Zero-dimensional nickel (II) coordination compound as well as preparation method and antibacterial application thereof

Abstract

The invention relates to the technical field of antibacterial material preparation, in particular to a zero-dimensional nickel (II) coordination compound and a preparation method and antibacterial application thereof. The chemical formula of the zero-dimensional nickel (II) coordination compound is [Ni (dpb) 2] (NO3) 2, nickel (II) is used as a central ion to form a brown crystalline product with a zero-dimensional structure through tridentate N chelation of a two-molecule 2 ', 6'-di (pyrazine-2-yl)-2, 4 '-bipyridine ligand, and the mass ratio of each element is as follows: 58.35% of carbon, 3.01% of hydrogen, 15.70% of nitrogen and 11.96% of oxygen. The prepared zero-dimensional nickel (II) coordination compound has good thermal stability, has a good inhibition effect on staphylococcus aureus, is non-toxic to human embryo kidney cells in 24 hours and 48 hours, and can be used as a bacteriostatic drug material carrier in the aspect of medicine.

Description

Technical Field

[0001] This invention relates to the field of antibacterial material preparation technology, and in particular to a zero-dimensional nickel(II) coordination compound, its preparation method and antibacterial application. Background Technology

[0002] Bacterial infections have become a major global health challenge. In recent years, antibiotics, especially bactericidal drugs, have played a crucial role in controlling bacterial infections. However, with the widespread spread of drug-resistant bacteria, the effectiveness of antibiotics has gradually declined, and drug-resistant microorganisms cause millions of deaths annually. The spread of drug-resistant strains has not only reduced the success rate of antibiotic treatment for bloodstream infections to 50%, but has also exacerbated the pressure on public health systems, showing an escalating trend. Therefore, there is an urgent need to develop innovative antimicrobial materials with clinical efficacy and tissue compatibility, providing non-antibiotic solutions to address the growing problem of drug-resistant bacteria.

[0003] Nickel, a common transition metal element, typically exists in its +2 oxidation state in aqueous solution and participates extensively in various important functions within organisms. Studies have shown that the interaction between nickel and iron is crucial for human health, particularly in promoting oxygen transport in hemoglobin. Furthermore, nickel acts as a cofactor for multiple enzymes, widely participating in metabolic processes in both plants and animals, and may be closely related to the transmission of genetic information. These biological properties of nickel make it a potential antibacterial component. In the field of antibacterial research, nickel coordination compounds have attracted widespread attention in recent years due to their redox activity, tunable coordination structures, and ability to target multiple bacterial defense mechanisms. In particular, nickel-based coordination compounds, as a novel type of antibacterial material, have become a key research focus in antibacterial agent development due to their unique potential in regulating antibacterial activity. Constructing coordination compounds with excellent antibacterial properties by selecting appropriate ligands to bind with nickel metal has become one of the important directions in current scientific research.

[0004] Therefore, developing nickel-based coordination compounds as antibacterial materials not only provides a new approach to solving the problem of bacterial resistance but also opens up broad prospects for the development of antibacterial drugs. These innovative materials may become an effective means of replacing traditional antibiotics, providing more options for antibacterial therapy. Summary of the Invention

[0005] The technical problem to be solved by this invention is to address the shortcomings of the prior art by providing a zero-dimensional nickel(II) coordination compound, its preparation method, and its antibacterial application. The compound is [Ni(dpb)2](NO3)2. This complex, with nickel(II) as the central ion, forms a zero-dimensional brown crystalline product through the tridentate N-chelation of two molecules of 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine ligands. The mass percentages of the elements are: carbon: 58.35%, hydrogen: 3.01%, nitrogen: 15.70%, and oxygen: 11.96%. This coordination compound exhibits excellent thermal stability, good inhibitory effect against Staphylococcus aureus, and no toxicity to human embryonic kidney cells at 24h and 48h. This coordination compound can be used as a carrier for antibacterial drugs in pharmaceutical applications.

[0006] This invention provides a zero-dimensional nickel(II) coordination compound, the chemical formula of which is [Ni(dpb)2](NO3)2; the molecular formula of which is C 36 H 24 NiN 14 O6.

