Oxidation-responsive cationic water-soluble pillararene, method for producing the same, and use

Abstract

This invention discloses an oxidation-responsive cationic water-soluble pillararene, a method for producing the same, and its use. The oxidation-responsive water-soluble cationic [A2]pilarene is a cyclic low-molecular-weight nucleic acid vector obtained by a quaternization reaction of a 4-methylboronic acid ester with a tertiary amine-modified pillararene. This invention achieves the synthesis of a low-molecular-weight delivery vector having a high positive charge density, which can tightly bind to negatively charged nucleic acid substances to form nanocomplexes. Upon entering a cell, the positive charge of the vector is released in an oxidative environment, the nucleic acid substance is released, and nucleic acid information is efficiently expressed. This delivery vector is easy to synthesize, has high delivery efficiency, and is biologically safe, and is expected to have promising future applications.

Description

Technical Field

[0001] The present invention relates to the field of organic synthetic biomedicine, and specifically, to an oxidation-responsive cationic water-soluble pillararene, a manufacturing method, and its use as a nucleic acid delivery vector.

Background Art

[0002] Among many existing cancer treatment methods, gene therapy can obtain a therapeutic effect that cannot be achieved by conventional drugs by directly repairing and improving gene defects. Thanks to the development and completion of the Human Genome Project, many genes causing diseases have been identified, providing broad ideas and methods for gene therapy, and enabling researchers to explore innovative and efficient gene therapy strategies by more targeted methods. The research and development of gene delivery vectors is an important part of this.

[0003] Gene delivery technologies mainly include three types: viral vectors, non-viral vectors, and physical transfection technologies. Non-viral vectors have great advantages because they are easier to overcome the disadvantages of the vector itself such as pathogenicity and immunogenicity compared with the other two major types of gene delivery methods, have high biological safety, and are low-cost. Currently, the main research issues faced by the development of non-viral vectors include: 1. improving the in vivo circulation stability of the gene delivery system; 2. efficient targeting to the lesion site; and 3. breaking through the bottleneck of low transfection efficiency. Therefore, improving the performance of the gene delivery system through innovative optimization of the vector structure is a powerful way to solve the research issues of non-viral gene vectors.

[0004] Host-guest recognition based on macrocyclic molecules is one of the promising methods for research and development in the field of supramolecular chemistry. Host-guest recognition of macrocyclic molecules and guest molecules, achieved through the synergistic effect of multiple weak interactions, provides researchers with simpler and more efficient new ideas and methods for constructing stimulus-responsive materials and innovative materials. Pillararenes, with their unique structural properties, show promising future applications in research and represent a new generation of excellent macrocyclic bodies. The repeating unit of pillararenes, 1,4-dimethoxybenzene, is bonded at positions 2 and 5 via methylene crosslinks, forming a symmetrical columnar structure. This gives pillararenes the following further unique property advantages and characteristics: (a) The molecular cavity is electron-rich and readily forms novel host-guest complexes. (b) The molecular structure is easy to chemically synthesize and modify, and pillararene molecules with the desired structure can be obtained through simple and efficient chemical reactions. (c) They exhibit rich stimulus responsiveness, which can be achieved not only through dynamically reversible host-guest complexing interactions but also through the introduction of specific responsive modifiers. These properties are also key to the wide range of applications and achievements that pillararene-based functional materials can achieve in various fields.

[0005] Accordingly, the present invention provides a method for producing oxidation-responsive cationic water-soluble pillararenes, which bind firmly to negatively charged nucleic acids through electrostatic interactions and, in combination with the physiological microenvironmental characteristics of cancer, injury, inflammation, and other lesion sites, which contain a large amount of reactive oxygen species (ROS), can effectively support nucleic acid drugs. At the same time, upon reaching the lesion site, the positive charge of the pillararene is removed by oxidizing and detaching the borate ester, thereby releasing the nucleic acid drug, and thereby improving the efficient delivery and release of nucleic acid drugs in gene therapy.

