Preparation method of novel dodecacrowntetraether covalent organic framework material and application of novel dodecacrowntetraether covalent organic framework material in chiral screening

Abstract

The invention provides a synthesis method of a novel covalent organic framework material of a twelve-crown tetraether group based on chiral screening, the covalent organic framework material with the novel twelve-crown tetraether group is prepared, and CCOF-HTOD-1 can be used as a fluorescent probe for realizing chiral screening of different chiral drugs (L-PGL, D-PGL, L-PAL, D-TPL, L-TPL and D-TPL). The prepared CCOF-HTOD-1 has the advantages that the preparation method is simple, large-scale preparation can be achieved, the prepared novel dodecacrowntetraether covalent organic framework material is uniform in structure and beneficial to dispersion and has excellent CD optical activity, and the CCOF-HTOD-1 has the excellent performance of being high in detection efficiency, high in selectivity and capable of being recycled for different chiral drugs. The problems of difficult separation, low detection efficiency and the like of common chiral drugs can be solved.

Description

Technical Field

[0001] The invention relates to a preparation method of a novel dodecacrown tetraether covalent organic framework material with simple preparation method and mild synthesis conditions and application thereof in chiral screening, and belongs to the field of fluorescence detection. Background Art

[0002] Chirality is a fundamental characteristic of life and plays a vital role in various chemical and biological processes. Since chirality has many potential applications, it is very important to test the chirality in various drugs. Common testing and separation methods such as asymmetric catalysis, chiral separation and magnetism have the disadvantages of high cost and complex operation, while the use of fluorescence sensing for chiral screening is an efficient and effective strategy. The use of fluorescence sensing for chiral screening requires the preparation of chiral fluorescent materials. At present, the common strategy for preparing chiral fluorescent materials is to use chiral modules to manufacture chiral skeleton structures. The principle is to use optically active chiral monomers to form chiral materials, and convert the inherent chirality of the monomers into the chirality of the chiral materials through the chirality conservation process. Based on the above principle, according to the physicochemical properties of the target chiral drug, it is a feasible strategy to prepare fluorescent probes by chemically bonding functional ligands (such as crown ethers, etc.) that can interact with the target chiral drug to porous materials.

[0003] Covalent organic frameworks (COFs) are an emerging class of crystalline polymers with tunable molecular composition, structure and function, similar to metal organic frameworks (MOFs). Compared with MOFs, COFs are less developed, especially crown ether functionalized vinyl COFs for chiral screening. The vinyl COFs reported so far not only have high fluorescence properties, but also have stability that makes them suitable for most chiral screening scenarios. Therefore, it is innovative and reasonable to prepare ligands with functional crown ether chemical bond structures and their derived vinyl CCOFs for chiral screening. Therefore, we prepared a new dodecapron tetraether covalent organic framework material for chiral screening of common chiral drugs, which is expected to have high efficiency, high selectivity and recyclable detection for these common chiral drugs. Summary of the invention

[0004] The present invention aims to screen the chirality of different chiral drugs and based on the above-described methods and strategies, provides a method for synthesizing a novel dodecapron tetraether covalent organic framework material, wherein the chiral drug is selected from L -phenylglycinol ( L -PGL)、 D -phenylglycinol ( D -PGL)、 L -Phenylalaninol ( L -PAL),D -Phenylalaninol ( D -PAL), L -Tryptophanol ( L -TPL)、 D -Tryptophanol ( D -TPL). The material developed by the present invention has the advantages of high efficiency, high selectivity and recyclability for the detection of chiral drugs, and can effectively solve the shortcomings of traditional chiral screening materials such as instability and low efficiency.

