Temperature-sensitive spiral polyisocyanide as well as preparation method, regulation and control method and application thereof

Abstract

The invention relates to temperature-sensitive spiral polyisocyanide and a preparation method, a regulation and control method and application of the temperature-sensitive spiral polyisocyanide, a polymer is endowed with temperature responsiveness by introducing an oligopolyethylene glycol unit to a polyisocyanide side group through molecular design, a chiral amino acid unit is connected through an amido bond to provide a chiral source, and the prepared temperature-sensitive spiral polyisocyanide has good water solubility and can be used for preparing temperature-sensitive spiral polyisocyanide. The polyisocyanide has excellent temperature sensitivity, and in the temperature-sensitive process, oligomeric ethylene glycol units of polyisocyanide side groups are dehydrated and collapsed, so that chiral signals of chiral amino acid units of the oligomeric ethylene glycol units are promoted to be transmitted to a polyisocyanide main chain, and further polyisocyanide is induced to form helical conformation; in addition, the helical conformation and the temperature-sensitive phase change behavior of polyisocyanide are regulated and controlled through a small amount of small-molecule additives. Compared with the prior art, the helical conformation can be finely regulated and controlled by adding additives, and due to the unique performance and controllability of the helical conformation, the polymer shows wide application potential in the fields of biosensing, chiral drug delivery, biological tissue engineering and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of bionic intelligent materials, and in particular to a temperature-sensitive spiral polyisocyanate and a preparation method, a control method and an application thereof. Background Art

[0002] Helical macromolecules, such as nucleic acids and proteins, are common in nature. Helical structures play a crucial role in their biological functions. The biomimetic synthesis of helical polymers is of great significance for understanding and mimicking the functions of biomacromolecules and developing new chiral materials. Artificially synthesized helical polymers primarily fall into two categories: dynamic helical polymers and static helical polymers. Polyisocyanate, a reported polymer with a stable helical conformation, exhibits high rigidity and high-density packing, making its helical conformation less susceptible to changes in the external environment. However, the high rigidity of its backbone and the presence of multiple modified side groups give it enormous potential for application in the field of smart materials (new functional materials that can sense external stimuli, determine and appropriately process them, and perform their own actions). However, the difficulty in modifying its helical conformation limits its practical applications. Therefore, research on the regulation of the helical conformation of polyisocyanate is of profound significance.

[0003] The helical conformation of helical polymers is primarily controlled through mechanisms such as the "general-soldier effect," "majority rule," "domino effect," "long-range chiral end group effect," "bridge effect," and "substituent priority effect." Overall, the helical conformation is controlled by altering the polymer state. By endowing polyisocyanates with intelligent responsiveness, they can alter their state in response to external stimuli, further expanding their application in the fields of intelligent and biomimetic materials. Modulating the polymer's state through external stimuli can also be explored as a way to control the helical conformation of polymers.

[0004] There are many reports on the regulation of the helical conformation of helical polyisocyanate, but most of them are regulated by using chiral initiators or changing the polymerization environment during the polymerization process, or by inducing the helical conformation of the polymer in an organic solvent. For example, CN106432693A relates to a class of polyisocyanate derivatives with reversible regulation of temperature-induced helical conformation and a preparation method thereof, wherein an isocyanate copolymer containing an alkoxy ether and a hydrazide group is obtained by copolymerization of two monomers and then hydrazinolysis, while giving the polymer a temperature-sensitive behavior. By grafting chiral small molecules to the polymer side chains through acylhydrazone dynamic bonds, the phase transition temperature of the polymer aqueous solution can be regulated, and the conformation of the polyisocyanate can be reversibly regulated by temperature and phase transition processes. However, it is very difficult to induce it to form a helical conformation and regulate it in water, which seriously limits its application in directions such as biology and materials. Summary of the Invention

[0005] The purpose of the present invention is to solve the above problems and provide a temperature-sensitive helical polyisocyanate and its preparation method, regulation method and application, and provide a synthesis of an amphiphilic helical polyisocyanate based on oligoethylene glycol and a method for regulating its helical conformation. The temperature-sensitive helical polyisocyanate grafts oligoethylene glycol units and amino acid chiral units to the polyisocyanate main chain through covalent amide bonds. The polyisocyanate has good water solubility and temperature responsiveness, and can transmit amino acid chiral signals to the polyisocyanate main chain through dehydration and collapse of the oligoethylene glycol unit during the temperature-sensitive process, thereby inducing the polyisocyanate to form a helical conformation. The method of regulating the helical conformation of the polyisocyanate by using a small molecule additive is also provided. The dehydration and collapse process of the oligoethylene glycol unit during the temperature-sensitive process affects the transmission process of the amino acid chiral signal, thereby regulating the helical conformation of the polyisocyanate. Depending on the additive, the polyisocyanate exhibits chirality enhancement or chirality silencing.

[0006] The purpose of the present invention is achieved through the following technical solutions:

[0007] The first object of the present invention is to provide a thermosensitive helical polyisocyanate (polymer A (R-Glu-PPI)), the structural formula of which is:

[0008]

[0009] Wherein: m, n, q are integers, m = 100-500, n = 10-50, q = 0-4; R is a lower alkyl group.