[0007] According to the zero-dimensional nickel (II) coordination compound provided by the present invention, the ligand dpb in the chemical formula of the zero-dimensional nickel (II) coordination compound is 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine, the zero-dimensional nickel (II) coordination compound is triclinic, the space group is P-1, and the unit cell parameters include a=10.583(15)Å, b=12.681(6)Å, c=15.540(15)Å, α=104.639°, β=97.530° and γ=103.008°;

[0008] The structural formula of the 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine is:

[0009] .

[0010] This invention provides a method for preparing the above-mentioned zero-dimensional nickel(II) coordination compound, comprising the following steps:

[0011] S1. Dissolve 2-acetylpyrazine 1 in anhydrous ethanol. Add 2-pyridinecarboxaldehyde in small amounts several times while stirring continuously. After the addition of 2-pyridinecarboxaldehyde is complete, add NaOH solution dropwise to the solution. After the addition is complete, continue stirring the reaction under ice-water bath conditions, and then add 2-acetylpyrazine 2 and ammonium acetate. Reflux under constant temperature conditions and cool to room temperature. Filter to obtain the precipitate, and recrystallize to obtain the ligand dpb.

[0012] S2. Nickel nitrate hexahydrate, dpb, acetonitrile and distilled water are mixed and subjected to a solvothermal reaction to obtain the reaction product;

[0013] S3. After the reaction product prepared in S2 is allowed to cool naturally and crystallize, it is washed, filtered under reduced pressure and dried to obtain a zero-dimensional nickel (II) coordination compound.

[0014] According to the preparation method provided by the present invention, the ratio of 2-acetylpyrazine 1, anhydrous ethanol, 2-pyridinecarboxaldehyde, NaOH solution, 2-acetylpyrazine 2 and ammonium acetate in S1 is 3.26 g: 50 mL: 3.26 g: 20 mL: 3.26 g: 10.00 g, and the concentration of the NaOH solution is 2 mol / L.

[0015] According to the preparation method provided by the present invention, the temperature of the ice-water bath in S1 is 0 ℃, the stirring time under the ice-water bath condition is 2 h, the constant temperature is 80 ℃, the reflux time is 5 h, and the solvent used for recrystallization is ethanol.

[0016] According to the preparation method provided by the present invention, the ratio of nickel nitrate hexahydrate, dpb, acetonitrile and distilled water in S2 is 0.05-0.1 mmol: 0.05-0.1 mmol: 38.3 mmol: 360.75-388.5 mmol.

[0017] According to the preparation method provided by the present invention, the temperature of the solvothermal reaction in S2 is 90-110 °C, the time of the solvothermal reaction in S2 is 4-6 days, and the cleaning agent used for cleaning in S3 is anhydrous ethanol.

[0018] The present invention also provides an application of the above-mentioned zero-dimensional nickel(II) coordination compound, which can be used as a carrier for antibacterial drug materials.

[0019] Compared with the prior art, the present invention has the following advantages:

[0020] This invention provides a zero-dimensional nickel(II) coordination compound, its preparation method, and its application. The coordination compound forms a zero-dimensional structure with nickel(II) as the central ion through the chelation of two molecules of 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine. The coordination compound has good thermal stability and a significant inhibitory effect on Escherichia coli. In in vitro experiments on human embryonic kidney cells (HEK-293T), it showed no toxicity. This zero-dimensional nickel(II) coordination compound can be used as a special antibacterial pharmaceutical carrier.

[0021] This invention utilizes a one-pot solvothermal reaction to prepare zero-dimensional nickel(II) coordination compounds that exhibit antibacterial effects against Escherichia coli and are non-toxic to human embryonic kidney cells. The preparation method is simple, convenient, has high yield, and good reproducibility. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0023] Figure 1 Diagram of the coordination environment of nickel in nickel(II) coordination compounds;

[0024] Figure 2 Infrared spectroscopy of nickel(II) coordination compounds

[0025] Figure 3 Powder X-ray diffraction pattern of nickel(II) coordination compounds;

[0026] Figure 4 Thermogravimetric curves of nickel(II) coordination compounds;

[0027] Figure 5 The graph shows the inhibitory effect of nickel(II) coordination compounds on Escherichia coli.

