Nickel-based metal organic framework and preparation method and detection application thereof

Abstract

The application discloses a nickel-based metal organic framework and a preparation method and detection application thereof. The nickel-based metal organic framework is formed by coordination of 2,6-bis(1H-pyrazol-1-yl) isonicotinic acid (H2BPIA) and nickel ions Ni(II). The H2BPIA and NiCl2·6H2O are prepared by a hydrothermal / solvothermal method in a water-acetonitrile mixed solvent, and the obtained nickel-based metal organic framework has high thermal stability and can be used for detection of marbofloxacin and has the advantages of high selectivity, strong anti-environmental interference capability and fast response speed.

Description

Technical Field

[0001] This invention relates to the field of new materials technology for environmental testing, specifically to a metal-organic framework and its preparation and testing applications, and more particularly to a nickel-based metal-organic framework, its preparation method, and its application in detecting the antibiotic marbofloxacin. Background Technology

[0002] Marbofloxacin (MBF) is a third-generation quinolone antibiotic for animal use. It exerts its antibacterial effect by inhibiting bacterial DNA gyrase activity, thus preventing DNA synthesis and replication. It has a broad antibacterial spectrum, showing good efficacy against Gram-negative bacteria, Gram-positive bacteria, and mycoplasma. Marbofloxacin has strong tissue penetration, achieving high concentrations in the respiratory and gastrointestinal tracts. It is rapidly absorbed after administration, has high bioavailability, and is unlikely to develop cross-resistance with other drugs. Therefore, it is commonly used for respiratory infections and acute mastitis in cattle, agalactia syndrome in pigs, and infectious diseases in dogs and cats.

[0003] However, the misuse of marbofloxacin occurs frequently, leading to excessive residues in the environment and animal tissues, adversely affecting the ecological environment and posing varying degrees of harm to consumer health through the food chain, such as the development of drug-resistant strains, allergic reactions, and disruption of gut microbiota. To ensure the safety of animal-derived food and maintain environmental ecology, developing efficient and sensitive marbofloxacin detection technologies has become a research focus in the fields of environmental monitoring and food safety.

[0004] Traditional methods for detecting marbofloxacin mainly include ultra-high performance liquid chromatography (UHPLC) and UHPLC-tandem mass spectrometry (USMS). While offering high accuracy, these methods are expensive, involve complex pretreatment, require highly skilled technicians, and are difficult to monitor in real-time. Other methods, such as enzyme-linked immunosorbent assay (ELISA), are time-consuming, and their results are highly susceptible to environmental interference, leading to false negatives or false positives. Gold-labeled immunochromatography (IGIA) is slightly faster, but its sensitivity is low, and the labeled material is unstable. In contrast, fluorescence analysis is simple to operate, has a rapid response, and high sensitivity, making it an important tool for trace and real-time detection. The key to fluorescence analysis lies in the performance of the fluorescent sensing material (fluorescent probe). However, most fluorescent probes currently suffer from insufficient selectivity, weak anti-interference ability, and poor thermal stability. Developing fluorescent probe materials with high sensitivity, high selectivity, and high thermal stability is a crucial aspect of fluorescence analysis. Summary of the Invention

[0005] The purpose of this invention is to provide a nickel-based metal-organic framework material, its preparation method, and its applications, in order to solve the problems mentioned in the background art. The nickel-based metal-organic framework material of this invention is simple to prepare, has high thermal stability, and as a fluorescent probe for the detection of marbofloxacin antibiotics, it has the advantages of low detection limit, rapid response, and strong anti-interference ability. It can be used for rapid and highly selective detection of marbofloxacin residues in the environment and animal tissues.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] This invention provides a nickel-based metal-organic framework, which is a crystal structure formed by coordination of 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid (H2BPIA) with nickel ions Ni(II). The asymmetric unit in the crystal structure is composed of two Ni(II) ions with different coordination environments and two H2BPIA ligand molecules. One Ni(II) coordinates with the carboxyl oxygen of one H2BPIA, three nitrogen atoms and two chloride ions of the other H2BPIA to form an octahedral structure. The other Ni(II) coordinates with the carboxyl oxygen of one H2BPIA, three nitrogen atoms and two water molecules of the other H2BPIA to form an octahedral structure, thereby forming a chain structure of "—Ni(II)—H2BPIA—Ni(II)—H2BPIA—". The chain structure is arranged in parallel to form a two-dimensional layered structure. The two-dimensional layers are stacked to form a three-dimensional metal-organic framework crystal structure.