[0005] The technical solution of the present invention is as follows: A novel CCOF-HTOD-1 material with twelve-crown tetraether groups is prepared according to the following method: In a 10 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP), 2,3,5,6,8,9-hexahydrobenzo[B][1,4,7,10]tetraoxacyclododecene-11,14-benzaldehyde (HTOD), benzoic anhydride and benzoic acid were placed in the Schlenk reaction tube, shaken thoroughly and nitrogen protection was performed three times, and then the reaction system was heated in an oven for a period of time. After the reaction was completed, it was cooled, washed several times with a mixed solution of NaOH solution and methanol, then washed several times with DMF, and then washed several times with ethanol, and dried in vacuum at 100°C to obtain yellow CCOF-HTOD-1; The molar ratio of TMP:HTOD is 1:0.1-5; The molar ratio of HTOD:benzoic anhydride is 1:0.1-10; The molar ratio of benzoic anhydride to benzoic acid is 1:0.01-50; The reaction temperature is 100°C-220°C; The reaction time is 0.1-7 days.

[0006] Compared with the prior art, the present invention has the following substantial advantages: (1) The preparation method is simple and can be prepared on a large scale; (2) The prepared novel dodecacrown tetraether covalent organic framework material has a uniform structure and is easy to disperse; (3) CCOF-HTOD-1 has excellent CD optical activity and is suitable for chiral screening of chiral drugs; (4) CCOF-HTOD-1 has the advantages of high detection efficiency, high selectivity and recyclability for chiral drugs. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 This is a schematic diagram of the synthesis of CCOF-HTOD-1 in the present invention. Figure 2is a BET schematic diagram of CCOF-HTOD-1 in Example 1 of the present invention; Figure 3 is an XRD schematic diagram of CCOF-HTOD-1 in Example 1 of the present invention; Figure 4 It is a schematic diagram of the molecular structure of the chiral drug detected by CCOF-HTOD-1 in Example 1 of the present invention; Figure 5 This is a schematic diagram of the detection performance of CCOF-HTOD-1 for chiral drugs in Example 1 of the present invention; Figure 6 This is a schematic diagram of the selectivity of CCOF-HTOD-1 to chiral drugs in Comparative Example 1 of the present invention; Figure 7 This is a schematic diagram of the cyclic detection of chiral drugs by CCOF-HTOD-1 in Comparative Example 1 of the present invention. DETAILED DESCRIPTION The present invention is described in detail below in conjunction with specific embodiments, but the present invention is not limited to the following embodiments. Without departing from the content and scope of the present invention, changes in implementation should be included in the technical scope of the present invention.

[0007] Example 1: Preparation of CCOF-HTOD-1 In a 10 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 2,3,5,6,8,9-hexahydrobenzo[B][1,4,7,10]tetraoxadodecene-11,14-benzaldehyde (HTOD) (0.5 mmol, 140.1 mg), benzoic anhydride (2 mmol, 452 mg) and benzoic acid (0.2 mmol, 24.6 mg) were placed in the Schlenk reaction tube, shaken thoroughly and nitrogen protection was performed three times. The reaction system was then reacted in an oven at 180°C for 4 days. After the reaction was completed, it was cooled, washed three times with a mixed solution of NaOH solution and methanol, then washed three times with DMF, and then washed three times with ethanol, and dried in vacuum at 100°C to obtain yellow CCOF-HTOD-1.

[0008] Example 2: Preparation of CCOF-HTOD-1 In a 10 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (1 mmol, 136.2 mg), 2,3,5,6,8,9-hexahydrobenzo[B][1,4,7,10]tetraoxacyclododecene-11,14-benzaldehyde (HTOD) (0.5 mmol, 140.1 mg), benzoic anhydride (2 mmol, 452 mg) and benzoic acid (0.2 mmol, 24.6 mg) were placed in the Schlenk reaction tube, shaken thoroughly and nitrogen protection was performed three times. The reaction system was then reacted in an oven at 180°C for 4 days. After the reaction was completed, it was cooled, washed three times with a mixed solution of NaOH solution and methanol, then washed three times with DMF, and then washed three times with ethanol, and dried in vacuum at 100°C to obtain yellow CCOF-HTOD-1.

