Molecularly imprinted magnetic stirrers for real-time mass spectrometry analysis, their preparation methods, and applications.

Abstract

This invention relates to the field of analytical chemistry, and discloses a molecularly imprinted magnetic stirrer for real-time mass spectrometry analysis, its preparation method, and its application. One aspect of this invention provides a method for preparing a molecularly imprinted magnetic stirrer for real-time mass spectrometry analysis, comprising the following steps: (1) mixing imidacloprid, monomer, crosslinking agent, and initiator in the presence of a first solvent to obtain a reaction solution; (2) immersing an activated magnetic stirrer in the reaction solution to perform a prepolymerization reaction, thereby obtaining the molecularly imprinted magnetic stirrer. For trace sample analysis, the molecularly imprinted magnetic stirrer of this invention can specifically adsorb and effectively enrich target analytes, achieving rapid detection of target analytes and improving detection sensitivity.

Description

Technical Field

[0001] This invention relates to the field of analytical chemistry, specifically to a molecularly imprinted stirring magnet for real-time mass spectrometry analysis, its preparation method, and its application. Background Technology

[0002] Direct analytical ionization (DART) is an in-situ ionization source that operates under atmospheric pressure, enabling rapid ionization and direct analysis of solid, liquid, and gaseous samples. DART ionization utilizes an excited-state plasma thermal flow generated by glow discharge to thermally desorb compounds, followed by Penning ionization (PI) between the plasma and the sample. Currently, DART is widely used in chemical and pharmaceutical fields, primarily for screening and analyzing specific compounds. However, its sensitivity and selectivity limit its practical application in trace sample analysis within the chemical industry. Therefore, a detection method that combines rapid efficiency with high sensitivity is needed.

[0003] Molecular imprinting technology uses a specific target molecule as a template molecule. The template molecule and functional monomers synthesize a three-dimensional polymer through intermolecular covalent and non-covalent interactions. The cavities in this three-dimensional structure can selectively rebind with the template molecule. Utilizing the specific recognition sites generated during the polymerization process, the template molecule and functional monomer exhibit strong molecular recognition capabilities. Before adsorption, the template molecule must be removed, resulting in cavities in the polymer that match the spatial structure of the template molecule, allowing for specific recognition. Due to its predictability, recognizability, and practicality, this technology has been applied in analytical separation in many fields and shows great promise for future development. Summary of the Invention

[0004] For trace sample analysis, the molecularly imprinted stirred magnetic extraction of the present invention can be used to specifically adsorb the target analyte, enabling rapid detection of the target analyte while improving detection sensitivity.

[0005] To achieve the above objectives, the present invention provides a method for preparing a molecularly imprinted stirring magnet for real-time mass spectrometry analysis, comprising the following steps:

[0006] (1) In the presence of the first solvent, imidacloprid, monomer, crosslinking agent and initiator are mixed to obtain a reaction solution;

[0007] (2) Immerse the activated stirring magnet into the reaction solution to carry out a prepolymerization reaction and obtain a molecularly imprinted stirring magnet.

[0008] The second aspect of the present invention provides a molecularly imprinted stirring magnet prepared by the method described in the first aspect.

[0009] The third aspect of this invention provides an application of the molecularly imprinted stirring magnet described in the second aspect in the detection of imidacloprid.

[0010] The beneficial effects of this invention include:

[0011] This invention utilizes the synergistic effect of template molecular compounds and specific monomers to generate specific recognition sites during the polymerization process, forming a molecularly imprinted polymer on the surface of a magnetic stirrer. For trace sample analysis, the molecularly imprinted magnetic stirrer of this invention specifically adsorbs the target analyte, enabling rapid detection and improving detection sensitivity.

[0012] For trace sample analysis, the molecularly imprinted stirring magnetic particle of the present invention specifically adsorbs and effectively enriches the target analyte, resulting in a lower detection limit by mass spectrometry. Attached Figure Description

[0013] Figure 1 This is the infrared spectrum of the molecularly imprinted stirring magnet obtained in Example 1 after removing the imidacloprid molecules;

[0014] Figure 2 This is a mass spectrum of molecularly imprinted magnetic stirrer adsorbing imidazolium after removing imidazolium molecules, obtained in Example 1.