[0028] Figure 6 A graph showing the survival rate of human embryonic kidney cells from 0 to 24 hours for nickel(II) coordination compounds;

[0029] Figure 7 The graph shows the survival rate of human embryonic kidney cells from 0 to 48 hours for nickel(II) coordination compounds. Detailed Implementation

[0030] The specific preparation method of 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine (dpb) provided by this invention is as follows:

[0031] Dissolve 3.26g of the first portion of 2-acetylpyrazine in 50 mL of anhydrous ethanol and stir until completely dissolved. Then, add 3.26g of 2-pyridinecarboxaldehyde in portions while stirring. After the addition is complete, add 20 mL of 2.0 mol / L sodium hydroxide solution dropwise to the reaction system. After the addition is complete, place the reaction system in an ice-water bath and continue stirring for two hours.

[0032] Subsequently, 3.26 g of the second part of 2-acetylpyrazine and 10.00 g of excess ammonium acetate were added to the system, and the reaction mixture was heated to reflux and reacted for five hours. After the reaction was completed, the system was cooled to room temperature, the precipitate was collected by filtration, and the precipitate was purified by recrystallization with ethanol to obtain the powdered target product (dpb) with a yield of 52.6%.

[0033] The structural formula of 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine is:

[0034] .

[0035] Example 1

[0036] This embodiment provides a zero-dimensional nickel(II) coordination compound and its preparation method, including the following steps:

[0037] S1. Mix 0.05 mmol nickel nitrate, 0.1 mmol 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine (dpb), 38.3 mmol acetonitrile and 360.75 mmol distilled water to obtain a mixture, place it in a 25 mL sealed glass bottle and heat it to 90 °C at a heating rate of 5-10 °C per hour. Carry out a solvothermal reaction at this temperature for 5 days to obtain the reaction product.

[0038] S2. The reaction product prepared in S1 was allowed to cool naturally and crystallize. The crystals were washed with anhydrous ethanol, filtered under reduced pressure to obtain brownish crystal particles, and then dried naturally to obtain zero-dimensional nickel(II) coordination compound 1 with a yield of 45.2%.

[0039] In the preparation reaction of this invention, a cooling and crystallization step is necessary, which means that the cooling process is also a reaction process.

[0040] Compared with existing technologies, this invention employs a slow cooling crystallization step after the solvothermal reaction, allowing the crystals to grow fully in the solvent system, thus improving the cleanliness and phase purity of the product. Direct cooling after the reaction, on the other hand, cannot yield high-quality single crystals, making precise structural analysis difficult.

[0041] Example 2

[0042] This embodiment provides a zero-dimensional nickel(II) coordination compound and its preparation method, including the following steps:

[0043] S1. Mix 0.1 mmol nickel nitrate, 0.05 mmol 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine (dpb), 38.3 mmol acetonitrile and 388.5 mmol distilled water to obtain a mixture, place it in a 25 mL sealed glass bottle and heat it to 110 °C at a heating rate of 5-10 °C per hour. Carry out a solvothermal reaction at this temperature for 6 days to obtain the reaction product.

[0044] S2. The reaction product prepared in S1 was allowed to cool naturally and crystallize. The crystals were washed with anhydrous ethanol, filtered under reduced pressure to obtain brownish crystal particles, and then dried naturally to obtain zero-dimensional nickel(II) coordination compound 1 with a yield of 41.31%.

[0045] Example 3

[0046] This embodiment provides a zero-dimensional nickel(II) coordination compound and its preparation method, including the following steps:

[0047] S1. Mix 0.05 mmol nickel nitrate, 0.05 mmol 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine (dpb), 38.3 mmol acetonitrile and 388.5 mmol distilled water to obtain a mixture, place it in a 25 mL sealed glass bottle and heat it to 95 °C at a heating rate of 5-10 °C per hour. Carry out a solvothermal reaction at this temperature for 4-5 days to obtain the reaction product.

