Antibiotic selection identification based on mixed MOFs composite material

Abstract

The invention relates to the technical field of recognition of porous composite materials, in particular to antibiotic selective recognition based on a mixed MOFs composite material, the Eu-MOF composite material obtained through the preparation method can conduct efficient and selective fluorescence sensing on biological medicine molecules such as antibiotics and is simple and easy to operate, and the obtained functional material is stable in chemical property and high in sensitivity. The MOFs has good optical performance, comprehensive analysis by using multiple detection methods finds that the MOFs have special fluorescence response to tetracycline, titration experiments and anti-interference experiments prove that the complex has high sensitivity and selectivity on tetracycline fluorescence recognition, the lowest detection limit is 0.23 mu M, the obtained material is prepared into test paper, and the test paper can be used for detecting tetracycline fluorescence. Therefore, rapid and visual detection is realized. Compared with the prior art, the compound synthesized in the invention is based on a mixed MOFs composite material, can be applied to molecular recognition of biological drugs such as antibiotics through fluorescence double response signals of the compound, and has a good application prospect in molecular recognition and detection of biological drugs such as antibiotics working in water or other solution systems.

Description

Technical Field

[0001] The invention relates to a type of antibiotic selective identification based on a mixed MOFs composite material, belonging to the technical field of identification of porous composite materials. Background Art

[0002] Antibiotics, as an important class of drugs, can effectively inhibit the proliferation of pathogenic microorganisms and are widely used in various fields of human medicine, animal husbandry, agriculture, aquaculture and other related disciplines. However, the abuse and widespread use of antibiotics can cause serious concerns. The presence of antibiotics in animals and the environment may penetrate into the human body through the food chain, disrupt normal metabolic processes, and change the microbial ecosystem, thus posing a direct threat to humans. Among the well-known antibiotics, tetracycline (TC) is widely used due to its high efficiency, low cost and broad-spectrum antimicrobial activity. At present, various conventional techniques such as high-performance liquid chromatography, tandem mass spectrometry, and surface-enhanced Raman spectroscopy have been widely reported for the detection of tetracycline. However, these methods usually require professional operating skills and need to perform complex sample pretreatment procedures, which are not suitable for real-time on-site detection to achieve the goal of rapid analytical detection. Therefore, a more rapid, selective and easy-to-handle detection method is essential for the development of antibiotic detection.

[0003] Metal-organic frameworks (MOFs) materials based on coordination are an important branch of porous materials. They are a type of crystalline porous materials with a periodic network structure formed by the self-assembly of inorganic metal centers (metal ions or metal clusters) and bridging organic ligands. MOFs materials have diverse pore structures, high surface area and porosity, pores with adjustable shapes and sizes, and easy-to-modify structures. As crystalline materials, MOFs have shown great potential in many fields, including gas storage, proton conductivity, molecular recognition, solid-phase catalysis, and separation and purification. With the continuous development of fluorescence sensing technology, MOFs-based fluorescence quenching methods have advantages such as low detection limit and low visual response, as well as the adjustable and stable size of MOFs cavities and channels, which make them highly selective and recyclable. In particular, Ln-MOFs composed of lanthanide ions (Ln) and organic ligands have attracted attention due to their strong, long-lived and precise emission in the visible light range. They can be used as multifunctional fluorescent probes, induced by significant fluorescence emission from lanthanide ions or constructed ligands under appropriate excitation. However, due to the forbidden ff transition, the excitation or emission of lanthanides in water faces major challenges. It is worth noting that functional groups, such as -NH2 and -COOH, can serve as potential sites for interaction with organic analytes, thus endowing them with good recognition ability, which is conducive to further study of their application in the detection of biopharmaceutical molecules such as antibiotics. Comprehensive analysis using multiple detection methods such as X-ray diffraction, fluorescence spectroscopy, infrared spectroscopy, ultraviolet spectroscopy, and X-ray photoelectron spectroscopy revealed that this MOFs has a special fluorescence response to tetracycline, which has important research significance in the rapid detection of antibiotic compounds in solution. Summary of the invention

[0004] In order to overcome the deficiencies in the prior art, the purpose of the present invention is to provide a class of antibiotic selection and identification based on mixed MOFs composite materials. The Eu-MOF composite material obtained by the preparation method of the present invention can perform efficient and selective fluorescence sensing of biological drug molecules such as antibiotics. It is simple and easy to operate. The obtained functional material has stable chemical properties and good optical properties, which provides the possibility for rapid and visual detection of tetracycline in solution.

[0005] In order to achieve the above-mentioned invention purpose and solve the problems existing in the prior art, the technical solution adopted by the present invention is: select two organic units with different characteristic luminescent properties as connecting ligands L1 and L2, and use Eu with a specific coordination mode in the rare earth metal salt Ln 3+ As nodes, a series of Eu-based 3 +The MOFs composite material, combined with its good dual-luminescence performance and structural characteristics, was further studied for its application in the detection of biological drug molecules such as antibiotics. Using a variety of detection methods such as X-ray diffraction, fluorescence spectroscopy, infrared spectroscopy, ultraviolet spectroscopy, and X-ray photoelectron spectroscopy, it was found that this MOFs has a special fluorescence response to tetracycline. Through titration experiments and anti-interference experiments, it was confirmed that the complex has high sensitivity and selectivity for fluorescence recognition of tetracycline, and its minimum detection limit is 0.23 μM. The obtained material was made into test paper to achieve rapid and visual detection.