[0006] As described above, the oxidation-responsive cationic water-soluble pillararene in this invention utilizes the intracellular ROS microenvironment at the lesion site to induce a charge change, thereby achieving the release of nucleic acid-supported drugs. There are currently no reports on such oxidation-responsive cationic pillararenes, nor are there any reports on their manufacturing method or use. [Overview of the project] [Problems that the invention aims to solve]

[0007] This invention addresses the shortcomings of the prior art by providing the use of oxidation-responsive cationic water-soluble pillararenes as nucleic acid vectors in gene therapy. This invention offers advantages such as efficient loading and release, excellent biocompatibility, and the ability to form nanocomplexes with DNA, RNA, and other short-chain nucleic acids, thereby producing oxidation-responsive cationic pillararenes with high transfection efficiency. [Means for solving the problem]

[0008] Oxidation-responsive cationic water-soluble pillararenes include the following structure. TIFF2026510610000002.tif67149 (in the formula, X is an integer between 1 and 4, and R1 and R2 are each independently the following fragment, where R3 and R4 are each independently H, C1-C6 alkyl or acyl. TIFF2026510610000003.tif36151R5, R6, R7, and R8 are each independently C1-C6 alkyl or aryl compounds. R9, and R 10 Each of these is independently H, C1-C20 alkyl or aryl, Anions are either bromide ions or chloride ions.

[0009] Preferably, both the reaction monomers 1-(2-haloethoxy)-4-methoxybenzene and 4-alkoxymethoxy(ethoxy)benzene are reacted under Lewis acid catalyst conditions to copolymerize in monomer ratios of 2:3 and 1:4 to obtain copolymerized pillar[5]arenes, which are then reacted with dimethylamine and diethylamine to obtain copolymerized pillar[5]arenes substituted with tertiary amines, which are then reacted with benzyl boric acid bromide, benzyl borate ester bromide, benzene borate, or benzene chloride borate ester to obtain the product.

[0010] Preferably, the pillararene is a copolymerized pillar[5]arene, with a copolymerization ratio of 1:4 (i.e., x=1 or 4) or 2:3 (i.e., x=2 or 3).

[0011] Preferably, the copolymerized pillar[5]arene includes a pillar[5]arene obtained by carrying out a copolymerization cyclization reaction such that the molar ratio of the reaction monomers is 2:3 and the resulting product is x=2 or 3, or the molar ratio of the reaction monomers is 1:4 and the resulting product is x=1 or 4.

[0012] Preferably, R3 and R4 are boric acid, methyl borate, ethyl borate, or pinacol borate.

[0013] Preferably, R5, R6, R7, and R8 are methyl or ethyl.

[0014] Preferably, the above R9 is methyl or ethyl, and R 10 This is an alkyl or aryl group having more than 6 carbon atoms, more preferably an n-alkyl group.

[0015] Preferably, the above compounds may be produced by the following method.

[0016] Both 1-(2-haloethoxy)-4-methoxybenzene and 4-alkoxymethoxy(ethoxy)benzene are reacted under Lewis acid catalyst conditions and copolymerized in a monomer ratio of 1:4 to obtain copolymerized pillar[5]arenes, which are then reacted with dimethylamine and diethylamine to obtain copolymerized pillar[5]arenes substituted with tertiary amines, which are then reacted with benzyl boric acid bromide, benzyl borate ester bromide, benzene borate, or benzene chloride borate ester.

[0017] The manufacturing method is shown by the following formula. TIFF2026510610000004.tif110153

[0018] The oxidation-responsive cationic water-soluble pillararene of the present invention can remove the positive charge of a quaternary amine salt through an oxidation reaction with reactive oxygen species such as hydrogen peroxide, converting it into an electrically neutral tertiary amine. The reaction equation for this process is shown below. TIFF2026510610000005.tif71165

[0019] The present invention also provides the use of the above-mentioned oxidation-responsive cationic water-soluble pillararenes in the delivery of DNA, RNA, and other short-chain nucleic acids. [Effects of the Invention]

[0020] Compared to the prior art, the present invention has the following beneficial effects.

[0021] (1) The oxidation-responsive cationic water-soluble pillararene produced by the present invention is a low-molecular-weight gene delivery vector characterized by high charge density and high nucleic acid loading efficiency. In addition, it has a simple structure, low synthesis cost, and higher stability and reproducibility compared to conventional polymer nucleic acid vectors.

[0022] (2) The nucleic acid vector of the oxidation-responsive cationic water-soluble pillararene produced in the present invention efficiently releases nucleic acids by reacting with reactive oxygen species, thereby solving the problem of reduced transfection efficiency due to the fact that conventional quaternized vectors bind too tightly to nucleic acids and thus it is difficult to release nucleic acids.