[0048] S2. The reaction product prepared in S1 was allowed to cool naturally and crystallize. The crystals were washed with anhydrous ethanol, filtered under reduced pressure to obtain brownish crystal particles, and then dried naturally to obtain zero-dimensional nickel(II) coordination compound 1 with a yield of 42.4%.

[0049] Comparative Example 1

[0050] This comparative example provides a preparation method different from the above embodiments, and the specific steps are as follows:

[0051] S1. Mix 0.05 mmol nickel nitrate, 0.05 mmol dpb, 38.3 mmol acetonitrile and 388.5 mmol distilled water to obtain a mixture. Place the mixture in a sealed 25 mL glass bottle and heat it to 90 °C at a rate of 10 °C per hour. React at this temperature for 4 days.

[0052] S2. The temperature was lowered to room temperature at a rate of 10°C per hour. The crystals were washed with anhydrous ethanol and filtered under reduced pressure to obtain brown crystal particles. After being placed in an oven at 60°C for 3 hours, product 4 was obtained with a yield of 38.5%.

[0053] Powder XRD analysis revealed significant differences in the diffraction peaks of the product obtained in Comparative Example 1 compared to the sample in the examples, indicating that the crystal structure did not fully form a coordination compound framework and had low crystallinity. Thermogravimetric analysis showed that its thermal stability was significantly worse than that of the product obtained in Example 3. Therefore, the optimized reaction conditions of this invention effectively promoted the formation of zero-dimensional structures and improved product stability.

[0054] Example 4

[0055] The zero-dimensional nickel(II) coordination compound 3 prepared in Example 3 was used as a sample for further characterization, as detailed below:

[0056] ① Determination of the crystal structure of coordination compounds

[0057] X-ray diffraction experiments were conducted at room temperature on a single crystal with suitable dimensions of 0.21 mm × 0.15 mm × 0.14 mm under a microscope. Diffraction data were collected using a Bruker-Apex П X-ray single crystal diffractometer, with Mo-Kα rays (λ = 0.71073 Å) monochromated using a graphite monochromator, and diffraction points were collected using ω-2θ scanning. All data were corrected for factors and empirical absorption. The crystal structure was solved directly using a program, and hydrogen atoms were determined by difference Fourier synthesis and fixation at the calculated optimal positions. Using the SHELX-97 program, all non-hydrogen atoms and their anisotropic thermal parameters were corrected using the full matrix least squares method. Detailed crystal measurement data are shown in Table 1, important bond lengths and bond angles are shown in Table 2, and the crystal structure is shown in Table 3. Figure 1 and Figure 2 .

[0058] Table 1. Key crystallographic data of zero-dimensional nickel(II) coordination compound 3

[0059]

[0060] Table 2. Important bond lengths (Å) and bond angles (°) of zero-dimensional nickel(II) coordination compounds.

[0061] Chemical bonds Bond length / Å Chemical bonds Bond angle / (°) Ni(1)-N(1) 1.9924(39) Å N(1)-Ni(1)-N(2) 77.992(131)° Ni(1)-N(2) 2.1161 (29) Å N(1)-Ni(1)-N(4) 77.856(144)° Ni(1)-N(4) 2.1152(33) Å N(6)-Ni(1)-N(8) 77.923(134)° Ni(1)-N(6) 2.1151(32) Å N(6)-Ni(1)-N(2) 92.968(129)° Ni(1)-N(7) 2.1095(34) Å N(6)-Ni(1)-N(4) 91.078(133)° Ni(1)-N(8) 1.9917(39) Å N(8)-Ni(1)-N(4) 104.658(146)°

