Fe3O4-COOH-coated ZIF-8-pDA-coated MIPs composite material and preparation method and application thereof

Abstract

The invention discloses a Fe3O4-COOH (at) ZIF-8-pDA (at) MIPs composite material as well as a preparation method and application thereof. The material comprises carboxyl functionalized magnetic MOFs (Fe3O4-COOH (at) ZIF-8) and a synthesized molecularly imprinted composite material (Fe3O4-COOH (at) ZIF-8-pDA (at) MIPs) loaded on the carboxyl functionalized magnetic MOFs (Fe3O4-COOH (at) ZIF-8). The application of the composite material is that the composite material is applied to pretreatment and enrichment of macrolide antibiotics in an environmental water sample by a magnetic solid phase extraction (MSPE) technology. According to the molecularly imprinted composite material disclosed by the invention, rapid, sensitive and strong-specificity extraction can be realized by using a small amount of adsorbent and sample in a short time, and the molecularly imprinted composite material is economical and applicable. According to the method, the adsorption extraction agent can be screened, designed, regulated and controlled according to the structure of the target analyte, a new thought is provided for analysis of other environmental pollutants, and the method is of great significance to environmental risk assessment, pollutant control and public health.

Description

Technical Field

[0001] The present invention belongs to the technical field of materials, and specifically relates to a Fe3O4-COOH@ZIF-8-pDA@MIPs composite material and a preparation method and application thereof. Background Art

[0002] Macrolide antibiotics are a class of broad-spectrum antibiotics with macrolide rings in their structures. They are widely used in aquaculture, animal husbandry and human infection treatment. Due to their stable structure and low biodegradability, these antibiotics are difficult to completely remove in metabolism and water treatment, and are frequently detected in the water environment, posing a potential threat to human health and the ecological environment. Erythromycin, clarithromycin and azithromycin have been included in the watch list of potentially hazardous compounds in the aquatic environment, and countries have also included antibiotics in the list of new pollutants under key control. The existing detection technology of macrolide antibiotics has problems such as insufficient sensitivity, weak selectivity and high detection limit. Especially in complex water environments, it is difficult to achieve accurate and efficient detection due to their low concentration and numerous interfering substances. In addition, the traditional detection methods are not efficient in enriching and separating low-concentration samples, and it is difficult to ensure accurate detection in a variety of matrices. Therefore, it is necessary to develop new materials and methods to improve the sensitivity and selectivity of detection.

[0003] Although existing materials have shown potential in the detection of macrolide antibiotics, they still have some defects. Their synthesis process is complex and costly, which affects large-scale application; at the same time, the stability and repeatability of the materials may decrease in harsh environments or long-term use, and template removal may damage the recognition site, limiting reuse. In addition, the adsorption selectivity still needs to be improved in complex matrices. These problems further limit its wide range of practical applications.

[0004] Molecularly imprinted polymers (MIPs) are a class of cross-linked polymers with specific recognition functions, which are widely used in pollutant removal and environmental analysis, such as antibiotic detection, solid phase extraction and sensor recognition. The basic principle is to form specific recognition vacancies by combining functional monomers with target molecules and then cross-linking polymerization. After the template molecules are removed, these vacancies can efficiently recognize and capture similar molecules. MIPs play a key role in the separation and enrichment of target molecules due to their high selectivity. Metal-organic framework materials (MOFs) are porous materials composed of metal ions or metal clusters bridged by organic ligands. They have high specific surface area, adjustable pore size, good thermal stability and chemical resistance. One of the classic MOFs materials, the zeolite imidazolate framework (ZIF-8), is composed of low-toxic Zn 2+ The lattice structure is formed by coordination with 2-methylimidazole (2-MIM). These excellent structures and properties make MOFs show great application potential in the extraction and enrichment analysis of environmental pollutants.

[0005] Metal organic framework molecular imprinted polymer (MOFs@MIPs) as a composite material combines the specific adsorption of MIPs with the structural stability and multiple active sites of MOFs, significantly improving the adsorption efficiency. During the synthesis process, the introduction of MOFs increases the specific surface area, adjustable pore size and stable chemical properties, solving the problem of insufficient recognition sites. ZIF-8 has an adjustable pore structure and rich Zn 2+ and imidazole functional groups, effectively adsorbing macrolide antibiotics through non-covalent interactions such as hydrogen bonding, electrostatic interaction, and van der Waals forces. At the same time, the stability and mechanical properties of ZIF-8 enhance the durability of MIPs, making their application in complex environments more reliable. Summary of the invention

[0006] The present invention uses carboxyl functionalized ferroferric oxide (Fe3O4-COOH) loaded with a ZIF-8 skeleton as a precursor of a surface molecular imprinting polymer for the first time, and successfully prepares a composite material. This material is used as a magnetic solid phase extraction adsorbent for the pre-enrichment treatment of macrolide antibiotics in an aqueous phase, and has the characteristics of strong specificity, rapidity and sensitivity. By designing and screening for the structure of the target, this composite material exhibits excellent extraction and enrichment capabilities. This technology has important application significance in the development of high-performance adsorbents for pollutants.

[0007] The purpose of the present invention is to provide a composite material based on metal organic framework loaded molecular imprinting polymer and its preparation method and application. The method prepares a hydrophilic molecular imprinting composite material by in-situ growing a ZIF-8 skeleton on the surface of Fe3O4-COOH, using erythromycin (ERY) as a template molecule and dopamine (DA) as a functional monomer and cross-linking agent. This composite material is used for the first time as a high-specificity magnetic solid phase extractor for pre-enrichment of macrolide antibiotics, and is used to treat macrolide antibiotics in environmental water samples.

