Fluorine-containing triphenylmethyl free radical compound as well as preparation method and application thereof

Abstract

The invention discloses a fluorine-containing triphenylmethyl free radical compound as well as a preparation method and application thereof, the chemical structure of triphenylmethyl free radicals is reserved, and a fluorine-containing alkyl chain is connected in a relatively stable manner. The fluorine-containing triphenylmethyl free radical compound retains a core free radical structure, so that the fluorine-containing triphenylmethyl free radical compound can be applied to a melting dynamic nuclear polarization technology, high-efficiency polarization transfer from free electron spinning to specific nuclear spinning in a target sample is realized, and the intensity of a nuclear magnetic resonance signal is improved; the carboxylic acid functional group can be reasonably modified into an ester bond or an amido bond, so that free radicals of the carboxylic acid functional group are not influenced to be provided as electron spinning. The fluorine-containing triphenylmethyl free radical compound synthesized by the method disclosed by the invention has a fluorocarbon phase property, and the fluorine-containing triphenylmethyl free radical compound is quickly and completely separated from a polarized sample by performing solid-phase extraction by utilizing polytetrafluoroethylene micro powder or fluorine silica gel; the key problem (rapid removal of free radicals in a sample) existing in the existing melting dynamic nuclear polarization technology is solved.

Description

Technical Field

[0001] The invention belongs to the technical field of nuclear magnetic resonance, and in particular relates to a fluorine-containing trityl radical compound and a preparation method and application thereof. Background Art

[0002] Nuclear magnetic resonance (NMR) technology, operating in the radiofrequency band, offers unique advantages such as non-destructive detection, excellent tissue penetration, and low energy absorption, making it a significant tool in fields such as biochemistry and materials science. However, a core challenge facing this technology lies in its inherent low sensitivity, which severely restricts the detection of nuclei with low gyromagnetic ratios or low natural abundance.

[0003] To overcome this limitation, the research community has primarily pursued two technical approaches: one is instrument-based signal enhancement strategies, including high-intensity magnet enhancement and cryogenic probe technology. While these approaches have achieved remarkable results, their development has plateaued in recent years. The other is based on breakthroughs in hyperpolarization technology, with dynamic nuclear polarization (DNP) garnering significant attention due to its remarkable enhancement effects. The core mechanism of DNP lies in the highly polarizable properties of unpaired electrons (free radicals), which are transferred through electron-nuclear spin interactions. The implementation of this technology requires three key steps: first, polarizing the polarizing agent and sample at ultralow temperatures (typically 1-2K) and high magnetic fields (>3T); then, stimulating electron paramagnetic resonance through microwave irradiation; and finally, transferring the polarized sample to a conventional NMR / MRI system by rapid melting.

[0004] Currently, dynamic nuclear polarization polarizers are mainly divided into the following categories: 1) Nitroxyl compounds: such as bTbK, for example, TEKPol [Journal of the American Chemical Society, 2004, 126: 10844-10845]. These polarizers have a rigid spirocyclic skeleton that connects nitroxyl radicals in a specific direction and at a fixed distance, making it more efficient to meet the necessary polarization transfer conditions. However, the hydrophobicity of TEKPol molecules limits their application to a certain extent. AMUPol-like molecules developed by introducing hydrophilic side chains [Angewandte Chemie-International Edition, 2013, 52: 10858-10861] have good hydrophilicity. However, due to the wide EPR line width of nitroxyl compounds, their application in high magnetic fields is limited. 2) Trityl radicals and BDPA: Polarizer molecules have the characteristics of narrow EPR line width, stable structure, and easy chemical modification. To further enhance the stability of polarizers, long-chain alkyl groups or functionalized side chains are often introduced into their molecular structures to regulate the spatial distribution and chemical environment of the polarization center in the system. For example, DTR1 [Chemical Communications, 2008, 4336-4338] has a highly symmetrical dendritic structure that enables covalent encapsulation, thereby enhancing the stability of the polarizer. 3) Hybrid diradicals: By combining narrow-linewidth radicals (such as trityl) and nitroxyl radicals, they exhibit excellent performance in high-field DNP. Their advantages are that the narrow-linewidth component facilitates microwave excitation, while the polarization can be efficiently transferred to the nitroxyl group through spin coupling, and ultimately to the target nuclear spin. Compared with traditional nitroxyl diradicals, this design significantly improves the polarization efficiency under high fields.

