A preparation method of a hydrophobic MOF material and its application in 129 enhancing the Xe magnetic resonance signal

Abstract

The present invention relates to the field of magnetic resonance spectroscopy technology, and in particular to a method for preparing a hydrophobic metal organic framework (MOF) material and its application in enhancing 129 The present invention uses CAU-1-OH-NH2 as the basic skeleton and uses chemical vapor deposition to wrap polydimethylsiloxane (PDMS) on the surface of CAU-1-OH-NH2 material to form PDMS@CAU-1-OH-NH2 with certain hydrophobicity. Compared with CAU-1-OH-NH2 without hydrophobic film, the PDMS@CAU-1-OH-NH2 obtained by this strategy has significantly enhanced Hyper-CEST signal. 129 The signal of Xe direct sampling has also been generated from scratch. Hydrophobic strategy enhancement 129 Xe signal for subsequent 129 Optimization and novel Xe molecular cage signal 129 The design of Xe molecular cages provides new ideas.

Description

Technical Field

[0001] The present invention relates to the technical field of magnetic resonance spectroscopy, and particularly relates to a preparation method of a hydrophobic metal-organic framework material and its application in 129 enhancing the Xe magnetic resonance signal. Background Art

[0002] Magnetic resonance imaging (MRI) is a non-ionizing radiation imaging method. Due to its high tissue penetration and spatial resolution, it has been widely used in many fields such as clinical diagnosis and analytical testing. Traditional 1 H MRI uses the water protons in the living body to image specific parts, with low sensitivity and strong background interference. Hyperpolarized 129 Xe magnetic resonance imaging is a new imaging method that has emerged in recent years. 129 Xe, as an exogenous substance, has no background signal interference in the living body. When the spin-exchange optical pumping technology (SEOP) is used, the magnetic resonance signal of hyperpolarized 129 Xe can be enhanced by more than 80,000 times compared with thermal polarization, thus realizing lung magnetic resonance imaging and obtaining lung structure and function information for the evaluation of clinical lung diseases.

[0003] 129 Xe itself is not specific and it is difficult to achieve specific detection of the target. When a cage molecule is used to bind with 129 Xe, the cage molecule can be functionalized to endow 129 Xe with specificity. Further combined with the chemical exchange saturation transfer (CEST) method, specific hypersensitive detection of trace targets can be achieved through the Hyper-CEST method. However, compared with direct sampling, Hyper-CEST sampling takes longer time, and the data needs to go through a series of post-processing to see the final result, while direct sampling is faster and the experimental result is more intuitive. So far, researchers have developed a variety of molecular cages including cryptophane, airbag, nanoemulsion, cucurbituril, β-lactamase, MOF, etc. And MOF materials have attracted much attention due to their customizable spatial structures.

[0004] MOF materials are a class of porous materials with a spatial network structure formed by the self-assembly of metal ions and organic ligands. The organic ligands in these materials generally contain coordination atoms such as nitrogen and oxygen, which can form strong coordination bonds with metal ions. The MOF structure is highly ordered and has permanent pores, and its structure can be customized according to research needs. Due to its high porosity and specific surface area, it has attracted much attention in the fields of separation, catalysis, storage, gas adsorption, etc. After loading hyperpolarized 129 Xe gas molecules, it can be used to detect the pore properties of MOF itself or to construct hyperpolarized 129Xe molecular probe. Previous studies have shown that some MOF materials such as ZIF-8 have a high affinity for 129 Xe and can encapsulate it 129 Xe for constructing hyperpolarized 129 Xe molecular probe. At the same time, many studies have shown that there are various MOF solid powders with a very high affinity for Xe and excellent performance in Xe / Kr separation. However, after dispersing the solid powder in water, due to the too fast exchange rate, the Xe signal in the cages of the material cannot be captured, resulting in most MOF materials being unable to collect the in-cage Xe signal in the solution. Therefore, the types of MOF that can be used as hyperpolarized 129 Xe molecular cages are very limited, mainly including ZIF-8, IRMOF, etc. The 129 Xe signal of ZIF-8 is significantly enhanced compared with that of traditional cavitand molecular cages, and both ZIF-8 and cavitand have hydrophobic internal cavities, and good 129 Xe signals can be obtained even when dispersed in water. Chinese Patent Application with the application number 202111651962.X and the title "A Multicomponent Metal-Organic Framework Material and Its Application" discloses that CAU-1-OH-NH2 is prepared using 2-aminoterephthalic acid and 2-hydroxyterephthalic acid as ligands and aluminum chloride hexahydrate or aluminum chloride as raw materials. This material can be used as 129 Xe molecular cage for hyperpolarized 129 Xe magnetic resonance contrast agent, but CAU-1-OH-NH2 does not have a completely hydrophobic cavity structure. Summary of the Invention

