Preparation method of novel chiral covalent organic framework material and application of novel chiral covalent organic framework material in chiral screening
By constructing active crown ether groups in vinyl covalent organic framework materials and preparing COF-OHTBA materials, the problems of low efficiency and low selectivity of chiral screening technology are solved, and the identification and detection of efficient chiral drugs are achieved. And the material can be recycled.
Patent Information
- Application Number
- CN202411594452.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-09
- Publication Date
- 2024-12-31
AI Technical Summary
The existing chiral screening technology is inefficient, low selectivity, and difficult to recycle, making it impossible to effectively identify and detect chiral drugs.
By constructing the active crown ether group into a vinyl covalent organic framework material, a novel COF-OHTBA material with 18 crown hexaether group is prepared, and using its excellent optical activity and CD activity to achieve efficient chiral drugs. identification and detection.
It achieves high chiral screening efficiency, excellent selectivity, short detection time and high sensitivity, and the material can be recycled to maintain efficient detection performance.
Smart Images
Figure FT_1 
Figure FT_2 
Figure FT_3
Abstract
Description
Technical Field
[0001] The invention relates to a method for preparing a novel chiral covalent organic framework material with a simple synthesis route and mild reaction conditions, which is applied to chiral screening and belongs to the field of new materials. Background Art
[0002] Chirality is an important element in the fields of art, fashion, health and manufacturing, and has a wide range of applications, from fragrances and clinical analysis to pharmaceuticals, agricultural chemicals and other fine chemical industries. Chiral compounds (CCs), especially chiral drugs, have already had a large market. CCs usually exhibit obvious optical rotation or circular dichroism. In view of this feature, chiral science and technology such as the synthesis, separation, structural analysis and application of CCs have attracted more and more attention. In view of the shortcomings of traditional chiral screening technologies such as low efficiency, low selectivity and difficulty in recycling, it is imperative to develop high-performance fluorescent probes with high chiral screening efficiency, high selectivity and recyclability. According to the physicochemical properties of CCs, it is a feasible strategy to prepare fluorescent probes by chemically bonding functional ligands (such as crown ethers) that can coordinate with CCs to porous materials.
[0003] Covalent organic frameworks (COFs) are an attractive class of porous crystalline polymers that have been widely used in various fields such as storage, separation, and catalysis due to their tunable structures and chemical properties. The crystallinity, stability, and functionality of COFs are determined by the type of covalent bonds connecting the ligands. Currently, the reported vinyl bond COFs can not only solve the problem of chemical stability of the skeleton connection, but also prepare materials with new fluorescent properties. Moreover, COFs have potential applications in sensing such as chiral screening, especially vinyl chiral COFs (CCOFs) have not been reported for chiral screening. At the same time, it is innovative and reasonable to prepare ligands with functional crown ether chemical bond structures and their derived vinyl CCOFs for chiral screening. Therefore, building active crown ether groups into the internal skeleton structure of vinyl CCOFs is an effective way to successfully realize efficient chiral screening applications. Summary of the invention
[0004] Aiming at the chirality screening of different chiral compounds and overcoming the above-mentioned existing technical problems, the present invention aims to provide a method for preparing a novel chiral covalent organic framework material, wherein the chiral compound 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 present invention can effectively solve the shortcomings of low efficiency, low selectivity and difficulty in recycling in traditional chiral screening technologies, and the prepared novel chiral covalent organic framework material has high chiral screening efficiency, high selectivity and recyclable properties for chiral compounds.
[0005] The technical solution of the present invention is as follows: A novel 18-crown hexaether group COF-OHTBA material is prepared according to the following method: In a 20 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP), 4,4',4'',4'''-(6,7,9,10,17,18,20,21-octahydrodibenzo[B,K][1,4,7,10,13,16]hexaoxacyclooctadecene-2,3,13,14-tetrayl)tetrabenzaldehyde (OHTBA), benzoic anhydride and benzoic acid were placed in the Schlenk reaction tube, shaken 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 with NaOH solution several times, washed with DMF several times, washed with ethanol several times, and dried in vacuum at 100°C to obtain dark red COF-OHTBA; The molar ratio of TMP:OHTBA is 1:0.5-5; The molar ratio of OHTBA:benzoic anhydride is 1:1-10; The molar ratio of benzoic anhydride to benzoic acid is 1:0.01-10; The reaction temperature is 120°C-200°C; The reaction time is 0.5-7 days.