[0008] —Ni(II)—H2BPIA—Ni(II)—H2BPIA—chain structure:

[0009] .

[0010] The nickel-based metal-organic framework material provided by this invention is crystallized in the triclinic system, space group P-1, with cell parameters a=8.9411(9) Å, b=10.7445(11) Å, c=14.8864(16) Å, α=69.207(2)°, β=89.682(3)°, and γ=85.311(2)°.

[0011] This invention also provides a nickel-based metal-organic framework, prepared by a hydrothermal / solvothermal method, with the specific steps as follows:

[0012] (1) Dissolve 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid (H2BPIA) and NiCl2·6H2O in a mixed solvent of ultrapure water and acetonitrile to form a mixed solution;

[0013] (2) Transfer the mixture to a stainless steel autoclave lined with polytetrafluoroethylene, place the autoclave in an oven and heat it at 120~160℃ for 1~3 days, and then slowly cool it to room temperature at a cooling rate of 5~20℃ / h.

[0014] (3) The solid in the reaction solution is collected by filtration, then thoroughly washed with acetonitrile and dried under vacuum.

[0015] Further, in step (1), the total concentration of H2BPIA and NiCl2·6H2O in the mixed solution is 0.01 mol / L~1 mol / L, and the molar ratio of H2BPIA to NiCl2·6H2O is 1:1.

[0016] Further, in the mixed solvent of step (1), the volume ratio of water to acetonitrile is 0.5:1 to 2:1.

[0017] This invention also provides the application of the above-described nickel-based organic framework in the detection of marbofloxacin antibiotic.

[0018] Compared with the prior art, the beneficial effects of the present invention are:

[0019] The metal-organic framework of this invention emits fluorescence, which is quenched in the presence of marbofloxacin, thus enabling detection. The concentration of marbofloxacin can be calculated based on the fluorescence quenching rate. It has a low detection limit and fast response speed, enabling trace and rapid detection of marbofloxacin. The fluorescence quenching of marbofloxacin by the invented metal-organic framework is not affected by other coexisting antibiotics, exhibiting high selectivity and strong resistance to environmental interference. Furthermore, the invented metal-organic framework maintains structural stability below 200-300℃, demonstrating high thermal stability and overcoming the problem of poor thermal stability found in other fluorescent probes. Attached Figure Description

[0020] Figure 1 This is a schematic diagram of the asymmetric unit cell of the nickel-based metal-organic framework crystal structure of the present invention;

[0021] Figure 2 This is a schematic diagram of the two-dimensional layered structure formed by the parallel arrangement of chain structural units in the nickel-based metal-organic framework crystal structure of the present invention;

[0022] Figure 3 This is a schematic diagram of the three-dimensional stacking state of the nickel-based metal-organic framework crystal structure of the present invention;

[0023] Figure 4 The stacked views of the nickel-based metal-organic framework crystal structure of the present invention are shown from the a-axis, b-axis, and c-axis, respectively.

[0024] Figure 5 Thermogravimetric analysis of the nickel-based metal-organic framework prepared in Example 1;

[0025] Figure 6 The XRD pattern of the nickel-based metal-organic framework prepared in Example 2;

[0026] Figure 7 The curve shows the relationship between fluorescence intensity and mabofloxacin concentration. Detailed Implementation

[0027] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] Example 1

[0029] Preparation of nickel-based metal-organic frameworks

[0030] 0.05 mmol of 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid and 0.05 mmol of NiCl2·6H2O were dissolved in a mixed solvent of ultrapure water (3 mL) and acetonitrile (3 mL) to obtain a mixed solution. The mixed solution was transferred into a 15 mL stainless steel autoclave lined with polytetrafluoroethylene, sealed, and placed in a constant temperature oven. The reaction was carried out at 140 °C for 2 days, and then slowly cooled to room temperature at a rate of 5 °C / h. The solid was filtered, thoroughly washed with acetonitrile, and then vacuum dried to obtain a nickel-based metal-organic framework material.

[0031] The obtained material is in the form of crystalline particles of varying sizes, with the largest size exceeding 0.2 mm. A single crystal was selected for single-crystal X-ray diffraction testing to obtain the crystal structure of the material. The obtained material crystallizes in the triclinic system, space group P-1, with cell parameters a=8.9411(9) Å, b=10.7445(11) Å, c=14.8864(16) Å, α=69.207(2)°, β=89.682(3)°, and γ=85.311(2)°.