[0010] Furthermore, the lower alkyl group is a C1-C6 alkyl group, such as methyl, ethyl, etc.

[0011] More preferably, q=1-4.

[0012] Furthermore, the chiral configuration of the chiral amino alcohol is R-type or S-type. * represents the connection site, and * represents S configuration or R configuration.

[0013] Furthermore, the temperature-sensitive helical polyisocyanate is a low-polyethylene glycol type temperature-sensitive helical polyisocyanate constructed by covalent amide bonds.

[0014] A second object of the present invention is to provide a method for preparing a temperature-sensitive helical polyisocyanate, the method comprising the following steps:

[0015] a. Pentafluorophenol active ester isocyanate monomer Pfp-PI was synthesized by amidation reaction using pentafluorophenol and 4-formamidobenzoic acid as raw materials;

[0016] b. The pentafluorophenol active ester isocyanate monomer Pfp-PI obtained in step a and the amino-modified oligoethylene glycol moiety were used as raw materials to synthesize ethyl isocyanate monomer R-PI by amidation reaction;

[0017] c. Using the pentafluorophenol active ester isocyanate monomer Pfp-PI obtained in step a and dimethyl glutamate hydrochloride as raw materials, an amidation reaction was performed to synthesize an ethyl isocyanate monomer Glu-PI;

[0018] d. The thermosensitive helical polyisocyanate is synthesized by polymerization reaction using the ethyl isocyanate monomer R-PI obtained in step b and the ethyl isocyanate monomer Glu-PI obtained in step c as raw materials.

[0019] Furthermore, step a includes the following specific steps:

[0020] Pentafluorophenol and 4-formamidobenzoic acid were dissolved in dichloromethane (DCM), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, CAS No.: 25952-53-8) was added in an ice-salt bath under inert gas protection. After the reaction was complete, the obtained compound was separated and purified. Triphosgene was added, and the mixture was stirred until the reaction was complete. After separation and purification, ethyl isocyanate monomer Pfp-PI was obtained.

[0021] Furthermore, the structural formula of the ethyl isocyanate monomer Pfp-PI is:

[0022]

[0023] Furthermore, step b includes the following specific steps:

[0024] The pentafluorophenol active ester isocyanate monomer Pfp-PI obtained in step a and the amino-modified oligoethylene glycol unit are dissolved in dichloromethane (DCM) to carry out an amidation reaction, and stirred until the reaction is complete. After separation and purification, the ethyl isocyanate monomer R-PI is obtained.

[0025] Furthermore, in step b, the amidation reaction is carried out under ice bath conditions;

[0026] Furthermore, the structural formula of the ethyl isocyanate monomer R-PI is:

[0027]

[0028] Furthermore, step c includes the following specific steps:

[0029] Mix glutamic acid dimethyl ester hydrochloride with the pentafluorophenol active ester isocyanate monomer Pfp-PI obtained in step a, add dichloromethane (DCM), and carry out amidation reaction. After the reaction is complete, purify to obtain the ethyl isocyanate monomer Glu-PI.

[0030] Furthermore, in step c, the amidation reaction is carried out under ice bath conditions.

[0031] Furthermore, the structural formula of the ethyl isocyanate monomer Glu-PI is:

[0032]

[0033] Furthermore, step d includes the following specific steps:

[0034] The ethyl isocyanate monomer R-PI obtained in step b and the ethyl isocyanate monomer Glu-PI obtained in step c are dissolved in tetrahydrofuran (THF), a polymerization catalyst is added under the protection of an inert gas, and a polymerization reaction is carried out at room temperature for 1 day. After the reaction is completed, the mixture is purified by column to obtain the thermosensitive spiral polyisocyanate.

[0035] Furthermore, in step d, the polymerization reaction catalyst may be nickel chloride hexahydrate or o-Tol(dppe)NiBr.

[0036] Furthermore, in step d, the polymerization reaction is carried out under stirring at a stirring rate of 200 to 800 rpm.

[0037] The third object of the present invention is to provide an application of a temperature-sensitive spiral polyisocyanate, wherein the temperature-sensitive spiral polyisocyanate is used as a bionic intelligent material.

[0038] Furthermore, bionic smart materials are bionic and intelligent responsive materials.

[0039] Furthermore, the temperature-sensitive helical polyisocyanate is used in fields such as biosensing, chiral drug delivery and biological tissue engineering.

[0040] The fourth object of the present invention is to provide a method for regulating the helical conformation of a temperature-sensitive helical polyisocyanate, wherein the helical conformation regulation method adopts the following method:

[0041] The helical conformation of the thermosensitive helical polyisocyanate is regulated by small molecule additives.

[0042] Furthermore, the small molecule additive is selected from one or more of metal ions, diol derivatives, benzene derivatives, and the like.

[0043] Furthermore, the addition of the metal ions promotes the formation of a helical conformation of the thermosensitive helical polyisocyanate (chirality enhancement).