[0006] Compared with the prior art, the present invention has the following substantial advantages: (1) The synthesis method is simple and easy to prepare in large quantities; (2) The prepared chiral covalent organic framework materials are uniform in size and well dispersed; (3) COF-OHTBA has excellent optical activity and CD activity in the visible light region, and can be used for the identification and detection of chiral drugs; (4) COF-OHTBA has a short detection time for chiral drugs, high sensitivity, excellent selectivity, and can be recycled. BRIEF DESCRIPTION OF THE DRAWINGS
[0007] Figure 1is a BET schematic diagram of COF-OHTBA in Example 1 of the present invention; Figure 2 is an XRD schematic diagram of COF-OHTBA in Example 1 of the present invention; Figure 3 This is a schematic diagram of the detection performance of COF-OHTBA for chiral drugs in Example 1 of the present invention; Figure 4 Schematic diagram of the selectivity of COF-OHTBA to chiral drugs in Comparative Example 1 of the present invention; Figure 5 This is a schematic diagram of the cyclic detection of chiral drugs by COF-OHTBA in Comparative Example 1 of the present invention. DETAILED DESCRIPTION
[0008] 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.
[0009] Example 1: Preparation of COF-OHTBA In a 20 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 4,4',4'',4'''-(6,7,9,10,17,18,20,21-octahydrodibenzo[B,K][1,4,7,10,13,16]hexaoxacyclooctadecene-2,3,13,14-tetrayl)tetrabenzaldehyde (OHTBA) (0.5 mmol, 310.2 mg), benzoic anhydride (1 mmol, 226 mg) and benzoic acid (0.1 mmol, 12.3 The reaction system was then placed in an oven at 180 °C for 4 days. After the reaction was completed, it was cooled, washed with NaOH solution for 3 times, washed with DMF for 3 times, washed with ethanol for 3 times, and dried in vacuum at 100 °C to obtain dark red COF-OHTBA.
[0010] Example 2: Preparation of COF-OHTBA In a 20 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (1 mmol, 136.2 mg), 4,4',4'',4'''-(6,7,9,10,17,18,20,21-octahydrodibenzo[B,K][1,4,7,10,13,16]hexaoxacyclooctadecene-2,3,13,14-tetrayl)tetrabenzaldehyde (OHTBA) (0.5 mmol, 310.2 mg), benzoic anhydride (1 mmol, 226 mg) and benzoic acid (0.1 mmol, 12.3 The reaction system was then placed in an oven at 180 °C for 4 days. After the reaction was completed, it was cooled, washed with NaOH solution for 3 times, washed with DMF for 3 times, washed with ethanol for 3 times, and dried in vacuum at 100 °C to obtain dark red COF-OHTBA.
[0011] Example 3: Preparation of COF-OHTBA In a 20 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 4,4',4'',4'''-(6,7,9,10,17,18,20,21-octahydrodibenzo[B,K][1,4,7,10,13,16]hexaoxacyclooctadecene-2,3,13,14-tetrayl)tetrabenzaldehyde (OHTBA) (0.5 mmol, 310.2 mg), benzoic anhydride (2 mmol, 452 mg) and benzoic acid (0.1 mmol, 12.3 The reaction system was then placed in an oven at 180 °C for 4 days. After the reaction was completed, it was cooled, washed with NaOH solution for 3 times, washed with DMF for 3 times, washed with ethanol for 3 times, and dried in vacuum at 100 °C to obtain dark red COF-OHTBA.
[0012] Example 4: Preparation of COF-OHTBA In a 20 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 4,4',4'',4'''-(6,7,9,10,17,18,20,21-octahydrodibenzo[B,K][1,4,7,10,13,16]hexaoxacyclooctadecene-2,3,13,14-tetrayl)tetrabenzaldehyde (OHTBA) (0.5 mmol, 310.2 mg), benzoic anhydride (1 mmol, 226 mg) and benzoic acid (1 mmol, 123 The reaction system was then placed in an oven at 180 °C for 4 days. After the reaction was completed, it was cooled, washed with NaOH solution for 3 times, washed with DMF for 3 times, washed with ethanol for 3 times, and dried in vacuum at 100 °C to obtain dark red COF-OHTBA.
[0013] Example 5: Preparation of COF-OHTBA In a 20 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 4,4',4'',4'''-(6,7,9,10,17,18,20,21-octahydrodibenzo[B,K][1,4,7,10,13,16]hexaoxacyclooctadecene-2,3,13,14-tetrayl)tetrabenzaldehyde (OHTBA) (0.5 mmol, 310.2 mg), benzoic anhydride (1 mmol, 226 mg) and benzoic acid (0.1 mmol, 12.3 The reaction system was then placed in an oven at 150 °C for 4 days. After the reaction was completed, it was cooled, washed with NaOH solution for 3 times, washed with DMF for 3 times, washed with ethanol for 3 times, and dried in vacuum at 100 °C to obtain dark red COF-OHTBA.
