And compound 1 showed much more excellent biological activities than other CPs.