A temperature-sensitive helical polymer based on quinoline structure and preparation method and application thereof
By constructing a proton transmembrane transport channel using a thermosensitive helical polymer based on a quinoline structure, the problem of proton transmembrane transport selectivity was solved, proton selective transport was realized, and the research on ion transmembrane transport was expanded.
Patent Information
- Application Number
- CN202310874406.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-07-17
- Publication Date
- 2026-01-27
- Estimated Expiration
- 2043-07-17
AI Technical Summary
Existing technologies struggle to effectively construct proton transmembrane transport channels, particularly due to the small size of protons, which makes highly selective transmembrane transport difficult.
A thermosensitive helical polymer based on quinoline structure was designed to mimic the α-helical structure of the natural proton channel protein M2. The oxygen line structure on the outer side of the helix serves as a hydrogen bond acceptor for proton transfer, thereby constructing a proton transmembrane transport channel that allows only protons to pass through while excluding other alkali metal ions.
This invention achieves highly selective transmembrane transport of protons, provides a new direction for exploring transmembrane ion transport systems, expands the research on the structure and properties of artificial and natural channels, and the polymer has an inner diameter of 0.1 nm, which matches the requirements for proton transport.
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Figure CN116903853B_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of organic synthesis technology, and more specifically, to a thermosensitive helical polymer based on a quinoline structure, its preparation method, and its application. Background Technology
[0002] Nature constantly provides a rich source of inspiration for biomimetic chemistry, aiming to mimic or even imitate biological functions through purely chemical means, creating innovative solutions to various complex problems. In living systems, proton transport is crucial for regulating the pH levels of certain tissues or organelles to promote specific physiological functions, often mediated by specific protein channels. For example, ATP-driven proton channels (i.e., proton-ATPases) on lysosomes or gastric parietal cells can effectively acidify their internal environment to accelerate the digestive process. It is well known that dysfunction of protein channels can lead to serious ion channel diseases, such as arrhythmias, cystic fibrosis, and gastric ulcers. Developing artificial ion channels not only helps in understanding the relationship between the structure and function of natural protein channels but also contributes to the development of potential treatments for ion transport-related diseases.
[0003] The extraction of natural channel proteins is difficult and costly, leading scientists to seek artificially synthesized biomimetic ion channels to replace natural ones. In recent years, various novel artificial ion channel models have been developed, particularly those related to alkali metal ions, such as Li... + Na + K + Rb + Cs + There has been a lot of research on the construction of [the specific type of ion channel], but there are few reports on the preparation of another special type of ion channel, namely the proton transmembrane channel, mainly because the size of the proton is too small to achieve highly selective transmembrane transport of the proton. Summary of the Invention
[0004] The purpose of this application is to provide a thermosensitive helical polymer based on a quinoline structure, which constructs a novel proton transmembrane transport channel.
[0005] Another objective of this application is to provide a method for preparing a thermosensitive helical polymer based on a quinoline structure, through which the above-mentioned polymer is prepared.
[0006] To solve the above-mentioned technical problems, the technical solution adopted in this application is as follows:
[0007] On the one hand, this application provides a method for preparing a thermosensitive helical polymer based on a quinoline structure, comprising the following steps:
[0008] S1. Dissolve 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid in a solvent, add PyBOP condensing agent, purge with nitrogen, heat, then add triethylamine. After the reaction is complete, concentrate to dryness to obtain crude polymer.
[0009] S2. Dissolve the crude polymer in a good organic solvent, then add a poor organic solvent. A brown solid will precipitate. Repeat this process several times and collect the precipitate. Dialyze the precipitate with an organic solvent and concentrate the dialysate to dryness to obtain the pure polymer.
[0010] S3. The pure polymer is added to an organic solvent containing (-)-(1S,4R)-camphenyl chloride under a nitrogen atmosphere, stirred and mixed, and then triethylamine is added. After the reaction is complete, the reactants are precipitated with a poor solvent, then dissolved in a good solvent, dialyzed with an organic solvent, and dried to obtain the thermosensitive helical polymer based on the quinoline structure.
[0011] On the other hand, this application provides a thermosensitive helical polymer based on a quinoline structure prepared by the above method.
[0012] Furthermore, this application also provides an application of a thermosensitive helical polymer based on a quinoline structure in the field of proton transmembrane transport.