[0044] Furthermore, the metal ions are metal salt ions, and the metal ions include one or more of sodium ions, potassium ions, lithium ions, rubidium ions, cesium ions, magnesium ions, calcium ions, strontium ions, barium ions, aluminum ions, ferrous ions, ferric ions, stannous ions, tin ions, lead ions, copper ions, cuprous ions, silver ions, zinc ions, cadmium ions, manganese ions, chromium ions, cobalt ions, nickel ions, platinum ions, gold ions, titanium ions, bismuth ions, indium ions, etc.;

[0045] Furthermore, the addition of the diol derivative promotes the formation of a helical conformation of the thermosensitive helical polyisocyanate (chirality enhancement).

[0046] More preferably, the diol derivative is an ethylene glycol derivative.

[0047] Furthermore, the diol derivatives include one or more of glycol ether compounds, glycol ester compounds, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol (200-20000), propylene glycol, butanediol, pentanediol, hexanediol, tripropylene glycol, dipropylene glycol, octanediol, decanediol, dodecanediol, etc.;

[0048] Furthermore, the addition of the benzene derivative hinders the formation of the helical conformation of the thermosensitive helical polyisocyanate (chiral silencing).

[0049] Furthermore, the benzene derivatives include one or more of phenol compounds, aniline compounds, benzoic acid compounds, salicylic acid, phthalic acid compounds, vanillin, guaiacol, gallic acid, and benzenesulfonic acid.

[0050] Furthermore, the helical conformation regulation method comprises the following steps:

[0051] The thermosensitive spiral polyisocyanate is dissolved in water to prepare a thermosensitive spiral polyisocyanate aqueous solution, wherein the concentration of the thermosensitive spiral polyisocyanate aqueous solution is 0.001wt%-1wt%;

[0052] An aqueous solution of a small molecule additive or a small molecule additive is added dropwise to an aqueous solution of a thermosensitive helical polyisocyanate to regulate the helical conformation of the thermosensitive helical polyisocyanate, and the helical conformation of the polymer (thermosensitive helical polyisocyanate) is characterized by variable temperature circular dichroism spectroscopy.

[0053] Furthermore, when the small molecule additive is a diol derivative, the small molecule additive is added dropwise to the thermosensitive helical polyisocyanate aqueous solution to regulate the helical conformation of the thermosensitive helical polyisocyanate, and the helical conformation of the polymer (thermosensitive helical polyisocyanate) is characterized by variable temperature circular dichroism spectroscopy.

[0054] Furthermore, when the small molecule additive is a metal ion or a benzene derivative, the small molecule additive aqueous solution is added dropwise to the thermosensitive helical polyisocyanate aqueous solution to regulate the helical conformation of the thermosensitive helical polyisocyanate, and the helical conformation of the polymer (thermosensitive helical polyisocyanate) is characterized by variable temperature circular dichroism spectroscopy.

[0055] Furthermore, the preparation of the small molecule additive aqueous solution includes the following process: dissolving the small molecule additive in water to prepare the small molecule additive aqueous solution, wherein the concentration of the small molecule additive aqueous solution is 0.1 wt%-10 wt%.

[0056] Furthermore, the equivalent ratio of the small molecule additive to the temperature-sensitive helical polyisocyanate repeating unit is 1-500.

[0057] Furthermore, the oligoethylene glycol-based thermosensitive helical polyisocyanate R-Glu-PPI involved can transmit the amino acid chiral signal to the polyisocyanate main chain through the dehydration collapse of oligoethylene glycol during the thermosensitive process, thereby inducing the polyisocyanate to form a helical conformation.

[0058] Furthermore, oligoethylene glycol-based thermosensitive helical polyisocyanates can regulate the dehydration collapse process of oligoethylene glycol during the thermosensitive process by adding small molecule additives (various metal ions, various diol derivatives, and various benzene derivatives), thereby affecting the transmission process of amino acid chiral signals and thus regulating the helical conformation of polyisocyanates.

[0059] Furthermore, various metal ions were added to the oligoethylene glycol thermosensitive helical polyisocyanate R-Glu-PPI solution with an equivalent ratio of (polymer (thermosensitive helical polyisocyanate): metal ion = 1:1-500). The addition of metal ions can significantly promote the dehydration collapse of the oligoethylene glycol unit, thereby prompting the chiral signal of its chiral amino acid unit to be transmitted to the polymer main chain, thereby enhancing the orderliness of the polyisocyanate helical conformation.

[0060] Furthermore, a diol derivative (preferably an ethylene glycol derivative) is added to the oligoethylene glycol-based thermosensitive helical polyisocyanate R-Glu-PPI, wherein the volume ratio of the diol derivative to water is (water: diol derivative molecules = 1-10:1). The addition of the diol derivative can significantly promote the dehydration collapse of the oligoethylene glycol unit, thereby promoting the transmission of the chiral signal of its chiral amino acid unit to the polymer main chain, thereby enhancing the orderliness of the polyisocyanate helical conformation.

[0061] Furthermore, various benzene derivatives were added to the oligoethylene glycol-based thermosensitive helical polyisocyanate R-Glu-PPI with an equivalent ratio of (polymer: benzene derivative = 1:1-500). The addition of benzene derivatives can significantly hinder the dehydration collapse of the oligoethylene glycol unit, thereby making it difficult for the chiral signal of its chiral amino acid unit to be transmitted to the polymer main chain, thereby weakening the orderliness of the polyisocyanate helical conformation.