[0032] A schematic diagram of the asymmetric unit cell of a nickel-based metal-organic framework crystal structure is shown below. Figure 1 As shown, the asymmetric unit consists of two Ni(II) ions and two H2BPIA ligand molecules. The coordination environments of the two Ni(II) ions are different. One Ni(II) ion coordinates with three N and three O to form an octahedral configuration, and the entire octahedron exhibits a positive monovalent. The other Ni(II) ion coordinates with three N, one O, and two Cl to form an octahedral configuration, and the entire octahedron exhibits a negative monovalent.

[0033] A schematic diagram of a two-dimensional layered structure formed by parallel arrangement of chain structural units in a nickel-based metal-organic framework crystal structure is shown below. Figure 2 As shown. In each chain, positive monovalent octahedrons and negative monovalent octahedrons are arranged alternately.

[0034] A schematic diagram of the three-dimensional packing state of a nickel-based metal-organic framework crystal structure is shown below. Figure 3 As shown.

[0035] The stacking views of the nickel-based metal-organic framework crystal structure along the a-axis, b-axis, and c-axis are shown below. Figure 4 As shown, two different nickel-centered octahedrons can be seen arranged in the crystal.

[0036] Thermogravimetric diagram of nickel-based metal-organic frameworks is as follows Figure 5 As shown in the thermogravimetric analysis, the nickel-based metal-organic framework of this invention remains stable at temperatures below 300°C, demonstrating high thermal stability.

[0037] Application of nickel-based metal-organic frameworks in the detection of mabofloxacin

[0038] Nickel-based metal-organic framework (MOF) powder was ultrasonically dispersed in ultrapure water to form a suspension with a concentration of 0.33 mg / mL. Eleven aliquots, each approximately 3 mL, were taken. 0.1 mL each of the following eleven antibiotic solutions (100 μmol / L): marbofloxacin (MBF), enrofloxacin (ENR), norfloxacin (NOR), difloxacin hydrochloride (DIF), gentamicin sulfate (GM), amikacin sulfate (AMK), streptomycin sulfate (SM), ampicillin sodium (ABPC), clindamycin hydrochloride (ClM), lincomycin hydrochloride (LCM), and thiamphenicol (TMS) were added to one of the nickel-based MOF suspensions. After thorough dispersion, fluorescence changes were observed. At a wavelength of 368 nm, the fluorescence quenching rates caused by different antibiotics were as follows: MBF: 96%, NOR: 28%, ENR: 22%, ABPC: 17%, DIF: 13%, GM: 12%, SM: 10%, TMS: 9%, LCM: 7%, AMK: 4%, CLM: 3%. The extremely high fluorescence quenching rate of marbofloxacin indicates that the invented nickel-based metal-organic framework has a specific response to marbofloxacin.

[0039] Example 2

[0040] Preparation of nickel-based metal-organic frameworks

[0041] 5 mmol of 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid and 5 mmol of NiCl2·6H2O were dissolved in a mixed solvent of ultrapure water (8 mL) and acetonitrile (4 mL) to obtain a mixed solution. The mixed solution was transferred to a 15 mL stainless steel autoclave lined with polytetrafluoroethylene, sealed, and placed in a constant temperature oven. The reaction was carried out at 160 °C for 1 day, and then slowly cooled to room temperature at a rate of 20 °C / h. The solid was filtered, thoroughly washed with acetonitrile, and then vacuum dried to obtain a nickel-based metal-organic framework material.

[0042] The obtained material is in powder form and crystallizes well.

[0043] XRD patterns of nickel-based metal-organic frameworks are shown below. Figure 6 As shown, the diffraction peak positions of the simulated spectrum based on single-crystal diffraction data are consistent with those of the measured spectrum of the powder sample, indicating that the obtained metal-organic framework has extremely high phase purity.