[0005] In order to study whether the hydrophobic strategy can improve the loading capacity of MOF materials for 129 Xe in water, thereby enhancing the 129 Xe signal of the molecular cage. In the present invention, CAU-1-OH-NH2 is used as the main body, and polydimethylsiloxane (PDMS) is deposited on the surface of CAU-1-OH-NH2 by chemical vapor deposition to obtain hydrophobic PDMS@CAU-1-OH-NH2, reducing the degree of water ingress into the cavity of CAU-1-OH-NH2. Experiments have proved that PDMS@CAU-1-OH-NH2 has stronger hydrophobicity than CAU-1-OH-NH2, and the 129 Xe signal is also significantly enhanced. Compared with CAU-1-OH-NH2 without PDMS coating, the Hyper-CEST signal of PDMS@CAU-1-OH-NH2 material is enhanced, and a direct sampling signal can be obtained.

[0006] To achieve the above object of the present invention, the technical solution adopted by the present invention is as follows:

[0007] A hydrophobic MOF material, which is prepared by the following method: using the MOF material CAU-1-OH-NH2 as the basic framework of the molecular cage for hyperpolarized 129 Xe, and based on the chemical vapor deposition method, performing hydrophobic modification on CAU-1-OH-NH2, using PDMS as the hydrophobic film layer to obtain the hydrophobic MOF material PDMS@CAU-1-OH-NH2.

[0008] Furthermore, the particle size of PDMS@CAU-1-OH-NH2 is 200±30 nm, and the thickness of the PDMS hydrophobic film layer is 2.2 nm.

[0009] Furthermore, the specific preparation method of the hydrophobic MOF material is as follows:

[0010] Take the solid powder of CAU-1-OH-NH2 and place it in a polytetrafluoroethylene surface dish. Place the surface dish in the polytetrafluoroethylene inner liner of the reaction kettle. Then add PDMS to the polytetrafluoroethylene inner liner of the reaction kettle. After sealing the reaction kettle, place it in an oven and react at 220-250 °C for 4-8 h (preferably react at 235 °C for 6 h). Finally, collect the solid in the surface dish to obtain the hydrophobic MOF material PDMS@CAU-1-OH-NH2.

[0011] Furthermore, the dosage ratio of CAU-1-OH-NH2 to PDMS is (10-60) mg:(10-60) μL.

[0012] Even further, the dosage ratio of CAU-1-OH-NH2 to PDMS is 20 mg:20 μL.

[0013] Furthermore, the ratio of the mass of CAU-1-OH-NH2 to the volume of the reaction kettle is 20 mg:100 mL.

[0014] The present invention also provides the application of the hydrophobic MOF material PDMS@CAU-1-OH-NH2 obtained by the above preparation method in the preparation of a hyperpolarized 129 Xe signal enhancement reagent.

[0015] Furthermore, the application is: using the hydrophobic MOF material as a hyperpolarized 129 Xe magnetic resonance imaging contrast agent.

[0016] Compared with the prior art, the beneficial effects and advantages of the present invention are as follows:

[0017] 1. By performing hydrophobic modification through the chemical vapor deposition method, the operation is simple and the raw materials are cheap.

[0018] 2. The of the CAU-1-OH-NH2 material can be enhanced through the hydrophobic strategy.129 The Xe signal is of great guiding significance for subsequent optimization of existing molecular cages and development of new molecular cages.

[0019] 3. Through hydrophobic modification, CAU-1-OH-NH2 that does not have a direct sampling signal can be optimized to be able to collect a direct sampling signal. Compared with Hyper-CEST indirect sampling, the direct sampling has a shorter signal acquisition time, more intuitive experimental results, and a wider subsequent application range. Description of the Drawings

[0020] Figure 1 In [the figure], a is the transmission electron microscope (TEM) image of CAU-1-OH-NH2, and b is the TEM image of PDMS@CAU-1-OH-NH2.

[0021] Figure 2 In [the figure], a is the X-ray energy spectrum elemental analysis (EDS Mapping) image of CAU-1-OH-NH2, and b is the EDS Mapping image of PDMS@CAU-1-OH-NH2.