[0005] While significant progress has been made in strategies to enhance the performance of polarizers, efficient removal of polarizers after polarization transfer remains a key challenge. This issue is particularly acute in in vivo bioimaging applications: polarizer free radicals not only accelerate NMR signal decay but can also remain in the sample, potentially causing toxic side effects such as cell damage or other adverse reactions. Therefore, developing methods to rapidly separate free radicals from polarized samples to minimize signal attenuation and avoid in vivo toxicity is a core challenge currently underway in dynamic nuclear polarization (DNP) technology. Summary of the Invention

[0006] In order to solve the problems existing in the above-mentioned prior art, the present invention provides a fluorinated trityl radical compound, a preparation method and application thereof. The present invention rationally covalently links the trityl radical and the fluorinated alkyl chain Rf to prepare a fluorinated trityl radical compound. Using this compound as a DNP polarizer can not only achieve efficient polarization transfer from free electrons to target nuclear spins, but also solve the problem of separating polarized samples from free radicals, which can promote the application of DNP technology in multiple fields such as materials science, drug development and life science research.

[0007] The technical solution adopted to achieve the above-mentioned purpose of the present invention is: A fluorine-containing trityl radical compound, the molecular structure of which consists of two parts, the first part being a trityl radical and the second part being a fluorine-containing alkyl chain Rf. The general structural formula of the compound is as follows: , wherein k is an integer between 1 and 3, preferably k = 1; When k=1, the structural formula of the fluorinated trityl radical compound (abbreviated as FA) is as follows: ; When k=2, the structural formula of the fluorinated trityl radical compound (abbreviated as FB) is as follows: ; When k=3, the structural formula of the fluorinated trityl radical compound (abbreviated as FC) is as follows: ; Ra is selected from CH3, CD3, CH2CH2OH, CH2OCH2CH2OH, or two Ra on the same carbon atom are connected to form the following ring structure , where m is a positive integer and is not greater than 20; Rf is selected from O(CH2) m (CF2) n CF3, O(CH2CH2O) x (CH2) y OC(CF3)3, NH(CH2) m (CF2) n CF3, NH(CH2CH2O) x (CH2) y OC(CF3)3, wherein m and n are integers between 1 and 10, x and y are integers between 0 and 20, and F is fluorine-19.

[0008] Furthermore, the fluorine content in the compound is 5-65%, preferably, the fluorine content is 20%.

[0009] A method for preparing a fluorine-containing trityl radical compound comprises the following steps: In the presence of a base, a trityl radical compound or a salt thereof undergoes a nucleophilic substitution reaction with an activated fluorinated alkyl compound LGRf to obtain a fluorinated trityl radical compound constructed via an ester bond, and the reaction formula is as follows: , The activated fluorinated alkyl compound LGRf is a compound composed of an activating group LG and a fluorinated alkyl chain Rf.

[0010] Furthermore, the activating group LG is selected from one of p-toluenesulfonyl, methanesulfonyl, trifluoromethanesulfonyl, halogen and succinimide ester. Preferably, the activating group LG is p-toluenesulfonyl.

[0011] Furthermore, the salt of the trityl radical compound is its potassium salt or its sodium salt, and the molar ratio of the trityl radical compound or its salt, the fluorinated alkyl compound LGRf and the base is 1.0:1.0-8.0:2.0-4.0.