[0062] The present invention prepares thermosensitive polyisocyanates containing oligoethylene glycol chains and chiral glutamic acid moieties as side groups through random copolymerization. The introduction of the oligoethylene glycol moieties imparts excellent thermosensitive properties to the polymer. The chiral glutamic acid moieties provide a chiral source, and the addition of small molecule additives can promote or hinder the dehydration collapse of the oligoethylene glycol moieties, thereby affecting the transmission of chiral signals from the chiral amino acid moieties, thereby enabling the regulation of the helical conformation of the polyisocyanates.

[0063] Furthermore, the thermosensitive helical polyisocyanate grafts oligoethylene glycol units and amino acid chiral units to the polyisocyanate backbone through covalent amide bonds. It has good water solubility and temperature responsiveness, and can transmit amino acid chiral signals to the polyisocyanate backbone through the dehydration collapse of the oligoethylene glycol unit during the thermosensitive process, thereby inducing the polyisocyanate to form a helical conformation. The method developed by the small molecule additive to regulate the helical conformation of polyisocyanate can affect the transmission process of amino acid chiral signals by regulating the dehydration collapse process of the oligoethylene glycol unit during the thermosensitive process, thereby regulating the helical conformation of the polyisocyanate. Depending on the additive, the polyisocyanate exhibits chirality enhancement or chirality silencing. Thanks to its unique performance and controllability, the polymer shows broad application potential in the fields of biosensing, chiral drug delivery, and biological tissue engineering.

[0064] Compared with the prior art, the beneficial effects of the present invention are embodied in the following aspects:

[0065] 1. The present invention discloses a method for synthesizing a novel thermosensitive helical polyisocyanate, which has excellent water solubility and temperature responsiveness. During the thermosensitive process, accompanied by the dehydration collapse of the oligoethylene glycol motif, the chiral signal of the chiral amino acid motif can be transmitted to the polymer main chain, inducing the polyisocyanate to form a helical conformation.

[0066] 2. The present invention adds small molecule additives (various metal ions, various diol derivatives, and various benzene derivatives) to the aqueous solution of polyisocyanate to regulate the dehydration collapse of oligoethylene glycol units in a thermosensitive process, thereby affecting the transmission process of chiral signals of its chiral amino acid units, thereby achieving fine regulation of the helical conformation of polyisocyanate and broadening the application of polyisocyanate in the field of bionic and intelligent responsive materials.

[0067] 3. The present invention adds small molecule additives (various metal ions, various diol derivatives, and various benzene derivatives) to the aqueous solution of polyisocyanate, and can adjust the amount of the small molecule additives to regulate the hydrophilicity and hydrophobicity of the polymer and affect the cloud point temperature of the polymer, thereby broadening the application of polyisocyanate in the field of bionic and intelligent responsive materials.

[0068] 4. The method of the present invention is simple, easy to implement, low in cost, and suitable for popularization and use. BRIEF DESCRIPTION OF THE DRAWINGS

[0069] Figure 1 is the polymer A in Examples 1, 2, 3 and 4 1 H NMR spectrum;

[0070] Figure 2 is the turbidity curve of polymer A in Examples 1, 2, 3 and 4;

[0071] Figure 3This is the turbidity curve of polymer A after adding sodium ions in Example 2;

[0072] Figure 4 This is the turbidity curve of polymer A after adding triethylene glycol in Example 3;

[0073] Figure 5 This is the turbidity curve of polymer A after adding phenol in Example 4;

[0074] Figure 6 is the circular dichroism absorption curve of polymer A in Examples 1, 2, 3 and 4;

[0075] Figure 7 This is the circular dichroism absorption curve of polymer A after adding sodium ions in Example 2;

[0076] Figure 8 This is the circular dichroism absorption curve of polymer A in Example 3 after adding triethylene glycol;

[0077] Figure 9 This is the circular dichroism absorption curve of polymer A after adding phenol in Example 4;

[0078] Figure 10 Schematic diagram of adding small molecules to regulate the helical conformation of the polymer in the example. DETAILED DESCRIPTION

[0079] The present invention is described in detail below with reference to specific embodiments, but is by no means intended to limit the present invention. Any features, such as preparation methods, materials, structures, or composition ratios, that are not explicitly described in this technical solution are considered to be common technical features disclosed in the prior art.