[0022] Figure 3 are the X-ray diffraction (XRD) patterns of CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2, where CAU-1-Simulated is the standard XRD pattern of the MOF material CAU-1.

[0023] Figure 4 In [the figure], a is the water contact angle of CAU-1-OH-NH2, and b is the water contact angle of PDMS@CAU-1-OH-NH2.

[0024] Figure 5 is the comparison of Hyper-CEST results between CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2.

[0025] Figure 6 is for CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2 129 comparison of Xe direct sampling results. Detailed Implementation Modes

[0026] Next, the applicant elaborates on the technical solutions of the present invention in combination with specific embodiments.

[0027] The main reagents and instruments used in the following examples are as follows:

[0028] 2-Aminoterephthalic acid (NH2-BDC) and 2-hydroxyterephthalic acid (OH-BDC) were purchased from Aladdin Reagent Co., Ltd.; aluminum chloride hexahydrate and anhydrous methanol were both purchased from Sinopharm Chemical Reagent Co., Ltd.; polydimethylsiloxane (PDMS) was purchased from Shanghai Macklin Biochemical Co., Ltd., with a molecular weight of 162.4.

[0029] Nuclear magnetic resonance spectrometer (400MHz Bruker AV400 wide bore spectrometer).

[0030] Example 1 A preparation method of a hydrophobic metal-organic framework material, the specific steps are as follows:

[0031] 1. Preparation of the hydrophobic MOF material PDMS@CAU-1-OH-NH2

[0032] CAU-1-OH-NH2: Add 572.2 mg of AlCl3·6H2O, 71.5 mg of NH2-BDC, and 71.5 mg of OH-BDC to 7.9 mL of anhydrous CH3OH, and completely dissolve it under ultrasonic conditions. Then transfer the solution to a stainless steel reaction kettle with a polytetrafluoroethylene liner and a volume of 15 mL, seal it, and place it in an oven preheated to 125 °C for crystallization for 5.5 h. After the crystallization is completed, take out the reaction kettle from the oven, and let the reactants cool naturally to room temperature. Then centrifuge at 10000 r / min for 10 min, remove the supernatant, and the solid is the synthesized CAU-1-OH-NH2 material.

[0033] There are a large number of chloride ions and unreacted organic ligands in the above-mentioned CAU-1-OH-NH2 material obtained by centrifugation. Therefore, the above-mentioned MOF material CAU-1-OH-NH2 needs to be washed first with deionized water to remove chloride ions, and then washed with methanol to remove free water molecules and unreacted NH2-BDC and OH-BDC; after washing, centrifuge at a centrifugation speed of 11000 r / min for 10 min, and finally place the centrifuged product in a vacuum drying oven at 50 °C for drying for 24 h to obtain the dried CAU-1-OH-NH2.

[0034] PDMS@CAU-1-OH-NH2: Take 20 mg of the dried CAU-1-OH-NH2 solid powder and place it in a polytetrafluoroethylene watch glass. Place the watch glass in the polytetrafluoroethylene liner of a 100 mL reaction kettle, and then add 20 μL of PDMS to the polytetrafluoroethylene liner. Seal the reaction kettle and place it in the oven for reaction at 235 °C for 6 h. Finally, collect the solid powder in the watch glass to obtain the hydrophobic MOF material PDMS@CAU-1-OH-NH2.

[0035] 2. Characterization of MOF materials CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2:

[0036] 2.1 Morphology characterization

[0037] The dried CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2 prepared in this example were scanned with a transmission electron microscope (TEM). The obtained TEM images are as shown in Figure 1 Figure. According to the statistics of the TEM images, the particle size of the prepared PDMS@CAU-1-OH-NH2 is 200 ± 30 nm, and the thickness of the PDMS hydrophobic film layer is about 2.2 nm.

[0038] 2.2 Element distribution analysis

[0039] The dried MOF materials CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2 prepared in this example were analyzed by X-ray energy spectrum element analysis technology (EDS Mapping). The obtained EDS Mapping images are as shown in Figure 2 Figure. Compared with CAU-1-OH-NH2 without PDMS hydrophobic layer wrapping, Si elements in the hydrophobic PDMS@CAU-1-OH-NH2 are evenly distributed on the material surface, indicating that PDMS is successfully wrapped on CAU-1-OH-NH2.