[0012] Furthermore, in the nucleophilic substitution reaction, the reaction solvent is at least one of N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide, preferably N,N-dimethylformamide. The base is at least one of N,N-diisopropylethylamine, triethylamine, potassium carbonate, and sodium carbonate, preferably N,N-diisopropylethylamine. The reaction temperature is 0-100°C, preferably 50°C.

[0013] Application of a fluorinated trityl radical compound in the preparation of a DNP polarizer.

[0014] Further, the method for rapid separation of the fluorine-containing trityl radical compound is as follows: Using polytetrafluoroethylene powder or fluorosilica gel as a solid phase filler, solid phase extraction is performed on the mixture of the fluorine-containing trityl radical compound and the polarized sample to achieve rapid separation of the fluorine-containing trityl radical compound and the polarized sample.

[0015] Furthermore, the average particle size of the polytetrafluoroethylene powder is 1-1000 μm, preferably 200 μm. The average particle size of the fluorosilicone is 1-100 μm, preferably 40-60 μm.

[0016] Compared with the prior art, the advantages and beneficial effects of the present invention are: The fluorinated trityl radical compound of the present invention retains the chemical structure of the trityl radical and is connected to a fluorinated alkyl chain in a relatively stable manner. Since the fluorinated trityl radical compound retains the free radical structure at its core, it can be applied to the melt dynamic nuclear polarization technology to achieve efficient polarization transfer from the free electron spin to the specific nuclear spin in the target sample, which greatly improves the intensity of the nuclear magnetic resonance signal, thereby improving the detection sensitivity, and the carboxylic acid functional group can be reasonably modified to an ester bond or an amide bond so as not to affect its free radical as an electron spin. In addition, there are multiple methylene groups between the fluorinated group and the free radical structure in the fluorinated trityl radical compound, thereby avoiding the influence of the electron-pulling ability of the fluorinated group on the electronic effect of the free radical structure.

[0017] This method uses trityl radicals as electron spin mediators and fluorinated alkyl groups as labeling molecules, resulting in the unique properties of a fluorocarbon phase. The fluorocarbon phase exhibits unique hydrophobicity and oleophobicity, as well as a selective affinity for fluorinated compounds. This allows for the efficient purification of fluorinated compounds, offering advantages such as ease of operation, high selectivity, and structural friendliness. This method allows for the efficient separation of fluorinated free radical compounds from polarized samples containing non-fluorinated substances, achieving the goal of scavenging free radicals from the polarized samples.

[0018] The fluorinated trityl radical compound synthesized by the present invention has fluorocarbon phase properties. Solid-phase extraction is performed using polytetrafluoroethylene micropowder or fluorosilica gel to achieve rapid and complete separation of the fluorinated trityl radical compound from a polarized sample. The separation process is short in time and highly efficient. No complicated scavenging methods such as chromatographic column purification or addition of chemical reagents are required. This greatly simplifies the operation of scavenging the radical compound, reduces the loss of sample polarization, helps maintain the sample polarization, enhances the sensitivity of nuclear magnetic resonance, and solves the key problem of current melt dynamic nuclear polarization technology (rapid scavenging of free radicals in the sample).

[0019] The fluorinated trityl radical compound synthesized by the present invention can be completely separated from the polarized sample, reducing the impact of the free radicals on subsequent experiments, especially the toxic side effects on biological systems, and providing an efficient and safe sample preparation method for in vivo molecular imaging in the biomedical field.

[0020] The fluorine-containing trityl radical compound of the present invention is suitable for use as a polarizing agent in dynamic nuclear polarization experiments due to its narrow EPR spectrum and good water solubility.

[0021] The synthetic route of the invention is efficient, the reaction conditions are mild, and the stability of free radicals is not affected. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is the MALDI-TOF-MS spectrum of the fluorine-containing trityl radical compound 1a prepared in Example 1.

[0023] Figure 2 This is the MALDI-TOF-MS spectrum of the fluorinated trityl radical compound 1b prepared in Example 1.

[0024] Figure 3 This is the MALDI-TOF-MS spectrum of the fluorinated trityl radical compound 1c prepared in Example 1.