[0080] The present invention relates to a thermosensitive helical polyisocyanate and its preparation, control, and application. Through molecular design, oligoethylene glycol moieties are introduced into the side groups of the polyisocyanate to impart temperature responsiveness to the polymer. Chiral amino acid moieties are then connected via amide bonds to provide a chiral source. The synthesis process is simple and the reaction is rapid. The prepared thermosensitive helical polyisocyanate has good water solubility and excellent temperature sensitivity. During the temperature-sensitive process, the oligoethylene glycol moieties on the side groups of the polyisocyanate dehydrate and collapse, prompting the chiral signal of the chiral amino acid moieties to be transmitted to the polyisocyanate backbone, thereby inducing the polyisocyanate to form a helical conformation. Furthermore, the helical conformation and thermosensitive phase transition behavior of the polyisocyanate can be controlled by a small amount of small molecule additives, providing a new approach for the preparation of stimulus-responsive chiral materials. The helical conformation can be finely controlled by adding external additives. This strategy significantly expands the application prospects of thermosensitive polyisocyanate in the field of smart materials. Thanks to its unique properties and controllability, the polymer exhibits broad application potential in fields such as biosensing, chiral drug delivery, and biotissue engineering.

[0081] The present invention relates to a thermosensitive helical polyisocyanate A (R-Glu-PPI) constructed with covalent amide bonds. The preparation method includes the following steps.

[0082] a. Pentafluorophenol and 4-formamidobenzoic acid were dissolved in DCM, and EDC·HCl was added under ice-salt bath and inert gas protection. After the reaction was complete, the obtained compound was separated and purified, and triphosgene was added and stirred until the reaction was complete. After separation and purification, the monomer Pfp-PI was obtained.

[0083] b. The monomer Pfp-PI and the amino-modified oligoethylene glycol unit were dissolved in DCM, and the amidation reaction was carried out. The reaction was stirred until the reaction was complete. After separation and purification, the monomer R-PI was obtained. The structural formula is

[0084]

[0085] c. Mix glutamic acid dimethyl ester hydrochloride with monomer Pfp-PI and carry out amidation reaction. After the reaction is complete, purify to obtain monomer Glu-PI, whose structural formula is

[0086] d. The R-PI obtained in step b and the monomer Glu-PI obtained in step c were dissolved in THF, and under inert gas protection, a catalytic amount of catalyst was added and reacted at room temperature for 1 day; after the reaction, the reaction was purified by column to obtain the target product, thermosensitive helical polyisocyanate A (R-Glu-PPI), having the structural formula:

[0087] Furthermore, the order of steps b and c can be adjusted, that is, step c can be performed first and then step b, or steps b and c can be performed simultaneously.

[0088] The following examples will help those skilled in the art further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that those skilled in the art may make several variations and improvements without departing from the scope of the present invention. These variations and improvements are all within the scope of protection of the present invention.

[0089] The Et-OEG used in the examples is 2-(2-(2-ethoxyethoxy)ethoxy)ethylamine, purchased from Sigma-Aldrich, CAS No.: 145373-80-4.

[0090] In the embodiment, the temperature point at which the transmittance drops to 50% of the original value is the cloud point, so as to obtain the corresponding cloud point temperature.

[0091] Example 1: Synthesis of a Thermosensitive Helical Polyisocyanate (Polymer A)

[0092] In this example, the following synthetic route was used to prepare thermosensitive helical polyisocyanate (polymer A):

[0093] The specific steps include:

[0094] Step a. Process of synthesizing pentafluorophenol active ester isocyanate monomer Pfp-PI by amidation reaction

[0095] Pentafluorophenol (1 g, 5.43 mmol) and 4-formamidobenzoic acid (1.79 g, 11.42 mmol) were dissolved in DCM (20 mL) and the mixture was placed in an ice-salt bath (-15°C, the same below) under inert gas (nitrogen, the same below). EDC·HCl (2.08 g, 10.86 mmol) was added with stirring. The reaction was allowed to complete after 12 h, and then the mixture was separated and purified. Triphosgene (1.41 g, 4.76 mmol) was added to the resulting compound under ice-salt bath conditions, and the mixture was stirred for 3 h until the reaction was complete. After separation and purification with DCM, pentafluorophenol active ester isocyanate monomer Pfp-PI (1.43 g, 78%) was obtained, whose structural formula is:

[0096] Step b. Process of synthesizing ethyl isocyanate monomer Et-PI by amidation reaction

[0097] Pentafluorophenol active ester isocyanate monomer Pfp-PI (1 g, 3.19 mmol) and ethyl Et-OEG (0.47 g, 2.66 mmol) were dissolved in DCM (20 mL), placed in an ice-salt bath and protected by inert gas, and triethylamine (0.65 g, 6.39 mmol) was added with stirring to adjust the solution to alkalinity. After the reaction was complete for 8 h, the solution was purified by column chromatography to obtain ethyl isocyanate monomer Et-PI (0.79 g, 71%), whose structural formula is:

[0098] Step c. Process of synthesizing ethyl isocyanate monomer Glu-PI by amidation reaction

[0099] Glutamic acid dimethyl ester hydrochloride (0.5 g, 2.36 mmol) and pentafluorophenol active ester isocyanate monomer Pfp-PI (0.46 g, 3.07 mmol) were mixed and dissolved in DCM (20 mL). The mixture was placed in an ice-salt bath under inert gas protection. Triethylamine (0.65 g, 6.39 mmol) was added under stirring to adjust the solution to alkalinity for amidation. After the reaction was complete for 12 hours, the mixture was purified by column chromatography to obtain monomer Glu-PI (0.49 g, 82%), whose structural formula is