[0023] (3) The nucleic acid vector of the oxidation-responsive cationic water-soluble pillararene produced in the present invention shows high transfection efficiency in cells, has low cytotoxicity and good biocompatibility compared with the golden standard PEI for gene transfection.

Brief Description of Drawings

[0024] [Figure 1] 1H NMR spectrum under the oxidation reaction conditions of Compound 1 in Examples 1 and 2 of the present invention. [Figure 2] Particle size and Zeta potential of various N / P nano-complexes formed by the complexation of Compound 1 and plasmid DNA in Example 3 of the present invention. [Figure 3] Gel retardation electrophoresis diagram of various N / P nano-complexes formed by the complexation of Compound 1 and plasmid DNA in Example 3 of the present invention. [Figure 4] Gel retardation electrophoresis diagram under the oxidation reaction conditions of the nano-complex formed by the complexation of Compound 1 and plasmid DNA in Example 3 of the present invention. [Figure 5] Figure 5A shows the particle size of the nano-complex formed by the complexation of Compound 1 and plasmid DNA in Example 3 of the present invention under the oxidation reaction conditions, and Figure 5B shows the change diagram of the corresponding Zeta potential. [Figure 6] Transmission electron microscope image of the nano-complex formed by the complexation of Compound 1 and plasmid DNA in Example 3 of the present invention. [Figure 7] Cytotoxicity diagram of Compound 1 under various concentration conditions in Example 4 of the present invention. [Figure 8]This diagram illustrates the effect of cell transfection of the nanocomplex formed by compound 1 and plasmid DNA in Example 5 of the present invention under various N / P conditions. [Figure 9] This diagram illustrates the effect of cell transfection of the nanocomplex formed by compound 1 and mRNA in Example 6 of the present invention under various N / P conditions. [Figure 10] This diagram illustrates the effect of cell transfection of compound 1 / DNA nanocomplex under oxidation reaction conditions in Example 7 of the present invention. [Modes for carrying out the invention]

[0025] The present invention provides several specific embodiments, but is not limited by these embodiments. [Examples]

[0026] Example 1 Synthesis of Compound 1 1-Methoxy-4-cetylbenzene (1.74 g, 5.00 mmol) and 4-bis(2-bromoethoxy)benzene (6.48 g, 20.0 mmol) were added to 80 mL of 1,2-dichloroethane, then boron trifluoride ether (3.20 mL, 25 mM) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction mixture was poured into methanol, and a large amount of white solid precipitated. The precipitate was filtered and dissolved in dichloromethane. The insoluble material was removed by further filtration, and the dichloromethane solution was washed twice with water to obtain the organic phase. After drying over anhydrous sodium sulfate, the crude product was obtained by dry evaporation, and the crude product was subjected to column chromatography (mobile phase: petroleum ether / ethyl acetate = 50:1 (R f The compound 3 of the product was dry evaporated over a pressure of 0.50 to obtain a white powdery solid (0.85 g, 10%).

[0027] Compound 3 (1.64 g, 1.00 mmol) and excess diethylamine (7.50 g, 100 mmol) were added to 100 ml of anhydrous ethanol, heated and stirred at 80°C, and refluxed for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the mixture was added to 200 ml of 1 M sodium hydroxide solution and stirred for 1 hour. Next, the reaction mixture was thoroughly extracted with ethyl acetate, and the organic phase was dry evaporated to obtain a dark yellow oily compound 2 (1.55 g, 98%).

[0028] Compound 2 (0.49 g, 0.30 mM) and 4-bromomethylphenylboronic acid pinacol ester (0.78 g, 2.64 mmol) were dissolved in 25 mL of acetonitrile, heated and stirred at 75°C, and refluxed for 24 hours. After the reaction was complete, the resulting mixed solution was concentrated to 2.0 mL, added to excess ethyl ether, filtered, and the precipitated white precipitate was collected. The precipitate was thoroughly washed with ethyl ether, and the resulting white precipitate was dried in a vacuum oven to obtain the product, Compound 1 (0.98 g, 81.6%). TIFF2026510610000006.tif65163

