Chiral self-aggregating microporous polymer fluorescent probe, preparation method and fluorescent recognition application thereof

Abstract

A chiral self-polymerization microporous polymer fluorescent probe and a preparation method and fluorescent recognition application thereof have a chiral soluble chain self-polymerization microporous polymer shown in the following formula I or an enantiomer of the polymer, and the chiral spiro-bis-indenyl microporous polymer has specific recognition to small molecule enantiomers, especially specific fluorescence enhancement performance to enantiomers of phenylalanine, and can be used for molecular enantiomer identification.

Description

Technical Field

[0001] This invention relates to a chiral self-polymerizing microporous polymer fluorescent probe, its preparation method, and its fluorescent recognition application, belonging to the field of organic polymer materials and molecular probe technology. Background Technology

[0002] Chirality is a widespread phenomenon in nature, profoundly influencing the properties and functions of various substances. Constructing accurate chiral systems and developing efficient enantiomer differentiation techniques are considered core driving forces in many fields, including pharmaceutical research and development, information technology, advanced materials science, and computational science. However, it still faces numerous technical bottlenecks and challenges. Among various chiral recognition strategies, chromatographic separation, electrochemical analysis, and spectroscopic analysis techniques occupy a crucial position, especially their outstanding contributions to the identification of enantiomers of chiral molecules. However, the widespread application of traditional chromatographic techniques is significantly limited by their high cost, complex pretreatment processes, and lengthy processing times. In contrast, fluorescence spectroscopy, as a rising star in the field of chiral recognition, is gradually gaining widespread recognition and attention from the scientific community due to its significant advantages such as rapid response, high selectivity, and low detection threshold.

[0003] To further improve the sensitivity and selectivity of chiral recognition, the design and synthesis of high-performance chiral fluorescent probes has become a research hotspot. Currently, various chiral fluorescent recognition materials have been successfully developed, including but not limited to chiral ionic liquids, chiral covalent organic frameworks (COFs), chiral metal-organic frameworks (MOFs), porous organic cages, and natural proteins. Of particular note are self-supporting microporous materials, which, with their ultra-high specific surface area, excellent structural stability, and outstanding functionalization potential, are expected to play a more important role in the innovation of chiral recognition technology, demonstrating enormous application prospects.

[0004] Porous micromolecular materials (PIMs), as a unique class of chain polymers, are characterized by their rigid backbone structure. This rigidity restricts the free rotation of the molecular chains, thus preventing effective stacking between chains and naturally forming a continuous microporous network within the material. These materials not only exhibit excellent solubility and film-forming ability but have also attracted widespread attention in cutting-edge fields such as gas separation and sensing technology. However, research on chiral PIMs is still in its early stages within the PIMs family. The literature Angew. Chem. Int. Ed. 2015, 54, 11214-11218 reports a chiral PIM-1 prepared by the condensation of chiral spirodiindenyl TTSBI with 2,3,5,6-tetrafluoroterephthalonitrile, used for chiral membrane separation of small molecules; the literature Angew. Chem. Int. Ed. 2021, 60, 12781-12785 reports a chiral porous polymer FTPI based on a tripterene structure, also used for small molecule membrane separation; the literature Macromolecules... A chiral CCS-PIM with [5,5,6]-ringed spirodiindene units was reported in 2021, 54, 11180-11186, exhibiting circularly polarized luminescence properties. Despite this, chiral PIMs remain extremely rare, and research using PIMs as fluorescent sensing materials for enantiomeric recognition of small molecules has yet to be reported. Furthermore, the preparation processes of reported chiral PIMs are complex, the reagents are expensive, and large-scale production is difficult. Therefore, exploring and developing novel chiral PIMs materials not only has profound academic value but also significant practical implications, potentially bringing technological innovation and breakthroughs to the field of chiral recognition.

[0005] A search revealed no literature reports on chiral PIMs materials based on the 3,3,3′,3′-tetramethyl-1,1′-spirodiindene-7,7′-diol structural unit, or on small molecule enantiomer recognition using PIMs as fluorescent probes. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a chiral self-polymerizing microporous polymer fluorescent probe, its preparation method, and its fluorescent recognition application.