[0100] d. The process of synthesizing thermosensitive helical polyisocyanate by polymerization reaction

[0101] The ethyl isocyanate monomer Et-PI (100 mg, 0.32 mmol) obtained in step b and the monomer Glu-PI (4.1 mg, 0.03 mmol) obtained in step c were dissolved in THF (20 mL). Under the protection of inert gas, a catalytic amount of nickel chloride hexahydrate (0.07 mg, 0.0003 mmol) was added and reacted at room temperature for 1 day. After the reaction, the mixture was purified by column to obtain the target product, thermosensitive helical polyisocyanate Et-Glu-PPI (85 mg, 85%), whose structural formula is: Depend on Figure 1 1HNMR (DMSO-d6): δ = 0.93-1.11 (br, 9H, CH3), 1.23-1.37 (br, 2H, CH2), 3.07-4.06 (br, 12H, CH2), 5.25-5.51 (br, 2H, NH), 6.52-6.93 (br, 4H, Ph), 8.17-8.43 (br, 4H, Ph) proved that the target product was obtained.

[0102] According to GPC, the molecular weight of the target product obtained in Example 1 is about 15w, and the molecular weight distribution is about 1.43.

[0103] Example 2: Method for regulating the conformation of thermosensitive helical polyisocyanate by sodium ions

[0104] In this embodiment, sodium ions are used to achieve the regulation of the helical conformation of the thermosensitive helical polyisocyanate.

[0105] like Figure 10 As shown, the specific steps include:

[0106] Polymer A (Et-Glu-PPI) prepared in Example 1 was dissolved in water to prepare a 0.05 wt% aqueous solution of the polymer. NaCl was dissolved in water to prepare a 1 wt% aqueous solution of NaCl. 3 ml of the aqueous polymer solution was aspirated, and 10-75 times the equivalent of NaCl solution was added to the solution, calculated based on the equivalent weight of the repeating units of the polymer molecules, to achieve control.

[0107] Experimental test analysis:

[0108] The physical properties of Et-Glu-PPI in this embodiment were tested as a sample:

[0109] 1. Turbidity test:

[0110] The turbidity of the polymer was tested by UV spectrophotometer, such as Figure 2The polymer Et-Glu-PPI has a characteristic amphiphilic structure with a hydrophilic oligoethylene glycol moiety and a hydrophobic polyisocyanate backbone. It can be completely dissolved in water at low temperatures and presents a clear and transparent state. However, at high temperatures, the oligoethylene glycol chains collapse and aggregate, and the solution appears turbid. The cloud point temperature (T cp ) is 39.8℃.

[0111] The cloud point temperature of Et-Glu-PPI decreases after adding sodium ions, such as Figure 3 As shown, it is 25.4°C. And the polyisocyanate has excellent temperature sensitivity.

[0112] 2. Temperature-dependent circular dichroism spectroscopy test:

[0113] The helical conformation of the polymer was characterized by circular dichroism spectroscopy, e.g. Figure 6 As shown in the variable temperature CD images (25-75°C) of polymerized Et-Glu-PPI in aqueous solution, a significant Cotton effect is observed in the 300-550nm wavelength range, indicating that the polymer forms a helical conformation. Furthermore, the helical conformation of the main chain is highly temperature-dependent. Before the phase transition temperature, the polymer exhibits no Cotton signal, but after the phase transition temperature, the polymer solution displays a distinct Cotton signal.

[0114] After sodium ions were added to the polymer Et-Glu-PPI solution, the helical conformation of the polymer was characterized by circular dichroism spectrometry, such as Figure 7 The variable temperature CD images (25-75°C) show that at the phase transition temperature, the polymer exhibits a helical conformation, and the Cotton signal intensity of the sample with sodium ions is significantly enhanced compared to the sample without sodium ions.

[0115] The above examples demonstrate that the addition of sodium ions significantly enhances the conformational order of polyisocyanurate, resulting in enhanced chirality in the polymer. Furthermore, the phase transition temperature of the polymer can be controlled by adjusting the actual amount of sodium ions added. This provides a new approach to chirality control and has potential applications in biomimetic smart materials.

[0116] Example 3: Method for regulating the conformation of thermosensitive helical polyisocyanate by triethylene glycol

[0117] In this embodiment, triethylene glycol is used to achieve the regulation of the helical conformation of the thermosensitive helical polyisocyanate.

[0118] like Figure 10 As shown, the specific steps include:

[0119] The polymer Et-Glu-PPI prepared in Example 1 was dissolved in water to prepare a 0.05 wt% polymer aqueous solution. 3 ml of the polymer aqueous solution was taken, and 1-25 times the equivalent of triethylene glycol was added to the solution according to the calculated equivalent weight of the polymer molecular repeating unit to achieve regulation.

[0120] Experimental test analysis:

[0121] The Et-Glu-PPI prepared in this example was used as a sample to test its physical properties:

[0122] 1. Turbidity test:

[0123] The cloud point temperature (T cp ) to test, such as Figure 4 The cloud point temperature (T cp ) is 29.8°C. Compared with the cloud point temperature of the sample without adding triethylene glycol, the cloud point temperature of the sample decreases after adding triethylene glycol, and the polyisocyanate still has excellent temperature sensitivity at this time.