[0040] 2.3 Crystal structure characterization

[0041] The dried MOF materials CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2 obtained in this example were subjected to X-ray diffraction analysis (XRD). The obtained powder X-ray diffraction patterns are as shown in Figure 3 Figure. The comparison between the hydrophobic MOF material PDMS@CAU-1-OH-NH2 prepared in this example and the CAU-1 standard card shows that there are no any other diffraction peaks in the spectrum, indicating that the hydrophobic nanomaterial synthesized in this example has the same crystal structure as CAU-1 reported in the literature of the prior art, and the hydrophobic film layer does not affect the topological structure of the material.

[0042] 2.4 Contact angle measurement

[0043] The dried MOF materials CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2 obtained in this example were subjected to water contact angle measurement. The obtained water contact angle measurement results are as shown in Figure 4As shown in the figure, the water contact angle of the hydrophobic MOF material PDMS@CAU-1-OH-NH2 prepared in this example is significantly greater than that of CAU-1-OH-NH2 without PDMS coating, indicating that the synthesized PDMS@CAU-1-OH-NH2 in this example has significantly stronger hydrophobicity than CAU-1-OH-NH2.

[0044] Example 2 Application of a hydrophobic MOF material in 129 enhancing the Xe nuclear magnetic resonance signal, the specific steps are as follows:

[0045] 1. Hyper-CEST effect test of the hydrophobic MOF material PDMS@CAU-1-OH-NH2

[0046] 1.1 Hyper-CEST experimental procedure

[0047] 1.1.1 Weigh 4.0 mg of the hydrophobic MOF material PDMS@CAU-1-OH-NH2 obtained in Example 1 and 4.0 mg of dried CAU-1-OH-NH2, and add them to 2 mL of ultrapure water respectively. Ultrasonic for 30 min at room temperature (25 °C, the same below, not repeated), so that the two materials are fully dispersed in water to obtain a dispersion;

[0048] 1.1.2 Take 100 μL of the dispersion, dilute it to 2 mL with ultrapure water, mix well and transfer it to a 10 mm nuclear magnetic resonance sample tube for testing experiments;

[0049] 1.1.3 During the test, Xe gas (10% N2, 88% He, 2% Xe, volume ratio) is introduced into the nuclear magnetic resonance sample tube after flowing through the hyperpolarization instrument. After 20 s of ventilation, stop ventilation, and then use a selective pulse to saturate part of the hyperpolarized 129 Xe signal, use a 90° pulse to excite 129 the Xe signal, then perform sampling, use the temperature control unit of the nuclear magnetic resonance instrument to control the test temperature at 298 K, the selected spectral width for the test is 110 ppm, the saturation irradiation range is 120 ppm - 230 ppm, the saturation irradiation pulse intensity is 6.5 μT, take a point every 2 ppm, each point is saturated irradiated for 10 s, and then a series of 129 Xe spectra are collected, the dissolved 129 Xe signal is integrated, and its integral value is recorded as M z , after turning off the saturation irradiation pulse, collect 129 the Xe spectrum, integrate the dissolved 129 Xe signal, record its integral value M0, and then use M z / M0 as the ordinate and the saturation irradiation site as the abscissa to plot a graph, and the Hyper-CEST spectrum can be obtained.

[0050] 1.2 Experimental results:

[0051] The above Hyper-CEST experiments were respectively carried out using the dried CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2 obtained in Example 1. The experimental results are as Figure 5 shown. The CAU-1-OH-NH2 material without the hydrophobic film wrapping has about 65% Hyper-CEST signal at 150 ppm, while the PDMS@CAU-1-OH-NH2 material with the hydrophobic film wrapping has about 95% Hyper-CEST signal at 124 ppm, and the Hyper-CEST signal is enhanced by about 30%. And the chemical shift of Xe in the cage of the hydrophobic material PDMS@CAU-1-OH-NH2 shifts to the high field compared with that of CAU-1-OH-NH2, and it is farther from the dissolved state 129 Xe, further proving that less water enters the pores of the hydrophobic PDMS@CAU-1-OH-NH2. The above results show that the hydrophobic strategy of the present invention can enhance the 129 Xe Hyper-CEST signal intensity to a certain extent. 129

[0052] 2. Testing the direct sampling effect of the hydrophobic MOF material PDMS@CAU-1-OH-NH2

[0053] 2.1 129 Xe direct sampling procedure

[0054] 2.1.1 Weigh 10.0 mg of the hydrophobic MOF material PDMS@CAU-1-OH-NH2 obtained in Example 1 and 10.0 mg of the dried CAU-1-OH-NH2, and add them to 2 mL of ultrapure water respectively. Ultrasonic for 30 min at room temperature to fully disperse the two materials in water, and obtain a dispersion of 5 mg / mL. After the dispersion is prepared, transfer it to a 10 mm NMR tube for subsequent testing.