[0015] Figure 3 This is a schematic diagram of the process of molecularly imprinted stirring magnetic adsorption of imidacloprid as described in this invention.

[0016] Explanation of reference numerals in the attached figures

[0017] Figure 3 In China: 1. Magnetic stirring; 2. Molecularly imprinted magnetic stirring; 3. Enrichment of molecularly imprinted magnetic stirring in a solution containing imidacloprid; 4. GC-MS detection. Detailed Implementation

[0018] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, which can be understood to include values ​​close to them. For numerical ranges, the endpoint values ​​of the ranges, the endpoint values ​​of the ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0019] This invention provides a method for preparing a molecularly imprinted stirring magnet for real-time mass spectrometry analysis, comprising the following steps:

[0020] (1) In the presence of the first solvent, imidacloprid, monomer, crosslinking agent and initiator are mixed to obtain a reaction solution;

[0021] (2) Immerse the activated stirring magnet into the reaction solution to carry out a prepolymerization reaction and obtain a molecularly imprinted stirring magnet.

[0022] According to the present invention, preferably, the molar ratio of imidacloprid, monomer, crosslinking agent, first solvent and initiator is 1:(1-10):(5-30):(30-60):(0.05-0.5), more preferably 1:(4-8):(10-25):(30-50):(0.05-0.2). Using this preferred method, the molecularly imprinted stirred magnetic adsorption effect is better.

[0023] In this invention, there is no particular limitation on the order of adding each material during the mixing process of imidacloprid, monomer, crosslinking agent, initiator and first solvent in step (1). They can be added separately or together, as long as the purpose of uniform mixing is achieved. In the embodiments of this invention, the method of adding them together is used as an example.

[0024] According to the present invention, preferably, the mixing in step (1) is performed under ultrasonic conditions.

[0025] This invention does not impose particular limitations on the ultrasonic conditions; they can be appropriately selected according to specific circumstances, as long as the goal of uniform mixing is achieved. Preferably, the ultrasonic conditions include: a temperature of 0-30°C and a time of 0.5-2 hours. Using this preferred embodiment can further avoid explosive polymerization during the mixing process and interference from oxygen in the system.

[0026] The specific monomers of this invention, in synergy with imazalil, facilitate the generation of specific recognition sites during the polymerization process. According to this invention, preferably, the monomers are selected from at least one of α-methacrylic acid, 4-vinylpyridine, acrylamide, and o-phenylenediamine.

[0027] According to the present invention, preferably, the crosslinking agent is selected from at least one of ethylene glycol dimethacrylate, divinylbenzene and N,N-methylenebisacrylamide.

[0028] According to the present invention, preferably, the initiator is selected from at least one of azobisisobutyronitrile, azobisisoheptanenitrile, and dimethyl azobisisobutyrate.

[0029] The present invention has a wide range of choices for the first solvent. Preferably, the first solvent is selected from at least one of dichloromethane, chloroform, acetone and acetonitrile.

[0030] According to the present invention, preferably, the conditions for the prepolymerization reaction in step (2) include: a temperature of 30-80°C, preferably 40-60°C; and a time of 0.5-6h, preferably 0.5-2h.

[0031] The activated magnetic stir bar in this invention is more conducive to its binding with molecularly imprinted polymers. This invention does not particularly limit the preparation process of the activated magnetic stir bar, as long as the activation purpose is achieved. Preferably, the preparation process of the activated magnetic stir bar includes: immersing the magnetic stir bar in a silanizing agent, and then drying it with a protective gas.

[0032] According to the present invention, preferably, the silanizing agent is provided in the form of a mixed solution, the mixed solution further containing at least one of acetone, toluene, ethanol and dimethyl sulfoxide.

[0033] According to the present invention, preferably, the content of the silanizing agent in the mixed solution is 1-25 wt%.