[0124] 2. Temperature-dependent circular dichroism spectroscopy test:

[0125] After adding triethylene glycol to the polymer Et-Glu-PPI solution, the helical conformation of the polymer was characterized by circular dichroism spectrometry, as shown in Figure 8 As shown, it can be seen from the variable temperature CD map (25-75°C) that at the phase transition temperature, the polymer induces a helical conformation, and the Cotton signal intensity of the polymer is significantly enhanced compared with the sample without adding triethylene glycol.

[0126] The above examples demonstrate that triethylene glycol significantly enhances the conformational order of polyisocyanurate, resulting in enhanced chirality in the polymer. Furthermore, the phase transition temperature of the polymer can be controlled by adjusting the actual amount of triethylene glycol added. This provides a promising approach for chirality control and has potential applications in biomimetic smart materials.

[0127] Example 4: Method for regulating the conformation of thermosensitive helical polyisocyanate by phenol

[0128] In this embodiment, phenol is used to achieve the regulation of the helical conformation of the thermosensitive helical polyisocyanate.

[0129] like Figure 10 As shown, the specific steps include:

[0130] The polymer Et-Glu-PPI prepared in Example 1 was dissolved in water to prepare a 0.05 wt% aqueous solution. Phenol was dissolved in water to prepare a 1 wt% aqueous solution. 3 ml of the aqueous solution was aspirated, and 1-5 equivalents of the phenol solution were added to the solution, calculated based on the equivalent weight of the repeating units of the polymer molecules, to achieve control.

[0131] Experimental test analysis:

[0132] The Et-Glu-PPI prepared in this example was used as a sample to test its physical properties:

[0133] 1. Turbidity test:

[0134] The cloud point temperature (T cp ) to test, such as Figure 5 The cloud point temperature of the polymer Et-Glu-PPI after adding phenol solution is 31.2℃. Compared with the cloud point temperature of the sample without adding phenol, the cloud point temperature of the sample decreases after adding phenol, and the polyisocyanate still has temperature-sensitive properties at this time.

[0135] 2. Temperature-dependent circular dichroism spectroscopy test:

[0136] After adding phenol to the polymer Et-Glu-PPI solution, the helical conformation of the polymer was characterized by circular dichroism spectroscopy, as shown in Figure 2. Figure 9 As shown in the CD diagram of variable temperature (25-75℃), it can be seen that at the phase transition temperature, polyisocyanate is difficult to induce a helical conformation.

[0137] The above examples demonstrate that the addition of phenol significantly inhibits the formation of a helical conformation in polyisocyanate, rendering the polymer chirally silent. Furthermore, the phase transition temperature of polyisocyanate can be controlled by adjusting the actual addition amount. This provides a new approach to chirality control and has potential applications in biomimetic smart materials.

[0138] In summary, the present invention discloses a method for synthesizing a novel thermosensitive helical polyisocyanate, and the helical conformation of the main chain of the thermosensitive polyisocyanate can be regulated by small molecule additives. This type of polyisocyanate has excellent thermosensitive properties, and in the thermosensitive process, accompanied by the dehydration collapse of the oligoethylene glycol motif, the chiral signal of its chiral amino acid motif can be transmitted to the polyisocyanate main chain, inducing the polyisocyanate to form a helical conformation. In addition, the small molecule additive can regulate the thermosensitive phase transition behavior of the polymer, and can also finely regulate the helical conformation of the polyisocyanate. The synthesis method of this novel thermosensitive helical polyisocyanate provides a new idea for the preparation of stimulus-responsive chiral materials, and the fine regulation of the helical conformation of the polyisocyanate by small molecule additives expands the application prospects of thermosensitive polyisocyanate in the field of smart materials.

[0139] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above-mentioned embodiments. The description of the embodiments is for the convenience of ordinary technicians in this technical field to understand and use the invention. It is obvious that those familiar with the technology in this field can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without having to go through creative work. Therefore, the present invention is not limited to the above-mentioned embodiments. Improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. A temperature-sensitive spiral polyisocyanate, characterized in that: The structural formula of the polyisocyanate is: Wherein: m = 100-500, n = 10-50, q = 0-4; R is a lower alkyl group; The lower alkyl group is a C1-C6 alkyl group.

2. A method for preparing the temperature-sensitive spiral polyisocyanate according to claim 1, characterized in that: The preparation method comprises the following steps: a. Pentafluorophenol active ester isocyanate monomer Pfp-PI was synthesized by amidation reaction using pentafluorophenol and 4-formamidobenzoic acid as raw materials; b. The pentafluorophenol active ester isocyanate monomer Pfp-PI obtained in step a and the amino-modified oligoethylene glycol moiety were used as raw materials to synthesize ethyl isocyanate monomer R-PI by amidation reaction; c. Using the pentafluorophenol active ester isocyanate monomer Pfp-PI obtained in step a and dimethyl glutamate hydrochloride as raw materials, an amidation reaction was performed to synthesize an ethyl isocyanate monomer Glu-PI; d. The thermosensitive helical polyisocyanate is synthesized by polymerization reaction using the ethyl isocyanate monomer R-PI obtained in step b and the ethyl isocyanate monomer Glu-PI obtained in step c as raw materials.