[0013] Compared with the prior art, the embodiments of this application have at least the following advantages or beneficial effects:
[0014] This application, guided by the structure and function of the α-helix in the natural proton channel protein M2, constructs a thermosensitive artificial helical polymer based on quinoline derivatives as structural units. This helical polymer utilizes a unique oxygen line structure on the outer side of the helix as a hydrogen bond acceptor for proton transport, thus creating a novel proton transmembrane transport channel. This provides a new direction for constructing diverse ion transmembrane transport systems and offers new ideas and pathways for exploring the relationship between artificial and natural channels in terms of structure and properties, as well as for developing novel intelligent nanopore structures. Furthermore, the thermosensitive helical polymer has an inner diameter of 0.1 nm, which is mismatched with the size of other alkali metal ions, allowing only protons to pass through and thus excluding other ions, achieving high proton selectivity. Attached Figure Description
[0015] To more clearly illustrate the technical solutions of the embodiments of this application, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this application and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.
[0016] Figure 1 The reaction equation of this application is as follows;
[0017] Figure 2 This is a schematic diagram of the polymer pure product in Example 1 of this application and its calculated simulated size;
[0018] Figure 3 This is a circular dichroism chromatogram of the helical polymer in Example 1 of this application;
[0019] Figure 4 This is a MALDI-TOF mass spectrometry analysis chromatogram of the polymer pure product in Example 1 of this application;
[0020] Figure 5 This is a graph showing the chiral signal intensity of the helical polymer as a function of temperature in Example 1 of this application;
[0021] Figure 6 In Example 1 of this application, the proton transport activity of the helical polymer was evaluated using a pH-sensitive HPTS fluorescent probe (pH=7.0 inside, pH=6.0 outside, pure HEPES buffer solution, phospholipid=100 μM). Detailed Implementation
[0022] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions in the embodiments of this application will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.
[0023] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. The present application will now be described in detail with reference to specific embodiments.
[0024] A method for preparing a thermosensitive helical polymer based on a quinoline structure includes the following steps:
[0025] S1. Dissolve 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid in a solvent, add PyBOP condensing agent, purge with nitrogen, heat, then add triethylamine. After the reaction is complete, concentrate to dryness to obtain crude polymer.
[0026] S2. Dissolve the crude polymer in a good organic solvent, then add a poor organic solvent. A brown solid will precipitate. Repeat this process several times and collect the precipitate. Dialyze the precipitate with an organic solvent and concentrate the dialysate to dryness to obtain the pure polymer.
[0027] S3. The pure polymer is added to an organic solvent containing (-)-(1S,4R)-camphenyl chloride under a nitrogen atmosphere, stirred and mixed, and then triethylamine is added. After the reaction is complete, the reactants are precipitated with a poor solvent, then dissolved in a good solvent, dialyzed with an organic solvent, and dried to obtain the thermosensitive helical polymer based on the quinoline structure.
[0028] The chemical reaction formula of this application is as follows: Figure 1 As shown, 1 is 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid, 2 is a polymer of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid, and 3 is a thermosensitive helical polymer based on a quinoline structure.
[0029] In some embodiments of this application, the mass ratio of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid to solvent in step S1 above is 1.0:2.0 to 4.0, and the solvent is dichloromethane or tetrahydrofuran.
[0030] In some embodiments of this application, the molar ratio of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid to PyBOP condensing agent in step S1 above is 1.0:1.5 to 2.0.
[0031] In some embodiments of this application, the heating temperature in step S1 is 40–60°C, the amount of triethylamine added is 7–15% of the reaction solvent, and the reaction time is 72–96 h.
[0032] In some embodiments of this application, the benign organic solvent in step S2 above is one or both of dichloromethane and ethyl acetate, and the undesirable organic solvent is one or more of methanol, diethyl ether and ethanol.
[0033] In some embodiments of this application, the molecular weight of the dialysis bag in step S2 is in the range of 1k to 3k, and the organic solvent used for dialysis is selected from one or more of tetrahydrofuran, dichloromethane, and N,N-dimethylformamide; the organic solvent used for dialysis in step S3 is selected from one or two of dichloromethane and N,N-dimethylformamide.