[0025] Figure 4 The fluorine-containing trityl radical compound 1a prepared in Example 1 19 F NMR spectrum.

[0026] Figure 5 The fluorine-containing trityl radical compound 1b prepared in Example 1 19 F NMR spectrum.

[0027] Figure 6 The fluorine-containing trityl radical compound 1c prepared in Example 1 19 F NMR spectrum.

[0028] Figure 7 This is the MALDI-TOF-MS spectrum of the fluorine-containing trityl radical compound 2a prepared in Example 2.

[0029] Figure 8 This is the HPLC spectrum of the fluorinated trityl radical compound 2a prepared in Example 2.

[0030] Figure 9 This is the MALDI-TOF-MS spectrum of the fluorinated trityl radical compound 2b prepared in Example 2.

[0031] Figure 10 This is the HPLC spectrum of the fluorinated trityl radical compound 2b prepared in Example 2.

[0032] Figure 11 This is the MALDI-TOF-MS spectrum of the fluorinated trityl radical compound 2c prepared in Example 2.

[0033] Figure 12 This is the HPLC spectrum of the fluorinated trityl radical compound 2c prepared in Example 2.

[0034] Figure 13 The fluorine-containing trityl radical compound 2a prepared in Example 1 19 F NMR spectrum.

[0035] Figure 14 The fluorine-containing trityl radical compound 2b prepared in Example 1 19F NMR spectrum.

[0036] Figure 15 The fluorine-containing trityl radical compound 2c prepared in Example 1 19 F NMR spectrum.

[0037] Figure 16 These are the EPR spectra of the fluorinated trityl radical compounds 2a, 2b, and 2c prepared in Example 2.

[0038] Figure 17 HPLC chart of the mixture of free radical OX063 and sodium pyruvate before and after solid phase extraction.

[0039] Figure 18 HPLC chart of the mixture of fluorine-containing trityl radical compound 2a prepared in Example 2 and sodium pyruvate before and after solid phase extraction. DETAILED DESCRIPTION

[0040] In order to facilitate those skilled in the art to understand and implement the present invention, the present invention is further described in detail below in conjunction with embodiments. It should be understood that the embodiments described herein are only used to illustrate and explain the present invention and are not used to limit the present invention. Example 1

[0041]

[0042] Free radical CT-03 (commercially available, CAS number: 372515-55-4, 9.97 mg, 0.01 mmol), 3-perfluorooctylpropyl p-toluenesulfonate (CAS number: 228570-07-8; 6.32 mg, 0.01 mmol) and N,N-diisopropylethylamine (2.58 mg, 0.02 mmol) were dissolved in N,N-dimethylformamide (1 mL) and then stirred at 50°C for 24 h. After the reaction was completed, the obtained mixed product was distilled under reduced pressure to remove the solvent, and the residue was purified by semi-preparative high performance liquid chromatography (HPLC parameters: chromatographic column: Shimadzu-Shim-pack GIS, 5 µm C18, 30*250 mm; mobile phase: aqueous phase: water containing 0.1% v / v trifluoroacetic acid, organic phase: methanol containing 0.1% v / v trifluoroacetic acid) to obtain fluorinated trityl radical compound 1a (3.68 mg, yield 25%), fluorinated trityl radical compound 1b (0.31 mg, yield 1.3%), and fluorinated trityl radical compound 1c (0.68 mg, yield 2.8%).

[0043] The MALDI-TOF-MS spectra of fluorinated trityl radical compounds 1a-1c are shown in Figure 2. Figure 1-3 shown.

[0044] 1a: MALDI-TOF-MS m / z: [M] - calcd for C 51 H 44 F 17 O6S 12 • - , 1457.94; found,1458.09.

[0045] 1b: MALDI-TOF-MS m / z: [M] - calcd for C 62 H 49 F 34 O6S 12 • - , 1918.96; found,1920.26.