[0029] The structural detection data for compound 1 is as follows: 1H NMR (400 MHz, D2O, 298 K) δ (ppm): 7.80-7.73 (m, 16H), 7.54-7.45 (m, 16H), 6.97-6.63 (m, 10H), 4.79-4.58 (m, 16H), 4.48-4.38 (m, 16H), 4.30-4.25 (t, 2H), 3.86-3.77 (m, 16H), 3.68 (s, 3H), 3.65-3.50 (s, 10H), 3.50-3.42 (m, 32H), 1.46-1.39 (m, 48H), 1.23 (s, 96H), 0.71-0.41 (m, 31H). 13C NMR (600 MHz, CD3OD, 298 K) δ (ppm): 151.45, 136.54, 135.77, 133.44, 133.01, 131.50, 117.47, 85.54, 75.81, 70.92, 63.47, 58.05, 55.57, 33.05, 30.79, 30.46, 25.27, 25.03, 23.72, 14.47, 8.96. HR-MS: [M-8Br] 8+ The measured m / z value was 422.8757, [M-7Br] 7+ The m / z value was measured to be 494.5405. The melting point is 162.4-162.9°C. [Examples]

[0030] Example 2 H2O2 responsiveness of compounds A fixed amount of compound 1 was weighed and dissolved in D2O (1 mM), and a small amount of hydrogen peroxide was added dropwise to a final concentration of 10 mM. Under oxidative conditions, compound 1 reacted rapidly to produce a quinone, which was converted to p-hydroxybenzyl alcohol in water. This process change can be observed as corresponding proton peaks a, b, and c in 1H NMR. It was demonstrated that compound 1 undergoes a redox response, and the detection results are shown in Figure 1. [Examples]

[0031] Example 3 Preparation and characterization of nanocomplexes of compound 1 and plasmid DNA. A fixed amount of compound 1 was dissolved in HEPES buffer (pH=7.4, 10 mM) to a concentration of 2.0 mg / ml, and plasmid DNA was also diluted to a concentration of 40 μg / ml in HEPES buffer. After diluting the compounds to the corresponding concentrations according to the corresponding N / P molar ratios, they were rapidly added to the plasmid DNA solution in a volume ratio of 1:1, vortexed for 30 seconds, and then allowed to stand for 30 minutes to obtain a series of nanocomplexes with different N / P ratios.

[0032] Particle size and potential of nanocomposites: Appropriate amounts of the series of different N / P nanocomposites prepared above were taken and placed in a sample cell. Using a dynamic light scattering instrument, the particle size and Zeta potential of the different N / P nanocomposite solutions were measured, and the experiment was repeated three times for each sample to obtain the average value. As shown in Figure 2, the nanocomposites have a particle size of approximately 70–100 nm and a Zeta potential of 20–30 mV.

[0033] Nanocomplex Gel Retardation Experiment: A 1.0% agarose gel (containing gelred 2 μg / ml) was prepared and placed in 1×TAE buffer. 20 μL of various N / P nanocomplexes to be tested and 20 μL of the same concentration of pure plasmid DNA as a control were added to each gel well. A voltage of 120 mV was applied, and electrophoresis was performed for 30 minutes. After electrophoresis, the gel was placed in a gel imaging system, and a photograph was taken. The results are shown in Figure 3. Compound 1 effectively blocks DNA movement when it encapsulates DNA, thus effectively protecting DNA during gene delivery.

[0034] Gel retardation experiment of nanocomplexes under oxidative conditions: Nanocomplexes with an N / P ratio of 15 were obtained and incubated in H2O2 solutions of various concentrations at 37°C for 30 minutes. Then, 1.0% agarose gels (containing gelred 2 μg / ml) were prepared in the same manner and placed in 1×TAE buffer. 20 μL of the incubated nanocomplexes and 20 μL of pure plasmid DNA of the same concentration as a control were added to the gel wells, and electrophoresis was performed by applying a voltage of 120 mV for 30 minutes. After electrophoresis, the gels were placed in a gel imaging system and photographs were taken. The results are shown in Figure 4. This demonstrates that the nanocomplexes can effectively release DNA under oxidative conditions.

[0035] Changes in particle size and potential of nanocomplexes under oxidative conditions: Nanocomplexes with an N / P ratio of 15 were obtained and incubated in H2O2 solutions of various concentrations at 37°C for 30 minutes. Appropriate amounts were taken and placed in sample cells, and the particle size of nanocomplex solutions with different N / P ratios was measured using a dynamic light scattering instrument. The experiment was repeated three times for each sample, and the average value was calculated. Nanocomplexes with an N / P ratio of 15 were incubated at 37°C in an environment with an H2O2 concentration of 1.0 mM. Appropriate amounts of samples were taken at various time points, placed in sample cells, and point measurements were performed using a dynamic light scattering instrument. The experiment was repeated three times for each sample, and the average value was calculated. As shown in Figures 5A and 5B, as the concentration of hydrogen peroxide increases, the particle size of the nanocomplexes gradually increases, strong bonds are formed and dissociate, and over time, the surface potential of the nanocomplexes changes from positive to negative, and the electrostatic attraction with negatively charged DNA disappears.