[0008] The specific technical solution for achieving the purpose of the present invention is:

[0009] A method for preparing a Fe3O4-COOH@ZIF-8-pDA@MIPs composite material, characterized in that the method comprises the following steps:

[0010] (1) Preparation of Fe3O4-COOH materials

[0011] First, ferric chloride hexahydrate, sodium acetate and sodium polyacrylate in a molar ratio of 4:50:1 are dispersed in a mixed solution of ethylene glycol and diethylene glycol in a volume ratio of 1:2; then, the solution is transferred to a polytetrafluoroethylene-lined autoclave reactor, sealed and placed in an oven at 180-220°C for reaction for 8-12 hours; after the reaction is completed, the autoclave is cooled to room temperature, and the product is washed with water and ethanol for multiple times; finally, it is dried in a vacuum oven to constant weight to obtain Fe3O4-COOH;

[0012] (2) Preparation of Fe3O4-COOH@ZIF-8 materials

[0013] Zinc nitrate hexahydrate and hexadecyltrimethylammonium bromide in a molar ratio of 200:3 were dispersed in a methanol solution and stirred to form solution A; at the same time, Fe3O4-COOH and 2-MIM were dispersed in 80 mL of methanol solution in a mass ratio of 1:15 and stirred to form solution B; then, solution A was quickly poured into solution B, and then stirred at room temperature for 1-3 hours; separated by a magnet, washed with methanol 3 times, and finally dried in a vacuum drying oven at 40-60°C to obtain Fe3O4-COOH@ZIF-8 material;

[0014] (3) Preparation of Fe3O4-COOH@ZIF-8-pDA@MIPs

[0015] First, the Fe3O4-COOH@ZIF-8 obtained in step (2) is dispersed in a Tris-HCl buffer solution with a pH of 8.5 and a concentration of 0.010M, and ultrasonically treated for 5-10 minutes. Erythromycin (ERY) is added and stirred for 1-2 hours. Dopamine (DA) is then added and mechanically stirred for 4-6 hours. The product is washed three times with water. Finally, a methanol-acetic acid solution with a volume ratio of 95-90:5-10 is used as an eluent to assist ultrasonic oscillation in removing the template molecule ERY. The eluent is replaced every 2 hours until the elution is terminated when no ERY is detected in the supernatant. The composite material is separated from the eluent by a magnet, washed with water six times, and vacuum dried at 40-60°C for 10-12 hours to obtain the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material.

[0016] A Fe3O4-COOH@ZIF-8-pDA@MIPs composite material prepared by the above method.

[0017] Furthermore, the composite material Fe3O4-COOH@ZIF-8-pDA@MIPs has a specific surface area of ​​600-900m 2 g -1 , has a stable three-dimensional pore structure, and contains coordination, hydrogen bonding and electrostatic units.

[0018] The composite material, wherein the imprinting factor (IF) is expressed as the binding ability of the material to the target molecule (Q MIPs ) and the binding capacity to non-target molecules or interferents (Q NIPs ) is used to measure the selectivity and recognition ability of the material to the target molecule. It can be calculated by the following formula: The imprinting factor of the composite material to macrolide antibiotics is 8-13.

[0019] The composite material, wherein the enrichment factor (EF) is defined as the concentration of the target analyte after the sample is enriched (C m ) to the concentration before enrichment (C0), which is used to evaluate the efficiency of the extraction method and its ability to increase the concentration of the target analyte. It can be calculated by the following formula: The extraction and enrichment capacity of the macrolide antibiotics of the composite material is 500×R, and the material has units such as coordination, hydrogen bonding and electrostatic action.

[0020] An application of the composite material in detecting macrolide antibiotics in water samples. The composite material can effectively improve the detection sensitivity through enrichment and extraction, thereby significantly reducing the detection limit.

[0021] The applications specifically include:

[0022] 1) Using the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material as a magnetic solid phase extraction adsorbent, the composite material and the water sample were evenly mixed at a ratio of 1 mg / mL;

[0023] 2) After adsorption and extraction equilibrium for 5-10 minutes, the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material is separated by a permanent magnet, and desorption is completed by ultrasonic oscillation of acetonitrile solvent for 2-10 minutes;

[0024] 3) After desorption is complete, collect the eluate and filter it with a 0.22 μm glass fiber organic filter membrane;

[0025] 4) The original water sample and the eluate obtained after filtration were purged and concentrated under nitrogen protection at a ratio of 500:1;

[0026] 5) After HPLC injection analysis, export the data for processing;

[0027] 6) The standard curve was drawn based on the concentration of macrolide antibiotics and their peak area, and the linear regression equation and correlation coefficient (R 2 ), where R 2It is an indicator of the ability of the model to interpret data in linear regression. The closer the value is to 1, the better the model fitting effect is. The linear range of the method for detecting macrolide antibiotics in water based on Fe3O4-COOH@ZIF-8-pDA@MIPs composite material is 0.10-500μg L -1 , R 2 >0.9994;

[0028] 7) Calculate the specific concentration of the macrolide antibiotic in the application according to the linear regression equation; calculate the specific enrichment multiple of the macrolide antibiotic in the application according to the enrichment factor formula; calculate the specific extraction recovery rate of the macrolide antibiotic in the application according to the extraction recovery rate calculation formula; the detection limit (LOD) is usually defined as the lowest concentration corresponding to the signal-to-noise ratio (S / N) of the chromatographic peak equal to 3.

[0029] Furthermore, the macrolide antibiotics in the water sample include any one or more of erythromycin (ERY), dirithromycin (DIR), clarithromycin (CLA), roxithromycin (ROX) and azithromycin (AZI).

[0030] Furthermore, the adsorption capacity of macrolide antibiotics by the application is 100-300 mg g -1 , imprinting factors were 8-13, extraction recoveries were 90.6-109.0%, enrichment factors were 295-582, and the detection limit was 0.02 μg L -1 -0.05 μg L -1 .