[0007] This invention is achieved through the following technical solution:

[0008] A chiral, soluble, chain-like self-polymerizing microporous polymer or an enantiomer of said polymer, as shown in Formula I:

[0009]

[0010] R1, R2, R3, and R4 are each independently hydrogen, alkyl, cycloalkyl, alkoxy, aryl, fluorine, chlorine, bromine, iodine, hydroxyl, or mercapto, and n is a positive integer.

[0011] In a further preferred embodiment, R1, R2, R3, and R4 are each hydrogen atoms, and n is a positive integer ≥ 1.

[0012] According to a preferred embodiment of the present invention, in the structure shown in Formula I, the spirodiinden unit or its enantiomer structure is as shown in Formula II:

[0013]

[0014] According to a preferred embodiment of the present invention, the spirodiinden unit or its enantiomer is prepared by the following method:

[0015] Bisphenol A undergoes cracking rearrangement in an acidic solution under stirring to generate racemic bisphenol spirodiindene compound 1. Racemic bisphenol spirodiindene compound 1 undergoes esterification under an alkaline catalyst and an optically pure chiral cofactor to generate a diastereomer mixture RL-2 and SL-2. Then, it is recrystallized at low temperature to precipitate RL-2. Finally, the cofactor is hydrolyzed to obtain an optically pure spirodiindene unit.

[0016] According to a preferred embodiment of the present invention, the acid solution is methanesulfonic acid;

[0017] According to a preferred embodiment of the present invention, the base catalyst is 4-dimethylaminopyridine (DMAP);

[0018] According to a preferred embodiment of the present invention, the chiral cofactor is L-menthol formyl chloride;

[0019] According to a preferred embodiment of the present invention, the mass-to-volume ratio of bisphenol A to acid solution is (2-6):(15-25), unit: g / mL, the cracking rearrangement temperature is room temperature, and the reaction time is 1-3 days.

[0020] According to a preferred embodiment of the present invention, the mass ratio of racemic diphenol spirodiinden compound 1 to the base catalyst is (450-550):(10-20).

[0021] According to a preferred embodiment of the present invention, the mass-to-volume ratio of racemic diphenol spirodiinden compound 1 to chiral cofactor reagent is (450-550):(0.5-2), unit, g / mL.

[0022] According to a preferred embodiment of the present invention, the esterification reaction is carried out in dichloromethane, with the addition of triethylamine. The mass-to-volume ratio of racemic diphenol spirodiindene compound 1 to dichloromethane is (450-550):(2-10), and the mass-to-volume ratio of racemic diphenol spirodiindene compound 1 to triethylamine is (450-550):(0.5-2), in g / mL.

[0023] According to a preferred embodiment of the present invention, the crystallization temperature is -15 to -20°C.

[0024] According to a preferred embodiment of the present invention, the hydrolysis of the cofactor is carried out by reflux in an ethanol solution of potassium hydroxide.

[0025] The reaction pathway of the spirodiinden unit or its enantiomer is shown in III below:

[0026]

[0027] This invention also provides a method for preparing the above-mentioned self-polymerizing microporous polymer. The method includes the following steps:

[0028] Optically pure monomer II and indigo were mixed, and anhydrous dichloromethane was added under ice-water bath cooling. Trifluoroacetic acid was added dropwise, and the mixture was stirred for half an hour until the solution was homogeneous. Then, trifluoromethanesulfonic acid was added dropwise, and the mixture was stirred at room temperature until the solution became viscous. The reaction solution was then added to a methanol / water mixture to form a flocculent precipitate. Ammonia was added to remove excess acid, and the filter cake was collected. After dissolution and precipitation, the target polymer brown solid product was obtained.

[0029] The self-polymerizing microporous polymer obtained by this invention has a specific surface area of ​​50 m². 2 / g-1000m 2 / g.

[0030] According to a preferred embodiment of the present invention, the molar ratio of optically pure compound monomer II to indigo is 1:1.

[0031] According to a preferred embodiment of the present invention, the molar ratio of the monomer to the total volume of anhydrous dichloromethane, trifluoroacetic acid, and trifluoromethanesulfonic acid is 0.01:(10-35), in mol / mL.