[0036] Transmission electron microscopy observation experiment of nanocomplexes: Nanocomplexes with an N / P ratio of 15 were dropped onto a 300-mesh copper mesh, negatively stained with phosphotungstic acid, the liquid was aspirated at the edge of the filter paper, and then air-dried at room temperature. Subsequently, the nanocomplex samples on the copper mesh were observed with a transmission electron microscope. As shown in Figure 6, when compound 1 and plasmid DNA were complexed, nearly spherical nanoparticles were formed. The spheres were regular in shape and had a particle diameter of approximately 80 nm, which was in good agreement with the results of dynamic light scattering detection. [Examples]

[0037] Example 4 Cytotoxicity Experiment of Compound 1: The cytotoxicity of Compound 1 was evaluated using the CCK8 kit. Cells were cultured in vectors of Compound 1 at different concentrations and incubated for 48 hours with the conventional polymer gene vector PEI as a control. After incubation, the culture medium was discarded, diluted CCK8 reagent was added, and incubation was continued for 1-2 hours. Absorbance at a wavelength of 450 nm was measured using a microplate reader and compared with the control group to calculate cell viability. As shown in Figure 7, as the concentration increased, the viability of cells treated with PEI decreased rapidly, while the viability of cells treated with Compound 1 decreased slowly and was significantly higher than that of PEI, demonstrating that Compound 1 has higher biological safety within the test concentration range. [Examples]

[0038] Example 5 Luciferase gene transfection experiment: A549 cells were cultured at a cell density of 15,000 cells / well in a 96-well plate containing 200 μL of culture medium. After 24 hours of incubation in an incubator at 5% CO2, 95% humidity, and 37°C, the medium was discarded and replaced with fresh serum-free medium. Compound 1 was conjugated with the luciferase gene plasmid to form various N / P nanocomplexes, which were added to the medium and incubated at 37°C for 4 hours. The medium was discarded again and replaced with fresh medium, and incubation was continued for 48 hours. After the incubation period, the medium was discarded, 20 μL of 1× cell lysate was added, and after lysis for 10 minutes, 5 μL of supernatant was collected, 20 μL of luciferase substrate was added, and the chemiluminescence intensity was measured using a chemiluminescence detector. Protein concentration was measured using the Bradford protein detection kit, with parallel measurements performed on three repeat wells for each set of data, and the mean was calculated. The chemiluminescence intensity was normalized by the protein concentration to obtain the luminescence intensity per milligram of protein (RLU / mg protein). As shown in Figure 8, the transfection efficiency of compound 1 was improved by 1 to 2 orders of magnitude compared to commonly used non-viral gene vectors PEI, indicating that compound 1 is a more efficient gene vector. [Examples]

[0039] Example 6 Green fluorescent protein mRNA transfection experiment: RAW264.7 cells were cultured in glass-bottomed culture dishes with a radius of 15 mm, at a cell density of 25,000 cells per dish. 1.5 mL of culture medium was added, and the cells were cultured for 24 hours in an incubator at 37°C, 5% CO2, and 95% humidity. Subsequently, the culture medium in the culture dish was replaced with serum-free medium, and the complex of prepared compound 1 and green fluorescent protein mRNA was added. The mixture was incubated at 37°C for 4 hours. The medium was discarded again and replaced with fresh medium, and the culture was continued for 48 hours. After the culture period, the expression of green fluorescent protein was observed using a laser confocal microscope with an excitation wavelength of 488 nm and an emission wavelength of 510-540 nm. All images were taken under a 10x objective lens, and the light intensity was kept constant. As shown in Figure 9, compound 1 with mRNA supported exhibited higher transfection efficiency compared to PEI. [Examples]

