阅读说明：本技术 动态酰腙键构筑的温敏螺旋聚异氰衍生物及其制备方法 (Temperature-sensitive spiral polyisocyan derivative constructed by dynamic acylhydrazone bond and preparation method thereof ) 是由 张阿方 肖莉 吴迪 武剑慧 刘坤 张夏聪 李文 于 2020-06-08 设计创作，主要内容包括：本发明公开了一种动态酰腙键构筑的温敏螺旋聚异氰衍生物及其制备方法,螺旋聚异氰衍生物结构式为：<Image he="575" wi="390" file="DDA0002528043900000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>其中：m＝0.9-0.95,n＝1-m。R为谷氨酸二甲酯(Glu)、丙氨酸甲酯(Ala)、苯丙氨酸甲酯(Phe)或亮氨酸甲酯(Leu)。本发明利用将军士兵原理,用少量的手性谷氨酸类或者其它带醛基的氨基酸的小分子来诱导主链的螺旋构象。该类聚异氰衍生物具有优异的温敏特性,且可以通过温敏相变行为对聚合物螺旋构象进行调控。此外,螺旋构象的有序性也会影响聚合物的温敏行为。该类新型聚异氰衍生物的发明为制备刺激响应型手性材料提供了新的思路,并拓展了聚异氰衍生物在智能材料领域的应用前景。(The invention discloses a temperature-sensitive spiral polyisocyan derivative constructed by dynamic acylhydrazone bonds and a preparation method thereof, wherein the structural formula of the spiral polyisocyan derivative is as follows: wherein: m is 0.9-0.95 and n is 1-m. R is glutamic acidDimethyl ester (Glu), alanine methyl ester (Ala), phenylalanine methyl ester (Phe) or leucine methyl ester (Leu). The invention utilizes general soldier principle to induce the main chain helical conformation by using a small amount of chiral glutamic acid or other amino acid micromolecules with aldehyde group. The polyisocyan derivative has excellent temperature-sensitive characteristic, and can regulate and control the helical conformation of the polymer through temperature-sensitive phase transition behavior. Furthermore, the order of the helical conformation also affects the temperature-sensitive behavior of the polymer. The invention of the novel polyisocyan derivative provides a new thought for preparing a stimulus-responsive chiral material, and expands the application prospect of the polyisocyan derivative in the field of intelligent materials.)

1. A temperature-sensitive spiral polyisocyan derivative constructed by dynamic acylhydrazone bonds is characterized in that the structural formula of the polyisocyan derivative is as follows:

wherein: m is 0.95-0.9, n is 1-m; r is glutamic acid dimethyl ester (Glu), alanine methyl ester (Ala), phenylalanine methyl ester (Phe) or leucine methyl ester (Leu).

2. The dynamic acylhydrazone bond-building temperature-sensitive helical polyisocyanurate derivative according to claim 1, wherein: small molecules of glutamic acid, alanine, phenylalanine and leucine are used as chiral elements to induce main chain helical conformation.

3. The dynamic acylhydrazone bond-building temperature-sensitive helical polyisocyanurate derivative according to claim 1, wherein: the regulation and control of the helical conformation of the polyisocyanic main chain are realized by regulating the temperature.

4. The preparation method of the temperature-sensitive spiral polyisocyanurate derivative constructed by the dynamic acylhydrazone bond as claimed in claim 1 is characterized by comprising the following steps:

a. performing amino modification on the methyl-terminated oligomeric alkoxy ether basic unit and 4-formamide benzoic acid according to the weight ratio of 1.25: 1 in DCM, carrying out ice salt bath on the mixed solution, adding 1-hydroxybenzotriazole (HOBt) into the mixed solution under the protection of inert gas, stirring for at least 30 minutes, and then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC & HCl), wherein the dosage of the hydrochloride is 1 time of the molar quantity of linear alkoxy ether units; stirring until the reaction is complete, after separation and purification, dissolving the obtained monomer and triethylamine into DCM, dissolving triphosgene into DCM, slowly dripping into the mixed solution reaction system under the condition of ice salt bath, and after the reaction is carried out for at least 30 minutes, adding NaHCO₃Heating the solution to 0 ℃, and stirring until the reaction is complete; extract the aqueous phase with DCM, anhydrous MgSO₄Drying the organic phase, and separating and purifying to obtain a monomer NC-Ph-Me, wherein the structural formula of the monomer NC-Ph-Me is as follows:

b. dissolving pentafluorophenol and 4-formamide benzoic acid in DMF (dimethyl formamide) according to a molar ratio of 1:1, adding EDC & HCl with the amount being 1 time of the molar amount of pentafluorophenol in an ice salt bath and under the protection of inert gas, stirring until the reaction is complete, after separation and purification, dissolving the obtained monomer and triethylamine in DCM, dissolving triphosgene in DCM, slowly dropwise adding into the reaction system under the ice salt bath, and after the reaction is carried out for at least 30 minutes, adding NaHCO₃Heating the solution to 0 ℃, and stirring until the reaction is complete; the aqueous phase was extracted with DCM, anhydrous MgSO₄The organic phase was dried to remove DCM to give crudeSeparating and purifying the product to obtain monomer NC-OPfp, wherein the structural formula of the monomer NC-OPfp is as follows:

c. dissolving the monomer NC-Ph-Me obtained in the step a and the monomer NC-Opfp obtained in the step b in THF according to a molar ratio of 9:1, and adding a catalytic amount of NiCl under the protection of inert gas₂·H₂O, and reacting for 1 day at room temperature; purifying and passing through a column after the reaction is finished to obtain the polyisocyanic PPI-N-Me with the structural formula

d. Dissolving the polyisocyanic PPI-N-Me obtained in the step c in methanol, adding hydrazine hydrate at the temperature of 0 ℃ under the protection of inert gas, reacting for at least 4 hours, dialyzing for at least 5 days by using distilled water, and freeze-drying to obtain the linear alkoxy ether modified polyisocyanic PPI-N-H-Me, wherein the structural formula of the polyisocyanic PPI-N-Me is as follows:wherein: m is 0.9-0.95, n is 1-m;

e. the small molecules of PPI-N-H-Me and glutamic acid obtained in the step d are mixed according to a molar ratio of 1:1, and reacting in water to obtain the target product temperature-sensitive spiral polyisocyanurate derivative.

Technical Field

The invention relates to a spiral polymer and a preparation method thereof, in particular to a spiral polyisocyan derivative and a preparation method thereof, which are applied to the technical field of bionic intelligent materials.

Background

Macromolecules with a spiral structure in a natural life body are very common, such as nucleic acid and protein, the spiral structure plays an important role in realizing biological functions of the macromolecules, and biomimetic synthesis of the spiral polymer has important significance in understanding and simulating functions of the biomacromolecules and developing novel chiral materials. Synthetic helical polymers mainly include two types: dynamic helical polymers and static helical polymers. The polyisocyan is used as the first reported polymer with stable helical conformation, and has the characteristics of high rigidity, high-density stacking and the like, so that the helical conformation of the polyisocyan is not easily changed by the change of an external environment. Endows the polyisocyanic intelligent response characteristic, and further expands the application value of the polyisocyanic intelligent response characteristic in the field of intelligent and bionic materials. A dynamic bond is a chemical bond that can be reversibly generated and broken by the change of external conditions, such as light, heat, pH, chemicals, etc. Acylhydrazone bonds are a typical class of dynamic chemical bonds, generally formed by the reaction of hydrazine and an aldehyde or ketone, and have the following characteristics: (1) is thermodynamically stable under acidic (5 < pH < 7); (2) exhibits dynamic behavior under meta-acidic (4 < pH < 5); (3) the acylhydrazone bonds are capable of undergoing hydrolysis and exchange reactions under acidic conditions at a pH <4 or at elevated temperatures.

Cornelissen (Cornelissen. J., et al. science,2001,293(5530),676-680) et al reported that introduction of a polypeptide capable of forming an ordered hydrogen-bonding network into a polyisocyanic side chain resulted in a polypeptide polyisocyanic having a stable helical conformation, successfully mimicking the β -helical conformation of a natural protein₁Effective hydrogen bonds can be formed between n and n +4 polypeptide side groups on the main chain of the helix, so that the helix conformation of the main chain is stabilized. In recent years, Zhang Arfang topic group (HuG, A Zhang, et al. macromolecules,2013,46,1124-1132) introduces temperature sensitive elements into a spiral polymer to prepare a series of temperature sensitive spiral polymers, alkoxy ether elements are bonded to polyisocyanurate through chiral amino acids by dynamic bonds to prepare water-soluble temperature sensitive polyisocyanurate, and the research on the temperature sensitive behavior of the polymer discovers that the bonding mode influences the hydrophilicity and hydrophobicity of the polymer, so that the temperature sensitive behavior of the polymer is greatly influenced, the temperature sensitive behavior of the polymer is influenced by the secondary structure of the spiral polymer, and the OEG elements of the side chain are arranged more and more along with the improvement of the regularity of the spiral structure of the polymer, so that the interaction of hydrogen bonds between the inside of the polymer and water molecules is better shielded, the hydrophilic polymer is reduced, and the phase transition temperature of the polymer is reduced. Many studies on the helical polyisocyanic acid have been reported, but most of them achieve the induction of polymer helical conformation in organic solvent, but are very difficult in water, so that the application of the helical polyisocyanic acid in the biological field is limited.