[0032] According to a preferred embodiment of the present invention, the volume ratio of anhydrous dichloromethane, trifluoroacetic acid, and trifluoromethanesulfonic acid is 1:1:1.

[0033] The reaction pathway of the chiral spirodiinene self-porous polymer is shown in Equation IV below:

[0034]

[0035] R1, R2, R3, and R4 are each independently hydrogen, alkyl, cycloalkyl, alkoxy, aryl, fluorine, chlorine, bromine, iodine, hydroxyl, or mercapto; n is a positive integer.

[0036] Applications of chiral, soluble, chain-like self-polymerizing microporous polymers as shown in Formula I for molecular fluorescence recognition.

[0037] According to a preferred embodiment of the present invention, the molecular fluorescence recognition method is as follows:

[0038] The chiral soluble chain-like self-aggregating microporous polymer shown in Formula I was dissolved in methanol to obtain mixed solution a. Mixed solution a was added to a quartz cuvette, and the ultraviolet absorption spectrum at the emission wavelength and the fluorescence emission spectrum at the excitation wavelength were measured as background values. The methanol solution of the chiral soluble chain-like self-aggregating microporous polymer shown in Formula I and the small molecule to be analyzed was accurately prepared to obtain mixed solution b. Mixed solution b was added to a quartz cuvette, and the fluorescence emission curve of the mixed solution at the excitation wavelength was measured.

[0039] Preferably, the concentration of the self-polymerizing microporous polymer in mixed solution a and mixed solution b is 1×10⁻⁶. -5 mol / L.

[0040] Preferably, the concentration of the small molecule to be analyzed in mixed solution b is 5 × 10⁻⁶. -5 The concentration was mol / L, and the small molecule to be analyzed was either D-phenylalanine or D-binaphthol.

[0041] Preferably, the ultraviolet absorption wavelength is 400 nm;

[0042] Preferably, the excitation wavelength is 270 nm;

[0043] Preferably, the fluorescence emission wavelength is 290–800 nm.

[0044] Technical features and advantages of the present invention:

[0045] 1. The self-porous polymer of the present invention is optically pure.

[0046] 2. The microporous polymer of the present invention is soluble in organic solvents such as methanol and tetrahydrofuran.

[0047] 3. The soluble self-porous polymer methanol solution of the present invention exhibits specific fluorescence enhancement for D-phenylalanine, which is significantly higher than that for L-phenylalanine, and can meet the requirements for practical recognition of phenylalanine enantiomers.

[0048] 4. Raw materials are readily available, operation is simple, and mass production is convenient. Attached Figure Description

[0049] Figure 1 This is the 1H NMR spectrum of the chiral compound II spirodiindene monomer from Example 1;

[0050] Figure 2 This is the carbon NMR spectrum of the chiral spirodiindene self-porous polymer prepared in Example 1;

[0051] Figure 3 This is a nitrogen physisorption isotherm of the chiral spirodiinden microporous polymer prepared in Example 1.

[0052] Figure 4The NMR spectrum (H1N) and UV absorption and fluorescence spectra of the chiral spirodiinden microporous polymer prepared in Example 1 are shown below.

[0053] Figure 5 This is the selective recognition of a series of small molecule enantiomers by the chiral spirodiindene self-porous polymer prepared in Example 1. Detailed Implementation

[0054] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0055] Example 1

[0056] Preparation method of self-polymerizing microporous polymers:

[0057] (1) Preparation of polymer monomers

[0058]

[0059] The preparation steps of compound 1 are as follows: 4 g of bisphenol A was added to 18 mL of methanesulfonic acid, stirred at room temperature for 3 days, and then crushed ice was added until no more solid precipitated. The reaction system was filtered, and the filter cake was washed with hot water and saturated sodium bicarbonate until neutral to obtain the crude product of racemic bisphenol spirodiindene compound 1. The obtained crude product solid was dissolved in ethanol, recrystallized, and filtered to obtain a white flocculent solid (3,3,3′,3′-tetramethyl-1,1′-spirodiindene-7,7′-diol (6,6′-TMSOL)), with a yield of 81.2%.