[0014] Example 6: Preparation of COF-OHTBA In a 20 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP) (0.5 mmol, 68.1 mg), 4,4',4'',4'''-(6,7,9,10,17,18,20,21-octahydrodibenzo[B,K][1,4,7,10,13,16]hexaoxacyclooctadecene-2,3,13,14-tetrayl)tetrabenzaldehyde (OHTBA) (0.5 mmol, 310.2 mg), benzoic anhydride (1 mmol, 226 mg) and benzoic acid (0.1 mmol, 12.3 The reaction system was then placed in an oven at 180 °C for 2 days. After the reaction was completed, it was cooled, washed with NaOH solution for 3 times, washed with DMF for 3 times, washed with ethanol for 3 times, and dried in vacuum at 100 °C to obtain dark red COF-OHTBA.
[0015] Example 7: Testing of the performance of COF-OHTBA in detecting chiral drugs COF-OHTBA (10 mg) of Example 1 was weighed, ground and added to a cuvette containing water (20 ml). After sufficient stirring and ultrasonication, the COF-OHTBA suspension (2 ml) was taken out for fluorescence detection experiment. 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 COF-OHTBA suspension (2 ml) was measured once each time the antibiotic 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 COF-OHTBA L Chiral drugs ( L -PGL, L -PAL, L -TPL) reached 92%, 96% and 94% quenching efficiencies, respectively, which far exceeded the detection performance of other fluorescent materials for chiral drugs.
[0016] Example 8: COF-OHTBA Selective Performance Test for Chiral Drugs The COF-OHTBA 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 COF-OHTBA sample of Example 1 was used to analyze the K of PGL, PAL and TPL. QR The values were 2.79, 5.85 and 4.30, respectively, indicating that the COF-OHTBA sample had obvious selectivity for the detection of PGL, PAL and TPL.
[0017] Example 9: Cyclic performance test of regenerated COF-OHTBA on chiral drugs After the COF-OHTBA of Example 1 was used for the chiral drug detection test, the COF-OHTBA after the chiral drug was detected was taken, stirred with ethanol at room temperature for 12 hours, washed 3 times, and filtered out. It was vacuum dried at 100°C, and the weight change of the COF-OHTBA chiral drug before and after elution was weighed. The eluted material was reused in the chiral drug detection experiment, and the cycle was tested at least 5 times.
[0018] COF-OHTBA 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.
[0019] 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 18-crown hexaether group COF-OHTBA material, characterized in that: The novel 18-crown hexaether group COF material is prepared according to the following method: In a 20 ml Schlenk reaction tube, 2,3,5,6-tetramethylpyrazine (TMP), 4,4',4'',4'''-(6,7,9,10,17,18,20,21-octahydrodibenzo[B,K][1,4,7,10,13,16]hexaoxacyclooctadecene-2,3,13,14-tetrayl)tetrabenzaldehyde (OHTBA), benzoic anhydride and benzoic acid were placed in the Schlenk reaction tube, shaken 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 with NaOH solution several times, washed with DMF several times, washed with ethanol several times, and dried in vacuum at 100°C to obtain dark red COF-OHTBA.
2. The novel 18-crown hexaether group COF-OHTBA material according to claim 1, characterized in that: The molar ratio of TMP:OHTBA is 1:0.5-5.
3. The novel 18-crown hexaether group COF-OHTBA material according to claim 1, characterized in that: The molar ratio of OHTBA:benzoic anhydride is 1:1-10.
4. The novel 18-crown hexaether group COF-OHTBA material according to claim 1, characterized in that: The molar ratio of benzoic anhydride to benzoic acid is 1:0.01-10.
5. The novel 18-crown hexaether group COF-OHTBA material according to claim 1, characterized in that: The reaction temperature is 120°C-200°C.
6. The novel 18-crown hexaether group COF-OHTBA material according to claim 1, characterized in that: The reaction temperature is 120°C-200°C.
7. The novel 18-crown hexaether group COF-OHTBA material according to claim 1, characterized in that: The COF-OHTBA L Chiral drugs ( L -PGL, L -PAL, L -TPL) reached 92%, 96% and 94% quenching efficiencies, respectively.
8. The novel 18-crown hexaether group COF-OHTBA material according to claim 1, characterized in that: The COF-OHTBA samples have a positive influence on the K of PGL, PAL and TPL. QR The values are 2.79, 5.85 and 4.30 respectively.
9. The novel 18-crown hexaether group COF-OHTBA material according to claim 1, characterized in that: The COF-OHTBA 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.