[0055] 2.1.2 During the test, Xe gas (10% N2, 88% He, 2% Xe, volume ratio) is introduced into the NMR sample tube after flowing through the hyperpolarization instrument. The gas flow rate is 0.1 slpm. After ventilating for 15 s, stop ventilating for 3 s, and use a rectangular pulse sequence (pulse length p1 = 31.8 μs) for direct sampling, and the number of sampling times NS = 16. Use the temperature control unit of the nuclear magnetic resonance instrument to control the test temperature at 298 K. The spectral width selected for the experiment is 300 ppm, and finally the direct sampling 129 Xe spectra of PDMS@CAU-1-OH-NH2 and CAU-1-OH-NH2 are obtained.

[0056] 2.2 129 ​Direct sampling results of Xe

[0057] The dried CAU-1-OH-NH2 and PDMS@CAU-1-OH-NH2 obtained in Example 1 were used for the above 129 direct sampling of Xe respectively, and the experimental results are as Figure 6 shown. Only the dissolved 129 Xe signal appeared in the direct sampling spectrum of the CAU-1-OH-NH2 material without the hydrophobic membrane wrapped, while an obvious direct sampling signal appeared at about 125 ppm for the PDMS@CAU-1-OH-NH2 material with the hydrophobic membrane wrapped, and the chemical shift of the direct sampling of the hydrophobic material PDMS@CAU-1-OH-NH2 was consistent with the 129 Xe chemical shift in the cage of Hyper-CEST at low concentration. The above results further prove that implementing the hydrophobic strategy on CAU-1-OH-NH2 can achieve 129 the enhancement of Xe signal.

Claims

1. Application of the hydrophobic MOF material PDMS@CAU-1-OH-NH2 in NMR direct sampling, characterized in that, The PDMS@CAU-1-OH-NH2 uses CAU-1-OH-NH2 as the basic framework of the molecular cage for hyperpolarized 129 Xe, and is coated with a PDMS hydrophobic film layer on the surface; The particle size of the PDMS@CAU-1-OH-NH2 is 200±30 nm, and the thickness of the PDMS hydrophobic film layer is 2.2 nm; The preparation method of the PDMS@CAU-1-OH-NH2 is as follows: First, prepare the MOF material CAU-1-OH-NH2, and then coat PDMS on the surface of CAU-1-OH-NH2 by chemical vapor deposition; The preparation method of the CAU-1-OH-NH2 is as follows: Add 572.2 mg of AlCl3·6H2O, 71.5 mg of 2-aminoterephthalic acid, and 71.5 mg of 2-hydroxyterephthalic acid to 7.9 mL of anhydrous CH3OH, and completely dissolve it under ultrasonic conditions; then transfer the solution to a 15 mL stainless steel autoclave with a polytetrafluoroethylene liner, seal it, and place it in an oven preheated to 125 °C for crystallization for 5.5 h; after crystallization, take out the autoclave from the oven, let the reactants cool naturally to room temperature, then centrifuge at 10000 r / min for 10 min, remove the supernatant, collect the solid, and obtain the CAU-1-OH-NH2 material.

2. The application according to claim 1, wherein The application is: using the PDMS@CAU-1-OH-NH2 as a hyperpolarized 129 Xe magnetic resonance imaging contrast agent.

3. The application according to claim 1, wherein The preparation method of the PDMS@CAU-1-OH-NH2 includes the following steps: Take the solid powder of CAU-1-OH-NH2 and place it in a polytetrafluoroethylene watch glass, place the watch glass in the polytetrafluoroethylene liner of the autoclave, then add PDMS to the polytetrafluoroethylene liner of the autoclave, then seal the autoclave and place it at 220-250 °C for reaction for 4-8 h, and finally collect the solid in the polytetrafluoroethylene watch glass to obtain the hydrophobic PDMS@CAU-1-OH-NH2.

4. The application according to claim 3, wherein The reaction temperature is 235 °C and the reaction time is 6 h.

5. The application according to claim 3, characterized in that The dosage ratio of the CAU-1-OH-NH2 to PDMS is 10-60 mg : 10-60 µL.

6. The application according to claim 5, wherein The dosage ratio of the CAU-1-OH-NH2 to PDMS is 20 mg: 20 µL.

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