[0044] Application of nickel-based metal-organic frameworks in the detection of mabofloxacin

[0045] Nickel-based metal-organic framework powder was ultrasonically dispersed in ultrapure water to form a suspension with a concentration of 0.33 mg / mL. Eight portions, each approximately 3 mL, were taken. 0.1 mL of mabofloxacin solution with concentrations of 0 μmol / L, 1 μmol / L, 2 μmol / L, 3 μmol / L, 4 μmol / L, 5 μmol / L, 6 μmol / L, and 7 μmol / L, respectively, was added to each nickel-based metal-organic framework suspension. After uniform dispersion, fluorescence changes were observed, and the relationship between fluorescence intensity and mabofloxacin concentration was obtained, as shown in the figure. Figure 7 As shown.

[0046] Based on this curve, and using the Stern-Volmer equation (I0 / I = K) SV × [Q] + 1) The slope of the fitted regression equation is: K SV = 6.75 × 10 5 M -1 , which is the Stern-Volmer quenching constant. In the formula, I0 is the fluorescence intensity without the addition of marbofloxacin (quencher Q), I is the fluorescence intensity after the addition of marbofloxacin, and M is mol / L.

[0047] According to the formula for calculating the limit of detection: LOD = 3σ / K SV The calculated limit of detection (LOD) is as low as 0.013 μmol / L. In the formula, LOD is the limit of detection, and σ is the standard deviation of the blank sample. This demonstrates that the invented nickel-based metal-organic framework exhibits extremely high sensitivity to mabofloxacin, enabling rapid trace detection.

[0048] Example 3

[0049] Preparation of nickel-based metal-organic frameworks

[0050] 0.2 mmol of 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid and 0.2 mmol of NiCl2·6H2O were dissolved in a mixed solvent of ultrapure water (3 mL) and acetonitrile (6 mL) to obtain a mixed solution. The mixed solution was transferred into a 15 mL stainless steel autoclave lined with polytetrafluoroethylene, sealed, and placed in a constant temperature oven. The reaction was carried out at 120 °C for 3 days, and then slowly cooled to room temperature at a rate of 10 °C / h. The solid was filtered, thoroughly washed with acetonitrile, and then vacuum dried to obtain a nickel-based metal-organic framework material.

[0051] The resulting material is in the form of large-particle powder with good crystallization.

[0052] Application of nickel-based metal-organic frameworks in the detection of mabofloxacin

[0053] Nickel-based metal-organic framework powder was ultrasonically dispersed in ultrapure water to form a suspension with a concentration of 0.33 mg / mL. Five portions were taken, each about 3 mL. 0.1 mL of a mixed solution of different antibiotics with a concentration of 100 μmol / L was added to each portion of the nickel-based metal-organic framework suspension: (1) Marbofloxacin MBF + Enrofloxacin ENR, (2) Marbofloxacin MBF + Norfloxacin NOR + Difloxacin Hydrochloride DIF, (3) Marbofloxacin MBF + Gentamicin Sulfate GM + Amikacin Sulfate AMK + Streptomycin Sulfate SM, (4) Marbofloxacin MBF + Ampicillin Sodium ABPC + Clindamycin Hydrochloride ClM + Lincomycin Hydrochloride LCM + Thiamphenicol TMS, (5) Enrofloxacin ENR + Norfloxacin NOR + Streptomycin Sulfate SM + Ampicillin Sodium ABPC + Lincomycin Hydrochloride LCM. After uniform dispersion, the fluorescence changes were observed. The fluorescence quenching rates observed at 368 nm for different mixed antibiotics were 91%, 92%, 99%, 97%, and 26%, respectively. This shows that the invented nickel-based metal-organic framework has excellent environmental resistance to the detection of marbofloxacin. In the mixed solutions of different antibiotics in (1)-(5) above, each antibiotic was in equimolar proportion.

[0054] Example 4

[0055] 0.05 mmol of 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid and 0.05 mmol of NiCl₂·6H₂O were dissolved in a mixed solvent of ultrapure water (3 mL) and N,N-dimethylacetamide (3 mL) to obtain a mixed solution. This solution was transferred to a 15 mL stainless steel autoclave lined with polytetrafluoroethylene, sealed, and placed in a constant temperature oven. The reaction was carried out at 140 °C for 2 days, and then slowly cooled to room temperature at a rate of 5 °C / h. Nickel-based metal-organic framework materials were not obtained.

[0056] Example 5

[0057] 0.2 mmol of 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid and 0.2 mmol of NiCl₂·6H₂O were dissolved in a mixed solvent of ultrapure water (4 mL) and N-methylpyrrolidone (4 mL) to obtain a mixed solution. This solution was transferred to a 15 mL polytetrafluoroethylene-lined stainless steel autoclave, sealed, and placed in a constant temperature oven. The reaction was carried out at 140 °C for 2 days, and then slowly cooled to room temperature at a rate of 5 °C / h. Nickel-based metal-organic framework materials were not obtained.