[0006] 1. A type of antibiotic selection and identification based on mixed MOFs composite materials, which is characterized by the following steps: (1) Select two organic units with different characteristic luminescent properties as connecting ligands L1 and L2; (2) Eu with a specific coordination mode in rare earth metal salt Ln 3+ As nodes, a series of Eu-based 3+ The MOFs composite material has the following synthesis route: Ln + L1 + L2 → Ln-L; (3) The prepared MOFs composite material is used for selectively identifying a series of antibiotic compounds, using the good luminescence performance of the mixed ligand as a visual output dual signal, and performing a specific identification process based on the difference in fluorescence between a series of antibiotic compounds and the selected MOFs composite material; The rare earth metal salt is selected from Eu(NO3)3; The organic linking ligand L1 is 2,6-dicarboxylic acid pyridine (DPA), and L2 is 2-aminoterephthalic acid (BDC-NH2).

[0007] 2. The antibiotic selection and identification based on the mixed MOFs composite material comprises the following steps: (1) dissolving organic ligands L1 and L2 in a certain proportion in a mixed solvent of a certain amount of ethanol and triethylamine, and stirring the mixture at room temperature to obtain solution A; (2) Dissolve the rare earth metal salt EuCl3·6H2O in 5 mL of deionized water to obtain solution B; (3) The solution A and solution B prepared in the above steps were mixed and reacted at 40°C for 2 hours. The cooled samples were collected, washed with ethanol and dried at low temperature to obtain the final product; The ratio of L1 to L2 used in the synthesis method is in the range of 1 to 24:1.

[0008] 3. The selective identification of antibiotics based on mixed MOFs composite materials comprises the following steps: (1) The properties of the prepared series of composite materials were screened, and finally the Eu-DMB-2 sample with the best morphology, crystal phase, and double-peak fluorescence emission was selected as the fluorescence recognition sensor; (2) The fluorescence effects of various antibiotic compounds were examined in a 3 mL Eu-DMB-2 suspension, and the different quenching effects on the fluorescence response of the suspension were ranked under the same conditions; (3) Compare the differences in the fluorescence effects of different antibiotics and amino acid compounds on the selected Eu-DMB-2 MOFs composite material based on the algorithm to determine the specific selectivity and sensitivity of recognition; The antibiotic and amino acid compound are selected from one of HIS, SER, ARG, MET, TYR, ERY, AZI, MTZ, SDZ, AMO and TC.

[0009] Beneficial results of the present invention The advantages of the present invention are: a type of lanthanide metals with dual fluorescence response are selected as building nodes and assembled with mixed ligands to obtain a type of lanthanide-mixed MOFs composite materials with dual fluorescence response; its good dual response signal can selectively identify tetracycline in a series of antibiotics and amino acid compounds, and realize a visualized identification and detection process; and further design this identification process as a test paper, providing convenient conditions for more convenient and rapid tetracycline detection; compared with the existing technology, the compound synthesized in the present invention is a lanthanide-mixed MOFs composite material with dual fluorescence response, and the composite material with the optimal mixing ratio is used in the identification application of antibiotic compounds through performance evaluation, and this work has good application prospects in the identification and detection of antibiotic compounds in water or other solution systems. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 This is a schematic diagram of the synthesis of mixed MOFs composite materials.

[0011] Figure 2 This is a scanning electron microscope image of the mixed MOFs composite material.

[0012] Figure 3 It is the X-ray powder diffraction pattern of mixed MOFs composite material.

[0013] Figure 4 This is the fluorescence spectrum of the mixed MOFs composite material under 254 nm excitation.

[0014] Figure 5 It is a molecular structure diagram of antibiotics and amino acid chemicals used in identification research.

[0015] Figure 6 This is a histogram of the fluorescence intensity of the target material tetracycline in Example 1.

[0016] Figure 7 This is a graph of the target material identification tetracycline titration experiment in Example 1. DETAILED DESCRIPTION

[0017] The present invention will be further described below in conjunction with the embodiments.

[0018] Weigh 0.5 mmol of the ligand DPA and BDC-NH2 in total, mix and dissolve them in 15 mL of ethanol and 1 mmol of triethylamine in a ratio of 2:1, 5:2, 9:1 and 24:1, respectively, then add 5 mL of the dissolved EuCl3·6H2O (0.23 mmol, 91.5 mg) solution, mix the two and react at 40°C for 2 hours, collect the cooled samples, wash with ethanol and dry at low temperature to obtain the final product.