[0034] Unless otherwise specified, in the embodiments of this application, the molar ratio of the polymer pure product to (-)-(1S,4R)-camphenyl chloride in step S3 is 1:1.5, and the amount of triethylamine used is 2-7%.
[0035] In some embodiments of this application, the undesirable solvent in step S3 is methanol, preferably methanol at 0°C to achieve even lower solubility; the good solvent is one or both of tetrahydrofuran and dichloromethane.
[0036] A thermosensitive helical polymer based on a quinoline structure was prepared using the method described above.
[0037] Application of a thermosensitive helical polymer based on a quinoline structure in the field of proton transmembrane transport.
[0038] The features and performance of this application will be further described in detail below with reference to the embodiments. Example 1
[0039] A thermosensitive helical polymer based on a quinoline structure is prepared by the following method:
[0040] S1. Synthesis of quinoline-based thermosensitive polymers with helical structures
[0041] 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid was dissolved in 4 times its mass of dichloromethane solution, and then added to a three-necked flask equipped with a thermometer and a condenser along with PyBOP catalyst. The molar ratio of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid to PyBOP catalyst was 1:1.5. After purging the air three times with nitrogen, the stirring device was started under a nitrogen atmosphere to ensure uniform mixing, and stirring was continued for 30 min. The heating system was then turned on to raise the temperature to 45°C, and 7% (by volume) of triethylamine was added under a nitrogen atmosphere. The reaction was allowed to proceed for 72 h. After the reaction was completed, the mixture was concentrated to dryness under reduced pressure at 60°C to obtain the crude polymer.
[0042] S2, Crude product purification
[0043] The crude polymer obtained above was dissolved in dichloromethane to prepare a 60% solution. Anhydrous methanol was rapidly added with stirring, resulting in the precipitation of a brown solid. This was filtered and repeated three times. The precipitate was placed in a dialysis bag with a molecular weight of 1k and dialyzed with dichloromethane for 48 hours. The dialysate was then vacuum dried and concentrated for 12 hours to obtain a pure, dry polymer. The pure polymer was analyzed by MALDI-TOF mass spectrometry. Figure 4 As shown, the MALDI-TOF mass spectrometry analysis results of the 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid polymer (crude polymer) obtained by polymerizing and purifying the monomer of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid can be seen from camphenyl chloride. The mass spectrometry signals of different molecular weights from dimer to undemer are clearly observed, which proves that the polymerization of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid was successful. Figure 2 This is a schematic diagram of the structure of the pure polymer and its calculated simulated dimensions. Figure 2As can be seen, after polymerization, the molecular morphology of the pure polymer is a helical structure with a diameter of about 1.0 nm. There is a channel structure at the center of the helical structure with a diameter of about 0.1 nm, which allows protons to pass through and thus achieve the purpose of transport.
[0044] S3, Chiral modification of thermosensitive polymers with helical structures
[0045] A certain amount of pure polymer was added to a three-necked flask, and nitrogen gas was introduced to replace the air three times. Then, a dichloromethane solution containing (-)-(1S,4R)-camphenyl chloride was added under a nitrogen atmosphere. The mixture was stirred for 30 minutes to mix thoroughly. Then, 2% triethylamine was added, and the reaction was carried out at 25°C for 24 hours. The reactants were precipitated with methanol at 0°C, redissolved in dichloromethane, and dialyzed in dichloromethane solution for 24 hours. The product was then dried under reduced pressure to obtain a thermosensitive helical polymer based on a quinoline structure.
[0046] Circular dichroism analysis of the helical polymer is as follows: Figure 3 As shown, from Figure 3 As can be seen, by using chemical modification, a chiral molecule (-)-(1S,4R)-camphenyl chloride is introduced into the pure thermosensitive helical polymer to form a thermosensitive helical polymer with a single chirality, thereby enabling the testing of its thermosensitive properties. When the temperature increases, the structure of this thermosensitive helical polymer folds, resulting in a gradual increase in the chiral signal, and the intensity of its chiral signal does not increase linearly with temperature. Figure 5 This is a graph showing the chiral signal intensity of the helical polymer as a function of temperature. Figure 5 As can be seen, the increase in temperature changes the helical structure of this temperature-sensitive helical polymer, causing its chiral signal to continuously increase. Moreover, the intensity of the chiral signal increases exponentially with temperature, which further verifies its excellent temperature-sensitive properties.