[0034] According to the present invention, preferably, the immersion time in the silanizing agent is 0.5-4 hours, more preferably 1-2 hours.

[0035] According to the present invention, preferably, the silanizing agent is selected from at least one of 3-(isobutenyloxy)propyltrimethoxysilane, vinyltriethoxysilane, vinyltrimethoxysilane, 3-aminopropyltriethoxysilane, and N-(2-aminoethyl)-3-aminopropyltrimethoxysilane. Using this silanizing agent is safe and non-toxic, has good biocompatibility, a moderate boiling point, is easily volatile, and will not remain on the molecular stirring magnet after the prepolymerization reaction.

[0036] According to the present invention, preferably, the protective gas is selected from at least one of argon, helium, and nitrogen, and preferably nitrogen. This preferred embodiment helps to prevent oxygen from interfering with the subsequent prepolymerization reaction.

[0037] According to the present invention, preferably, the stirring magnet is a glass stirring magnet with a length of 1-4 cm and a diameter of 0.2-0.8 cm.

[0038] More preferably, the stirring magnet is a glass stirring magnet with a length of 1.5-3cm and a diameter of 0.4-0.8cm.

[0039] According to the present invention, preferably, the method further includes immersing the molecularly imprinted stirring magnet obtained in step (2) into a second solvent.

[0040] According to the present invention, preferably, the immersion time in the second solvent is 1-10 hours, more preferably 3-8 hours.

[0041] According to the present invention, preferably, the molecularly imprinted stirring magnet is immersed in a second solvent under ultrasonic conditions.

[0042] The present invention does not impose any particular limitations on the conditions of ultrasound, which can be appropriately selected according to the specific circumstances, as long as the purpose of effectively removing imidacloprid molecules can be achieved.

[0043] According to the present invention, preferably, the molecularly imprinted magnetic stirrer is dried with a protective gas before immersion in the second solvent. This embodiment effectively prevents oxidation reactions.

[0044] According to the present invention, preferably, the second solvent is selected from at least one of dichloromethane, acetone, ethanol, acetonitrile, and chloroform.

[0045] According to the present invention, preferably, the protective gas is selected from at least one of argon, helium and nitrogen, more preferably nitrogen.

[0046] In a preferred embodiment, the molecularly imprinted material removed from the second solvent is washed with a stirring magnetic stirrer. This preferred embodiment allows for further removal of imidacloprid molecules.

[0047] Preferably, the washing agent is selected from at least one of methanol, dichloromethane, chloroform, acetone, and acetonitrile. More preferably, the washing agent is the same as the second solvent.

[0048] The washing process described in this invention can be performed once or multiple times. This invention does not require this, and the standard is that no imidacloprid is detected in the washing reagent.

[0049] In a preferred embodiment, the washed molecularly imprinted probe is subjected to vacuum drying. The present invention does not particularly limit the conditions for vacuum drying, which can be appropriately selected according to specific circumstances. Preferably, the vacuum drying conditions include: a temperature of 60-120°C and a time of 2-24 hours.

[0050] It should be noted that the terms "first" and "second" in this invention do not serve a limiting function, but are only used to distinguish the operations performed at different stages and the substances used.

[0051] The second aspect of the present invention provides a molecularly imprinted stirring magnet prepared by the method described in the first aspect.

[0052] The third aspect of this invention provides an application of the molecularly imprinted stirring magnet described in the second aspect in the detection of imidacloprid, preferably in the chemical industry.

[0053] The following is in conjunction with the appendix Figure 3 This invention is described below. After eluting imidazolium molecules, the molecularly imprinted magnetic stirring device prepared according to this invention forms a cavity on its surface with multiple recognition sites that matches the structure of the imidazolium molecule. In application, immersing the molecularly imprinted magnetic stirring device in a solution containing imidazolium molecules allows for specific recognition of imidazolium, followed by mass spectrometry analysis.