[0019] The fluorescence response of the prepared mixed MOFs composite materials in the solid state was tested respectively. Under the excitation wavelength of 254 nm, five characteristic absorption peaks were observed in the range of 550-720 nm, which were 580, 592, 616, 650 and 693 nm, respectively, which can be attributed to the rare earth ion Eu 3+ In addition, a strong absorption peak appears at 432 nm, which can be attributed to the ligand BDC-NH2, and the intensity of this absorption peak increases with the increase of the mixing ratio of the ligand BDC-NH2.

[0020] Eu-DMB-2 with the best dual fluorescence emission in Example 2 was selected as the fluorescent probe, and the characteristic emission peaks of 432 and 616 nm were selected as the dual fluorescence response signals. 0.6 mg of the composite material prepared in Example 1 was weighed and dispersed in 3 mL of water, and 80 μM of metronidazole (MTZ), sulfamethoxazole (SDZ), erythromycin (ERY), azithromycin (AZI), amoxicillin (AMO), and amino acid compounds methionine (MET), arginine (ARG), serine (SER), tyrosine (TYR) and histidine (HIS) were added thereto respectively, and ultrasonic vibration was performed for 30 min later, under the same test conditions, the above suspension system was subjected to fluorescence test, and it was observed that the fluorescence emission intensity was reduced to varying degrees. The fluorescence intensity after adding different aromatic nitro compounds was ranked in order from high to low according to the fluorescence signal intensity: HIS>SER>ARG>MET>TYR>ERY>AZI>MTZ>SDZ>AMO>>TC, and the fluorescence quenching effect on TC was the most significant. Photos of different fluorescence responses were taken.

[0021] According to the test results of Example 3, TC was prepared into a 0.2 g / L solution, and 20, 40, 60, 80, 100, 150, 200, and 300 μM TC solutions were respectively added dropwise to a solution containing 0.6 mg of the compound prepared in Example 1. Under excitation at a wavelength of 254 nm, it was observed that the fluorescence emission intensities at 432 and 616 nm gradually decreased. Compared with the case where no TC solution was added, after adding 300 μM TC solution, the fluorescence intensity was reduced to 9.1% of the previous level, and the fluorescence was almost quenched, so it had a sensitive detection effect, and its minimum detection limit was 0.23 μM.

[0022] In order to achieve rapid and convenient visual detection of tetracycline in the solution, the filter paper strip was immersed in an aqueous solution containing 2 mg of the compound prepared in Example 1, and taken out and dried after 24 h to prepare a test paper. The concentration gradient of 1.0 × 10 -6 mol / L, 1.0 × 10 -5 mol / L, 1.0 × 10 -4 mol / L, 1.0 × 10 -3 mol / L and 1.0 × 10 -2 mol / L tetracycline solution, the test paper fluorescence signal changes color as a colorimetric card, which can be used for qualitative analysis of the tetracycline concentration in the solution.

Claims

1. A class of antibiotic selection and identification based on mixed MOFs composite materials, which is characterized by the following steps: (1) Select two organic units with different characteristic luminescent properties as connecting ligands L1 and L2; (2) Eu with a specific coordination mode in rare earth metal salt Ln 3+ As nodes, a series of Eu-based 3+ The MOFs composite material has the following synthesis route: Ln + L1 + L2 → Ln-L; (3) The prepared MOFs composite material is used for selective identification of a series of antibiotics and amino acid compounds, and the good luminescence performance of the mixed ligand is used as a visual output dual signal. According to the difference in the fluorescence effect between a series of antibiotic compounds and the selected MOFs composite material, a specific identification process is performed; The rare earth metal salt is selected from Eu(NO3)3; The organic linking ligand L1 is 2,6-dicarboxylic acid pyridine (DPA), and L2 is 2-aminoterephthalic acid (BDC-NH2).

2. The aforementioned class of antibiotic selection and identification based on mixed MOFs composite materials, wherein the material synthesis method comprises the following steps: (1) dissolving organic ligands L1 and L2 in a certain proportion in a mixed solvent of a certain amount of ethanol and triethylamine, and stirring the mixture at room temperature to obtain solution A; (2) Dissolve the rare earth metal salt EuCl3·6H2O in 5 mL of deionized water to obtain solution B; (3) The solution A and solution B prepared in the above steps were mixed and reacted at 40°C for 2 hours. The cooled samples were collected, washed with ethanol and dried at low temperature to obtain the final product; The ratio of L1 to L2 used in the synthesis method is in the range of 1 to 24:

1.

3. The selective identification of antibiotics based on mixed MOFs composite materials comprises the following steps: (1) The properties of the prepared series of composite materials were screened, and finally the Eu-DMB-2 sample with the best morphology, crystal phase, and double-peak fluorescence emission was selected as the fluorescence recognition sensor; (2) The fluorescence effects of various antibiotics and amino acid compounds were examined in a 3 mL Eu-DMB-2 suspension, and the different quenching effects of the suspension fluorescence response were ranked under the same conditions; (3) Compare the differences in the fluorescence effects of different antibiotics and amino acid compounds on the selected Eu-DMB-2 MOFs composite material based on the algorithm to determine the specific selectivity and sensitivity of recognition; The antibiotic and amino acid compound are selected from one of HIS, SER, ARG, MET, TYR, ERY, AZI, MTZ, SDZ, AMO and TC.

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