[0040] Example 7 Cell transfection experiment of nanocomplexes under oxidative conditions: A549 cells were cultured at a cell density of 15,000 cells / well in a 96-well plate containing 200 μL of medium and incubated for 24 hours in an incubator at 5% CO2, 95% humidity, and 37°C. After incubation, the medium was discarded and replaced with fresh medium. H2O2 was added to the medium to prepare mediums with various concentrations of high oxidation environments (5 μM, 10 μM, 20 μM, 50 μM, 100 μM) to simulate the peroxidative microenvironment of tumors. Compound 1 was added and complexed with the luciferase gene plasmid to form nanocomplexes with different N / P ratios. This was added to the medium and incubated at 37°C for 4 hours. The medium was discarded again and replaced with fresh medium, and incubation was continued for 48 hours. After culturing, the culture medium was discarded, 20 μL of 1× cell lysate was added, and the cells were lysed for 10 minutes. 5 μL of the supernatant was collected, 20 μL of luciferase substrate was added, and the chemiluminescence intensity was measured using a chemiluminescence detector. Protein concentration was measured using a Bradford protein detection kit, with parallel measurements performed on three repeat wells for each set of data, and the average value was calculated. The chemiluminescence intensity was normalized by the protein concentration to obtain the luminescence intensity per milligram of protein (RLU / mg protein). As shown in Figure 10, the expression efficiency of plasmid DNA carrying compound 1 improved in an oxidized environment.

Claims

1. An oxidation-responsive cationic water-soluble pillararene characterized by containing the following structure. (In the formula, X is an integer from 1 to 4, and R １ , and R ２ These are, independently, the following fragments, where R ３ , and R ４ Each of these is independently H, C1-C6 alkyl or acyl, R ５ , R ６ , R ７ , and R ８ Each of these is independently a C1-C6 alkyl or aryl group. R ９ and R １０ are each independently H, C1-C20 alkyl or aryl, Anions are either bromide ions or chloride ions.

2. The oxidative-responsive cationic water-soluble pillararene according to claim 1, characterized in that the pillararene is produced by reacting a pillararene containing a primary, secondary, or tertiary amine with benzyl borate or benzyl borate.

3. The oxidation-responsive cationic water-soluble pillararene according to claim 2, characterized in that the pillararene is a copolymerized pillar[5]arene, with a copolymerization ratio of 1:4 (i.e., x = 1 or 4) or 2:3 (i.e., x = 2 or 3).

4. The copolymerized pillar[5]arene is characterized in that it includes a pillar[5]arene obtained by carrying out a copolymerization cyclization reaction such that the molar ratio of the reaction monomers is 2:3 and the resulting product is x=2 or 3, or the molar ratio of the reaction monomers is 1:4 and the resulting product is x=1 or 4, as described in claim 1 or 3.

5. R ５ , R ６ , R ７ , and R ８ is methyl or ethyl, R ９ These are methyl and ethyl, and R １０ The oxidation-responsive cationic water-soluble pillararene according to claim 1, 3, or 4, characterized in that is an alkyl or aryl group of C6 to 20.

6. The aforementioned pillararene compound is, specifically, A method for producing oxidation-responsive cationic water-soluble pillararenes according to 1, 2, 3, or 4, characterized in that both 1-(2-haloethoxy)-4-methoxybenzene and 4-alkoxymethoxy(ethoxy)benzene are reacted under Lewis acid catalyst conditions to copolymerize in molar ratios of 2:3 and 1:4 to obtain copolymerized pillararenes, which are then reacted with dimethylamine and diethylamine to obtain copolymerized pillararenes substituted with tertiary amines, and then reacted with benzyl boric acid bromide, benzyl borate ester bromide, benzene borate, or benzene chloride borate ester to obtain the product.

7. Use of oxidation-responsive cationic water-soluble pillararenes in the delivery of nucleic acid substances, including DNA, RNA, and other short-chain nucleic acids.

8. The method for producing the pillararene compound is, specifically, A method for producing oxidation-responsive cationic water-soluble pillararenes according to claim 2, characterized in that 1-(2-haloethoxy)-4-methoxybenzene is reacted with paraformaldehyde or trioxane under Lewis acid catalyst conditions to obtain a cyclic pillararene (where n = 5 to 15), which is then reacted with dimethylamine or diethylamine to obtain a pillararene substituted with a tertiary amine, which is then reacted with benzyl boric acid bromide, benzyl borate ester bromide, benzene borate, or benzene chloride borate ester.

9. The method for producing an oxidation-responsive cationic water-soluble pillararene according to claim 2, characterized in that the structure of the water-soluble pillararene produced by this method is as follows.

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