[0047] Application of the helical polymer in proton transmembrane transport: The proton transport properties of a quinoline-based thermosensitive helical polymer were detected using a pH-sensitive trisodium 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) assay. A suspension of large monolayer vesicles (pH 7.0) containing egg yolk L-phosphatidylcholine (EYPC) encapsulated with HPTS (1 mM) was prepared and then added to a buffer solution at pH 6.0 to create a pH gradient across the bilayer membrane. Subsequently, the proton transport characteristics of the helical-based channel-mediated permeation into the large monolayer vesicles were evaluated by continuously monitoring the fluorescence intensity changes of the encapsulated HPTS dye. + The proton transport activity of its helical polymer was assessed as follows: Figure 6 As shown ( Figure 6 Compound 3 in the text is the thermosensitive helical polymer based on the quinoline structure prepared in this embodiment. Figure 6As can be seen, we used monolayer phospholipid vesicles containing HPTS fluorescent probes to test the proton transport performance of this thermosensitive helical polymer. The phospholipid vesicles contained HEPES buffer at pH 7.0 inside and HEPES buffer at pH 6.0 outside. First, DMSO was added as a control group, and no significant change was detected in the fluorescence signal of the HPTS molecules inside the vesicles (excitation wavelength: 460 nm; emission wavelength: 510 nm). Subsequently, the thermosensitive helical polymer was added, and the intensity of the fluorescence signal changed, indicating that protons were transported into the vesicles through this proton channel, leading to the quenching of the HPTS fluorescent probe, thus proving that protons can achieve transmembrane transport via this proton channel. Example 2
[0048] A thermosensitive helical polymer based on a quinoline structure is prepared by the following method:
[0049] S1. Synthesis of quinoline-based thermosensitive polymers with helical structures
[0050] 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid was dissolved in three times its mass of dichloromethane solution, and then added to a three-necked flask equipped with a thermometer and a condenser along with PyBOP catalyst. The molar ratio of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid to PyBOP catalyst was 1:2. After purging the air three times with nitrogen, the stirring device was started under a nitrogen atmosphere to ensure uniform mixing, and stirring was continued for 40 min. The heating system was then turned on to raise the temperature to 50 °C, and 9% triethylamine was added under a nitrogen atmosphere. The reaction was allowed to proceed for 84 h. After the reaction was completed, the mixture was concentrated to dryness under reduced pressure at 60 °C to obtain the crude polymer.
[0051] S2, Crude product purification
[0052] The crude polymer obtained above was dissolved in dichloromethane solution to prepare a 60% solution. Anhydrous methanol was quickly added while stirring, and a brown solid precipitate was precipitated. The precipitate was filtered and repeated three times. The precipitate was placed in a dialysis bag with a molecular weight of 1k and dialyzed with dichloromethane for 60 hours. The dialysate was then vacuum dried and concentrated for 12 hours to obtain a pure and dry polymer product.
[0053] S3, Chiral modification of thermosensitive polymers with helical structures
[0054] A certain amount of pure polymer was added to a three-necked flask, and nitrogen gas was introduced to replace the air three times. Then, a dichloromethane solution containing (-)-(1S,4R)-camphenyl chloride was added under a nitrogen atmosphere. The mixture was stirred for 30 min to mix thoroughly. Then, 5% triethylamine was added, and the reaction was carried out at 30 °C for 24 h. The reactants were precipitated with methanol at 0 °C, redissolved in tetrahydrofuran, and dialyzed in dichloromethane solution for 24 h. The product was then dried under reduced pressure to obtain a thermosensitive helical polymer based on a quinoline structure.