[0009] Example 3: Preparation of CCOF-HTOD-1 In a 10 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 2,3,5,6,8,9-hexahydrobenzo[B][1,4,7,10]tetraoxadodecene-11,14-benzaldehyde (HTOD) (0.5 mmol, 140.1 mg), benzoic anhydride (4 mmol, 904 mg) and benzoic acid (0.2 mmol, 24.6 mg) were placed in the Schlenk reaction tube, shaken thoroughly and nitrogen protection was performed three times. The reaction system was then reacted in an oven at 180°C for 4 days. After the reaction was completed, it was cooled, washed three times with a mixed solution of NaOH solution and methanol, then washed three times with DMF, and then washed three times with ethanol, and dried in vacuum at 100°C to obtain yellow CCOF-HTOD-1.

[0010] Example 4: Preparation of CCOF-HTOD-1 In a 10 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 2,3,5,6,8,9-hexahydrobenzo[B][1,4,7,10]tetraoxadodecene-11,14-benzaldehyde (HTOD) (0.5 mmol, 140.1 mg), benzoic anhydride (2 mmol, 452 mg) and benzoic acid (0.4 mmol, 49.2 mg) were placed in the Schlenk reaction tube, shaken thoroughly and nitrogen protection was performed three times. The reaction system was then reacted in an oven at 180°C for 4 days. After the reaction was completed, it was cooled, washed three times with a mixed solution of NaOH solution and methanol, then washed three times with DMF, and then washed three times with ethanol, and dried in vacuum at 100°C to obtain yellow CCOF-HTOD-1.

[0011] Example 5: Preparation of CCOF-HTOD-1 In a 10 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 2,3,5,6,8,9-hexahydrobenzo[B][1,4,7,10]tetraoxadodecene-11,14-benzaldehyde (HTOD) (0.5 mmol, 140.1 mg), benzoic anhydride (2 mmol, 452 mg) and benzoic acid (0.2 mmol, 24.6 mg) were placed in the Schlenk reaction tube, shaken thoroughly and nitrogen protection was performed three times. The reaction system was then reacted in an oven at 150°C for 4 days. After the reaction was completed, it was cooled, washed three times with a mixed solution of NaOH solution and methanol, then washed three times with DMF, and then washed three times with ethanol, and dried in vacuum at 100°C to obtain yellow CCOF-HTOD-1.

[0012] Example 6: Preparation of CCOF-HTOD-1 In a 10 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 2,3,5,6,8,9-hexahydrobenzo[B][1,4,7,10]tetraoxadodecene-11,14-benzaldehyde (HTOD) (0.5 mmol, 140.1 mg), benzoic anhydride (2 mmol, 452 mg) and benzoic acid (0.2 mmol, 24.6 mg) were placed in the Schlenk reaction tube, shaken thoroughly and nitrogen protection was performed three times. The reaction system was then reacted in an oven at 180°C for 2 days. After the reaction was completed, it was cooled, washed three times with a mixed solution of NaOH solution and methanol, then washed three times with DMF, and then washed three times with ethanol, and dried in vacuum at 100°C to obtain yellow CCOF-HTOD-1.

[0013] Example 7: Testing the performance of CCOF-HTOD-1 on chiral drug detection Weigh CCOF-HTOD-1 (10 mg) from Example 1, grind it and add it to a vial containing water (20 ml). After sufficient stirring and ultrasonication, take out the CCOF-HTOD-1 suspension (2 ml) and put it into a cuvette for fluorescence detection experiment. Add chiral drugs ( L -PGL, D -PGL, L -PAL, D -TPL, L -TPL, D -TPL) solution (1 mM, 20 μL each time), and the fluorescence intensity of the CCOF-HTOD-1 suspension (2 ml) was measured once each time the chiral drug solution was added, for a total of 10 times. During the entire fluorescence detection experiment, the mixed solution was stirred at a constant rate to maintain its uniformity. Through the fluorescence detection experiment, it can be concluded that the CCOF-HTOD-1 L Chiral drugs ( L -PGL, L -PAL, L -TPL) reached 93%, 98% and 95% quenching efficiencies respectively, which far exceeded the detection performance of other traditional fluorescent materials for chiral drugs.

[0014] Example 8: Test of the Selective Performance of CCOF-HTOD-1 on Chiral Drugs The CCOF-HTOD-1 samples of Example 1 were respectively L Chiral drugs ( L -PGL, L -PAL, L -TPL) Ksv Value and D Chiral drugs ( D -PGL, D -PAL, D -TPL) K sv The value is used as a ratio. Taking PGL as an example, the calculation method is K QR =K sv[L-PGL] / K sv[D-PGL] The higher the value, the better the selectivity. The K of PGL, PAL and TPL was determined by the CCOF-HTOD-1 sample of Example 1. QR The values ​​were 3.56, 6.22 and 4.85, respectively, indicating that the CCOF-HTOD-1 sample had obvious selectivity for the detection of PGL, PAL and TPL.

[0015] Example 9: Cyclic Performance Test of Regenerated CCOF-HTOD-1 on Chiral Drugs After the CCOF-HTOD-1 of Example 1 is used for the chiral drug detection test, the CCOF-HTOD-1 after the chiral drug detection is taken, stirred with ethanol at room temperature for 12 hours, washed 3 times, and filtered out. It is vacuum dried at 100°C, and the weight change of the CCOF-HTOD-1 before and after the chiral drug is eluted is weighed. The eluted material is reused in the chiral drug detection experiment, and the cycle is tested at least 5 times.

[0016] CCOF-HTOD-1 pair L After five cycles of testing, the maximum detection performance of the chiral drug can still maintain more than 99% of its original maximum detection performance.

[0017] Of course, the above specific embodiments are only detailed explanations of the corresponding technical solutions of the present invention, and are not limited to the above implementation methods. For those skilled in the art, various changes or modifications can still be made on the basis of the above embodiments. All implementation methods are not listed here, and all changes or modifications derived from the above principles or mechanisms are within the protection scope of the present invention.

Claims

1. A novel CCOF-HTOD-1 material with twelve-crown tetraether groups, characterized in that: The novel COF material of twelve-crown tetraether group is prepared according to the following method: In a 10 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP), 2,3,5,6,8,9-hexahydrobenzo[B][1,4,7,10]tetraoxacyclododecene-11,14-benzaldehyde (HTOD), benzoic anhydride and benzoic acid were placed in the Schlenk reaction tube, shaken thoroughly and nitrogen protection was performed three times. The reaction system was then heated in an oven for a period of time. After the reaction was completed, it was cooled, washed several times with a mixed solution of NaOH solution and methanol, then washed several times with DMF, and then washed several times with ethanol, and dried in vacuum at 100°C to obtain yellow CCOF-HTOD-1.

2. The novel twelve-crown tetraether group CCOF-HTOD-1 material according to claim 1, characterized in that: The molar ratio of TMP:HTOD is 1:0.1-5.

3. The novel CCOF-HTOD-1 material of claim 1, characterized in that: The molar ratio of HTOD:benzoic anhydride is 1:0.1-10.

4. The novel CCOF-HTOD-1 material of claim 1, characterized in that: The molar ratio of the benzoic anhydride to the benzoic acid is 1:0.01-50.

5. The novel CCOF-HTOD-1 material of twelve-crown tetraether group as claimed in claim 1, characterized in that: The reaction temperature is 100°C-220°C.

6. The novel CCOF-HTOD-1 material of claim 1, characterized in that: The reaction time is 0.1-7 days.

7. The novel CCOF-HTOD-1 material of claim 1, characterized in that: The CCOF-HTOD-1 L Chiral drugs ( L -PGL, L -PAL, L -TPL) reached 93%, 98% and 95% quenching efficiencies, respectively.

8. The novel CCOF-HTOD-1 material of claim 1, characterized in that: The K of the CCOF-HTOD-1 sample for PGL, PAL and TPL QR The values ​​are 3.56, 6.22 and 4.85 respectively.

9. The novel CCOF-HTOD-1 material of claim 1, characterized in that: The CCOF-HTOD-1 L After five cycles of testing, the maximum detection performance of the chiral drug can still maintain more than 99% of its original maximum detection performance.

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