[0062] In Table 1, a, b, and c represent the edge lengths of the crystal along the three crystal axes, α, β, and γ represent the angles between axes a and b, a and c, and b and c, respectively; Z is the number of molecules in a unit cell; the diffraction index range of the restriction factor is (h, k, l); F(000) is the number of electrons in a unit cell; Final R indices [I>2σ(I)] is the residual factor R value for observable diffraction points; R is the unweighted consistency factor; R1 and wR2 are both weighted consistency factors; R1=∑(||F o |-|F c||) / ∑|F o |,wR2=[∑w(F o 2 -| F c 2 ) 2 / ∑w(F o ) 2 ] 1 / 2 ;

[0063] In Table 2, Ni (1) in the first row refers to Ni atom 1 in the zero-dimensional nickel (II) coordination compound, N (1) refers to N atom 1 in the zero-dimensional nickel (II) coordination compound, Ni (1)-N (1) represents the bond length between Ni atom 1 and N atom 1, which is 1.9924±39 Å, where 39 is the standard deviation; N (1)-Ni (1)-N (2) represents the bond angle between N atom 1, Ni atom 1 and N atom 2, which is 77.992±131.

[0064] The coordination compound forms a brown crystalline product with a zero-dimensional structure by chelating two molecules of 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine with nickel(II) as the central ion. The mass percentages of the elements are: carbon: 58.35%, hydrogen: 3.01%, nitrogen: 15.70%, and oxygen: 11.96%.

[0065] ② Phase purity characterization of zero-dimensional nickel(II) coordination compound 3

[0066] Powder XRD characterization of zero-dimensional nickel(II) coordination compound 3 showed reliable phase purity, ensuring its application as a pharmaceutical carrier material. (See...) Figure 3 The instrument used for testing is a Bruker / D8Advance.

[0067] ③ Characterization of the thermal stability of zero-dimensional nickel(II) coordination compound 3

[0068] The thermal stability of nickel(II) coordination compound 3 was studied under a nitrogen atmosphere from room temperature to 800°C. From room temperature to 160°C, a weight loss of 2.13% occurred, corresponding to the loss of one uncoordinated water molecule; the calculated weight loss was 2.23%. Furthermore, the zero-dimensional nickel(II) coordination compound 3 maintained good stability up to 320°C, providing a thermal stability guarantee for its further development as an application material. (See...) Figure 4 The instrument used for testing is model SDT Q600.

[0069] Example 5

[0070] This embodiment provides an application study of the zero-dimensional nickel(II) coordination compound 3 obtained in Example 3.

[0071] 10 mg of the zero-dimensional nickel(II) coordination compound 3 obtained in Example 3 was used as an antibacterial material. After being ground into powder, 1 mL of N,N-dimethylformamide (DMF) was added to prepare a solution. The solution was sonicated for 30 min and then used as a control group. Ligand solution, pyromellitic acid solution, nickel ion solution and DMF solution were prepared at the same concentration.

[0072] The inoculated Staphylococcus aureus and Escherichia coli solutions were diluted with sterile water to a concentration of 5 × 10⁻⁶ in a sterile operating chamber. 5 CFU / mL was evenly spread on the surface of a solid culture medium. Next, five 6 mm diameter filter paper discs were placed clockwise on the solid culture medium, labeled as zero-dimensional nickel(II) coordination compound, DMF, ligand, and nickel nitrate, respectively. 8 μL of each test solution was added to the corresponding filter paper disc. Each experiment was performed in six parallel trials and incubated at 37°C under constant temperature and light for 12 hours.

[0073] After the experiment, the diameter of the inhibition zone was observed and measured to evaluate the antibacterial effect, such as... Figure 5 As shown. From Figure 5 Data shows that the filter paper labeled with zero-dimensional nickel(II) coordination compounds exhibited a significant inhibition zone compared to the other three groups of filter paper, indicating that the present invention has a good inhibitory effect on Staphylococcus aureus. To evaluate the biosafety of the materials involved in this invention to human embryonic kidney cells, a non-toxicity test was conducted. Seven different concentrations of the material solution were used in the experiment, and cell viability was tested within the time periods of 0–24 hours and 0–48 hours. Seven different concentrations of coordination compound 3 were used, ranging from 0–1 mg / mL. The experimental cell line was human embryonic kidney cells (293t).