[0060] Nuclear magnetic resonance 1H NMR (600MHz, DMSO-d6) δ 8.97 (d, J = 1.2Hz, 1H), 6.97 (d, J = 8.2Hz, 2H), 6.57 (ddd, J = 8.2, 2.4, 0.8Hz, 2H), 6.07 (d, J = 2.3Hz, 2H), 2.23 (d, J = 12.9Hz, 2H), 2.07 (d, J = 12.9Hz, 2H), 1.29 (s, 6H), 1.22 (s, 6H).

[0061]

[0062] The preparation steps of the optically pure compound RL-2 are as follows:

[0063] a. 500 mg of compound 1 and 16.3 mg of 4-dimethylaminopyridine (DMAP) were added to a round-bottom flask, followed by the addition of 4 mL of dichloromethane, 0.75 mL of triethylamine, and 0.75 mL of L-mentholformyl chloride. The mixture was stirred at room temperature for 1 h under a nitrogen atmosphere. The mixture was then washed with 1 mol / L hydrochloric acid and saturated sodium chloride, respectively, and extracted with ethyl acetate. After separation, the oil phase was dried over anhydrous sodium sulfate, separated by silica gel column chromatography (ethyl acetate: petroleum ether 1:100), and dried by rotary evaporation to obtain a mixture of RL-2 and SL-2.

[0064] b. The crude mixture of RL-2 and SL-2 was dissolved in n-hexane and concentrated to near saturation. The solution was placed in a refrigerator overnight to precipitate crystals. The mother liquor was carefully removed with a pipette. The crystallized crystals were washed twice with cold n-hexane and dried to obtain white crystalline RL-2, yield: 31.4%. Product purity was analyzed by HPLC using a C18 column. The mobile phase was methanol:water = 90:10, and the retention times were RT(RL-2) = 37.5 min and RT(SL-2) = 41.1 min.

[0065] RL-2 NMR: 1H NMR(600MHz,Chloroform-d)δ7.14(d,J=8.3Hz,2H),7.03(dd,J=8.3,2.3Hz,2H),6.61(d ,J=2.2Hz,2H),4.55(td,J=10.9,4.5Hz,2H),2.36(d,J=13.1Hz,2H),2.27(d,J=13.1Hz, 2H),2.13(dq,J=12.0,4.9,4.3Hz,2H),2.06~1.94(m,2H),1.68(ddt,J=13.0,5.3,2.8Hz ,4H),1.51~1.27(m,16H),1.13~1.00(m,4H),0.93~0.87(m,14H),0.79(d,J=7.0Hz,6H).

[0066]

[0067] The preparation steps of optically pure polymerizable monomer R-1 are as follows: Solid RL-2 was dissolved in ethanol, potassium hydroxide was added, and the mixture was heated under reflux for 2 hours and then concentrated under vacuum. The resulting residue was extracted with dichloromethane, and the organic phase was washed with 1 mol / L hydrochloric acid and saturated sodium chloride solution. The solution was dried over anhydrous sodium sulfate and rotary evaporated to obtain white flocculent crystals ((R)-3,3,3′,3′-tetramethyl-1,1′-spirodiindene-7,7′-diol, (R)-6,6′-TMSOL) with a yield of 80.4%.

[0068] The NMR results are consistent with those of the racemic diphenol spirodiindene compound 1: ¹H NMR (600MHz, DMSO-d6) δ 8.97 (d, J = 1.2Hz, ¹H), 6.97 (d, J = 8.2Hz, 2H), 6.57 (ddd, J = 8.2, 2.4, 0.8Hz, 2H), 6.07 (d, J = 2.3Hz, 2H), 2.23 (d, J = 12.9Hz, 2H), 2.07 (d, J = 12.9Hz, 2H), 1.29 (s, 6H), 1.22 (s, 6H). The NMR spectrum of the spirodiindene unit is shown below. Figure 1 As shown.