[0055] Application of the helical polymer in proton transmembrane transport: The proton transport properties of a quinoline-based thermosensitive helical polymer were detected using a pH-sensitive trisodium 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) assay. A suspension of large monolayer vesicles (pH 7.0) containing egg yolk L-phosphatidylcholine (EYPC) encapsulated with HPTS (1 mM) was prepared and then added to a buffer solution at pH 6.4 to create a pH gradient across the bilayer membrane. Subsequently, the proton transport characteristics of the helical-based channel mediated by the helical polymer in transmembrane transport were evaluated by continuously monitoring the fluorescence intensity changes of the encapsulated HPTS dye. + . Example 3
[0056] A thermosensitive helical polymer based on a quinoline structure is prepared by the following method:
[0057] S1. Synthesis of quinoline-based thermosensitive polymers with helical structures
[0058] 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid was dissolved in 2.5 times its mass of dichloromethane solution, and then added to a three-necked flask equipped with a thermometer and a condenser along with PyBOP catalyst. The molar ratio of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid to PyBOP catalyst was 1:1.5. After purging the air three times with nitrogen, the stirring device was started under a nitrogen atmosphere to ensure uniform mixing, and stirring was continued for 60 min. The heating system was then turned on to raise the temperature to 40 °C, and 15% triethylamine was added under a nitrogen atmosphere. The reaction was allowed to proceed for 96 h. After the reaction was completed, the mixture was concentrated to dryness under reduced pressure at 45 °C to obtain the crude polymer.
[0059] S2, Crude product purification
[0060] The crude polymer obtained above was dissolved in dichloromethane solution to prepare an 80% solution. Anhydrous methanol was quickly added while stirring, and a brown solid precipitate was precipitated. The precipitate was filtered and repeated three times. The precipitate was placed in a dialysis bag with a molecular weight of 3k and dialyzed with dichloromethane for 72 hours. The dialysate was then vacuum dried and concentrated for 12 hours to obtain a pure and dry polymer product.
[0061] S3, Chiral modification of thermosensitive polymers with helical structures
[0062] A certain amount of pure polymer was added to a three-necked flask, and nitrogen gas was introduced to replace the air three times. Then, a dichloromethane solution containing (-)-(1S,4R)-camphenyl chloride was added under a nitrogen atmosphere. The mixture was stirred for 30 minutes to mix thoroughly. Then, 7% triethylamine was added, and the reaction was carried out at 37°C for 24 hours. The reactants were precipitated with methanol at 0°C, redissolved in dichloromethane, and dialyzed in dichloromethane solution for 24 hours. The product was then dried under reduced pressure to obtain a thermosensitive helical polymer based on a quinoline structure.
[0063] Application of the helical polymer in proton transmembrane transport: The proton transport properties of a quinoline-based thermosensitive helical polymer were detected using a pH-sensitive trisodium 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) assay. A suspension of large monolayer vesicles (pH 7.0) containing egg yolk L-phosphatidylcholine (EYPC) encapsulated with HPTS (1 mM) was prepared and then added to a buffer solution at pH 6.8 to create a pH gradient across the bilayer membrane. Subsequently, the proton transport characteristics of the helical-based channel mediated by the helical polymer in transmembrane transport were assessed by continuously monitoring the fluorescence intensity changes of the encapsulated HPTS dye. + . Example 4
[0064] A thermosensitive helical polymer based on a quinoline structure is prepared by the following method:
[0065] S1. Synthesis of quinoline-based thermosensitive polymers with helical structures
[0066] 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid was dissolved in four times its mass of dichloromethane solution, and then added to a three-necked flask equipped with a thermometer and a condenser along with PyBOP catalyst. The molar ratio of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid to PyBOP catalyst was 1:1.8. After purging the air three times with nitrogen, the stirring device was started under a nitrogen atmosphere to ensure uniform mixing, and stirring was continued for 30 min. The heating system was then turned on to raise the temperature to 55°C, and 15% triethylamine was added under a nitrogen atmosphere. The reaction was allowed to proceed for 86 h. After the reaction was completed, the mixture was concentrated to dryness under reduced pressure at 50°C to obtain the crude polymer.
[0067] S2, Crude product purification
[0068] The crude polymer obtained above was dissolved in dichloromethane solution to prepare a 60% solution. Anhydrous methanol was quickly added while stirring, and a brown solid precipitate was precipitated. The precipitate was filtered and repeated three times. The precipitate was placed in a dialysis bag with a molecular weight of 1k and dialyzed with dichloromethane for 72 hours. The dialysate was then vacuum dried and concentrated for 12 hours to obtain a pure and dry polymer product.