[0074] Test time: Two different time intervals were selected, namely 0-24 hours and 0-48 hours, to evaluate the effect of materials on cells at different time points.

[0075] Experimental methods: Cell viability was assessed using the CCK-8 assay, and the degree of toxicity was calculated based on cell survival rate.

[0076] Experimental results:

[0077] Cytotoxicity assessment results showed that the survival rates of human embryonic kidney cells (293T) in both the 0–24 h and 0–48 h time periods were higher than 90% and 60% respectively, indicating that the coordination compound had no significant toxicity to cells within the tested concentration range and possessed good biocompatibility. Figure 6 As shown in Figure 7.

[0078] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention in any way. Any simple modifications, alterations, and equivalent changes made to the above embodiments based on the inventive essence shall still fall within the protection scope of the present invention.

Claims

1. A zero-dimensional nickel(II) coordination compound, characterized in that, The chemical formula of the zero-dimensional nickel(II) coordination compound is [Ni(dpb)2](NO3)2; the molecular formula of the zero-dimensional nickel(II) coordination compound is C 36 H 24 NiN 14 O6.

2. The zero-dimensional nickel(II) coordination compound according to claim 1, characterized in that, The ligand dpb in the chemical formula of the zero-dimensional nickel (II) coordination compound is 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine. The zero-dimensional nickel (II) coordination compound is triclinic, space group P-1, and its cell parameters include a=10.583(15)Å, b=12.681(6)Å, c=15.540(15)Å, α=104.639°, β=97.530° and γ=103.008°. The structural formula of the 2',6'-bis(pyrazin-2-yl)-2,4'-bipyridine is: 。 3. A method for preparing a zero-dimensional nickel(II) coordination compound as described in any one of claims 1-2, characterized in that, Includes the following steps: S1. Dissolve 2-acetylpyrazine 1 in anhydrous ethanol. Add 2-pyridinecarboxaldehyde in small amounts several times while stirring continuously. After the addition of 2-pyridinecarboxaldehyde is complete, add NaOH solution dropwise to the solution. After the addition is complete, continue stirring the reaction under ice-water bath conditions, and then add 2-acetylpyrazine 2 and ammonium acetate. Reflux under constant temperature conditions and cool to room temperature. Filter to obtain the precipitate, and recrystallize to obtain the ligand dpb. S2. Nickel nitrate hexahydrate, dpb, acetonitrile and distilled water are mixed and subjected to a solvothermal reaction to obtain the reaction product; S3. After the reaction product prepared in S2 is allowed to cool naturally and crystallize, it is washed, filtered under reduced pressure and dried to obtain a zero-dimensional nickel (II) coordination compound.

4. The preparation method according to claim 3, characterized in that, The ratio of 2-acetylpyrazine 1, anhydrous ethanol, 2-pyridinecarboxaldehyde, NaOH solution, 2-acetylpyrazine 2, and ammonium acetate in S1 is 3.26 g: 50 mL: 3.26 g: 20 mL: 3.26 g: 10.00 g, and the concentration of the NaOH solution is 2.0 mol / L.

5. The preparation method according to claim 3, characterized in that, The temperature of the ice-water bath in S1 is 0 ℃, the stirring time under the ice-water bath condition is 2 h, the constant temperature is 80 ℃, the reflux time is 5 h, and the solvent used for recrystallization is ethanol.

6. The preparation method according to claim 3, characterized in that, The ratio of nickel nitrate hexahydrate, dpb, acetonitrile, and distilled water in S2 is 0.05–0.1 mmol: 0.05–0.1 mmol: 38.3 mmol: 360.75–388.5 mmol.

7. The preparation method according to claim 3, characterized in that, The temperature of the solvothermal reaction in S2 is 90–110 °C, the time of the solvothermal reaction in S2 is 4–6 days, and the cleaning agent used for cleaning in S3 is anhydrous ethanol.

8. The application of a zero-dimensional nickel(II) coordination compound as described in any one of claims 1-2, characterized in that, The zero-dimensional nickel(II) coordination compound can be used as a carrier for antibacterial drug materials.

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