[0031] In high performance liquid chromatography (HPLC), the signal-to-noise ratio (S / N) is an important parameter used to evaluate the performance of the detector and the quality of the signal. The signal-to-noise ratio is defined as the ratio of the average power of the signal (S) to the average power of the noise (N), where:

[0032] S represents the power of the signal, usually expressed in watts (W) or milliwatts (mW). Signal power refers to the signal strength of the sample component received by the detector.

[0033] N represents the power of the noise, also expressed in watts (W) or milliwatts (mW). Noise power includes various interference factors, such as electromagnetic wave interference, noise from electronic components inside the transmitter, etc.

[0034] The calculation formula of signal-to-noise ratio is: signal-to-noise ratio = 101g (S / N), the unit is dB (decibel). The higher this ratio is, the better the signal quality is and the less noise interference is. For example, if S / N = 1000, then signal-to-noise ratio = 10*3 = 30dB, which means that the signal strength is 1000 times the noise strength and the signal quality is good.

[0035] The advantages and beneficial effects of the present invention include:

[0036] The method of the present invention loads ZIF-8 onto carboxylated ferroferric oxide magnetic nanomaterials, and uses the material as a carrier to perform surface molecular imprinting polymerization on the surface of the material, thereby successfully preparing a Fe3O4-COOH@ZIF-8-pDA@MIPs composite material.

[0037] The method of the present invention makes full use of the metal organic framework material ZIF-8 with high porosity, large specific surface area and stable structure to increase the number and stability of active groups of the imprinted material, thereby effectively improving the specific adsorption efficiency of MIPs.

[0038] The method of the present invention makes full use of the advantages of surface molecular imprinting polymerization, such as simple synthesis steps, high mass transfer rate and easy template elution. It combines Fe3O4-COOH@ZIF-8 magnetic porous material for the first time and uses the hydrophilic compound dopamine as a functional monomer and cross-linking agent to synthesize MIPs, thereby achieving effective adsorption of macrolide antibiotics.

[0039] The method of the present invention designs and synthesizes the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material based on the structural and functional group characteristics of macrolide antibiotics, combining the specific adsorption capacity of molecular imprinting polymers (MIPs) with the structural stability and multiple active sites of metal organic frameworks (MOFs). This composite material is used for the first time as an adsorbent for magnetic solid phase extraction of macrolide antibiotics in pretreated water. Through coordination, hydrogen bonding and electrostatic forces, the composite material can efficiently extract and enrich macrolide antibiotics, achieving more accurate detection of macrolide antibiotics in complex environmental samples.

[0040] The composite nanomaterial provided by the present invention has efficient recovery and strong extraction ability for macrolide antibiotics. The method has strong specificity, high sensitivity, strong anti-interference ability, simple operation, small amount of sample and extractant, short extraction time, and is a fast, efficient, economical and applicable macrolide antibiotic detection and analysis technology. The present invention has been successfully applied to the simultaneous extraction and analysis of multiple macrolide antibiotics in complex environmental water samples, with excellent adsorption specificity and high detection sensitivity. This design concept provides a new solution for the monitoring and analysis of other environmental pollutants, and is of great significance for the monitoring and analysis of antibiotics in new pollutants. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1SEM and TEM characterization (A), XRD characterization (B), FTIR characterization (C), and N2 adsorption-desorption isotherm (D) of the composite material Fe3O4-COOH@ZIF-8-pDA@MIPs synthesized in Example 1;

[0042] Figure 2 The structural formulas of five macrolide antibiotics and competing compounds are shown below;

[0043] Figure 3 A is the adsorption efficiency of five macrolide antibiotics by Fe3O4-COOH@ZIF-8-pDA@MIPs at different pH; 3B is the Zeta potential of Fe3O4-COOH@ZIF-8-pDA@MIPs at different pH; 3C, 3D, 3E, and 3F are the effects of different pH, adsorbent dosage, eluent type, and eluent volume on the extraction efficiency of macrolide antibiotics.

[0044] Figure 4 A is the selective adsorption effect of the composite material Fe3O4-COOH@ZIF-8-pDA@MIPs / NIPs on the mixed antibiotic samples; Figure 4 B is the comparison of adsorption performance of composite materials based on different carriers; Figure 4 C is the effect of different mass ratios of Fe3O4-COOH and ZIF-8 on the composite material;

[0045] Figure 5 The chromatograms of five macrolide antibiotics are shown below: the chromatographic peaks correspond to ERY, DIR, CLA, ROX and AZI respectively. DETAILED DESCRIPTION

[0046] The present invention is further described in detail with reference to the following specific examples and drawings. The process, conditions, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are all common knowledge and common common sense in the art and are not particularly limited by the present invention.

[0047] The present invention aims to prepare MOFs porous materials by loading ZIF-8 onto Fe3O4-COOH through rationally designed functional groups according to the structural characteristics of macrolide antibiotics, and then participate in the preparation of surface molecular imprinting composite materials. This composite material is used as a magnetic solid phase extraction (MSPE) adsorbent, combined with high performance liquid chromatography (HPLC), to achieve rapid and accurate enrichment detection of macrolide antibiotics in environmental water samples.

[0048] The present invention proposes a Fe3O4-COOH@ZIF-8-pDA@MIPs composite material, in which the ratio of the adsorption amount of macrolide antibiotics by the imprinted material Fe3O4-COOH@ZIF-8-pDA@MIPs and the non-imprinted material Fe3O4-COOH@ZIF-8-pDA@NIPs is defined as the imprinting factor, that is, the ratio of the material's binding ability to the target molecule to its binding ability to the non-target molecule (or interferent), which is used to measure the material's selectivity and recognition ability to the target molecule.