[0046] 1c: MALDI-TOF-MS m / z: [M] - calcd for C 73 H 54 F 51 O6S 12 • - , 2377.98; found,2377.71.

[0047] Fluorinated trityl radical compounds 1a-1c 19 F NMR spectrum Figure 4-6 shown.

[0048] 1a: 19 FNMR (471 MHz, CD3OD) δ -81.87 (t, J = 9.9 Hz), -114.73– -115.30(m), -122.02 – -122.28 (m), -122.30– -122.59 (m), -123.08– -123.44 (m), -123.91– -124.26 (m), -126.64– -127.01(m).

[0049] 1b: 19 FNMR (471 MHz, CD3OD) δ-81.89 (t, J= 9.9 Hz), -114.80 – -115.28(m), -122.01– -122.30 (m), -122.31– -122.66 (m), -123.12– -123.48 (m), -123.95– -124.30 (m), -126.71– -126.98 (m).

[0050] 1c: 19 FNMR (471 MHz, CDCl3) δ-83.93 (t, J = 10.0 Hz), -117.32– -117.91(m), -124.67 – -124.99 (m), -124.99– -125.37 (m), -125.74– -126.11 (m), -126.53– -127.01 (m), -129.09– -129.50 (m).

[0051] Example 2

[0052] Free radical OX063 (commercially available, CAS number: 734519-63-2, 95.2 mg, 0.07 mmol) was dissolved in 7 mL of N,N-dimethylformamide, followed by the addition of N,N-diisopropylethylamine (18.06 mg, 0.14 mmol) and 3-perfluorooctylpropyl p-toluenesulfonate (66.36 mg, 0.105 mmol), and the reaction was stirred at 5 °C for 24 h. After the reaction was complete, the obtained mixed product was distilled under reduced pressure to remove the solvent, and the residue was purified by semi-preparative high performance liquid chromatography (HPLC parameters: column: Shimadzu-Shim-pack GIS, 5 µm C18, 30*250 mm; mobile phase: aqueous phase: 0.1% v / v trifluoroacetic acid in water, organic phase: 0.1% v / v trifluoroacetic acid in methanol) to obtain fluorinated trityl radical compound 2a (38 mg, yield 27.6%), fluorinated trityl radical compound 2b (34.6 mg, yield 21.7%), and fluorinated trityl radical compound 2c (12.0 mg, yield 6.3%).

[0053] The MALDI-TOF-MS spectra of fluorinated trityl radical compounds 2a-2c are shown in Figure 2. Figure 7 、 Figure 9 and Figure 11 shown.

[0054] 2a: MALDI-TOF-MS m / z: [M]- calcd for C 63 H 67 F 17 O 18 S 12 • - , 1818.07, found,1818.180.

[0055] 2b: MALDI-TOF-MS m / z: [M] - calcd for C 74 H 72 F 34 O 18 S 12 • - , 2278.08, found,2277.974.

[0056] 2c: MALDI-TOF-MS m / z: [M] - calcd for C 85 H 77 F 51 O 18 S 12 • - , 2738.09, found,2737.652.

[0057] The HPLC spectra of fluorinated trityl radical compounds 2a-2c are as follows: Figure 8 、 Figure 10 and Figure 12 shown.

[0058] Fluorinated trityl radical compounds 2a-2c 19 F NMR spectrum Figure 13-15 shown.

[0059] 2a: 19 FNMR (471 MHz, CD3OD) δ-81.91 (t, J = 10.0 Hz), -114.49– -115.19(m), -122.02– -122.27 (m), -122.28– -122.65 (m), -123.15– -123.44 (m), -123.55– -124.01 (m), -126.71– -127.04 (m).

[0060] 2b: 19 FNMR (471 MHz, CD3OD) δ-81.91 (t, J= 10.1 Hz), -114.44– -115.29(m), -122.02– -122.28 (m), -122.28– -122.69 (m), -123.15– -123.48 (m), -123.53– -124.04 (m), -126.72– -127.11(m).