[0069] (2) Preparation of chiral spirodiindene microporous polymer 3:

[0070]

[0071] The optically pure monomers R-1 (6,6'-TMSOL, 0.01 mol) and indigo (0.01 mol) obtained in step (1) were mixed in a round-bottom flask. Under ice-water bath cooling, 3 ml of anhydrous dichloromethane was added, followed by 3 ml of trifluoroacetic acid dropwise. The mixture was stirred for half an hour until the solution was homogeneous. Then, 3 ml of trifluoromethanesulfonic acid was added dropwise. The mixture was stirred at room temperature until the solution became viscous. The reaction solution was then added to a methanol:water mixture of 1:1 to form a flocculent precipitate. A small amount of ammonia was added to remove excess acid, and the precipitate was collected by filtration. The resulting solid was dissolved in tetrahydrofuran and then added to a methanol:water mixture of 1:1 to precipitate the polymer. The solid was dried under vacuum at 120 °C for 12 h to obtain a dark red solid with a yield of 87.7%.

[0072] 1H NMR (600MHz, DMSO-d6) δ10.92 (s, 1H), 10.01 (s, 1H), 9.04 (d, J = 77.0Hz, 1H), 7.53~5.59 (m, 8H), 2.09 (s, 4H), 1.67~0.5 (m, 12H).

[0073] The NMR spectrum, physical adsorption isotherm, UV and fluorescence spectra of polymer 3 are as follows: Figure 2 , Figure 3 , Figure 4 As shown, this invention successfully prepared a chiral spirodiindene self-porous polymer.

[0074] (3) Fluorescence selectivity of chiral polymers for phenylalanine enantiomers:

[0075] 1) Chiral polymer 3 was dissolved in methanol to prepare a solution of 2×10 -5Take 2 ml of solution A (mol / L) and mix it with 2 ml of methanol. Add the mixture to a quartz cuvette and measure the fluorescence emission spectrum at an excitation wavelength of 271 nm. Select the fluorescence intensity at a wavelength of 366 nm as I0.

[0076] 2) Configure the concentration of D-configuration phenylalanine to be 1×10 -4 Take 2 ml of a mol / L methanol solution and mix it with 2 ml of solution A. Add the mixture to a quartz cuvette and measure the fluorescence emission spectrum at an excitation wavelength of 271 nm. Record the fluorescence intensity at a wavelength of 366 nm as I. d .

[0077] 3) Accurately prepare the L-configuration phenylalanine concentration to 1×10 -4 Take 2 ml of a mol / L methanol solution and mix it with 2 ml of solution A. Add the mixture to a quartz cuvette and measure the fluorescence emission spectrum at an excitation wavelength of 271 nm. Record the fluorescence intensity at a wavelength of 366 nm as I. l .

[0078] The enantiomeric fluorescence selectivity is S = |(I l -I0) / (I d -I0)|.

[0079] Example 2

[0080] Preparation method of self-polymerized microporous polymers

[0081] (1) The preparation of polymer monomers was carried out according to step (1) of Example 1;

[0082] (2) Preparation of chiral soluble chain-like self-polymerizing microporous polymers:

[0083] Under a nitrogen atmosphere, optically pure monomers R-1 (6,6'-TMSOL, 0.05 mol) and indigo (0.015 mol) were mixed in a round-bottom flask. Under ice-water bath cooling, 10 mL of anhydrous dichloromethane was added, followed by dropwise addition of 10 mL of trifluoroacetic acid. The mixture was stirred for half an hour until homogeneous. Then, 10 mL of trifluoromethanesulfonic acid was added dropwise, and the mixture was stirred at room temperature until the solution became viscous. The reaction solution was then added to a 1:1 methanol:water mixture, forming a flocculent precipitate. A small amount of ammonia was added to remove excess acid, and the precipitate was collected by filtration. The resulting solid was dissolved in tetrahydrofuran, and the solution was again added to a 1:1 methanol:water mixture to precipitate the polymer. The precipitate was dried under vacuum at 120 °C for 12 h to obtain a dark red solid with a yield of 90.1%.

[0084] (3) Fluorescence selectivity test of chiral polymers for enantiomeric binatol:

[0085] 1) Chiral polymer 3 was dissolved in methanol to prepare a solution of 2×10-5 Take 2 ml of solution A (mol / L) and mix it with 2 ml of methanol. Add the mixture to a quartz cuvette and measure the fluorescence emission spectrum at an excitation wavelength of 271 nm. Select the fluorescence intensity at a wavelength of 366 nm as I0.