[0049] The carboxyl functionalized magnetic MOFs material is Fe3O4-COOH@ZIF-8, in which the carboxyl groups on the surface of Fe3O4-COOH interact with the imidazolate groups in ZIF-8 and the Zn 2+ Ionic interactions.

[0050] Characteristics of Fe3O4-COOH@ZIF-8: Fe3O4-COOH@ZIF-8 material has a stable structure and efficient adsorption capacity. The carboxyl groups on the surface of Fe3O4 and Zn in ZIF-8 2+ The ions are stably bound by coordination bonds, and the oxygen atoms of the carboxyl groups form hydrogen bonds with the imidazolate groups in ZIF-8 to enhance the adsorption performance. In addition, the negative charge on the surface of Fe3O4-COOH may interact electrostatically with the positively charged functional groups in ZIF-8, further enhancing the interaction.

[0051] Characteristics of dopamine: Dopamine (DA) is a hydrophilic compound rich in amino and catechol groups. Using DA as a functional monomer can increase the solubility of MIPs materials in water, which helps to improve their interaction with macrolide antibiotics in an aqueous environment. At the same time, the phenolic hydroxyl groups of DA can undergo oxidative polymerization under alkaline conditions to generate cross-linked polydopamine (pDA). Therefore, DA can be used as a functional monomer and a cross-linking agent at the same time, covalently linked to the surface of a solid matrix, and achieve molecular imprinting polymerization with the template through hydrogen bonding and electrostatic interactions.

[0052] Characteristics of Fe3O4-COOH@ZIF-8-pDA@MIPs composite material: Fe3O4-COOH@ZIF-8-pDA@MIPs is a molecular imprinting composite material that forms selective imprinting holes for template molecules by polymerizing dopamine on the surface of magnetic Fe3O4-COOH@ZIF-8. This material significantly improves the extraction performance of macrolide antibiotics compared with uncarboxylated Fe3O4@ZIF-8 by using multiple chemical interaction units such as coordination, hydrogen bonding and electrostatic forces. Only 10 mg of the material is required, the adsorption equilibrium time is 5 minutes, and the extraction enrichment multiple of macrolide antibiotics can reach 295-582 times.

[0053] The present invention proposes to use the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material as a magnetic solid phase extraction adsorbent for the detection and analysis of macrolide antibiotics in specific pre-enrichment water samples.

[0054] The macrolide antibiotics in the water sample include, but are not limited to, any one or more of erythromycin (ERY), dirithromycin (DIR), clarithromycin (CLA), roxithromycin (ROX) and azithromycin (AZI).

[0055] In the application of the present invention, the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material is used as an adsorbent in the magnetic solid phase extraction technology, combined with a high performance liquid chromatography-diode array detector (HPLC-DAD) to achieve accurate determination of macrolide antibiotics in water samples.

[0056] In the application of the present invention, the method combined with high performance liquid chromatography and its different detectors (such as ultraviolet detector, diode array detector, mass spectrometer detector, etc.) can complete the separation and detection analysis of various macrolide antibiotics.

[0057] The present invention also proposes a method for detecting and analyzing macrolide antibiotics in water samples using a Fe3O4-COOH@ZIF-8-pDA@MIPs composite material as an adsorbent. The method is a magnetic solid phase extraction technology for pre-treating water samples based on the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material, comprising:

[0058] (-) Preprocessing steps;

[0059] (ii) Chromatographic detection and analysis steps;

[0060] (III) Analysis and quantification steps of macrolide antibiotics.

[0061] Among them, (a) the pretreatment step specifically includes the following steps:

[0062] 1) Weigh 10 mg of Fe3O4-COOH@ZIF-8-pDA@MIPs composite material and disperse it in the water sample, and then ultrasonicate it for 5 min to form a uniform suspension;

[0063] 2) After 5 minutes of adsorption equilibrium, the adsorbent Fe3O4-COOH@ZIF-8-pDA@MIPs material was separated by a permanent magnet; the adsorbent was then soaked in acetonitrile (analytical grade) and desorbed under ultrasound;

[0064] 3) After desorption is complete, the adsorbent Fe3O4-COOH@ZIF-8-pDA@MIPs material is separated using a permanent magnet and the eluate is collected.

[0065] 4) The eluate was purged and concentrated to 200 μL under nitrogen protection, filtered with a 0.22 μm organic filter head, and bottled for HPLC-DAD injection analysis.

[0066] The (ii) chromatographic detection and analysis step uses a high performance liquid chromatography-diode array detector to complete the detection and analysis of macrolide antibiotics in the water sample.

[0067] In the (iii) analysis and quantification step of macrolide antibiotics, spiked water samples of macrolide antibiotics with different concentration gradients are prepared, and the peak area of ​​the measured component in each standard solution is used as the ordinate, and the concentration of the measured component in each standard solution is used as the abscissa to draw a standard working curve, and the sample is quantified using the standard working curve. Then, the spiked water sample is replaced with an environmental water sample of the same volume, and the detection concentration of each sulfonamide antibiotic in the environmental water sample is calculated using the standard working curve. The recovery rate of sulfonamide antibiotics is calculated according to the following formula (1):

[0068]

[0069] Among them, C sed and C0 represent the final concentrations of macrolide antibiotics in the concentrated and quantitative methanol and water samples, respectively; C sed and C0 are obtained by quantitative calculation of actual samples based on the standard working curve; V sed and V0 represent the volume of quantified methanol and the initial volume of water sample, respectively.