[0061] 2c: 19 FNMR (471 MHz, CD3OD) δ -81.90 (t, J = 10.1 Hz), -114.51– -115.20(m), -122.03– -122.27 (m), -122.27 – -122.63 (m), -123.16– -123.43 (m), -123.59– -123.96 (m), -126.73– -127.02 (m).

[0062] Example 3 1. Mix equal volumes of degassed PBS buffer (10 mM, pH 7.4) and ethanol to prepare a solvent. Dissolve fluorinated trityl radical compounds 2a, 2b, and 2c in the solvent to obtain radical solutions A1, A2, and A3, respectively.

[0063] 2. Free radical solutions A1, A2, and A3 were placed in sample tubes, respectively. ESR spectra of fluorinated trityl radical compounds 2a, 2b, and 2c were collected using an electron paramagnetic resonance spectrometer. The EPR spectrometer parameters were set as follows: microwave power 0.15 mW; modulation amplitude 7 mT; modulation frequency 100 kHz; sweep width 0.5 mT; sweep time 30 s; transition time 30.00 ms; and sampling points 2048.

[0064] 3. The EPR spectra of fluorinated trityl radical compounds 2a-2c were collected as follows: Figure 10 As shown by Figure 10 It can be seen that the EPR spectra of fluorinated trityl radical compounds 2a-2c all show narrow peaks, indicating that fluorinated trityl radical compounds 2a-2c have good electron paramagnetic homogeneity and structural stability, and are suitable as polarizers for dynamic nuclear polarization experiments.

[0065] Example 4 1. Glycerol and water were mixed in a volume ratio of 6:4 to obtain a mixed solvent. Fluorine-containing trityl radical compound 2a and sodium pyruvate were dissolved in the mixed solvent to obtain mixed solution B1. In mixed solution B1, the concentration of 2a was 15 mM and the concentration of sodium pyruvate was 0.76 M. Free radical OX063 and sodium pyruvate were dissolved in the mixed solvent to obtain mixed solution B2. In mixed solution B2, the concentration of free radical OX063 was 15 mM and the concentration of sodium pyruvate was 0.76 M.

[0066] 2. Add 1.5 mL of pure water to mixed solution B1 and mixed solution B2 to obtain sample solution C1 and sample solution C2, respectively. Take 100 μL of sample solution C1 and sample solution C2 for HPLC analysis.

[0067] 3. The sample solution C1 was subjected to solid phase extraction, and the extract D1 was subjected to HPLC analysis.

[0068] The specific solid-phase extraction process is as follows: 2 g of PTFE micropowder (average particle size 200 µm) is loaded into an empty solid-phase extraction column. The column is rinsed with 10 mL of methanol, then 20 mL of water, and then dried with nitrogen. Sample solution C1 is added to the column, and the extract D1 is collected.

[0069] HPLC conditions: Detector: Shanghai Tongwei UM5800 ELSD evaporative light scattering detector; Chromatographic column: Shimadzu-Shim-pack GIS, 5 μm C18, 4.6*250 mm; Flow rate: 0.8 mL / min; The mobile phase was a mixture of an organic phase and an aqueous phase: the aqueous phase was water containing 0.1% v / v trifluoroacetic acid; the organic phase was methanol containing 0.1% v / v trifluoroacetic acid; The conditions for gradient elution were: The first stage: elution time is 0-10 min, in which the volume content of the organic phase is 20%; The second stage: the elution time is 10-15 min, in which the volume content of the organic phase increases linearly from 20% to 98%; The third stage: elution time is 15-40 min, in which the volume content of the organic phase is 98%; The fourth stage: the elution time is 40-45 minutes, during which the volume content of the organic phase decreases linearly from 98% to 20%; The fifth stage: the elution time is 45-60 min, and the volume content of the organic phase is 20%.

[0070] 4. Treat sample solution C2 according to the method in step 3.