[0069] S3, Chiral modification of thermosensitive polymers with helical structures
[0070] A certain amount of pure polymer was added to a three-necked flask, and nitrogen gas was introduced to replace the air three times. Then, a dichloromethane solution containing (-)-(1S,4R)-camphenyl chloride was added under a nitrogen atmosphere. The mixture was stirred for 30 minutes to mix thoroughly. Then, 7% triethylamine was added, and the reaction was carried out at 25°C for 24 hours. The reactants were precipitated with methanol at 0°C, redissolved in dichloromethane, and dialyzed in dichloromethane solution for 24 hours. The product was then dried under reduced pressure to obtain a thermosensitive helical polymer based on a quinoline structure.
[0071] Application of the helical polymer in proton transmembrane transport: The proton transport properties of a quinoline-based thermosensitive helical polymer were detected using a pH-sensitive trisodium 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) assay. A suspension of large monolayer vesicles (pH 7.0) containing egg yolk L-phosphatidylcholine (EYPC) encapsulated with HPTS (1 mM) was prepared and then added to a buffer solution at pH 5.8 to create a pH gradient across the bilayer membrane. Subsequently, the proton transport characteristics of the helical-based channel-mediated permeation into the large monolayer vesicles were evaluated by continuously monitoring the fluorescence intensity changes of the encapsulated HPTS dye. + .
[0072] The embodiments described above are some, but not all, of the embodiments of this application. The detailed description of the embodiments of this application is not intended to limit the scope of the claimed application, but merely to illustrate selected embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.
Claims
1. A method for preparing a thermosensitive helical polymer based on a quinoline structure, characterized in that, Includes the following steps: S1. Dissolve 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid in a solvent, add PyBOP condensing agent, purge with nitrogen, heat, then add triethylamine, concentrate to dryness after the reaction is complete to obtain crude polymer; the heating temperature is 40-60℃, the amount of triethylamine added is 7-15% of the reaction solvent, and the reaction time is 72-96h; S2. Dissolve the crude polymer in a good organic solvent, then add a poor organic solvent. A brown solid will precipitate. Repeat this process several times and collect the precipitate. Dialyze the precipitate with an organic solvent and concentrate the dialysate to dryness to obtain the pure polymer. S3. The pure polymer is added to an organic solvent containing (-)-(1S,4R)-camphenyl chloride under a nitrogen atmosphere, stirred and mixed, and then triethylamine is added. After the reaction is complete, the reactants are precipitated with a poor solvent, then dissolved in a good solvent, dialyzed with an organic solvent, and dried to obtain the thermosensitive helical polymer based on the quinoline structure.
2. The method for preparing a thermosensitive helical polymer based on a quinoline structure according to claim 1, characterized in that, In step S1, the mass ratio of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid to solvent is 1.0:2.0-4.0, and the solvent is dichloromethane or tetrahydrofuran.
3. The method for preparing a thermosensitive helical polymer based on a quinoline structure according to claim 1, characterized in that, In step S1, the molar ratio of 8-(aminomethyl)-4-isobutoxyquinoline-2-carboxylic acid to PyBOP condensing agent is 1.0:1.5-2.
0.
4. The method for preparing a thermosensitive helical polymer based on a quinoline structure according to claim 1, characterized in that, The benign organic solvent in step S2 is one or both of dichloromethane and ethyl acetate, and the undesirable organic solvent is one or more of methanol, diethyl ether, and ethanol.
5. The method for preparing a thermosensitive helical polymer based on a quinoline structure according to claim 1, characterized in that, The molecular weight range of the dialysis bag in step S2 is 1k to 3k, and the organic solvent used for dialysis is selected from one or more of tetrahydrofuran, dichloromethane, and N,N-dimethylformamide; the organic solvent used for dialysis in step S3 is selected from one or two of dichloromethane and N,N-dimethylformamide.
6. The method for preparing a thermosensitive helical polymer based on a quinoline structure according to claim 1, characterized in that, In step S3, the molar ratio of the polymer pure product to (-)-(1S,4R)-camphenyl chloride is 1:1.5, and the amount of triethylamine used is 2-7% of the solvent.
7. The method for preparing a thermosensitive helical polymer based on a quinoline structure according to claim 1, characterized in that, In step S3, the undesirable solvent is methanol, and the good solvent is one or both of tetrahydrofuran and dichloromethane.
8. A thermosensitive helical polymer based on a quinoline structure, characterized in that, It is prepared by the method described in any one of claims 1 to 7.
9. The application of a thermosensitive helical polymer based on a quinoline structure as described in claim 8 in the field of proton transmembrane transport.