[0070] In the method, the ratio of the adsorption amount of macrolide antibiotics by the imprinted Fe3O4-COOH@ZIF-8-pDA@MIPs material and the non-imprinted Fe3O4-COOH@ZIF-8-pDA@NIPs material is the imprinting effect of the composite material, which is expressed by the imprinting factor (IF) and calculated according to the following formula:

[0071]

[0072] Q MIPs Q is the binding ability of the material to the target molecule; NIPs The material's ability to bind to non-target molecules or interferents;

[0073] The concentration ratio of the target analyte before and after enrichment of the material Fe3O4-COOH@ZIF-8-pDA@MIPs as an adsorbent is used to evaluate the efficiency of the extraction method and the ability to increase the concentration of the target analyte. It can be calculated by the following formula:

[0074]

[0075] C m , C0 are the concentrations of the target analyte after enrichment and before enrichment, respectively;

[0076] In the method, the imprinting factor of macrolide antibiotics is 8.04-12.51, the enrichment multiple is 295-582 times, the extraction recovery efficiency is 90.6-109.0%; the linear range is 0.10-500 μg L -1 , there may be slight deviations under different detectors.

[0077] In the present invention, the water samples include but are not limited to: environmental water samples such as river water, surface water, well water, tap water, and other water samples suitable for the application of the present invention.

[0078] Example 1

[0079] Synthesis of Fe3O4-COOH@ZIF-8-pDA@MIPs composites

[0080] (1) Preparation of Fe3O4-COOH material: First, 1.00 g of ferric chloride hexahydrate, 4.05 g of sodium acetate and 0.10 g of sodium polyacrylate were dispersed in a mixed solution of 14 mL of ethylene glycol and 26 mL of diethylene glycol. Then, the solution was transferred to a polytetrafluoroethylene-lined autoclave reactor, which was then sealed and placed in an oven at 200°C for reaction for 12 h. After the reaction, the autoclave was cooled to room temperature, and the product was washed with water and ethanol three times. Finally, it was vacuum dried at 40°C for 12 h to obtain Fe3O4-COOH.

[0081] (2) Preparation of Fe3O4-COOH@ZIF-8 material: 0.594 g of Zn(NO3)2·6H2O and 0.01 g of hexadecyltrimethylammonium bromide (CTAB) were dispersed in 20 mL of methanol solution and stirred to form solution A. At the same time, 0.30 g of Fe3O4-COOH obtained in step (1) above and 4.50 g of 2-MIM were weighed and dispersed in 80 mL of methanol solution and stirred to form solution B. Subsequently, solution A was quickly poured into solution B and then stirred at room temperature for 3 h. Separated by magnet, washed with methanol 3 times, and finally dried in a vacuum drying oven at 60 °C to obtain Fe3O4-COOH@ZIF-8 material.

[0082] (3) Preparation of Fe3O4-COOH@ZIF-8-pDA@MIPs / NIPs: First, 0.250 g of Fe3O4-COOH@ZIF-8 obtained in step (2) above was dispersed in 35 mL of Tris-HCl buffer (pH=8.5, 0.010 M), ultrasonically treated for 10 min, and 0.03 g of ERY was added and stirred for 2 h. Subsequently, 0.07 g of DA was added and mechanically stirred for 6 h. The product was washed three times with water. Finally, methanol-acetic acid solution (95:5, v / v) was used as an eluent to assist ultrasonic oscillation to remove the template molecule ERY. 20 mL of the eluent was replaced every 2 h until no ERY was detected in the supernatant. The composite material was separated from the eluent by a magnet, washed with water six times, and dried in vacuo at 40°C for 12 h before use. Without adding template molecule ERY, the same method was used to synthesize non-imprinted magnetic nanomaterials Fe3O4-COOH@ZIF-8-pDA@NIPs.

[0083] The Fe3O4-COOH@ZIF-8-pDA@MIPs composite material synthesized in Example 1 was characterized. Figure 1 SEM images of the MOFs porous materials Fe3O4-COOH@ZIF-8 and Fe3O4-COOH@ZIF-8-pDA@MIPs composites shown in A(a) and 1A(b). It can be seen from the figure that Fe3O4-COOH@ZIF-8 has a uniform particle size with an average particle size of about 250nm. Figure 1 The TEM images of Fe3O4-COOH and Fe3O4-COOH@ZIF-8 shown in A(c) and 1A(d) show that the ZIF-8 shell with a thickness of about 20 nm is coated on the Fe3O4-COOH surface in the form of clustered flowers, indicating that the surface of Fe3O4-COOH@ZIF-8 becomes rough due to the nanosized ZIF-8 crystals, which can provide a large specific surface area for the adsorbent. Figure 1 A(e) shows that DA forms a polydopamine imprinting layer of about 40 nm thick on the surface of Fe3O4-COOH@ZIF-8 through self-polymerization, and the overall coating layer of the material becomes thicker, which further illustrates the successful preparation of the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material. According to XRD characterization ( Figure 1B) It can be seen that the synthesized Fe3O4-COOH@ZIF-8-pDA@MIPs composite material presents the characteristic peaks of face-centered cubic Fe3O4, and the characteristic peaks in the range of 5-20° are consistent with the published ZIF-8 crystal form, indicating that the material was successfully prepared. According to the characteristic absorption peaks of Fe-O bonds, imidazole rings in ZIF-8 and Zn-N bonds observed in FT-IR characterization, it shows that Fe3O4-COOH was successfully prepared and ZIF-8 was successfully loaded.

[0084] Example 2

[0085] Application of the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material of the present invention as an adsorbent

[0086] The Fe3O4-COOH@ZIF-8-pDA@MIPs composite material prepared in Example 1 was used as an MSPE adsorbent, and combined with a high performance liquid chromatography-diode array detector (HPLC-DAD), a highly specific and sensitive enrichment detection of five macrolide antibiotics (including erythromycin (ERY), dirithromycin (DIR), clarithromycin (CLA), roxithromycin (ROX) and azithromycin (AZI)) in environmental water samples was achieved. The method includes a pretreatment step, a chromatographic detection and analysis step, and an analysis and quantification step of macrolide antibiotics.