[0054] In a preferred embodiment, the detection limit of the concentration of imidacloprid by the molecularly imprinted probe of the present invention as analyzed by mass spectrometry can be as low as 5 ng / L, preferably as low as 4.5 ng / L, and more preferably as low as 1 ng / L.

[0055] The present invention will be described in detail below through embodiments.

[0056] In the following examples, all reagents used were commercially available chemicals of analytical grade.

[0057] In the following embodiments, the infrared spectral parameters were measured using a NEXVS470 infrared spectrometer;

[0058] The mass spectra were obtained using a WATERS TQ-S mass spectrometer.

[0059] Example 1

[0060] Immerse a glass stirring magnet (approximately 2 cm long and 0.5 cm in diameter) in a 15 wt% acetone solution of 3-(isobutenyl chloride)propyltrimethoxysilane for 1 hour, then remove it and dry it with nitrogen gas.

[0061] A reaction solution was prepared by mixing 0.1 mmol / L imidazolium, 0.4 mmol / L acrylamide monomer, 2 mmol / L divinylbenzene, 0.01 mmol / L azobisisovalerate and 5 mmol / L acetonitrile.

[0062] The reaction solution was placed in a 0℃ water bath and sonicated for 0.5h. Then, a glass stirring magnet was immersed in the reaction solution and a prepolymerization reaction was carried out at 50℃. After 1h, the magnet was removed and dried with nitrogen to obtain a molecularly imprinted stirring magnet. The prepared molecularly imprinted probe was immersed in an ethanol solution and sonicated for 6h. It was rinsed three times with an ethanol solution and then vacuum dried at 120℃ for 2h to remove imidacloprid molecules.

[0063] An example is given of the infrared spectrum of the molecularly imprinted polymer after the removal of the imidacloprid molecule, such as Figure 1 As shown. Major peak assignment in the polymer infrared spectrum: 3500 cm⁻¹ -1 The left and right peaks are -OH stretching vibration peaks, 2900 cm⁻¹. -1 The peaks are for the stretching vibrations of -CH2 and C-H3, at 1730 cm⁻¹. -1 The left and right sides are the -C=O stretching vibration peaks, 1250cm. -1 The peaks at the left and right are the asymmetric stretching vibration peaks of COC, at 1150 cm⁻¹. -1 The peaks on the left and right are the symmetrical stretching vibration peaks of COC, which proves that the molecularly imprinted polymer has been formed.

[0064] Example 2

[0065] Immerse a glass stirring magnet (approximately 2 cm long and 0.5 cm in diameter) in a 15 wt% acetone solution of 3-(isobutenyl chloride)propyltrimethoxysilane for 1 hour, then remove it and dry it with nitrogen gas.

[0066] A reaction solution was prepared by mixing 0.1 mmol / L imidazolium, 0.6 mmol / L acrylamide monomer, 2 mmol / L divinylbenzene, 0.02 mmol / L azobisisovalerate and 5 mmol / L acetonitrile.

[0067] The reaction solution was placed in a 0℃ water bath and sonicated for 0.5h. Then, a glass stirring magnet was immersed in the reaction solution and a prepolymerization reaction was carried out at 50℃. After 1h, the magnet was removed and dried with nitrogen to obtain a molecularly imprinted stirring magnet. The prepared molecularly imprinted probe was immersed in an ethanol solution and sonicated for 6h. It was rinsed three times with an ethanol solution and then vacuum dried at 120℃ for 2h to remove imidacloprid molecules.

[0068] Example 3

[0069] Immerse a glass stirring magnet (approximately 2 cm long and 0.5 cm in diameter) in a 15 wt% acetone solution of 3-(isobutenyl chloride)propyltrimethoxysilane for 1 hour, then remove it and dry it with nitrogen gas.

[0070] A reaction solution was prepared by mixing 0.1 mmol / L imidazolium, 0.4 mmol / L acrylamide monomer, 2 mmol / L divinylbenzene, 0.01 mmol / L N,N-methylenebisacrylamide and 5 mmol / L acetonitrile.