[0058] Example 6

[0059] 0.05 mmol of 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid and 0.05 mmol of NiCl₂·6H₂O were dissolved in a mixed solvent of ultrapure water (3 mL) and acetonitrile (3 mL) to obtain a mixed solution. This solution was transferred to a 15 mL polytetrafluoroethylene-lined stainless steel autoclave, sealed, and placed in a constant temperature oven. The reaction was carried out at 100 °C for 2 days, and then slowly cooled to room temperature at a rate of 5 °C / h. Nickel-based metal-organic framework materials were not obtained.

[0060] Example 7

[0061] 0.05 mmol of 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid and 0.05 mmol of NiCl₂·6H₂O were dissolved in a mixed solvent of ultrapure water (3 mL) and acetonitrile (3 mL) to obtain a mixed solution. This solution was transferred to a 15 mL stainless steel autoclave lined with polytetrafluoroethylene, sealed, and placed in a constant temperature oven. The reaction was carried out at 180 °C for 2 days, and then slowly cooled to room temperature at a rate of 5 °C / h. Nickel-based metal-organic framework materials were not obtained.

[0062] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0063] It should be noted that the above content merely illustrates the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. For those skilled in the art, various improvements and modifications can be made without departing from the principle of the present invention, and all such improvements and modifications fall within the scope of protection of the claims of the present invention.

Claims

1. A nickel-based metal-organic framework, characterized in that, The nickel-based metal-organic framework is a crystal structure formed by coordination of 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid with nickel ions (Ni(II)). The asymmetric unit in the crystal structure consists of two Ni(II) ions with different coordination environments and two 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid ligand molecules. One Ni(II) ion coordinates with the carboxyl oxygen of one 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid ion, and the three nitrogen atoms and two chloride ions of the other 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid ion to form an octahedral structure. In this structure, another Ni(II) coordinates with the carboxyl oxygen of one 2,6-bis(1H-pyrazole-1-yl)isonicotinic acid, the three nitrogen atoms of the other 2,6-bis(1H-pyrazole-1-yl)isonicotinic acid, and two water molecules to form an octahedral structure, thereby forming a chain structure of "—Ni(II)—2,6-bis(1H-pyrazole-1-yl)isonicotinic acid—Ni(II)—2,6-bis(1H-pyrazole-1-yl)isonicotinic acid—". The chain structures are arranged in parallel to form a two-dimensional layered structure, and the two-dimensional layers are stacked to form a three-dimensional metal-organic framework crystal structure. The crystal structure is crystallized in the triclinic system, space group P-1, with cell parameters a=8.9411(9) Å, b=10.7445(11) Å, c=14.8864(16) Å, α=69.207(2)°, β=89.682(3)°, γ=85.311(2)°.

2. The method for preparing a nickel-based metal-organic framework as described in claim 1, characterized in that, Includes the following steps: (1) Dissolve 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid and NiCl2·6H2O in a mixed solvent of ultrapure water and acetonitrile to form a mixed solution; (2) Transfer the mixture to a stainless steel autoclave lined with polytetrafluoroethylene; place the autoclave in an oven and react at 120~160℃ for 1~3 days, then slowly cool it to room temperature at a cooling rate of 5~20℃ / h. (3) The solid in the reaction solution was collected by filtration, then washed thoroughly with acetonitrile, and dried under vacuum to obtain a nickel-based metal-organic framework.

3. The method for preparing a nickel-based metal-organic framework according to claim 2, characterized in that, In step (1), the molar ratio of 2,6-bis(1H-pyrazole-1-yl)isonicotinic acid to NiCl2·6H2O is 1:1; the total concentration of 2,6-bis(1H-pyrazole-1-yl)isonicotinic acid and NiCl2·6H2O in the mixture is 0.01 mol / L~1 mol / L.

4. The method for preparing a nickel-based metal-organic framework according to claim 2, characterized in that, In step (1), the volume ratio of ultrapure water to acetonitrile in the mixed solvent is 0.5:1 to 2:

1.

5. The application of the nickel-based metal-organic framework as described in claim 1 in the detection of marbofloxacin antibiotic.

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