[0086] 2) Accurately prepare the D-configuration binaphthol concentration to 1×10 -4 Take 2 ml of a mol / L methanol solution and mix it with 2 ml of solution A. Add the mixture to a quartz cuvette and measure the fluorescence emission spectrum at an excitation wavelength of 271 nm. Record the fluorescence intensity at a wavelength of 366 nm as I. d .

[0087] 3) Accurately prepare the L-configuration binaphthol concentration to 1×10 -4 Take 2 ml of a mol / L methanol solution and mix it with 2 ml of solution A. Add the mixture to a quartz cuvette and measure the fluorescence emission spectrum at an excitation wavelength of 271 nm. Record the fluorescence intensity at a wavelength of 366 nm as I. l .

[0088] The enantiomeric fluorescence selectivity is S = |(I l -I0) / (I d -I0)|.

Claims

1. The application of chiral soluble chain-like self-polymerizing microporous polymers or enantiomers of said polymers for molecular fluorescence recognition; The chiral, soluble, chain-like self-polymerizing microporous polymer or its enantiomers have the structure shown in Formula I: ； Formula I R1, R2, R3, and R4 are each hydrogen atoms, and n is a positive integer ≥ 1.

2. The application according to claim 1, characterized in that, The molecular fluorescence recognition method is as follows: The chiral soluble chain-like self-polymerizing microporous polymer shown in Formula I was dissolved in methanol to obtain mixed solution a. Mixed solution a was added to a quartz cuvette, and the ultraviolet absorption spectrum at the emission wavelength and the fluorescence emission spectrum at the excitation wavelength were measured as background values. The methanol solution of the chiral soluble chain-like self-polymerizing microporous polymer shown in Formula I and the small molecule to be analyzed was accurately prepared to obtain mixed solution b. Mixed solution b was added to a quartz cuvette, and the fluorescence emission curve of the mixed solution at the excitation wavelength was measured. The concentrations of the self-polymerizing microporous polymers in mixed solutions a and b are 1 × 10⁻⁶. -5 mol / L; The concentration of the small molecule to be analyzed in mixed solution b is 5 × 10⁻⁶. -5 mol / L, the small molecule to be analyzed is D-phenylalanine or D-binaphthol; The ultraviolet absorption wavelength is 400 nm, the excitation wavelength is 270 nm, and the fluorescence emission wavelength is 290–800 nm.

3. The application according to claim 1, characterized in that, In the structure shown in Equation I, the spirodiinden unit or its enantiomer structure is shown in Equation II as follows: ； Formula II.

4. The application according to claim 3, characterized in that, The spirodiinden unit or its enantiomer is prepared by the following method: Bisphenol A undergoes cracking rearrangement in an acidic solution under stirring to generate racemic bisphenol spirodiindene compound 1. Racemic bisphenol spirodiindene compound 1 undergoes esterification under an alkaline catalyst and an optically pure chiral cofactor to generate a diastereomer mixture RL-2 and SL-2. Then, it is recrystallized at low temperature to precipitate RL-2. Finally, the cofactor is hydrolyzed to obtain an optically pure spirodiindene unit.

5. The application according to claim 4, characterized in that, The acid solution is methanesulfonic acid; the base catalyst is 4-dimethylaminopyridine (DMAP); and the chiral cofactor is L-menthol formyl chloride.

6. The application according to claim 4, characterized in that, The mass-to-volume ratio of bisphenol A to acid solution was (2-6):(15-25), unit, g / mL; the cracking rearrangement temperature was room temperature; the reaction time was 1-3 days; the mass ratio of racemic bisphenol spirodiindene compound 1 to base catalyst was (450-550):(10-20); and the mass-to-volume ratio of racemic bisphenol spirodiindene compound 1 to chiral cofactor reagent was (450-550):(0.5-2), unit, g / mL.

7. The application according to claim 4, characterized in that, The esterification reaction was carried out in dichloromethane with the addition of triethylamine. The mass-to-volume ratio of racemic diphenol spirodiindene compound 1 to dichloromethane was (450-550):(2-10), and the mass-to-volume ratio of racemic diphenol spirodiindene compound 1 to triethylamine was (450-550):(0.5-2), with the unit being g / mL. The crystallization temperature was -15 to -20℃. The hydrolysis of the cofactor was carried out by reflux in an ethanol solution of potassium hydroxide.

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