[0087] (-) Preprocessing steps include the following:

[0088] 1) Weigh 10.0 mg of Fe3O4-COOH@ZIF-8-pDA@MIPs composite material, disperse it in 10.0 mL of water sample, and ultrasonicate it for 5 min to form a uniform suspension;

[0089] 2) After adsorption equilibrium, the permanent magnet is used to separate the adsorbent; the adsorbent is then soaked in 5.0 mL of acetonitrile and desorbed under ultrasound for 3 min;

[0090] 3) After desorption is complete, the permanent magnet separates the materials and collects the eluate;

[0091] 4) The eluate was purged and concentrated to 200 μL under nitrogen protection, filtered with a 0.22 μm organic filter head, and bottled for HPLC-DAD injection analysis.

[0092] (II) Chromatographic detection and analysis includes the following steps:

[0093] The detection and analysis of macrolide antibiotics in water samples was completed by high performance liquid chromatography-diode array detector, such as Figure 2 shown.

[0094] Among them, the liquid chromatography detection conditions are:

[0095] Chromatographic column: Shim-pack GIST C18-AQ, 5.0 μm, 4.6 mm id × 250 mm;

[0096] Flow rate: 0.9 mL min -1 ;

[0097] Injection volume: 20 μL;

[0098] Column temperature: 40°C;

[0099] Mobile phase: Mobile phase A, B, and C were composed of 50% methanol, 30% acetonitrile, and 20% dipotassium hydrogen phosphate solution (0.01 mol L -1 )composition.

[0100] (III) The analysis and quantification steps of macrolide antibiotics include the following:

[0101] 1) Prepare spiked water samples of macrolide antibiotics with different concentration gradients, preferably on the same day; use Fe3O4-COOH@ZIF-8-pDA@MIPs composite materials to complete the above pretreatment steps and chromatographic detection and analysis steps. Use the peak area of ​​the measured component in each standard solution as the ordinate and the concentration of the measured component in each standard solution as the abscissa to draw a standard working curve, and use the standard working curve to quantify the sample.

[0102] 2) Replace the spiked water sample with an environmental water sample of the same volume, complete the above pretreatment steps and chromatographic detection and analysis steps, and use the standard working curve to calculate the detection concentration of each macrolide antibiotic in the environmental water sample (ie, the actual sample).

[0103] 3) The recovery rate of macrolide antibiotics was calculated according to the following formula (1):

[0104]

[0105] Among them, C sed and C0 represent the final concentrations of macrolide antibiotics in the concentrated and quantitative methanol and water samples, respectively; C sed and C0 are obtained by quantitative calculation of actual samples based on the standard working curve; V sed and V0 represent the volume of quantified methanol and the initial volume of water sample, respectively.

[0106] Example 3

[0107] Comparison and optimization of adsorption conditions and properties of Fe3O4-COOH@ZIF-8-pDA@MIPs composites

[0108] (1) Design and performance comparison of MOFs porous materials:

[0109] As a MOFs material, imidazole framework-8 (ZIF-8) has many advantages in the application of composite materials MOFs@MIPs. First, the imidazole groups on its surface can form effective hydrogen bonds with functional groups such as hydroxyl and carbonyl in erythromycin to achieve the binding and adsorption of macrolide antibiotics, and the electrostatic effect provided by zinc ions further enhances the adsorption capacity. Secondly, ZIF-8 has the characteristics of medium-strength coordination bonds, stability in organic solvents or alkaline aqueous solutions, adjustable pore structure and huge specific surface area, and has a large number of active functional groups, which helps to enhance the adsorption of macrolide antibiotics.

[0110] In order to obtain molecular imprinting composites with better performance, Fe3O4@ZIF-8 and Fe3O4-COOH@ZIF-8 were used as carriers to synthesize MIPs, and the selective adsorption effects of the materials were compared. Figure 4 As shown in B, the adsorption rate of the target molecule by MIPs based on Fe3O4-COOH@ZIF-8 is significantly higher than that of MIPs based on Fe3O4@ZIF-8. This advantage stems from the fact that the carboxyl group (-COOH) provides more coordination atoms, which can form more coordination effects with the metal ions in ZIF-8, strengthen the binding of Fe3O4 nanoparticles to ZIF-8, and coat more ZIF-8 on the outer layer, effectively increasing the active sites and further improving the adsorption capacity and structural stability of the material. Therefore, the MIPs material based on Fe3O4-COOH@ZIF-8 performs better in terms of adsorption performance.

[0111] During material synthesis, the mass ratio of Fe3O4-COOH and ZIF-8 will affect the density of functional groups on the material surface and the pore structure. An appropriate amount of ZIF-8 can provide more adsorption sites and enhance the selectivity of MIPs, but too much may cause excessive coverage of the carrier surface, affecting the magnetic loading and adsorption performance of Fe3O4-COOH. Therefore, by optimizing the synthesis mass ratio, the best adsorption performance of the material can be achieved. Figure 4 As shown in Figure C, when the mass ratio of the two is 1:1.5, the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material has the best adsorption performance for template molecules.