[0071] The reaction solution was placed in a 0℃ water bath and sonicated for 0.5h. Then, a glass stirring magnet was immersed in the reaction solution and a prepolymerization reaction was carried out at 50℃. After 1h, the magnet was removed and dried with nitrogen to obtain a molecularly imprinted stirring magnet. The prepared molecularly imprinted probe was immersed in an ethanol solution and sonicated for 6h. It was rinsed three times with an ethanol solution and then vacuum dried at 120℃ for 2h to remove imidacloprid molecules.

[0072] Example 4

[0073] Immerse a glass stirring magnet (approximately 2 cm long and 0.5 cm in diameter) in a 15 wt% acetone solution of 3-(isobutenyl chloride)propyltrimethoxysilane for 1 hour, then remove it and dry it with nitrogen gas.

[0074] A reaction solution was prepared by mixing 0.1 mmol / L imazalil, 0.4 mmol / L o-phenylenediamine monomer, 2 mmol / L divinylbenzene, 0.01 mmol / L azobisisovalerate and 5 mmol / L acetonitrile.

[0075] The reaction solution was placed in a 0℃ water bath and sonicated for 0.5h. Then, a glass stirring magnet was immersed in the reaction solution and a prepolymerization reaction was carried out at 55℃. After 1h, the magnet was removed and dried with nitrogen to obtain a molecularly imprinted stirring magnet. The prepared molecularly imprinted probe was immersed in an ethanol solution and sonicated for 6h. It was then rinsed three times with an ethanol solution and then vacuum dried at 120℃ for 2h to remove imidacloprid molecules.

[0076] Comparative Example 1

[0077] The procedure was carried out according to Example 1, except that imazalil molecules were not added to the reaction solution.

[0078] A glass stirring magnet (approximately 2 cm long and 0.5 cm in diameter) was immersed in a 15 wt% acetone solution of 3-(isobutenyl chloride)propyltrimethoxysilane for 1 hour, and then removed and dried with nitrogen gas.

[0079] A reaction solution was prepared by mixing 0.4 mmol acrylamide monomer, 2 mmol divinylbenzene, 0.01 mmol azobisisovalerate and 5 mmol acetonitrile.

[0080] The reaction solution was placed in a 0℃ water bath and sonicated for 0.5h. Then, a glass stirring magnet was immersed in the reaction solution and a prepolymerization reaction was carried out at 55℃. After 1h, the magnet was removed and dried with nitrogen to obtain a molecularly imprinted stirring magnet. The prepared molecularly imprinted probe was immersed in an ethanol solution and sonicated for 6h. It was then rinsed three times with an ethanol solution and then vacuum dried at 120℃ for 2h to remove imidacloprid molecules.

[0081] Test Example 1

[0082] The molecularly imprinted magnetic stirrers of the examples and comparative examples after removing the imidazol molecules were immersed in a methanol solution of imidazol and stirred at 800 rpm for 1 hour. After removal, the surface of the molecularly imprinted magnetic stirrers was rinsed with ultrapure water and dried with lint-free paper. They were then applied to real-time mass spectrometry analysis.

[0083] Mass spectrometry conditions were set as follows: DART was performed in helium positive ion ionization mode at a gas temperature of 350°C.

[0084] Mass spectrometry was performed in Nano Scan mode, with a full scan acquisition range of m / z: 50-1000. Daughter Scan mode was used to acquire daughter ions of the target compound, with collision energies optimized between 15-50 eV.

[0085] The following is an exemplary mass spectrum of the molecularly imprinted magnetic stirrer adsorbing imidazolium after removing imidazolium molecules, prepared in Example 1. Figure 2 As shown, we can see its [M+H] +The peak m / z is 297, which indicates that the imidazolium molecules in the solution have been successfully adsorbed onto the molecularly imprinted stirring magnet after the imidazolium molecules have been removed.

[0086] Different concentrations of imazalil methanol solutions were prepared for detection limit determination, and the results are shown in Table 1.