3. The method for preparing a temperature-sensitive spiral polyisocyanate according to claim 2, wherein: Step a includes the following specific steps: Pentafluorophenol and 4-formamidobenzoic acid are dissolved in dichloromethane, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride is added under ice-salt bath and inert gas protection, and after the reaction is complete, the obtained compound is separated and purified, and triphosgene is added, and the mixture is stirred until the reaction is complete. After separation and purification, ethyl isocyanate monomer Pfp-PI is obtained; The structural formula of the ethyl isocyanate monomer Pfp-PI is:

4. The method for preparing a temperature-sensitive spiral polyisocyanate according to claim 2, wherein: Step b includes the following specific steps: The pentafluorophenol active ester isocyanate monomer Pfp-PI obtained in step a and the amino-modified oligoethylene glycol unit are dissolved in dichloromethane to carry out an amidation reaction, and stirred until the reaction is complete. After separation and purification, an ethyl isocyanate monomer R-PI is obtained; In step b, the amidation reaction is carried out under ice bath conditions; The structural formula of the ethyl isocyanate monomer R-PI is:

5. The method for preparing a temperature-sensitive spiral polyisocyanate according to claim 2, wherein: Step c includes the following specific steps: Mixing dimethyl glutamate hydrochloride with the pentafluorophenol active ester isocyanate monomer Pfp-PI obtained in step a, adding dichloromethane, and performing an amidation reaction. After the reaction is complete, purifying to obtain the ethyl isocyanate monomer Glu-PI; In step c, the amidation reaction is carried out under ice bath conditions; The structural formula of the ethyl isocyanate monomer Glu-PI is:

6. The method for preparing a temperature-sensitive spiral polyisocyanate according to claim 2, wherein: Step d includes the following specific steps: The ethyl isocyanate monomer R-PI obtained in step b and the ethyl isocyanate monomer Glu-PI obtained in step c are dissolved in tetrahydrofuran, a polymerization catalyst is added under the protection of an inert gas, and a polymerization reaction is carried out at room temperature for 1 day. After the reaction is completed, the product is purified by column to obtain the temperature-sensitive helical polyisocyanate; In step d, the polymerization catalyst is nickel chloride hexahydrate; In step d, the polymerization reaction is carried out under stirring at a stirring rate of 200 to 800 rpm.

7. A use of the temperature-sensitive spiral polyisocyanate according to claim 1, characterized in that: The temperature-sensitive helical polyisocyanate is used as a bionic intelligent material.

8. A method for regulating the helical conformation of a thermosensitive helical polyisocyanate according to claim 1, characterized in that: The helical conformation regulation method adopts the following method: regulating the helical conformation of the thermosensitive helical polyisocyanate by using small molecule additives; The small molecule additive is selected from one or more of metal ions, diol derivatives, and benzene derivatives.

9. The method for regulating the helical conformation of a temperature-sensitive helical polyisocyanate according to claim 8, wherein: The addition of the metal ions promotes the formation of a helical conformation of the thermosensitive helical polyisocyanate; The metal ions include one or more of sodium ions, potassium ions, lithium ions, rubidium ions, cesium ions, magnesium ions, calcium ions, strontium ions, barium ions, aluminum ions, ferrous ions, ferric ions, stannous ions, tin ions, lead ions, copper ions, cuprous ions, silver ions, zinc ions, cadmium ions, manganese ions, chromium ions, cobalt ions, nickel ions, platinum ions, gold ions, titanium ions, bismuth ions, and indium ions; The addition of the diol derivative promotes the formation of a helical conformation of the thermosensitive helical polyisocyanate; The diol derivatives include one or more of ethylene glycol ether compounds, ethylene glycol ester compounds, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol, tripropylene glycol, dipropylene glycol, octanediol, decanediol, and dodecanediol; The addition of the benzene derivative hinders the formation of the helical conformation of the thermosensitive helical polyisocyanate; The benzene derivatives include one or more of phenol compounds, aniline compounds, benzoic acid compounds, salicylic acid, phthalic acid compounds, vanillin, guaiacol, gallic acid, and benzenesulfonic acid.

10. The method for regulating the helical conformation of a temperature-sensitive helical polyisocyanate according to claim 8, characterized in that: The helical conformation regulation method comprises the following steps: The thermosensitive spiral polyisocyanate is dissolved in water to prepare a thermosensitive spiral polyisocyanate aqueous solution, wherein the concentration of the thermosensitive spiral polyisocyanate aqueous solution is 0.001wt%-1wt%; adding a small molecule additive aqueous solution or a small molecule additive dropwise into a thermosensitive helical polyisocyanate aqueous solution to regulate the helical conformation of the thermosensitive helical polyisocyanate; The preparation of the small molecule additive aqueous solution comprises the following steps: dissolving the small molecule additive in water to prepare the small molecule additive aqueous solution, wherein the concentration of the small molecule additive aqueous solution is 0.1 wt%-10 wt%.

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