[0071] 5. HPLC charts of sample solution C1 of fluorinated trityl radical compound 2a and sodium pyruvate before and after solid phase extraction are shown in Figure 5. Figure 12 As shown, the HPLC graphs of the sample solution C2 of free radical OX063 and sodium pyruvate before and after solid phase extraction are as follows Figure 11 As shown, compared Figure 11 and Figure 12 As shown, the PTFE micropowder-based solid-phase extraction method failed to separate the free radical OX063 from sample solution C2, but it was able to efficiently separate the fluorinated trityl radical compound 2a from sample solution C1. The purified raffinate contained only sodium pyruvate. This demonstrates that solid-phase extraction can quickly and completely separate fluorinated trityl radical compounds from polarized samples, achieving rapid scavenging of free radicals.

Claims

1. A fluorine-containing trityl radical compound, characterized in that: The molecular structure of the compound consists of two parts, the first part is a trityl radical, and the second part is a fluorinated alkyl chain Rf. The general structural formula of the compound is as follows: , wherein k is an integer between 1 and 3, and Ra is selected from CH3, CD3, CH2CH2OH, CH2OCH2CH2OH, or two Ra on the same carbon atom are connected to form the following ring structure: , where m is a positive integer and is not greater than 20; Rf is selected from O(CH2) m (CF2) n CF3, O(CH2CH2O) x (CH2) y OC(CF3)3, NH(CH2) m (CF2) n CF3, NH(CH2CH2O) x (CH2) y OC(CF3)3, wherein m and n are integers between 1 and 10, x and y are integers between 0 and 20, and F is fluorine-19.

2. The fluorine-containing trityl radical compound according to claim 1, wherein: The fluorine content in the fluorine-containing trityl radical compound is 5-65%.

3. A method for preparing a fluorine-containing trityl radical compound according to any one of claims 1 to 2, characterized in that The steps include: In the presence of a base, a trityl radical compound or a salt thereof undergoes a nucleophilic substitution reaction with an activated fluorinated alkyl compound LGRf to obtain a fluorinated trityl radical compound constructed via an ester bond, and the reaction formula is as follows: ， The activated fluorinated alkyl compound LGRf is a compound composed of an activating group LG and a fluorinated alkyl chain Rf.

4. The method for preparing a fluorine-containing trityl radical compound according to claim 3, wherein: The activating group LG is selected from one of p-toluenesulfonyl, methanesulfonyl, trifluoromethanesulfonyl, halogen and succinimide ester.

5. The method for preparing a fluorine-containing trityl radical compound according to claim 3, wherein: The salt of the trityl radical compound is its potassium salt or its sodium salt. The molar ratio of the trityl radical compound or its salt, the fluorinated alkyl compound LGRf and the base is 1.0:1.0-8.0:2.0-4.

0.

6. The method for preparing a fluorine-containing trityl radical compound according to claim 3, wherein: In the nucleophilic substitution reaction, the reaction solvent is at least one of N,N-dimethylformamide, N,N-dimethylacetamide and dimethyl sulfoxide, the base is at least one of N,N-diisopropylethylamine, triethylamine, potassium carbonate and sodium carbonate, and the reaction temperature is 0-100°C.

7. Use of the fluorine-containing trityl radical compound according to any one of claims 1 to 2 in the preparation of a DNP polarizer.

8. The use of the fluorine-containing trityl radical compound according to claim 7, characterized in that The method for rapid separation of the fluorine-containing trityl radical compound is as follows: Using polytetrafluoroethylene powder or fluorosilica gel as a solid phase filler, solid phase extraction is performed on the mixture of the fluorine-containing trityl radical compound and the polarized sample to achieve rapid separation of the fluorine-containing trityl radical compound and the polarized sample.

9. The use of the fluorine-containing trityl radical compound according to claim 8, characterized in that: The average particle size of the polytetrafluoroethylene powder is 1-1000 μm, and the average particle size of the fluorosilicone is 1-100 μm.

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