[0087] Table 1

[0088] Example 1 1 Example 2 3 Example 3 4.5 Example 4 5 Comparative Example 1 60

[0089] As shown in Table 1, the molecularly imprinted magnetic stirring device prepared according to this invention exhibits a lower detection limit by mass spectrometry. This demonstrates that, for trace sample analysis, the specific adsorption of the target analyte by the molecularly imprinted magnetic stirring device of this invention enables rapid detection of the target analyte and improves the sensitivity of target product detection.

[0090] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for detecting imazalil in the chemical industry, comprising: The molecularly imprinted stirring magnet was immersed in a solution containing imidazolium molecules to specifically recognize imidazolium, and then real-time mass spectrometry analysis was performed. The detection limit of the molecularly imprinted stirring magnetic device, analyzed by real-time mass spectrometry, was as low as 5 ng / L for the concentration of imidacloprid. The method for preparing the molecularly imprinted stirring magnetic head includes the following steps: (1) In the presence of the first solvent, imidacloprid, monomer, crosslinking agent and initiator are mixed to obtain a reaction solution; the molar ratio of imidacloprid, monomer, crosslinking agent, first solvent and initiator is 1:(1-4):(5-20):(30-50):(0.05-0.1). (2) Immerse the activated stirring magnet in the reaction solution to carry out a prepolymerization reaction to obtain a molecularly imprinted stirring magnet; the conditions for the prepolymerization reaction in step (2) include: temperature of 30-80℃; time of 0.5-6h; The monomer is o-phenylenediamine.

2. The method according to claim 1, wherein, The crosslinking agent is selected from at least one of ethylene glycol dimethacrylate, divinylbenzene, and N,N-methylenebisacrylamide; The initiator is selected from at least one of azobisisobutyronitrile, azobisisoheptanenitrile, and dimethyl azobisisobutyrate; The first solvent is selected from at least one of dichloromethane, chloroform, acetone, and acetonitrile.

3. The method according to claim 1, wherein, The conditions for the prepolymerization reaction in step (2) include: a temperature of 40-60℃ and a time of 0.5-2h.

4. The method according to any one of claims 1-3, wherein, The preparation process of the activated magnetic stirrer includes immersing the magnetic stirrer in a silanizing agent and then drying it with a protective gas.

5. The method according to claim 4, wherein, The silanizing agent is provided in the form of a mixed solution, which also contains at least one of acetone, toluene, ethanol and dimethyl sulfoxide; The content of the silanizing agent in the mixed solution is 1-25 wt%.

6. The method according to claim 4, wherein, The immersion time in the silanizing agent is 0.5-4 hours.

7. The method according to claim 6, wherein, The immersion time in the silanizing agent is 1-2 hours.

8. The method according to claim 4, wherein, The silanizing agent is selected from at least one of 3-(isobutenyloxy)propyltrimethoxysilane, vinyltriethoxysilane, vinyltrimethoxysilane, 3-aminopropyltriethoxysilane, and N-(2-aminoethyl)-3-aminopropyltrimethoxysilane.

9. The method according to claim 4, wherein, The protective gas is selected from at least one of argon, helium, and nitrogen.

10. The method according to any one of claims 1-3, wherein, The stirring magnet is a glass stirring magnet with a length of 1-4cm and a diameter of 0.2-0.8cm.

11. The method according to claim 10, wherein, The stirring magnet is a glass stirring magnet with a length of 1.5-3cm and a diameter of 0.4-0.8cm.

12. The method according to any one of claims 1-3, wherein, The method further includes immersing the molecularly imprinted stirring magnet obtained in step (2) into a second solvent; The second solvent is selected from at least one of dichloromethane, acetone, ethanol, acetonitrile, and chloroform.

13. The method according to claim 12, wherein, The immersion time in the second solvent is 1-10 hours.

14. The method according to claim 13, wherein, The immersion time in the second solvent is 3-8 hours.

15. The method according to claim 12, wherein, Before immersion in the second solvent, the molecular imprint was dried with a protective gas stirring magnetic wave. The protective gas is selected from at least one of argon, helium, and nitrogen.

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