[0112] (2) Effect of different pH on material adsorption performance:

[0113] Macrolide antibiotics are a class of lipophilic and basic antibiotics, characterized by containing a macrocycle with 12 - 16 carbon atoms and a sugar moiety with one or more glycosidic bonds. Existing studies have shown that under strong acid (pH ≤ 4) and strong base (pH ≥ 10) conditions, macrolide antibiotics will undergo intramolecular dehydration cyclization and lactone ring hydrolysis respectively, and erythromycin molecules decompose into by-products. Under weakly basic conditions, macrolide antibiotics can better maintain their original molecular state, which is beneficial to the formation of hydrogen bond interactions with MIPs. The pH value of the solution affects the ionic strength and charge state on the surface of the material and the target molecule. By changing the pH of the water sample between 5 - 10, the performance change of Fe3O4-COOH@ZIF-8-pDA@MIPs in adsorbing macrolide antibiotics was explored. As Figure 3 shown in A, MIPs have the best adsorption effect on macrolide antibiotics under weakly basic conditions (pH = 8 - 9), and the adsorption capacity of MIPs gradually decreases as the pH decreases. This is the result of the combined action of hydrogen bonds and electrostatic forces. Reported studies have shown that the pKa of macrolide antibiotics is between 8.73 - 9.03. When pH > 8.73, macrolide antibiotics are electrically neutral or negatively charged. Combining Figure 3 with the Zeta potential analysis in B, within this pH range, the material is positively charged. Therefore, the molecularly imprinted composite material and macrolide antibiotics can produce electrostatic attraction, further improving the adsorption capacity. Under weakly acidic conditions, the material is negatively charged, and when pH < pKa (macrolide antibiotics), macrolide antibiotics are positively charged. Although there is also electrostatic attraction between the two, under weakly acidic conditions, macrolide antibiotics will be protonated, inhibiting the hydrogen bond interaction between them and MIPs, and reducing the adsorption efficiency. Therefore, combining the experimental results and theoretical analysis, pH = 9 was selected as the optimal solution pH value for the adsorption experiment.

[0114] (3) Selective adsorption performance and extraction performance optimization of MOFs@MIPs:

[0115] To evaluate the adsorption specificity of Fe3O4-COOH@ZIF-8-pDA@MIPs, in addition to selecting 14-membered ring antibiotics with similar structures such as DIR, ROX, and CLA, and 15-membered ring antibiotics AZI with similar sizes, fluoroquinolone antibiotics (ofloxacin OFL), sulfonamide antibiotics (sulfadiazine SD), and tetracycline antibiotics (oxytetracycline OTC) were also selected as competitive targets to verify the adsorption selectivity of the material. As Figure 4As shown in A, macrolide antibiotics have a higher adsorption amount on the composite material, while antibiotics such as ofloxacin (OFL), sulfadiazine (SD) and oxytetracycline have a lower adsorption amount on MIPs due to their large structural differences and no or small effects on the recognition sites. The imprinting factors of macrolide antibiotics are as high as 8.04-12.51, while the imprinting factors of other types of antibiotics are only 0.96-1.37.

[0116] The optimized Fe3O4-COOH@ZIF-8-pDA@MIPs composite material was used as an MSPE adsorbent and combined with a high performance liquid chromatography-diode array detector to selectively pre-enrich macrolide antibiotics in environmental water samples. The specific steps were the same as those in Example 2. Figure 3 As can be seen from (CF), the extraction efficiency of macrolide antibiotics by the composite material based on Fe3O4-COOH@ZIF-8 gradually increases to 100%, and the chromatographic peak area of ​​the macrolide antibiotics recovered by extraction is sharp and symmetrical.

[0117] Example 4

[0118] Linear analysis and literature comparison of the present invention

[0119] The Fe3O4-COOH@ZIF-8 composite material prepared in Example 1 was used as an MSPE adsorbent and combined with a high performance liquid chromatography-diode array detector (HPLC-DAD) to achieve specific and sensitive detection of five macrolide antibiotics in environmental water samples. The specific steps were the same as those in Example 2.

[0120] In this embodiment, the data results of the linear analysis of macrolide antibiotics in the MSPE pretreated water samples are shown in Table 1 below; the spiked recovery data of macrolide antibiotics in the MSPE pretreated water samples are shown in Table 2; and the comparison of the MSPE method based on Fe3O4-COOH@ZIF-8-pDA@MIPs composite material as adsorbent and the methods in other literatures is shown in Table 3.

[0121] Table 1

[0122]

[0123]

[0124] Table 2

[0125]

[0126] ND:Not detectedTable 3

[0127]

[0128]

[0129] Comparison literature:

[0130] 1, Anal.Bioanal.Chem., 2008, 390, 2141-2150;

[0131] 2, Food Chem., 2012, 134, 553-558;

[0132] 3, Talanta, 2015, 137, 1-10;

[0133] 4, Microchim. Acta, 2018, 185, 203;

[0134] 5, Anal.Chim.Acta, 2011, 690, 269-274;

[0135] 6, J.Environ.Chem.Eng, 2022, 10(4): 108094;

[0136] 7, J.Pharm.Biomed, 2013, 86: 204-213;

[0137] 8, Anal. Methods, 2017, 9(20): 2990-2996.

[0138] Compared with other methods for determining macrolide antibiotics, the present invention has the advantages of fast adsorption (5 min) and high adsorption capacity (243.7 mg g -1 ), high enrichment factor (295-582) and low detection limit (0.02-0.05 μg L -1 ) and other advantages. In addition, while improving sensitivity, higher selectivity can be taken into account, and the imprinting factor reaches 8.04-12.51, indicating that the MOFs@MIPs composite material has better specific recognition performance for the target, achieving the purpose of pretreatment of high selectivity and trace analysis. All the results show that the MSPE method developed based on the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material of the present invention is an efficient, sensitive and economical detection and analysis method for macrolide antibiotics in water samples.

[0139] In summary, the present invention can be used in the carboxyl-functionalized magnetic MOF sThe surface of the (Fe3O4-COOH@ZIF-8) material is loaded with molecular imprinting polymers, and a Fe3O4-COOH@ZIF-8-pDA@MIPs molecular imprinting composite material is successfully prepared. The prepared composite material is used as an adsorbent for magnetic solid phase extraction. The present invention proposes for the first time the application of the composite material for the specific enrichment of macrolide antibiotics in the pre-treated water phase. The Fe3O4-COOH@ZIF-8-pDA@MIPs composite material of the present invention shows strong extraction and enrichment capabilities in actual water samples. The present invention combines high performance liquid chromatography to successfully develop a method for rapid, sensitive, efficient and economical detection of macrolide antibiotics in actual water samples. The method of the present invention has strong specificity, high sensitivity, strong anti-interference ability, simple operation, small sample and extractant dosage, short extraction time, and is a rapid, efficient and economical detection and analysis technology for macrolide antibiotics. The present invention has been successfully applied to the simultaneous extraction and analysis of multiple macrolide antibiotics in complex environmental water samples, and has excellent adsorption specificity and high detection sensitivity. This design idea provides a new solution for the monitoring and analysis of other environmental pollutants, and has important application value for the monitoring and analysis of antibiotics in new pollutants.

[0140] The protection content of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the present invention, changes and advantages that can be thought of by those skilled in the art are included in the present invention and are protected by the attached claims.

Claims

1. A method for preparing a Fe3O4-COOH@ZIF-8-pDA@MIPs composite material, characterized in that: The steps include: (1) Preparation of Fe3O4-COOH materials First, ferric chloride hexahydrate, sodium acetate and sodium polyacrylate in a molar ratio of 4:50:1 are dispersed in a mixed solution of ethylene glycol and diethylene glycol in a volume ratio of 1:2; then, the solution is transferred to a polytetrafluoroethylene-lined autoclave reactor, sealed and placed in an oven at 180-220°C for reaction for 8-12 hours; after the reaction is completed, the autoclave is cooled to room temperature, and the product is washed multiple times with water and ethanol respectively; finally, it is dried in a vacuum oven to constant weight to obtain Fe3O4-COOH; (2) Preparation of Fe3O4-COOH@ZIF-8 materials Disperse zinc nitrate hexahydrate and hexadecyltrimethylammonium bromide in a molar ratio of 200:3 in a methanol solution and stir to form solution A; at the same time, disperse Fe3O4-COOH and 2-MIM in a mass ratio of 1:15 in 80 mL of a methanol solution and stir to form solution B; then, quickly pour solution A into solution B and stir at room temperature for 1-3 hours; The mixture was separated by a magnet, washed with methanol for three times, and finally dried in a vacuum drying oven at 40-60°C to obtain Fe3O4-COOH@ZIF-8 material; (3) Preparation of Fe3O4-COOH@ZIF-8-pDA@MIPs First, the Fe3O4-COOH@ZIF-8 obtained in step (2) is dispersed in a Tris-HCl buffer solution with a pH of 8.5 and a concentration of 0.010M, and ultrasonically treated for 5-10 minutes. Erythromycin or ERY is added and stirred for 1-2 hours. Dopamine is then added and mechanically stirred for 4-6 hours. The product is washed three times with water. Finally, a methanol-acetic acid solution with a volume ratio of 95-90:5-10 is used as an eluent to assist ultrasonic oscillation in removing the template molecule ERY. The eluent is replaced every 2 hours until the elution is terminated when no ERY is detected in the supernatant. The Fe3O4-COOH@ZIF-8-pDA@MIPs composite material is obtained after separation from the eluent with a magnet and washing with water six times. After vacuum drying at 40-60°C for 10-12 hours, the Fe3O4-COOH@ZIF-8-pDA@MIPs composite material is obtained.

2. A Fe304-COOH@ZIF-8-pDA@MIPs composite material prepared by the method of claim 1.

3. The composite material according to claim 2, characterized in that The specific surface area of ​​Fe304-COOH@ZIF-8-pDA@MIPs is 600-900m 2 g -1 , has a stable three-dimensional pore structure, and contains coordination, hydrogen bonding and electrostatic units.

4. Use of the composite material according to claim 2 for detecting macrolide antibiotics in water samples.

5. The use according to claim 4, characterized in that: Specifically include: 1) Using the Fe304-COOH@ZIF-8-pDA@MIPs composite material as a magnetic solid phase extraction adsorbent, the composite material and the water sample were mixed evenly at a ratio of 1 mg / mL; 2) After adsorption and extraction equilibrium for 5-10 minutes, the Fe304-COOH@ZIF-8-pDA@MIPs composite material is separated by a permanent magnet, and desorption is completed by ultrasonic oscillation of acetonitrile solvent for 2-10 minutes; 3) After desorption is complete, collect the eluate and filter it with a 0.22 μm glass fiber organic filter membrane; 4) The original water sample and the eluate obtained after filtration were purged and concentrated under nitrogen protection at a ratio of 500:1; 5) After HPLC injection analysis, export the data for processing; 6) The standard curve is drawn based on the concentration of macrolide antibiotics and their peak area, and the linear regression equation and correlation coefficient R are obtained. 2 , where R 2 It is an indicator of the ability of the model to interpret data in linear regression. The closer the value is to 1, the better the model fitting effect is. The linear range of the method for detecting macrolide antibiotics in water based on Fe3O4-COOH@ZIF-8-pDA@MIPs composite material is 0.10-500μg L -1 , R 2 >0.9994; 7) Calculate the specific concentration of the macrolide antibiotic in the application according to the linear regression equation; calculate the specific enrichment multiple of the macrolide antibiotic in the application according to the enrichment factor formula; calculate the specific extraction recovery rate of the macrolide antibiotic in the application according to the extraction recovery rate calculation formula; the detection limit is defined as the lowest concentration corresponding to the signal-to-noise ratio of the chromatographic peak equal to 3.

6. The use according to claim 4, characterized in that: The macrolide antibiotics in the water sample include any one or more of erythromycin, dirithromycin, clarithromycin, roxithromycin and azithromycin.

7. The use according to claim 4, characterized in that: The adsorption capacity of macrolide antibiotics in the application is 100-300 mg g -1 , imprinting factors were 8-13, extraction recoveries were 90.6-109.0%, enrichment factors were 295-582, and the detection limit was 0.02 μg L -1 -0.05 μg L -1 .

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