Disclosure of Invention

In order to solve the problems in the prior art, the invention aims to overcome the defects in the prior art and provide a temperature-sensitive spiral polyisocyan derivative constructed by dynamic acylhydrazone bonds and a preparation method thereof.

In order to achieve the purpose of the invention, the invention adopts the following inventive concept:

the preparation method comprises the steps of carrying out amidation reaction on oligomerization linear alkoxy ether or dendritic alkoxy ether elements subjected to amino modification and pentafluorophenol active ester and 4-formamidobenzoic acid respectively, then carrying out triphosgene dehydration reaction to obtain two monomers NC-Ph-Me and NC-Opfp, carrying out catalytic polymerization on the two monomers in THF solution according to a certain proportion by using a metal nickel catalyst to obtain a polyisocyan derivative PPI-N-Me, purifying, adding hydrazine hydrate for hydrolysis, and finally obtaining the polyisocyan derivative PPI-N-H-Me, namely the polyisocyan derivative with temperature-sensitive regulation and control of spiral conformation. The specific reaction formula is as follows:

wherein: m is 0.95-0.9, n is 1-m. The polymer can induce the helical conformation through various chiral amino acid micromolecules with aldehyde groups, and can further regulate and control the helical conformation of the polyisocyan main chain by changing the temperature.

In order to achieve the purpose of the invention, the invention adopts the following technical scheme:

1. a temperature-sensitive spiral polyisocyan derivative constructed by dynamic acylhydrazone bonds is characterized in that the structural formula of the polyisocyan derivative is as follows:

wherein: m is 0.95-0.9, n is 1-m; r is glutamic acid dimethyl ester (Glu), alanine methyl ester (Ala), phenylalanine methyl ester (Phe) or leucine methyl ester (Leu).

As a preferred technical scheme of the invention, the temperature-sensitive spiral polyisocyanurate derivative is constructed by dynamic acylhydrazone bonds, and micromolecules of glutamic acid, alanine, phenylalanine and leucine are used as chiral elements to induce the main chain spiral conformation.

As the preferable technical scheme of the invention, the temperature-sensitive spiral polyisocyanurate derivative is constructed by dynamic acylhydrazone bonds, and the regulation and control of the spiral conformation of the polyisocyanurate main chain are realized by regulating the temperature.

The invention relates to a preparation method of a temperature-sensitive spiral polyisocyan derivative constructed by dynamic acylhydrazone bonds, which comprises the following steps:

a. performing amino modification on the methyl-terminated oligomeric alkoxy ether basic unit and 4-formamide benzoic acid according to the weight ratio of 1.25: 1 in DCM, carrying out ice salt bath on the mixed solution, adding 1-hydroxybenzotriazole (HOBt) into the mixed solution under the protection of inert gas, stirring for at least 30 minutes, and then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC & HCl), wherein the dosage of the hydrochloride is 1 time of the molar quantity of linear alkoxy ether units; stirring until the reaction is complete, after separation and purification, dissolving the obtained monomer and triethylamine into DCM, dissolving triphosgene into DCM, slowly dripping into the mixed solution reaction system under the condition of ice salt bath, and after the reaction is carried out for at least 30 minutes, adding NaHCO₃Heating the solution to 0 ℃, and stirring until the reaction is complete; extract the aqueous phase with DCM, anhydrous MgSO₄Drying the organic phase, and separating and purifying to obtain a monomer NC-Ph-Me, wherein the structural formula of the monomer NC-Ph-Me is as follows:

b. dissolving pentafluorophenol and 4-formamide benzoic acid in DMF (dimethyl formamide) according to a molar ratio of 1:1, adding EDC & HCl with the amount being 1 time of the molar amount of pentafluorophenol in an ice salt bath and under the protection of inert gas, stirring until the reaction is complete, after separation and purification, dissolving the obtained monomer and triethylamine in DCM, dissolving triphosgene in DCM, slowly dropwise adding into the reaction system under the ice salt bath, and after the reaction is carried out for at least 30 minutes, adding NaHCO₃Heating the solution to 0 ℃, and stirring until the reaction is complete; the aqueous phase was extracted with DCM, anhydrous MgSO₄Drying the organic phase, removing DCM to obtain a crude product, separating and purifying to obtain a monomer NC-OPfp, wherein the structural formula of the monomer NC-OPfp is as follows:

c. will be obtained in said step aDissolving the monomer NC-Ph-Me and the monomer NC-Opfp obtained in the step b in THF according to a molar ratio of 9:1, and adding a catalytic amount of NiCl under the protection of inert gas₂·H₂O, and reacting for 1 day at room temperature; purifying and passing through a column after the reaction is finished to obtain the polyisocyanic PPI-N-Me with the structural formula

d. Dissolving the polyisocyanic PPI-N-Me obtained in the step c in methanol, adding hydrazine hydrate at the temperature of 0 ℃ under the protection of inert gas, reacting for at least 4 hours, dialyzing for at least 5 days by using distilled water, and freeze-drying to obtain the linear alkoxy ether modified polyisocyanic PPI-N-H-Me, wherein the structural formula of the polyisocyanic PPI-N-Me is as follows:

wherein: m is 0.9-0.95, n is 1-m;

e. the small molecules of PPI-N-H-Me and glutamic acid obtained in the step d are mixed according to a molar ratio of 1:1, and reacting in water to obtain the target product temperature-sensitive spiral polyisocyanurate derivative.

The polyisocyan with the side group containing the oligomeric alkoxy ether chain and the hydrazide is prepared by a random copolymerization method, and the chiral micromolecule is simply, efficiently and reversibly grafted to the polyisocyan side chain through the reaction of the dynamic acylhydrazone bond between the acylhydrazone and the aldehyde group. The introduction of the oligomerization alkoxy ether element endows the polymer with excellent temperature-sensitive characteristic. In addition, the invention utilizes amino acid micromolecules with aldehyde groups to regulate the helical conformation of the polyisocyan derivative, and can also realize the regulation of the helical conformation of the main chain of the polyisocyan by regulating the temperature.

Compared with the prior art, the invention has the following obvious and prominent substantive characteristics and remarkable advantages:

1. the invention introduces methyl-terminated oligomeric alkoxy ether elements on the side chain of the polyisocyan, thereby endowing the polymer with excellent temperature-sensitive performance; chiral micromolecules are introduced into the polyisocyan main chain through a dynamic acylhydrazone bond, and the main chain is effectively induced to form a controllable spiral structure

2. The temperature-sensitive spiral polyisocyanurate derivative constructed by dynamic acylhydrazone bonds is prepared, the regulation and control of spiral conformation can be directly realized in a water phase by changing the temperature, and the application of the polyisocyanurate in the fields of bionic and intelligent response materials is widened;

3. the method is simple and easy to implement, low in cost and suitable for popularization and application.

Drawings

FIG. 1 shows the nuclear magnetic hydrogen spectrum characterization of PPI-N-H-Me in example one of the present invention: (¹H NMR CDCl₃，25℃，400MHz)。

Figure 2 is a UV-Vis survey (c 0.05 wt%, 700nm, 20 ℃) of PPI-N-H-Me and PPI-N-L-Glu according to example one of the present invention.

FIG. 3 is a turbidity curve of PPI-N-H-Me and PPI-N-L-Glu in an aqueous solution (c is 0.05 wt%, 700nm, and the heating/cooling rate is 0.2 ℃ C. min.)^-1)。

FIG. 4 is a temperature-variable circular dichroism spectrum of PPI-N-H-Me grafted chiral small molecule in aqueous solution (c is 0.05 wt%, 20 deg.C-80 deg.C, 240 nm, and scanning speed 500 nm. min.)^-1Temperature rise/decrease rate of 5 ℃ per minute^-1)。

FIG. 5 is a temperature-variable circular dichroism spectrum of PPI-N-H-Me grafted chiral small molecule in buffer solution (c ═ 0.05 wt%, 20 ℃ -80 ℃,240 nm, and scanning speed 500nm · min)^-1Temperature rise/decrease rate of 5 ℃ per minute^-1)。

Detailed Description

The preparation method of the oligomeric alkoxy ether element with the amino as the core adopted by the embodiment of the invention refers to documents Li, W.; zhang, a.; schl ü ter, a.d.chem.commun.2008,5523 and Yan J T; li W; liu K; wu D L; ChenF; wu P Y; zhang a. chem. asian j.2011,6,3260.

The above-described scheme is further illustrated below with reference to specific embodiments, which are detailed below: